{"topic_name": "coronavirus origin", "topic_id": "1", "title": "Virus\u2013Host Coevolution with a Focus on Animal and Human DNA Viruses", "abstract": "Viruses have been infecting their host cells since the dawn of life, and this extremely long-term coevolution gave rise to some surprising consequences for the entire tree of life. It is hypothesised that viruses might have contributed to the formation of the first cellular life form, or that even the eukaryotic cell nucleus originates from an infection by a coated virus. The continuous struggle between viruses and their hosts to maintain at least a constant fitness level led to the development of an unceasing arms race, where weapons are often shuttled between the participants. In this literature review we try to give a short insight into some general consequences or traits of virus\u2013host coevolution, and after this we zoom in to the viral clades of adenoviruses, herpesviruses, nucleo-cytoplasmic large DNA viruses, polyomaviruses and, finally, circoviruses.", "doc_id": "33fs6exl"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Origins of MERS-CoV, and lessons for 2019-nCoV", "abstract": "", "doc_id": "gyj5213f"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "The Origin and Evolution of Viruses", "abstract": "The lecture covers three main topics: (i) Viruses: properties, place in the living world, and possible origin; (ii) Molecular basis of viral variability and evolution; and (iii) Evolution of viral pathogenicity and emerging viral infections.", "doc_id": "gy8d8285"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Diversity of Coronaviruses in Bats: Insights Into Origin of SARS Coronavirus", "abstract": "", "doc_id": "6foz003n"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Intraspecies diversity of SARS-like coronaviruses in Rhinolophus sinicus and its implications for the origin of SARS coronaviruses in humans.", "abstract": "The Chinese rufous horseshoe bat (Rhinolophus sinicus) has been suggested to carry the direct ancestor of severe acute respiratory syndrome (SARS) coronavirus (SCoV), and the diversity of SARS-like CoVs (SLCoV) within this Rhinolophus species is therefore worth investigating. Here, we demonstrate the remarkable diversity of SLCoVs in R. sinicus and identify a strain with the same pattern of phylogenetic incongruence (i.e. an indication of recombination) as reported previously in another SLCoV strain. Moreover, this strain possesses a distinctive 579 nt deletion in the nsp3 region that was also found in a human SCoV from the late-phase epidemic. Phylogenetic analysis of the Orf1 region suggested that the human SCoVs are phylogenetically closer to SLCoVs in R. sinicus than to SLCoVs in other Rhinolophus species. These findings reveal a closer evolutionary linkage between SCoV in humans and SLCoVs in R. sinicus, defining the scope of surveillance to search for the direct ancestor of human SCoVs.", "doc_id": "0t2a5500"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Evidence for an Ancestral Association of Human Coronavirus 229E with Bats.", "abstract": "UNLABELLED We previously showed that close relatives of human coronavirus 229E (HCoV-229E) exist in African bats. The small sample and limited genomic characterizations have prevented further analyses so far. Here, we tested 2,087 fecal specimens from 11 bat species sampled in Ghana for HCoV-229E-related viruses by reverse transcription-PCR (RT-PCR). Only hipposiderid bats tested positive. To compare the genetic diversity of bat viruses and HCoV-229E, we tested historical isolates and diagnostic specimens sampled globally over 10 years. Bat viruses were 5- and 6-fold more diversified than HCoV-229E in the RNA-dependent RNA polymerase (RdRp) and spike genes. In phylogenetic analyses, HCoV-229E strains were monophyletic and not intermixed with animal viruses. Bat viruses formed three large clades in close and more distant sister relationships. A recently described 229E-related alpaca virus occupied an intermediate phylogenetic position between bat and human viruses. According to taxonomic criteria, human, alpaca, and bat viruses form a single CoV species showing evidence for multiple recombination events. HCoV-229E and the alpaca virus showed a major deletion in the spike S1 region compared to all bat viruses. Analyses of four full genomes from 229E-related bat CoVs revealed an eighth open reading frame (ORF8) located at the genomic 3' end. ORF8 also existed in the 229E-related alpaca virus. Reanalysis of HCoV-229E sequences showed a conserved transcription regulatory sequence preceding remnants of this ORF, suggesting its loss after acquisition of a 229E-related CoV by humans. These data suggested an evolutionary origin of 229E-related CoVs in hipposiderid bats, hypothetically with camelids as intermediate hosts preceding the establishment of HCoV-229E. IMPORTANCE The ancestral origins of major human coronaviruses (HCoVs) likely involve bat hosts. Here, we provide conclusive genetic evidence for an evolutionary origin of the common cold virus HCoV-229E in hipposiderid bats by analyzing a large sample of African bats and characterizing several bat viruses on a full-genome level. Our evolutionary analyses show that animal and human viruses are genetically closely related, can exchange genetic material, and form a single viral species. We show that the putative host switches leading to the formation of HCoV-229E were accompanied by major genomic changes, including deletions in the viral spike glycoprotein gene and loss of an open reading frame. We reanalyze a previously described genetically related alpaca virus and discuss the role of camelids as potential intermediate hosts between bat and human viruses. The evolutionary history of HCoV-229E likely shares important characteristics with that of the recently emerged highly pathogenic Middle East respiratory syndrome (MERS) coronavirus.", "doc_id": "n2o7iiew"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Animal source of the coronavirus continues to elude scientists.", "abstract": "", "doc_id": "4mtnqfqw"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination.", "abstract": "UNLABELLED Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr-BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high Ka/Ks ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS-CoV ORF8 originated from SARSr-CoVs of greater horseshoe bats through recombination, which may be important for animal-to-human transmission. IMPORTANCE Although horseshoe bats are the primary reservoir of SARS-related coronaviruses (SARSr-CoVs), it is still unclear how these bat viruses have evolved to cross the species barrier to infect civets and humans. Most human SARS-CoV epidemic strains contain a signature 29-nucleotide deletion in ORF8, compared to civet SARSr-CoVs, suggesting that ORF8 may be important for interspecies transmission. However, the origin of SARS-CoV ORF8 remains obscure. In particular, SARSr-Rs-BatCoVs from Chinese horseshoe bats (Rhinolophus sinicus) exhibited <40% amino acid identities to human/civet SARS-CoV in the ORF8 protein. We detected diverse alphacoronaviruses and betacoronaviruses among various bat species in Yunnan, China, including two SARSr-Rf-BatCoVs from greater horseshoe bats that possessed ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs. We demonstrated recombination events around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. Our findings offer insight into the evolutionary origin of SARS-CoV ORF8 protein, which was likely acquired from SARSr-CoVs of greater horseshoe bats through recombination.", "doc_id": "phlxsez8"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "COVID-19-A Novel Zoonotic Disease: A Review of the Disease, the Virus, and Public Health Measures.", "abstract": "A cluster of cases of pneumonia of unknown etiology emerged in Wuhan, China, at the end of December 2019. The cluster was largely associated with a seafood and animal market. A novel Betacoronavirus was quickly identified as the causative agent, and it is shown to be related genetically to SARS-CoV and other bat-borne SARS-related Betacoronaviruses. The number of cases increased rapidly and spread to other provinces in China, as well as to another 4 countries. To help control the spread of the virus, a \"cordon sanitaire\" was instituted for Wuhan on January 23, 2020, and subsequently extended to other cities in Hubei Province, and the outbreak declared a Public Health Emergency of International Concern by the Director General of the World Health Organization on January 30, 2020. The virus was named SARS-CoV-2 by the International Committee for the Taxonomy of Viruses, and the disease it causes was named COVID-19 by the World Health Organization. This article described the evolution of the outbreak, and the known properties of the novel virus, SARS-CoV-2 and the clinical disease it causes, and the major public health measures being used to help control it's spread. These measures include social distancing, intensive surveillance and quarantining of cases, contact tracing and isolation, cancellation of mass gatherings, and community containment. The virus is the third zoonotic coronavirus, after SARS-CoV and MERS-CoV, but appears to be the only one with pandemic potential. However, a number of important properties of the virus are still not well understood, and there is an urgent need to learn more about its transmission dynamics, its spectrum of clinical severity, its wildlife origin, and its genetic stability. In addition, more research is needed on possible interventions, particularly therapeutic and vaccines.", "doc_id": "qkl2yiqa"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "COVID-19: animals, veterinary and zoonotic links.", "abstract": "Coronavirus disease 2019 (COVID-19), has spread over 210 countries and territories beyond China shortly. On February 29, 2020, the World Health Organization (WHO) denoted it in a high-risk category, and on March 11, 2020, this virus was designated pandemic, after its declaration being a Public Health International Emergency on January 30, 2020. World over high efforts are being made to counter and contain this virus. The COVID-19 outbreak once again proves the potential of the animal-human interface to act as the primary source of emerging zoonotic diseases. Even though the circumstantial evidence suggests the possibility of an initial zoonotic emergence, it is too early to confirm the role of intermediate hosts such as snakes, pangolins, turtles, and other wild animals in the origin of SARS-CoV-2, in addition to bats, the natural hosts of multiple coronaviruses such as SARS-CoV and MERS-CoV. The lessons learned from past episodes of MERS-CoV and SARS-CoV are being exploited to retort this virus. Best efforts are being taken up by worldwide nations to implement effective diagnosis, strict vigilance, heightened surveillance, and monitoring, along with adopting appropriate preventive and control strategies. Identifying the possible zoonotic emergence and the exact mechanism responsible for its initial transmission will help us to design and implement appropriate preventive barriers against the further transmission of SARS-CoV-2. This review discusses in brief about the COVID-19/SARS-CoV-2 with a particular focus on the role of animals, the veterinary and associated zoonotic links along with prevention and control strategies based on One-health approaches.", "doc_id": "3uvuo4sf"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Global genetic patterns reveal host tropism versus cross-taxon transmission of bat Betacoronaviruses", "abstract": "Emerging infectious diseases due to coronavirus (CoV) infections have received significant global attention in the past decade and have been linked to bats as the original source. The diversity, distribution, and host associations of bat CoVs were investigated to assess their potential for zoonotic transmission. Phylogenetic, network, and principal coordinate analysis confirmed the classification of betacoronaviruses (BetaCoVs) into five groups (2A to 2E) and a potentially novel group, with further division of 2D into five subgroups. The genetic co-clustering of BetaCoVs among closely related bats reflects host taxon-specificity with each bat family as the host for a specific BetaCoV group, potentially a natural barrier against random transmission. The divergent pathway of BetaCoV and host evolution suggests that the viruses were introduced just prior to bat dispersal and speciation. As such, deviant patterns were observed such as for 2D-IV, wherein cross-taxon transmission due to overlap in bat habitats and geographic range among genetically divergent African bat hosts could have played a strong role on their shared CoV lineages. In fact, a few bat taxa especially the subfamily Pteropodinae were shown to host diverse groups of BetaCoVs. Therefore, ecological imbalances that disturb bat distribution may lead to loss of host specificity through cross-taxon transmission and multi-CoV infection. Hence, initiatives that minimize the destruction of wildlife habitats and limit wildlife-livestock-human interfaces are encouraged to help maintain the natural state of bat BetaCoVs in the wild. Importance Bat Betacoronaviruses (BetaCoVs) pose a significant threat to global public health and have been implicated in several epidemics such as the recent pandemic by severe acute respiratory syndrome coronavirus 2. Here, we show that bat BetaCoVs are predominantly host-specific, which could be a natural barrier against infection of other host types. However, a strong overlap in bat habitat and geographic range may facilitate viral transmission to unrelated hosts, and a few bat families have already been shown to host multi-CoV variants. We predict that continued disturbances on the ecological balance may eventually lead to loss of host specificity. When combined with enhanced wildlife-livestock-human interfaces, spillover to humans may be further facilitated. We should therefore start to define the ecological mechanisms surrounding zoonotic events. Global surveillance should be expanded and strengthened to assess the complete picture of bat coronavirus diversity and distribution and their potential to cause spillover infections.", "doc_id": "d8n9711b"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "2019 Novel Coronavirus Disease Outbreak and Molecular Genetic Characteristics of Severe Acute Respiratory Syndrome-coronavirus-2", "abstract": "The 2019 novel coronavirus disease (COVID-19) outbreaks that emerged in Wuhan city, Hubei province, have led to a formidable number of confirmed cases that resulted in >5,700 deaths globally, including 143 countries in all 6 continents. The World Health Organization declared a Public Health Emergency of International Concern with a very high level of global risk assessment. Severe acute respiratory syndrome (SARS)-coronavirus-2 (SARS-CoV-2), the agent of COVID-19, has >79% nucleotide sequence homology to SARS-CoV; therefore, both belong to the genus betacoronavirus and subgenus sarbecovirus. The S1 domains of the two appeared to share the cellular receptor ACE2, but revealed a much higher S1-ACE2 binding affinity. As seen in many other human coronaviruses, SARS-CoV-2 also shows respiratory infection, but the basic reproductive number (R0) in transmission and the clinical latency are quite dissimilar from those of SARS-or MERS-CoVs. Many scientists infer that the time point of cross-barrier transfer from bats to mediate animals or to humans should be a rather recent event based on the full-length genome analyses obtained from the very first patients. Copy-choice polymerization, which often leads to a significant genome recombination rate in most coronaviruses, predicts the continued emergence of novel coronaviruses.", "doc_id": "9a475qhj"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Predicting wildlife hosts of betacoronaviruses for SARS-CoV-2 sampling prioritization", "abstract": "Despite massive investment in research on reservoirs of emerging pathogens, it remains difficult to rapidly identify the wildlife origins of novel zoonotic viruses. Viral surveillance is costly but rarely optimized using model-guided prioritization strategies, and predictions from a single model may be highly uncertain. Here, we generate an ensemble of eight network- and trait-based statistical models that predict mammal-virus associations, and we use model predictions to develop a set of priority recommendations for sampling potential bat reservoirs and intermediate hosts for SARS-CoV-2 and related betacoronaviruses. We find over 200 bat species globally could be undetected hosts of betacoronaviruses. Although over a dozen species of Asian horseshoe bats (Rhinolophus spp.) are known to harbor SARS-like coronaviruses, we find at least two thirds of betacoronavirus reservoirs in this bat genus might still be undetected. Although identification of other probable mammal reservoirs is likely beyond existing predictive capacity, some of our findings are surprisingly plausible; for example, several civet and pangolin species were highlighted as high-priority species for viral sampling. Our results should not be over-interpreted as novel information about the plausibility or likelihood of SARS-CoV-2\u2019s ultimate origin, but rather these predictions could help guide sampling for novel potentially zoonotic viruses; immunological research to characterize key receptors (e.g., ACE2) and identify mechanisms of viral tolerance; and experimental infections to quantify competence of suspected host species.", "doc_id": "9q5zckir"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "The origin of SARS-CoV-2 in Istanbul: Sequencing findings from the epicenter of the pandemic in Turkey", "abstract": "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", "doc_id": "9mrtic2k"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Animal origins of SARS coronavirus: possible links with the international trade in small carnivores.", "abstract": "The search for animal host origins of severe acute respiratory syndrome (SARS) coronavirus has so far remained focused on wildlife markets, restaurants and farms within China. A significant proportion of this wildlife enters China through an expanding regional network of illegal, international wildlife trade. We present the case for extending the search for ancestral coronaviruses and their hosts across international borders into countries such as Vietnam and Lao People's Democratic Republic, where the same guilds of species are found on sale in similar wildlife markets or food outlets. The three species that have so far been implicated, a viverrid, a mustelid and a canid, are part of a large suite of small carnivores distributed across this region currently overexploited by this international wildlife trade. A major lesson from SARS is that the underlying roots of newly emergent zoonotic diseases may lie in the parallel biodiversity crisis of massive species loss as a result of overexploitation of wild animal populations and the destruction of their natural habitats by increasing human populations. To address these dual threats to the long-term future of biodiversity, including man, requires a less anthropocentric and more interdisciplinary approach to problems that require the combined research expertise of ecologists, conservation biologists, veterinarians, epidemiologists, virologists, as well as human health professionals.", "doc_id": "ur4eua83"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Mosaic evolution of the severe acute respiratory syndrome coronavirus.", "abstract": "Severe acute respiratory syndrome (SARS) is a deadly form of pneumonia caused by a novel coronavirus, a viral family responsible for mild respiratory tract infections in a wide variety of animals including humans, pigs, cows, mice, cats, and birds. Analyses to date have been unable to identify the precise origin of the SARS coronavirus. We used Bayesian, neighbor-joining, and split decomposition phylogenetic techniques on the SARS virus replicase, surface spike, matrix, and nucleocapsid proteins to reveal the evolutionary origin of this recently emerging infectious agent. The analyses support a mammalian-like origin for the replicase protein, an avian-like origin for the matrix and nucleocapsid proteins, and a mammalian-avian mosaic origin for the host-determining spike protein. A bootscan recombination analysis of the spike gene revealed high nucleotide identity between the SARS virus and a feline infectious peritonitis virus throughout the gene, except for a 200- base-pair region of high identity to an avian sequence. These data support the phylogenetic analyses and suggest a possible past recombination event between mammalian-like and avian-like parent viruses. This event occurred near a region that has been implicated to be the human receptor binding site and may have been directly responsible for the switch of host of the SARS coronavirus from animals to humans.", "doc_id": "8ccl9aui"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Evidence of the recombinant origin of a bat severe acute respiratory syndrome (SARS)-like coronavirus and its implications on the direct ancestor of SARS coronavirus.", "abstract": "Bats have been identified as the natural reservoir of severe acute respiratory syndrome (SARS)-like and SARS coronaviruses (SLCoV and SCoV). However, previous studies suggested that none of the currently sampled bat SLCoVs is the descendant of the direct ancestor of SCoV, based on their relatively distant phylogenetic relationship. In this study, evidence of the recombinant origin of the genome of a bat SLCoV is demonstrated. We identified a potential recombination breakpoint immediately after the consensus intergenic sequence between open reading frame 1 and the S coding region, suggesting the replication intermediates may participate in the recombination event, as previously speculated for other CoVs. Phylogenetic analysis of its parental regions suggests the presence of an uncharacterized SLCoV lineage that is phylogenetically closer to SCoVs than any of the currently sampled bat SLCoVs. Using various Bayesian molecular-clock models, interspecies transfer of this SLCoV lineage from bats to the amplifying host (e.g., civets) was estimated to have happened a median of 4.08 years before the SARS outbreak. Based on this relatively short window period, we speculate that this uncharacterized SLCoV lineage may contain the direct ancestor of SCoV. This study sheds light on the possible host bat species of the direct ancestor of SCoV, providing valuable information on the scope and focus of surveillance for the origin of SCoV.", "doc_id": "6zfmjq9p"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "SARS coronavirus without reservoir originated from an unnatural evolution, experienced the reverse evolution, and finally disappeared in the world.", "abstract": "", "doc_id": "jdpxu0ef"} {"topic_name": "coronavirus origin", "topic_id": "1", "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).]", "abstract": "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 \u00abCoronavirus - a global challenge to science\u00bc of the Scientific Council \u00abLife Science\u00bc 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).", "doc_id": "ia3rct46"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Novel human coronavirus (SARS-CoV-2): A lesson from animal coronaviruses", "abstract": "The recent pandemic caused by the novel human coronavirus, referrred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), not only is having a great impact on the health care systems and economies in all continents but it is also causing radical changes of common habits and life styles. The novel coronavirus (CoV) recognises, with high probability, a zoonotic origin but the role of animals in the SARS-CoV-2 epidemiology is still largely unknown. However, CoVs have been known in animals since several decades, so that veterinary coronavirologists have a great expertise on how to face CoV infections in animals, which could represent a model for SARS-CoV-2 infection in humans. In the present paper, we provide an up-to-date review of the literature currently available on animal CoVs, focusing on the molecular mechanisms that are responsible for the emergence of novel CoV strains with different antigenic, biologic and/or pathogenetic features. A full comprehension of the mechanisms driving the evolution of animal CoVs will help better understand the emergence, spreading, and evolution of SARS-CoV-2.", "doc_id": "su8czd4x"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives", "abstract": "The recent outbreak of COVID-19 in Wuhan turned into a public health emergency of international concern. With no antiviral drugs nor vaccines, and the presence of carriers without obvious symptoms, traditional public health intervention measures are significantly less effective. Here, we report the epidemiological and virological characteristics of the COVID-19 outbreak. Originated in bats, 2019-nCoV/ severe acute respiratory syndrome coronavirus (SARS-CoV)-2 likely experienced adaptive evolution in intermediate hosts before transfer to humans at a concentrated source of transmission. Similarities of receptor sequence binding to 2019-nCoV between humans and animals suggest a low species barrier for transmission of the virus to farm animals. We propose, based on the One Health model, that veterinarians and animal specialists should be involved in a cross-disciplinary collaboration in the fight against this epidemic.", "doc_id": "oi0zsdtd"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Cross-species transmission of the newly identified coronavirus 2019-nCoV", "abstract": "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.", "doc_id": "niytf3wo"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "2019_nCoV/SARS-CoV-2: rapid classification of betacoronaviruses and identification of Traditional Chinese Medicine as potential origin of zoonotic coronaviruses", "abstract": "The current outbreak of a novel severe acute respiratory syndrome-like coronavirus, 2019_nCoV (now named SARS-CoV-2), illustrated difficulties in identifying a novel coronavirus and its natural host, as the coding sequences of various Betacoronavirus species can be highly diverse. By means of whole-genome sequence comparisons, we demonstrate that the noncoding flanks of the viral genome can be used to correctly separate the recognized four betacoronavirus subspecies. The conservation would be sufficient to define target sequences that could, in theory, classify novel virus species into their subspecies. Only 253 upstream noncoding sequences of Sarbecovirus are sufficient to identify genetic similarities between species of this subgenus. Furthermore, it was investigated which bat species have commercial value in China, and would thus likely be handled for trading purposes. A number of coronavirus genomes have been published that were obtained from such bat species. These bats are used in Traditional Chinese Medicine, and their handling poses a potential risk to cause zoonotic coronavirus epidemics. SIGNIFICANCE AND IMPACT OF THE STUDY: The noncoding upstream and downstream flanks of coronavirus genomes allow for rapid classification of novel Betacoronavirus species and correct identification of genetic relationships. Although bats are the likely natural host of 2019_nCoV, the exact bat species that serves as the natural host of the virus remains as yet unknown. Chinese bat species with commercial value were identified as natural reservoirs of coronaviruses and are used in Traditional Chinese Medicine. Since their trading provides a potential risk for spreading zoonoses, a change in these practices is highly recommended.", "doc_id": "ex7rta8f"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Spillover of SARS-CoV-2 into novel wild hosts in North America: A conceptual model for perpetuation of the pathogen", "abstract": "There is evidence that the current outbreak of the novel coronavirus SARS-CoV-2, which causes COVID-19, is of animal origin. As with a number of zoonotic pathogens, there is a risk of spillover into novel hosts. Here, we propose a hypothesized conceptual model that illustrates the mechanism whereby the SARS-CoV-2 could spillover from infected humans to naive wildlife hosts in North America. This proposed model is premised on transmission of SARS-CoV-2 from human feces through municipal waste water treatment plants into the natural aquatic environment where potential wildlife hosts become infected. We use the existing literature on human coronaviruses, including SARS CoV, to support the potential pathways and mechanisms in the conceptual model. Although we focus on North America, our conceptual model could apply to other parts of the globe as well.", "doc_id": "lhh2b4r0"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Origin and evolution of the 2019 novel coronavirus", "abstract": "", "doc_id": "xwi9pdd2"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Response to \"Comments on \"Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human\" and \"Codon bias analysis alone is uninformative for identifying host(s) of new virus\"", "abstract": "We have recently reported for the first time that SARS-CoV-2 maybe a bat-originated coronavirus with a recombination occurred within the spike (S) protein gene based on phylogenetic and simplot analyses1 . These two conclusions are supported by findings recently reported by others and are well accepted in the field of SARS-CoV-2 research2-4 . This article is protected by copyright. All rights reserved.", "doc_id": "3x2psny9"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Mystery deepens over animal source of coronavirus", "abstract": "", "doc_id": "3840bxvn"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "A pneumonia outbreak associated with a new coronavirus of probable bat origin", "abstract": "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.", "doc_id": "w53u5ive"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "COVID-19 and veterinarians for one health, zoonotic- and reverse-zoonotic transmissions", "abstract": "A novel coronavirus emerged in human populations and spread rapidly to cause the global coronavirus disease 2019 pandemic. Although the origin of the associated virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) remains unclear, genetic evidence suggests that bats are a reservoir host of the virus, and pangolins are a probable intermediate. SARS-CoV-2 has crossed the species barrier to infect humans and other animal species, and infected humans can facilitate reverse-zoonotic transmission to animals. Considering the rapidly changing interconnections among people, animals, and ecosystems, traditional roles of veterinarians should evolve to include transdisciplinary roles.", "doc_id": "3jgedokv"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Genomic variance of the 2019-nCoV coronavirus", "abstract": "There is a rising global concern for the recently emerged novel coronavirus (2019-nCoV). Full genomic sequences have been released by the worldwide scientific community in the last few weeks to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and severe acute respiratory syndrome. We confirm high sequence similarity (>99%) between all sequenced 2019-nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019-nCoV. Despite the low heterogeneity of the 2019-nCoV genomes, we could identify at least two hypervariable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8-encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti-coronavirus approaches.", "doc_id": "uaoyounl"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Zoonotic origins of human coronaviruses", "abstract": "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.", "doc_id": "dnla56uh"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study", "abstract": "BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown \u00df-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.", "doc_id": "klzen04m"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Detection of novel coronaviruses in bats in Myanmar", "abstract": "The recent emergence of bat-borne zoonotic viruses warrants vigilant surveillance in their natural hosts. Of particular concern is the family of coronaviruses, which includes the causative agents of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and most recently, Coronavirus Disease 2019 (COVID-19), an epidemic of acute respiratory illness originating from Wuhan, China in December 2019. Viral detection, discovery, and surveillance activities were undertaken in Myanmar to identify viruses in animals at high risk contact interfaces with people. Free-ranging bats were captured, and rectal and oral swabs and guano samples collected for coronaviral screening using broadly reactive consensus conventional polymerase chain reaction. Sequences from positives were compared to known coronaviruses. Three novel alphacoronaviruses, three novel betacoronaviruses, and one known alphacoronavirus previously identified in other southeast Asian countries were detected for the first time in bats in Myanmar. Ongoing land use change remains a prominent driver of zoonotic disease emergence in Myanmar, bringing humans into ever closer contact with wildlife, and justifying continued surveillance and vigilance at broad scales.", "doc_id": "yon280y8"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Possible Bat Origin of Severe Acute Respiratory Syndrome Coronavirus 2", "abstract": "We showed that severe acute respiratory syndrome coronavirus 2 is probably a novel recombinant virus. Its genome is closest to that of severe acute respiratory syndrome-related coronaviruses from horseshoe bats, and its receptor-binding domain is closest to that of pangolin viruses. Its origin and direct ancestral viruses have not been identified.", "doc_id": "kqqantwg"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Zoonotic origins of human coronavirus 2019 (HCoV-19 / SARS-CoV-2): why is this work important?", "abstract": "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.", "doc_id": "75773gwg"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Master Regulator Analysis of the SARS-CoV-2/Human Interactome", "abstract": "The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. In this paper, we set out to shed light on the SARS-CoV-2/host receptor recognition, a crucial factor for successful virus infection. Based on the current knowledge of the interactome between SARS-CoV-2 and host cell proteins, we performed Master Regulator Analysis to detect which parts of the human interactome are most affected by the infection. We detected, amongst others, affected apoptotic and mitochondrial mechanisms, and a downregulation of the ACE2 protein receptor, notions that can be used to develop specific therapies against this new virus.", "doc_id": "tvoxbi3q"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Coronaviruses: origin and evolution", "abstract": "", "doc_id": "jkejiuf2"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Mapping the genomic landscape & diversity of COVID-19 based on >3950 clinical isolates of SARS-CoV-2: Likely origin & transmission dynamics of isolates sequenced in India", "abstract": "", "doc_id": "q8dq3alv"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Pangolins Harbor SARS-CoV-2-Related Coronaviruses", "abstract": "The pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed a severe threat to global public health. Yet, the origin of SARS-CoV-2 remains mysterious. Several recent studies (e.g., Lam et al.,Xiao et al.) identified SARS-CoV-2-related viruses in pangolins, providing novel insights into the evolution and diversity of SARS-CoV-2-related viruses.", "doc_id": "pfv7q4v6"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Genomic characterization and infectivity of a novel SARS-like coronavirus in Chinese bats", "abstract": "SARS coronavirus (SARS-CoV), the causative agent of the large SARS outbreak in 2003, originated in bats. Many SARS-like coronaviruses (SL-CoVs) have been detected in bats, particularly those that reside in China, Europe, and Africa. To further understand the evolutionary relationship between SARS-CoV and its reservoirs, 334 bats were collected from Zhoushan city, Zhejiang province, China, between 2015 and 2017. PCR amplification of the conserved coronaviral protein RdRp detected coronaviruses in 26.65% of bats belonging to this region, and this number was influenced by seasonal changes. Full genomic analyses of the two new SL-CoVs from Zhoushan (ZXC21 and ZC45) showed that their genomes were 29,732 nucleotides (nt) and 29,802 nt in length, respectively, with 13 open reading frames (ORFs). These results revealed 81% shared nucleotide identity with human/civet SARS CoVs, which was more distant than that observed previously for bat SL-CoVs in China. Importantly, using pathogenic tests, we found that the virus can reproduce and cause disease in suckling rats, and further studies showed that the virus-like particles can be observed in the brains of suckling rats by electron microscopy. Thus, this study increased our understanding of the genetic diversity of the SL-CoVs carried by bats and also provided a new perspective to study the possibility of cross-species transmission of SL-CoVs using suckling rats as an animal model.", "doc_id": "vp1r00m9"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "The virus whose family expanded", "abstract": "The discovery of many new species of hepaciviruses and pegiviruses, which exhibit enormous genetic diversity, in wild rodent and bat populations might help us to understand the origins of the hepatitis C virus.", "doc_id": "nw0jbs1s"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Comments to the predecessor of human SARS coronavirus in 2003\u20132004 epidemic", "abstract": "", "doc_id": "xa8b1nuo"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "2019-nCoV in context: lessons learned?", "abstract": "", "doc_id": "oxs4o9xe"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Host-related nucleotide composition and codon usage as driving forces in the recent evolution of the Astroviridae", "abstract": "Abstract The evolutionary history of the Astroviridae comprises the ancient separation between avian and mammalian astrovirus lineages followed by diversification among mammalian astroviruses. The latter process included several cross-species transmissions. We found that the recent, but not the ancient, evolution of astroviruses was associated with a switch in nucleotide composition and codon usage among non-human mammalian versus human/avian astroviruses. Virus and hosts phylogenies based on codon usage agreed with each other and matched the hosts' evolutionary emergence order. This recent switch in driving forces acting at the synonymous level points to the adaptation of codon usage by viruses to that of their hosts after cross-species transmissions. This is the first demonstration of nucleotide composition and codon usage being active driving forces during the recent evolutionary history of a virus group in the host\u2013parasite system.", "doc_id": "vlpdirjs"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Exceptional diversity and selection pressure on SARS-CoV and SARS-CoV-2 host receptor in bats compared to other mammals", "abstract": "Pandemics originating from pathogen transmission between animals and humans highlight the broader need to understand how natural hosts have evolved in response to emerging human pathogens and which groups may be susceptible to infection. Here, we investigate angiotensin-converting enzyme 2 (ACE2), the host protein bound by SARS-CoV and SARS-CoV-2. We find that the ACE2 gene is under strong selection pressure in bats, the group in which the progenitors of SARS-CoV and SARS-CoV-2 are hypothesized to have evolved, particularly in residues that contact SARS-CoV and SARS-CoV-2. We detect positive selection in non-bat mammals in ACE2 but in a smaller proportion of branches than in bats, without enrichment of selection in residues that contact SARS-CoV or SARS-CoV-2. Additionally, we evaluate similarity between humans and other species in residues that contact SARS-CoV or SARS-CoV-2, revealing potential susceptible species but also highlighting the difficulties of predicting spillover events. This work increases our understanding of the relationship between mammals, particularly bats, and coronaviruses, and provides data that can be used in functional studies of how host proteins are bound by SARS-CoV and SARS-CoV-2 strains.", "doc_id": "ijsn8d7b"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Newly identified viral genomes in pangolins with fatal disease", "abstract": "Epizootic pathogens pose a major threat to many wildlife species, particularly in the context of rapidly changing environments. Pangolins (order Pholidota) are highly threatened mammals, in large part due to the trade in illegal wildlife. During July to August 2018 four sick wild pangolins (three Manis javanica and one Manis pentadactyla) exhibiting a variety of clinical symptoms were rescued by the Jinhua Wildlife Protection Station in Zhejiang province, China. Although three of these animals died, fortunately one recovered after 2 weeks of symptomatic treatment. Using meta-transcriptomics combined with reverse transcription polymerase chain reaction (RT-PCR), we identified two novel RNA viruses in two of the dead pangolins. Genomic analysis revealed that these viruses were most closely related to pestiviruses and coltiviruses, although still highly genetically distinct, with more than 48 and 25 per cent sequence divergence at the amino acid level, respectively. We named these Dongyang pangolin virus (DYPV) and Lishui pangolin virus (LSPV) based on the sampling site and hosts. Although coltiviruses (LSPV) are known to be transmitted by ticks, we found no evidence of LSPV in ticks sampled close to where the pangolins were collected. In addition, although DYPV was present in nymph ticks (Amblyomma javanense) collected from a diseased pangolin, they were not found in the local tick population. Epidemiological investigation revealed that both novel viruses might have been imported following the illegal international trade of pangolins. Hence, these data indicate that illegal wildlife trafficking not only threatens the status of pangolin populations, but may also spread epizootic pathogens.", "doc_id": "h3imwhss"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Origins of major human infectious diseases", "abstract": "Many of the major human infectious diseases, including some now confined to humans and absent from animals, are \u2018new\u2019 ones that arose only after the origins of agriculture. Where did they come from? Why are they overwhelmingly of Old World origins? Here we show that answers to these questions are different for tropical and temperate diseases; for instance, in the relative importance of domestic animals and wild primates as sources. We identify five intermediate stages through which a pathogen exclusively infecting animals may become transformed into a pathogen exclusively infecting humans. We propose an initiative to resolve disputed origins of major diseases, and a global early warning system to monitor pathogens infecting individuals exposed to wild animals. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature05775) contains supplementary material, which is available to authorized users.", "doc_id": "a1chcrk8"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "A Mathematical Model of the Evolution and Spread of Pathogenic Coronaviruses from Natural Host to Human Host", "abstract": "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.", "doc_id": "afx977mr"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Common RNA replication signals exist among group 2 coronaviruses: evidence for in vivo recombination between animal and human coronavius molecules", "abstract": "Abstract 5\u2032 and 3\u2032 UTR sequences on the coronavirus genome are known to carry cis-acting elements for DI RNA replication and presumably also virus genome replication. 5\u2032 UTR-adjacent coding sequences are also thought to harbor cis-acting elements. Here we have determined the 5\u2032 UTR and adjacent 289-nt sequences, and 3\u2032 UTR sequences, for six group 2 coronaviruses and have compared them to each other and to three previously reported group 2 members. Extensive regions of highly similar UTR sequences were found but small regions of divergence were also found indicating group 2 coronaviruses could be subdivided into those that are bovine coronavirus (BCoV)-like (BCoV, human respiratory coronavirus-OC43, human enteric coronavirus, porcine hemagglutinating encephalomyelitis virus, and equine coronavirus) and those that are murine hepatitis virus (MHV)-like (A59, 2, and JHM strains of MHV, puffinosis virus, and rat sialodacryoadenitis virus). The 3\u2032 UTRs of BCoV and MHV have been previously shown to be interchangeable. Here, a reporter-containing BCoV DI RNA was shown to be replicated by all five BCoV-like helper viruses and by MHV-H2 (a human cell-adapted MHV strain), a representative of the MHV-like subgroup, demonstrating group 2 common 5\u2032 and 3\u2032 replication signaling elements. BCoV DI RNA, furthermore, acquired the leader of HCoV-OC43 by leader switching, demonstrating for the first time in vivo recombination between animal and human coronavirus molecules. These results indicate that common replication signaling elements exist among group 2 coronaviruses despite a two-cluster pattern within the group and imply there could exist a high potential for recombination among group members.", "doc_id": "2l4xxu3v"} {"topic_name": "coronavirus origin", "topic_id": "1", "title": "Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins", "abstract": "The outbreak of 2019-nCoV in the central Chinese city of Wuhan at the end of 2019 poses unprecedent public health challenges to both China and the rest world1. The new coronavirus shares high sequence identity to SARS-CoV and a newly identified bat coronavirus2. While bats may be the reservoir host for various coronaviruses, whether 2019-nCoV has other hosts is still ambiguous. In this study, one coronavirus isolated from Malayan pangolins showed 100%, 98.2%, 96.7% and 90.4% amino acid identity with 2019-nCoV in the E, M, N and S genes, respectively. In particular, the receptor-binding domain of the S protein of the Pangolin-CoV is virtually identical to that of 2019-nCoV, with one amino acid difference. Comparison of available genomes suggests 2019-nCoV might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. Infected pangolins showed clinical signs and histopathological changes, and the circulating antibodies reacted with the S protein of 2019-nCoV. The isolation of a coronavirus that is highly related to 2019-nCoV in the pangolins suggests that these animals have the potential to act as the intermediate host of 2019-nCoV. The newly identified coronavirus in the most-trafficked mammal could represent a continuous threat to public health if wildlife trade is not effectively controlled.", "doc_id": "mw0wb8a8"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Effect modification of environmental factors on influenza-associated mortality: a time-series study in two Chinese cities", "abstract": "BACKGROUND: Environmental factors have been associated with transmission and survival of influenza viruses but no studies have ever explored the role of environmental factors on severity of influenza infection. METHODS: We applied a Poisson regression model to the mortality data of two Chinese metropolitan cities located within the subtropical zone, to calculate the influenza associated excess mortality risks during the periods with different levels of temperature and humidity. RESULTS: The results showed that high absolute humidity (measured by vapor pressure) was significantly (p < 0.05) associated with increased risks of all-cause and cardiorespiratory deaths, but not with increased risks of pneumonia and influenza deaths. The association between absolute humidity and mortality risks was found consistent among the two cities. An increasing pattern of influenza associated mortality risks was also found across the strata of low to high relative humidity, but the results were less consistent for temperature. CONCLUSIONS: These findings highlight the need for people with chronic cardiovascular and respiratory diseases to take extra caution against influenza during hot and humid days in the subtropics and tropics.", "doc_id": "crla8vrj"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Nature of transmission of Covid19 in India", "abstract": "We examine available data on the number of individuals infected by the Covid-19 virus, across several different states in India, over the period January 30, 2020 to April 10, 2020. It is found that the growth of the number of infected individuals $N(t)$ can be modeled across different states with a simple linear function $N(t)=\\gamma+\\alpha t$ beyond the date when reasonable number of individuals were tested (and when a countrywide lockdown was imposed). The slope $\\alpha$ is different for different states. Following recent work by Notari (arxiv:2003.12417), we then consider the dependency of the $\\alpha$ for different states on the average maximum and minimum temperatures, the average relative humidity and the population density in each state. It turns out that like other countries, the parameter $\\alpha$, which determines the rate of rise of the number of infected individuals, seems to have a weak correlation with the average maximum temperature of the state. In contrast, any significant variation of $\\alpha$ with humidity or minimum temperature seems absent with almost no meaningful correlation. Expectedly, $\\alpha$ increases (slightly) with increase in the population density of the states; however, the degree of correlation here too is negligible. These results seem to barely suggest that a natural cause like a hot summer (larger maximum temperatures) may contribute towards reducing the transmission of the virus, though the role of minimum temperature, humidity and population density remains somewhat obscure from the inferences which may be drawn from presently available data.", "doc_id": "iv7dok0v"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Any contribution of the season change to the spread of covid-19 caused by sars-cov-2?", "abstract": "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.", "doc_id": "q3tc522t"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "An environmental determinant of viral respiratory disease", "abstract": "The evident seasonality of influenza suggests a significant role for weather and climate as one of several determinants of viral respiratory disease (VRD), including social determinants which play a major role in shaping these phenomena. Based on the current mechanistic understanding of how VRDs are transmitted by small droplets, we identify an environmental variable, Air Drying Capacity (ADC), as an atmospheric state-variable with significant and direct relevance to the transmission of VRD. ADC dictates the evolution and fate of droplets under given temperature and humidity conditions. The definition of this variable is rooted in the Maxwell theory of droplet evolution via coupled heat and mass transfer between droplets and the surrounding environment. We present the climatology of ADC, and compare its observed distribution in space and time to the observed prevalence of influenza and COVID-19 from extensive global data sets. Globally, large ADC values appear to significantly constrain the observed transmission and spread of VRD, consistent with the significant coherency of the observed seasonal cycles of ADC and influenza. Our results introduce a new environmental determinant, rooted in the mechanism of VRD transmission, with potential implications for explaining seasonality of influenza, and for describing how environmental conditions may impact to some degree the evolution of similar VRDs, such as COVID-19.", "doc_id": "24pp67fw"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Impact Of Temperature and Sunshine Duration on Daily New Cases and Death due to COVID-19", "abstract": "Background: The coronavirus pandemic (COVID-19) control has now become a critical issue for public health. Many ecological factors are proven to influence the transmission and survival of the virus. In this study, we aim to determine the association of different climate factors with the spread and mortality due to COVID-19. Methods: The climate indicators included in the study were duration of sunshine, average minimum temperature and average maximum temperature, with cumulative confirmed cases, deceased and recovered cases. The data was performed for 138 different countries of the world, between January 2020 to May 2020. Both univariate and multivariate was performed for cumulative and month-wise analysis using SPSS software. Results: The average maximum temperature, and sunshine duration was significantly associated with COVID-19 confirmed cases, deceased and recovered. For every one degree increase in mean average temperature, the confirmed, deceased and recovered cases decreased by 2047(p=0.03), 157(p=0.016), 743 (p=0.005) individuals. The association remained significant even after adjusting for environmental such as sunshine duration as well as non-environmental variables. Average sunshine duration was inversely correlated with increase in daily new cases ({rho}= -2261) and deaths ({rho}= -0.2985). Conclusion: Higher average temperature and longer sunshine duration was strongly associated with COVID-19 cases and deaths in 138 countries. Hence the temperature is an important factor in SARS CoV-2 survival and this study will help in formulating better preventive measures to combat COVID-19 based on their climatic conditions.", "doc_id": "t3e8bfnr"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Impact of Daily Weather on COVID-19 outbreak in India", "abstract": "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.", "doc_id": "uj8a09t3"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Effect of Temperature on the Transmission of COVID-19: A Machine Learning Case Study in Spain", "abstract": "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.", "doc_id": "r9yrr45q"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Associations of ambient air pollutants and meteorological factors with COVID-19 transmission in 31 Chinese provinces: A time-series study", "abstract": "Background: Evidence regarding the effects of ambient air pollutants and meteorological factors on COVID-19 transmission is limited. Objectives: To explore the associations of air pollutants and meteorological factors with COVID-19 confirmed cases across 31 Chinese provinces during the outbreak period. Methods: The number of COVID-19 confirmed cases, air pollutant concentrations and meteorological factors in 31 Chinese provinces from January 25 to February 29, 2020 were extracted from authoritative electronic databases. The associations were estimated for a single-day lag (lag0-lag6) as well as moving averages lag (lag01-lag05) using generalized additive mixed models (GAMMs), adjusted for time trends, day of the week, holidays and meteorological variables. Region-specific analyses and meta-analysis were conducted in five selected regions with diverse air pollution levels and weather conditions. Nonlinear exposure-response analyses were performed. Results: We examined 77,578 COVID-19 confirmed cases across 31 Chinese provinces during the study period. An increase of each interquartile range in PM2.5, PM10, SO2, NO2, O3 and CO at lag4 corresponded to 1.40 (1.37-1.43), 1.35 (1.32-1.37), 1.01 (1.00-1.02), 1.08 (1.07-1.10), 1.28 (1.27-1.29) and 1.26 (1.24-1.28) odds ratios (ORs) of daily COVID-19 confirmed new cases, respectively. For 1 oc, 1% and 1 m/s increase in temperature, relative humidity and wind velocity, the ORs were 0.97 (0.97-0.98), 0.96 (0.96-0.97), and 0.94 (0.92-0.95), respectively. The estimates of PM2.5, PM10, NO2 and all meteorological factors remained statistically significant after meta-analysis for the five selected regions. The exposure-response relationships showed that higher concentrations of air pollutants and lower meteorological factors were associated with daily COVID-19 confirmed new cases increasing. Conclusions: Higher air pollutant concentrations and lower temperature, relative humidity and wind velocity may favor COVID-19 transmission. As summer months are arriving in the Northern Hemisphere, the environmental factors and implementation of public health control measures may play an optimistic role in controlling COVID-19 epidemic.", "doc_id": "aqozmk1t"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "The Association of Social Distancing, Population Density, and Temperature with the SARS-CoV-2 Instantaneous Reproduction Number in Counties Across the United States", "abstract": "Importance: The Covid-19 pandemic has been marked by considerable heterogeneity in outbreaks across the United States. Local factors that may be associated with variation in SARS-CoV-2 transmission have not been well studied. Objective: To examine the association of county-level factors with variation in the SARS-CoV-2 reproduction number over time. Design: Observational study Setting: 211 counties in 46 states and the District of Columbia between February 25, 2020 and April 23, 2020. Participants: Residents within the counties (55% of the US population) Exposures: Social distancing as measured by percent change in visits to non-essential businesses, population density, lagged daily wet bulb temperatures. Main Outcomes and Measures: The instantaneous reproduction number (Rt) which is the estimated number of cases generated by one case at a given time during the pandemic. Results: Median case incidence was 1185 cases and fatality rate was 43.7 deaths per 100,000 people for the top decile of 21 counties, nearly ten times the incidence and fatality rate in the lowest density quartile. Average Rt in the first two weeks was 5.7 (SD 2.5) in the top decile, compared to 3.1 (SD 1.2) in the lowest quartile. In multivariable analysis, a 50% decrease in visits to non-essential businesses was associated with a 57% decrease in Rt (95% confidence interval, 56% to 58%). Cumulative temperature effects over 4 to 10 days prior to case incidence were nonlinear; relative Rt decreased as temperatures warmed above 32F to 53F, which was the point of minimum Rt, then increased between 53F and 66F, at which point Rt began to decrease. At 55F, and with a 70% reduction in visits to non-essential business, 96% of counties were estimated to fall below a threshold Rt of 1.0, including 86% of counties among the top density decile and 98% of counties in the lowest density quartile. Conclusions and Relevance: Social distancing, lower population density, and temperate weather change were associated with a decreased SARS-Co-V-2 Rt in counties across the United States. These relationships can inform selective public policy planning in communities during the SARS-CoV-2 pandemic.", "doc_id": "tqnwk4o6"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Diverse local epidemics reveal the distinct effects of population density, demographics, climate, depletion of susceptibles, and intervention in the first wave of COVID-19 in the United States", "abstract": "The SARS-CoV-2 pandemic has caused significant mortality and morbidity worldwide, sparing almost no community. As the disease will likely remain a threat for years to come, an understanding of the precise influences of human demographics and settlement, as well as the dynamic factors of climate, susceptible depletion, and intervention, on the spread of localized epidemics will be vital for mounting an effective response. We consider the entire set of local epidemics in the United States; a broad selection of demographic, population density, and climate factors; and local mobility data, tracking social distancing interventions, to determine the key factors driving the spread and containment of the virus. Assuming first a linear model for the rate of exponential growth (or decay) in cases/mortality, we find that population-weighted density, humidity, and median age dominate the dynamics of growth and decline, once interventions are accounted for. A focus on distinct metropolitan areas suggests that some locales benefited from the timing of a nearly simultaneous nationwide shutdown, and/or the regional climate conditions in mid-March; while others suffered significant outbreaks prior to intervention. Using a first-principles model of the infection spread, we then develop predictions for the impact of the relaxation of social distancing and local climate conditions. A few regions, where a significant fraction of the population was infected, show evidence that the epidemic has partially resolved via depletion of the susceptible population (i.e., \"herd immunity\"), while most regions in the United States remain overwhelmingly susceptible. These results will be important for optimal management of intervention strategies, which can be facilitated using our online dashboard.", "doc_id": "t70lnidk"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Correlation of the global spread of coronavirus disease-19 with atmospheric air temperature", "abstract": "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.", "doc_id": "foha7ozb"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Temperature and Humidity Do Not Influence Global COVID-19 Incidence as Inferred from Causal Models", "abstract": "The relationship between meteorological factors such as temperature and humidity with COVID-19 incidence is still unclear after 6 months of the beginning of the pandemic. Some literature confirms the association of temperature with disease transmission while some oppose the same. This work intends to determine whether there is a causal association between temperature, humidity and Covid-19 cases. Three different causal models were used to capture stochastic, chaotic and symbolic natured time-series data and to provide a robust & unbiased analysis by constructing networks of causal relationships between the variables. Granger-Causality method, Transfer Entropy method & Convergent Cross-Mapping (CCM) was done on data from regions with different temperatures and cases greater than 50,000 as of 13th May 2020. From the Granger-Causality test we found that in only Canada, the United Kingdom, temperature and daily new infections are causally linked. The same results were obtained from Convergent Cross Mapping for India. Again using Granger-Causality test, we found that in Russia only, relative humidity is causally linked to daily new cases. Thus, a Generalized Additive Model with a smoothing spline function was fitted for these countries to understand the directionality. Using the combined results of the said models, we were able to conclude that there is no evidence of a causal association between temperature, humidity and Covid-19 cases.", "doc_id": "3yzxljjf"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Temperature and relative humidity are not major contributing factor on the occurrence of COVID-19 pandemic: An observational study in 57 countries", "abstract": "The world searching for hope has already experienced a huge loss of lives due to COVID-19 caused by SARS-CoV-2 started in Wuhan, China. There are speculations that climatic conditions can slowdown the transmission of COVID-19.Findings from the early outbreak indicated the possible association of air temperature and relative humidity in COVID-19 occurrence in China. Current study focused on whether climatic conditions(temperature and relative humidity)are having any influence in the occurrence of COVID-19 when the outbreak has been classified as pandemic. To determine the effect of daily average temperature and average relative humidity on log-transformed total daily cases of COVID-19, polynomial regression as a quadratic term and linear regression were done. Linear regression analysis was also carried out to explore the same effect on selected countries. Present study observed no correlation between the climatic conditions (the daily average temperature and relative humidity) and the number of cases of COVID-19. Similar result was found in relation between daily average temperature and average number of cases per day in country-wise analysis. However, about 93.5% cases of COVID-19 occurred between 10C to 160C and the average number of cases per day was lower in high temperature country than low temperature country with exceptions. The minimum effect of summer temperature may not be effective to control the pandemic rather need to apply the control measures of COVID-19.", "doc_id": "51k50ebv"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Impacts of regional climate on the COVID-19 pandemic", "abstract": "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.", "doc_id": "k1l16pmm"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Climatic influence on the magnitude of COVID-19 outbreak: a stochastic model-based global analysis", "abstract": "This study examines the association between community transmission of COVID-19 cases and climatic predictors, considering travel information and annual parasite index across the three climatic zones, i.e., tropical, subtropical, and temperate. A Boosted Regression Tree model has been employed to understand the association between the COVID-19 cases. The results show that average temperature and average relative humidity are the major contributors in explaining the differentials of COVID-19 transmission in temperate and subtropical regions whereas the mean diurnal temperature range and temperature seasonality are the most significant determinants in tropical regions. The average temperature is the most influential factor affecting the number of COVID-19 cases in France, Turkey, the US, the UK, and Germany, and the cases decrease sharply above 10oC. Among the tropical countries, India found to be most affected by mean diurnal temperature, and Brazil fazed by temperature seasonality. Most of the temperate countries like France, USA, Turkey, UK, and Germany with an average temperature between 5-12oC had high number of COVID-19 cases. The findings are expected to add to the ongoing debates on the influence of climatic factors influencing the number of COVID-19 cases and could help researchers and policymakers to make appropriate decisions for preventing the spread.", "doc_id": "ioyl1gla"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Early transmission of COVID-19 has an optimal temperature but late transmission decreases in warm climate", "abstract": "The COVID-19 novel virus, as an emerging highly pathogenic agent, has caused a pandemic. Revealing the influencing factors affecting transmission of COVID-19 is essential to take effective control measures. Several previous studies suggested that the spread of COVID-19 was likely associated with temperature and/or humidity. But, a recent extensive review indicated that conclusions on associations between climate and COVID-19 were elusive with high uncertainty due to caveats in most previous studies, such as limitations in time and space, data quality and confounding factors. In this study, by using a more extensive global dataset covering 578 time series from China, USA, Europe and the rest of the world, we show that climate show distinct impacts on early and late transmission of COVID-19 in the world after excluding the confounding factors. The early transmission ability of COVID-19 peaked around 6.3{degrees}C without or with little human intervention, but the later transmission ability was reduced in high temperature conditions under human intervention, probably driven by increased control efficiency of COVID-19. The transmission ability was positively associated with the founding population size of early reported cases and population size of a location. Our study suggested that with the coming summer seasons, the transmission risk of COVID-19 would increase in the high-latitude or high-altitude regions but decrease in low-latitude or low-altitude regions; human intervention is essential in containing the spread of COVID-19 around the world.", "doc_id": "t4k5csgy"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Meteorological Conditions and Covid-19 in Large U.S. Cities", "abstract": "To determine whether prevalence of Coronavirus disease 2019 (Covid-19) is modulated by meteorological conditions, we herein conducted meta-regression of data in large U.S. cities. We selected 33 large U.S. cities with a population of >500,000. The integrated numbers of confirmed Covid-19 cases in the country to which the city belongs on 14 May 2020, the estimated population in 2019 in the country, and monthly meteorological conditions at the city for 4 months (from January to April 2020) were obtained. Meteorological conditions consisted of mean temperature (F), total precipitation (inch), mean wind speed (MPH), mean sky cover, and mean relative humidity (%). Monthly data for 4 months were averaged or integrated. The Covid-19 prevalence was defined as the integrated number of Covid-19 cases divided by the population. Random-effects meta-regression was performed by means of OpenMetaAnalyst. In a meta-regression graph, Covid-19 prevalence (plotted as the logarithm transformed prevalence on the y-axis) was depicted as a function of a given factor (plotted as a meteorological datum on the x-axis). A slope of the meta-regression line was significantly negative (coefficient, -0.069; P < 0.001) for the mean temperature and significantly positive for the mean wind speed (coefficient, 0.174; P = 0.027) and the sky cover (coefficient, 2.220; P = 0.023). In conclusion, lower temperature and higher wind speed/sky cover may be associated with higher Covid-19 prevalence, which should be confirmed by further epidemiological researches adjusting for various risk and protective factors (in addition to meteorological conditions) of Covid-19.", "doc_id": "7usv3ljo"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Study of the Dependence of Effective Reproduction Number of COVID-19 on the Temperature and Humidity: A Case Study with the Indian States", "abstract": "Corona Virus Disease 2019 (COVID-19) started in Wuhan province of China in November 2019 and within a short time, it was declared as a worldwide pandemic by World Health Organisation due to very fast worldwide spread of the virus. In the absence of any vaccine, various mitigation measures were used. In the past, the effect of temperature and humidity on the spread of the virus was studied for a very early phase of the data with mixed results. We are studying the impact of COVID-19 on the maximum temperature and relative humidity of a place using Indian states as test cases for SIR, SIRD, and SEIR models. We used a linear regression method to look for any dependency between effective reproduction number with maximum temperature and relative humidity. Most of the states show a correlation with the negative slope between the effective reproduction number with the maximum temperature and the relative humidity. It indicates that the effective reproduction number goes down as maximum temperature or relative humidity rise. But, the regression coefficient R2 is low for these correlations which means that the correlation is not strong.", "doc_id": "n59q479q"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "UV light influences covid-19 activity through big data: trade offs between northern subtropical, tropical, and southern subtropical countries", "abstract": "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.", "doc_id": "odbi4yvz"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Warmer weather and global trends in the coronavirus COVID-19", "abstract": "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.", "doc_id": "fj3a2y1o"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "REGIONAL DETERMINANTS OF THE EXPANSION OF COVID-19 IN BRAZIL", "abstract": "Objective: This study investigates the regional differences in the occurrence of COVID-19 in Brazil and its relationship with climatic and demographic factors, for this, using data about identified cases of COVID-19 on Brazil from February 26 to April 04, 2020. Methods: A model using the Polynomial Regression with cubic adjustments of the number of days of contagion, demographic density, city population and climatic factors was designed to explain the spread of COVID-19 in Brazil. Main results: It was evidenced that temperature variation maintains a relationship with the reduction in the number of cases of COVID-19, but on a very small scale. With a simulation of 30 days of contagion, a variation of -0.9% was found for each increase of 1 C. Conclusion: Temperature, despite being an intervening factor in the variation in the number of COVID-19 cases, has a reduced magnitude effect. Cities with higher temperatures do not necessarily it is more protected from the SARS-CoV-2 than those with lower temperatures, however, strong statistical significance was found, this relationship deserves to be investigated in other tests with longer time series, wide and with especially non-linear data adjustments.", "doc_id": "epa6m6nq"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "No Evidence for Temperature-Dependence of the COVID-19 Epidemic", "abstract": "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.", "doc_id": "bnrmh1qs"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "ICU admissions and in-hospital deaths linked to covid-19 in the Paris region are correlated with previously observed ambient temperature", "abstract": "OBJECTIVE To study the effect of weather on severity indicators of coronavirus disease 2019 (covid-19). DESIGN Ecological study. SETTING Paris region. POPULATION Severely ill patients with covid-19. MAIN OUTCOME MEASURES Daily covid-19-related intensive care unit (ICU) admission and in-hospital deaths in the Paris region, and the daily weather characteristics of Paris midtown. RESULTS Daily ICU admissions and in-hospital deaths were strongly and negatively correlated to ambient temperatures, with a time lag. The highest Pearson correlation coefficients and statistically significant P values were found 8 days before occurrence of ICU admissions and 15 days before deaths. CONCLUSIONS The study findings show a strong effect of previously observed ambient temperature that has an effect on severity indicators of covid-19.", "doc_id": "gmlbbw9u"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Temperature dependence of COVID-19 transmission", "abstract": "The recent coronavirus pandemic follows in its early stages an almost exponential expansion, with the number of cases N reasonably well fit by N e\u03b1t, in many countries. We analyze the rate \u03b1 in different countries, choosing as a starting point in each country the first day with 30 cases and fitting for the following 12 days, capturing thus the early exponential growth in a rather homogeneous way. We look for a link between the rate \u03b1 and the average temperature T of each country, in the month of the epidemic growth. We analyze a {\\it base} set of 42 countries, which developed the epidemic at an earlier stage, an {\\it intermediate} set of 88 countries and an {\\it extended} set of 125 countries, which developed the epidemic more recently. Fitting with a linear behavior \u03b1(T), we find increasing evidence in the three datasets for a decreasing growth rate as a function of T, at $99.66\\%$C.L., $99.86\\%$C.L. and $99.99995 \\%$ C.L. ($p$-value $5 \\cdot 10^{-7}$, or 5$\\sigma$ detection) in the {\\it base}, {\\it intermediate} and {\\it extended} dataset, respectively. The doubling time is expected to increase by $40\\%\\sim 50\\%$, going from $5^\\circ$ C to $25^\\circ$ C. In the {\\it base} set, going beyond a linear model, a peak at about $(7.7\\pm 3.6)^\\circ C$ seems to be present in the data, but such evidence disappears for the larger datasets. Moreover we have analyzed the possible existence of a bias: poor countries, typically located in warm regions, might have less intense testing. By excluding countries below a given GDP per capita from the dataset, we find that this affects our conclusions only slightly and only for the {\\it extended} dataset. The significance always remains high, with a $p$-value of about $10^{-3}-10^{-4}$ or less. Our findings give hope that, for northern hemisphere countries, the growth rate should significantly decrease as a result of both warmer weather and lockdown policies. In general the propagation should be hopefully stopped by strong lockdown, testing and tracking policies, before the arrival of the next cold season.", "doc_id": "0oma7hdu"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Higher Air Temperature, Pressure, and Ultraviolet Are Associated with Less Covid-19 Incidence", "abstract": "A recent study from China suggests that high temperature and ultraviolet (UV) radiation cannot decrease the epidemics of Coronavirus disease 2019 (Covid-19). To determine whether COVID-19 incidence is modulated by meteorological factors, meta-regression of Japanese prefectural data was herein conducted. We extracted 1) cumulative numbers of confirmed Covid-19 patients in each Japanese prefecture from January to April 2020; 2) populations per 1-km2 inhabitable area in each prefecture in 2020; and 3) meteorological factors at each prefectural capital city from January to April 2020. Meteorological factors included monthly mean air temperature (degree Celsius), wind speed (m/s), sea level air pressure (hPa), relative humidity (%), and percentage of possible sunshine (%); monthly total of sunshine duration (h) and precipitation (mm); and monthly mean daily maximum ultraviolet (UV) index. To adjust for prefectural population density, we defined the incidence of Covid-19 as the cumulative number of Covid-19 patients divided by the population per 100-km2 inhabitable area. Random-effects meta-regression was performed, and its graph depicted Covid-19 incidence (plotted as the logarithm transformed incidence on the y-axis) as a function of a given meteorological factor (plotted on the x-axis). A slope of the meta-regression line was significantly negative as a function of the mean air temperature (coefficient, -0.127; P = 0.023), the mean sea level air pressure (coefficient, -0.351; P < 0.001), and the mean daily maximum UV index (coefficient, -0.001; P = 0.012) which indicated that Covid-19 incidence decreased significantly as air temperature, air pressure, and UV increased. In conclusion, higher air temperature, air pressure, and UV may be associated with less Covid-19 incidence.", "doc_id": "9nicryzs"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Weather variables impact on COVID-19 incidence", "abstract": "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.", "doc_id": "hadnxjeo"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Impact of weather on COVID-19 pandemic in Turkey", "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 (\u00b0C), dew point (\u00b0C), humidity (%), and wind speed (mph) are considered as parameters of weather. Research states that the incubation period of COVID-19 varies from 1\u00e2\u0080\u00afday to 14\u00e2\u0080\u00afdays. Therefore, the effects of each parameter within 1, 3, 7, and 14\u00e2\u0080\u00afdays 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\u00e2\u0080\u00afdays ago, and temperature on the day, respectively. The study results may guide authorities and decision-makers on taking specific measures for the cities.", "doc_id": "ds3nmssp"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Investigation of effective climatology parameters on COVID-19 outbreak in Iran", "abstract": "SARS CoV-2 (COVID-19) Coronavirus cases are confirmed throughout the world and millions of people are being put into quarantine. A better understanding of the effective parameters in infection spreading can bring about a logical measurement toward COVID-19. The effect of climatic factors on spreading of COVID-19 can play an important role in the new Coronavirus outbreak. In this study, the main parameters, including the number of infected people with COVID-19, population density, intra-provincial movement, and infection days to end of the study period, average temperature, average precipitation, humidity, wind speed, and average solar radiation investigated to understand how can these parameters effects on COVID-19 spreading in Iran? The Partial correlation coefficient (PCC) and Sobol'-Jansen methods are used for analyzing the effect and correlation of variables with the COVID-19 spreading rate. The result of sensitivity analysis shows that the population density, intra-provincial movement have a direct relationship with the infection outbreak. Conversely, areas with low values of wind speed, humidity, and solar radiation exposure to a high rate of infection that support the virus's survival. The provinces such as Tehran, Mazandaran, Alborz, Gilan, and Qom are more susceptible to infection because of high population density, intra-provincial movements and high humidity rate in comparison with Southern provinces.", "doc_id": "15slu3kk"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Distribution of the SARS-CoV-2 Pandemic and Its Monthly Forecast Based on Seasonal Climate Patterns", "abstract": "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.", "doc_id": "04rbtmmi"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Statistical analysis of the impact of environmental temperature on the exponential growth rate of cases infected by COVID-19", "abstract": "We perform a statistical analysis for understanding the effect of the environmental temperature on the exponential growth rate of the cases infected by COVID-19 for US and Italian regions. In particular, we analyze the datasets of regional infected cases, derive the growth rates for regions characterized by a readable exponential growth phase in their evolution spread curve and plot them against the environmental temperatures averaged within the same regions, derive the relationship between temperature and growth rate, and evaluate its statistical confidence. The results clearly support the first reported statistically significant relationship of negative correlation between the average environmental temperature and exponential growth rates of the infected cases. The critical temperature, which eliminates the exponential growth, and thus the COVID-19 spread in US regions, is estimated to be TC = 86.1 \u00b1 4.3 F0.", "doc_id": "q12b7uyr"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Asymmetric nexus between temperature and COVID-19 in the top ten affected provinces of China: A current application of quantile-on-quantile approach", "abstract": "The present study examines the asymmetrical effect of temperature on COVID-19 (Coronavirus Disease) from 22 January 2020 to 31 March 2020 in the 10 most affected provinces in China. This study used the Sim & Zhou' quantile-on-quantile (QQ) approach to analyze how the temperature quantities affect the different quantiles of COVID-19. Daily COVID-19 and, temperature data collected from the official websites of the Chinese National Health Commission and Weather Underground Company (WUC) respectively. Empirical results have shown that the relationship between temperature and COVID-19 is mostly positive for Hubei, Hunan, and Anhui, while mostly negative for Zhejiang and Shandong provinces. The remaining five provinces Guangdong, Henan, Jiangxi, Jiangsu, and Heilongjiang are showing the mixed trends. These differences among the provinces can be explained by the differences in the number of COVID-19 cases, temperature, and the province's overall hospital facilitations. The study concludes that maintaining a safe and comfortable atmosphere for patients while COVID-19 is being treated may be rational.", "doc_id": "3tow59gc"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Maximum Daily Temperature, Precipitation, Ultra-Violet Light and Rates of Transmission of SARS-Cov-2 in the United States", "abstract": "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\u00b0F 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\u00b0F, 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\u00b0F 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\u00b0F 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.", "doc_id": "7vwjcp53"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "The Weather Impacts the Outbreak of COVID-19 in Mainland China", "abstract": "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.", "doc_id": "akb96git"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Anomalous atmospheric circulation favored the spread of COVID-19 in Europe", "abstract": "The current pandemic caused by the coronavirus SARS-CoV-2 is having negative health, social and economic consequences worldwide. In Europe, the pandemic started to develop strongly at the end of February and beginning of March 2020. It has subsequently spread over the continent, with special virulence in northern Italy and inland Spain. In this study we show that an unusual persistent anticyclonic situation prevailing in southwestern Europe during February 2020 (i.e. anomalously strong positive phase of the North Atlantic and Arctic Oscillations) could have resulted in favorable conditions, in terms of air temperature and humidity, in Italy and Spain for a quicker spread of the virus compared with the rest of the European countries. It seems plausible that the strong atmospheric stability and associated dry conditions that dominated in these regions may have favored the virus's propagation, by short-range droplet transmission as well as likely by long-range aerosol (airborne) transmission.", "doc_id": "kpvxdhcu"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Evidence that high temperatures and intermediate relative humidity might favor the spread of COVID-19 in tropical climate: A case study for the most affected Brazilian cities", "abstract": "This study aimed to analyze how meteorological conditions such as temperature, humidity and rainfall can affect the spread of COVID-19 in five Brazilian (S\u00e3o Paulo, Rio de Janeiro, Bras\u00edlia, Manaus and Fortaleza) cities. The cities selected were those with the largest number of confirmed cases considering data of April 13. Variables such as number of cumulative cases, new daily cases and contamination rate were employed for this study. Our results showed that higher mean temperatures and average relative humidity favored the COVID-19 transmission, differently from reports from coldest countries or periods of time under cool temperatures. Thus, considering the results obtained, intersectoral policies and actions are necessary, mainly in cities where the contamination rate is increasing rapidly. Thus, prevention and protection measures should be adopted in these cities aiming to reduce transmission and the possible collapse of the health system.", "doc_id": "5b9xjvwm"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Association between climate variables and global transmission oF SARS-CoV-2", "abstract": "In this study, we aimed at analyzing the associations between transmission of and deaths caused by SARS-CoV-2 and meteorological variables, such as average temperature, minimum temperature, maximum temperature, and precipitation. Two outcome measures were considered, with the first aiming to study SARS-CoV-2 infections and the second aiming to study COVID-19 mortality. Daily data as well as data on SARS-CoV-2 infections and COVID-19 mortality obtained between December 1, 2019 and March 28, 2020 were collected from weather stations around the world. The country's population density and time of exposure to the disease were used as control variables. Finally, a month dummy variable was added. Daily data by country were analyzed using the panel data model. An increase in the average daily temperature by one degree Fahrenheit reduced the number of cases by approximately 6.4 cases/day. There was a negative correlation between the average temperature per country and the number of cases of SARS-CoV-2 infections. This association remained strong even with the incorporation of additional variables and controls (maximum temperature, average temperature, minimum temperature, and precipitation) and fixed country effects. There was a positive correlation between precipitation and SARS-CoV-2 transmission. Countries with higher rainfall measurements showed an increase in disease transmission. For each average inch/day, there was an increase of 56.01 cases/day. COVID-19 mortality showed no significant association with temperature.", "doc_id": "aekywz71"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Effects of temperature and humidity on the daily new cases and new deaths of COVID-19 in 166 countries", "abstract": "The coronavirus disease 2019 (COVID-19) pandemic is the defining global health crisis of our time and the greatest challenge facing the world. Meteorological parameters are reportedly crucial factors affecting respiratory infectious disease epidemics; however, the effect of meteorological parameters on COVID-19 remains controversial. This study investigated the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, which has useful implications for policymakers and the public. Daily data on meteorological conditions, new cases and new deaths of COVID-19 were collected for 166 countries (excluding China) as of March 27, 2020. Log-linear generalized additive model was used to analyze the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, with potential confounders controlled for, including wind speed, median age of the national population, Global Health Security Index, Human Development Index and population density. Our findings revealed that temperature and relative humidity were both negatively related to daily new cases and deaths. A 1 \u00b0C increase in temperature was associated with a 3.08% (95% CI: 1.53%, 4.63%) reduction in daily new cases and a 1.19% (95% CI: 0.44%, 1.95%) reduction in daily new deaths, whereas a 1% increase in relative humidity was associated with a 0.85% (95% CI: 0.51%, 1.19%) reduction in daily new cases and a 0.51% (95% CI: 0.34%, 0.67%) reduction in daily new deaths. The results remained robust when different lag structures and the sensitivity analysis were used. These findings provide preliminary evidence that the COVID-19 pandemic may be partially suppressed with temperature and humidity increases. However, active measures must be taken to control the source of infection, block transmission and prevent further spread of COVID-19.", "doc_id": "axn5dgkh"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "A mechanism-based parameterisation scheme to investigate the association between transmission rate of COVID-19 and meteorological factors on plains in China", "abstract": "The novel coronavirus disease 2019 (COVID-19), which first emerged in Hubei province, China, has become a pandemic. However, data regarding the effects of meteorological factors on its transmission are limited and inconsistent. A mechanism-based parameterisation scheme was developed to investigate the association between the scaled transmission rate (STR) of COVID-19 and the meteorological parameters in 20 provinces/municipalities located on the plains in China. We obtained information on the scale of population migrated from Wuhan, the world epicentre of the COVID-19 outbreak, into the study provinces/municipalities using mobile-phone positioning system and big data techniques. The highest STRs were found in densely populated metropolitan areas and in cold provinces located in north-eastern China. Population density had a non-linear relationship with disease spread (linearity index, 0.9). Among various meteorological factors, only temperature was significantly associated with the STR after controlling for the effect of population density. A negative and exponential relationship was identified between the transmission rate and the temperature (correlation coefficient, -0.56; 99% confidence level). The STR increased substantially as the temperature in north-eastern China decreased below 0 \u00b0C (the STR ranged from 3.5 to 12.3 when the temperature was between -9.41 \u00b0C and -13.87 \u00b0C), whilst the STR showed less temperature dependence in the study areas with temperate weather conditions (the STR was 1.21 \u00b1 0.57 when the temperature was above 0 \u00b0C). Therefore, a higher population density was linearly whereas a lower temperature (<0 \u00b0C) was exponentially associated with an increased transmission rate of COVID-19. These findings suggest that the mitigation of COVID-19 spread in densely populated and/or cold regions will be a great challenge.", "doc_id": "o2lr936b"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Effect of weather on COVID-19 spread in the US: A prediction model for India in 2020", "abstract": "The effect of weather on COVID-19 spread is poorly understood. Recently, few studies have claimed that warm weather can possibly slowdown the global pandemic, which has already affected over 1.6 million people worldwide. Clarification of such relationships in the worst affected country, the US, can be immensely beneficial to understand the role of weather in transmission of the disease in the highly populated countries, such as India. We collected the daily data of new cases in 50 US states between Jan 1-Apr 9, 2020 and also the corresponding weather information (i.e., temperature (T) and absolute humidity (AH)). Distribution modeling of new cases across AH and T, helped identify the narrow and vulnerable AH range. We validated the results for 10-day intervals against monthly observations, and also worldwide trends. The results were used to predict Indian regions which would be vulnerable to weather based spread in upcoming months of 2020. COVID-19 spread in the US is significant for states with 4 < AH < 6 g/m3 and number of new cases > 10,000, irrespective of the chosen time intervals for study parameters. These trends are consistent with worldwide observations, but do not correlate well with India so far possibly due the total cases reported per interval < 10,000. The results clarify the relationship between weather parameters and COVID-19 spread. The vulnerable weather parameters will help classify the risky geographic areas in different countries. Specifically, with further reporting of new cases in India, prediction of states with high risk of weather based spread will be apparent.", "doc_id": "q2mn9y70"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Short-term effects of specific humidity and temperature on COVID-19 morbidity in select US cities", "abstract": "Little is known about the environmental conditions that drive the spatiotemporal patterns of SARS-CoV-2. Preliminary research suggests an association with meteorological parameters. However, the relationship with temperature and humidity is not yet apparent for COVID-19 cases in US cities first impacted. The objective of this study is to evaluate the association between COVID-19 cases and meteorological parameters in select US cities. A case-crossover design with a distributed lag nonlinear model was used to evaluate the contribution of ambient temperature and specific humidity on COVID-19 cases in select US cities. The case-crossover examines each COVID case as its own control at different time periods (before and after transmission occurred). We modeled the effect of temperature and humidity on COVID-19 transmission using a lag period of 7 days. A subset of 8 cities were evaluated for the relationship with meteorological parameters and 5 cities were evaluated in detail. Short-term exposure to humidity was positively associated with COVID-19 transmission in 4 cities. The associations were small with 3 out of 4 cities exhibiting higher COVID19 transmission with specific humidity that ranged from 6 to 9 g/kg. Our results suggest that weather should be considered in infectious disease modeling efforts. Future work is needed over a longer time period and across different locations to clearly establish the weather-COVID19 relationship.", "doc_id": "qnkntgnv"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Impact of meteorological factors on the COVID-19 transmission: A multi-city study in China", "abstract": "The purpose of the present study is to explore the associations between novel coronavirus disease 2019 (COVID-19) case counts and meteorological factors in 30 provincial capital cities of China. We compiled a daily dataset including confirmed case counts, ambient temperature (AT), diurnal temperature range (DTR), absolute humidity (AH) and migration scale index (MSI) for each city during the period of January 20th to March 2nd, 2020. First, we explored the associations between COVID-19 confirmed case counts, meteorological factors, and MSI using non-linear regression. Then, we conducted a two-stage analysis for 17 cities with more than 50 confirmed cases. In the first stage, generalized linear models with negative binomial distribution were fitted to estimate city-specific effects of meteorological factors on confirmed case counts. In the second stage, the meta-analysis was conducted to estimate the pooled effects. Our results showed that among 13 cities that have less than 50 confirmed cases, 9 cities locate in the Northern China with average AT below 0 \u00b0C, 12 cities had average AH below 4 g/m3, and one city (Haikou) had the highest AH (14.05 g/m3). Those 17 cities with 50 and more cases accounted for 90.6% of all cases in our study. Each 1 \u00b0C increase in AT and DTR was related to the decline of daily confirmed case counts, and the corresponding pooled RRs were 0.80 (95% CI: 0.75, 0.85) and 0.90 (95% CI: 0.86, 0.95), respectively. For AH, the association with COVID-19 case counts were statistically significant in lag 07 and lag 014. In addition, we found the all these associations increased with accumulated time duration up to 14 days. In conclusions, meteorological factors play an independent role in the COVID-19 transmission after controlling population migration. Local weather condition with low temperature, mild diurnal temperature range and low humidity likely favor the transmission.", "doc_id": "c32lvwcc"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Temperature significantly changes COVID-19 transmission in (sub)tropical cities of Brazil", "abstract": "The coronavirus disease 2019 (COVID-19) outbreak has become a severe public health issue. The novelty of the virus prompts a search for understanding of how ecological factors affect the transmission and survival of the virus. Several studies have robustly identified a relationship between temperature and the number of cases. However, there is no specific study for a tropical climate such as Brazil. This work aims to determine the relationship of temperature to COVID-19 infection for the state capital cities of Brazil. Cumulative data with the daily number of confirmed cases was collected from February 27 to April 1, 2020, for all 27 state capital cities of Brazil affected by COVID-19. A generalized additive model (GAM) was applied to explore the linear and nonlinear relationship between annual average temperature compensation and confirmed cases. Also, a polynomial linear regression model was proposed to represent the behavior of the growth curve of COVID-19 in the capital cities of Brazil. The GAM dose-response curve suggested a negative linear relationship between temperatures and daily cumulative confirmed cases of COVID-19 in the range from 16.8 \u00b0C to 27.4 \u00b0C. Each 1 \u00b0C rise of temperature was associated with a -4.8951% (t = -2.29, p = 0.0226) decrease in the number of daily cumulative confirmed cases of COVID-19. A sensitivity analysis assessed the robustness of the results of the model. The predicted R-squared of the polynomial linear regression model was 0.81053. In this study, which features the tropical temperatures of Brazil, the variation in annual average temperatures ranged from 16.8 \u00b0C to 27.4 \u00b0C. Results indicated that temperatures had a negative linear relationship with the number of confirmed cases. The curve flattened at a threshold of 25.8 \u00b0C. There is no evidence supporting that the curve declined for temperatures above 25.8 \u00b0C. The study had the goal of supporting governance for healthcare policymakers.", "doc_id": "dekdf7vu"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Projections for COVID-19 pandemic in India and effect of temperature and humidity", "abstract": "BACKGROUND AND AIMS: As, the COVID-19 has been deemed a pandemic by World Health Organization (WHO), and since it spreads everywhere throughout the world, investigation in relation to this disease is very much essential. Investigation of pattern in the occurrence of COVID-19, to check the influence of different meteorological factors on the incidence of COVID-19 and prediction of incidence of COVID-19 are the objectives of this paper. METHODS: For trend analysis, Sen's Slope and Man-Kendall test have been used, Generalized Additive Model (GAM) of regression has been used to check the influence of different meteorological factors on the incidence and to predict the frequency of COVID-19, and Verhulst (Logistic) Population Model has been used. RESULTS: Statistically significant linear trend found for the daily-confirmed cases of COVID-19. The regression analysis indicates that there is some influence of the interaction of average temperature (AT) and average relative humidity (ARH) on the incidence of COVID-19. However, this result is not consistent throughout the study area. The projections have been made up to 21st May, 2020. CONCLUSIONS: Trend and regression analysis give an idea of the incidence of COVID-19 in India while projection made by Verhulst (Logistic) Population Model for the confirmed cases of the study area are encouraging as the sample prediction is as same as the actual number of confirmed COVID-19 cases.", "doc_id": "ipxvnlu2"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Development of an Assessment Method for Investigating the Impact of Climate and Urban Parameters in Confirmed Cases of COVID-19: A New Challenge in Sustainable Development", "abstract": "Sustainable development has been a controversial global topic, and as a complex concept in recent years, it plays a key role in creating a favorable future for societies. Meanwhile, there are several problems in the process of implementing this approach, like epidemic diseases. Hence, in this study, the impact of climate and urban factors on confirmed cases of COVID-19 (a new type of coronavirus) with the trend and multivariate linear regression (MLR) has been investigated to propose a more accurate prediction model. For this propose, some important climate parameters, including daily average temperature, relative humidity, and wind speed, in addition to urban parameters such as population density, were considered, and their impacts on confirmed cases of COVID-19 were analyzed. The analysis was performed for three case studies in Italy, and the application of the proposed method has been investigated. The impacts of parameters have been considered with a delay time from one to nine days to find out the most suitable combination. The result of the analysis demonstrates the effectiveness of the proposed model and the impact of climate parameters on the trend of confirmed cases. The research hypothesis approved by the MLR model and the present assessment method could be applied by considering several variables that exhibit the exact delay of them to new confirmed cases of COVID-19.", "doc_id": "qmrgkkpr"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Factors determining the diffusion of COVID-19 and suggested strategy to prevent future accelerated viral infectivity similar to COVID", "abstract": "This study has two goals. The first is to explain the geo-environmental determinants of the accelerated diffusion of COVID-19 that is generating a high level of deaths. The second is to suggest a strategy to cope with future epidemic threats similar to COVID-19 having an accelerated viral infectivity in society. Using data on sample of N = 55 Italian province capitals, and data of infected individuals at as of April 7th, 2020, results reveal that the accelerate and vast diffusion of COVID-19 in North Italy has a high association with air pollution of cities measured with days exceeding the limits set for PM10 (particulate matter 10 \u00b5m or less in diameter) or ozone. In particular, hinterland cities with average high number of days exceeding the limits set for PM10 (and also having a low wind speed) have a very high number of infected people on 7th April 2020 (arithmetic mean is about 2200 infected individuals, with average polluted days greater than 80 days per year), whereas coastal cities also having days exceeding the limits set for PM10 or ozone but with high wind speed have about 944.70 average infected individuals, with about 60 average polluted days per year; moreover, cities having more than 100 days of air pollution (exceeding the limits set for PM10), they have a very high average number of infected people (about 3350 infected individuals, 7th April 2020), whereas cities having less than 100 days of air pollution per year, they have a lower average number of infected people (about 1014 individuals). The findings here also suggest that to minimize the impact of future epidemics similar to COVID-19, the max number of days per year that Italian provincial capitals or similar industrialized cities can exceed the limits set for PM10 or for ozone, considering their meteorological conditions, is about 48 days. Moreover, results here reveal that the explanatory variable of air pollution in cities seems to be a more important predictor in the initial phase of diffusion of viral infectivity (on 17th March 2020, b1 = 1.27, p < 0.001) than interpersonal contacts (b2 = 0.31, p < 0.05). In the second phase of maturity of the transmission dynamics of COVID-19, air pollution reduces intensity (on 7th April 2020 with b'1 = 0.81, p < 0.001) also because of the indirect effect of lockdown, whereas regression coefficient of transmission based on interpersonal contacts has a stable level (b'2 = 0.31, p < 0.01). This result reveals that accelerated transmission dynamics of COVID-19 is due to mainly to the mechanism of \"air pollution-to-human transmission\" (airborne viral infectivity) rather than \"human-to-human transmission\". Overall, then, transmission dynamics of viral infectivity, such as COVID-19, is due to systemic causes: general factors that are the same for all regions (e.g., biological characteristics of virus, incubation period, etc.) and specific factors which are different for each region and/or city (e.g., complex interaction between air pollution, meteorological conditions and biological characteristics of viral infectivity) and health level of individuals (habits, immune system, age, sex, etc.). Lessons learned for COVID-19 in the case study here suggest that a proactive strategy to cope with future epidemics is also to apply especially an environmental and sustainable policy based on reduction of levels of air pollution mainly in hinterland and polluting cities- (having low wind speed, high percentage of moisture and number of fog days) -that seem to have an environment that foster a fast transmission dynamics of viral infectivity in society. Hence, in the presence of polluting industrialization in regions that can trigger the mechanism of air pollution-to-human transmission dynamics of viral infectivity, this study must conclude that a comprehensive strategy to prevent future epidemics similar to COVID-19 has to be also designed in environmental and socioeconomic terms, that is also based on sustainability science and environmental science, and not only in terms of biology, medicine, healthcare and health sector.", "doc_id": "kysm5eq2"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Impact of temperature on the dynamics of the COVID-19 outbreak in China", "abstract": "A COVID-19 outbreak emerged in Wuhan, China at the end of 2019 and developed into a global pandemic during March 2020. The effects of temperature on the dynamics of the COVID-19 epidemic in China are unknown. Data on COVID-19 daily confirmed cases and daily mean temperatures were collected from 31 provincial-level regions in mainland China between Jan. 20 and Feb. 29, 2020. Locally weighted regression and smoothing scatterplot (LOESS), distributed lag nonlinear models (DLNMs), and random-effects meta-analysis were used to examine the relationship between daily confirmed cases rate of COVID-19 and temperature conditions. The daily number of new cases peaked on Feb. 12, and then decreased. The daily confirmed cases rate of COVID-19 had a biphasic relationship with temperature (with a peak at 10 \u00b0C), and the daily incidence of COVID-19 decreased at values below and above these values. The overall epidemic intensity of COVID-19 reduced slightly following days with higher temperatures with a relative risk (RR) was 0.96 (95% CI: 0.93, 0.99). A random-effect meta-analysis including 28 provinces in mainland China, we confirmed the statistically significant association between temperature and RR during the study period (Coefficient = -0.0100, 95% CI: -0.0125, -0.0074). The DLNMs in Hubei Province (outside of Wuhan) and Wuhan showed similar patterns of temperature. Additionally, a modified susceptible-exposed-infectious-recovered (M-SEIR) model, with adjustment for climatic factors, was used to provide a complete characterization of the impact of climate on the dynamics of the COVID-19 epidemic.", "doc_id": "u1mrvjjf"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Arctic Oscillation: possible trigger of COVID-19 outbreak", "abstract": "The current COVID-19 pandemic is having detrimental consequences worldwide. The pandemic started to develop strongly by the end of January and beginning of February 2020, first in China with subsequent rapid spread to other countries with new epicenters of the outbreaks concentrated mainly within the 30-50 degrees North latitudinal band (e.g., South Korea, Japan, Iran, Italy, Spain). Simultaneously, an unusual persistent anticyclonic situation prevailing at latitudes around 40 degrees North was observed on global scale, in line with an anomalously strong positive phase of the Arctic Oscillation. This atypical situation could have resulted in favorable meteorological conditions for a quicker spread of the virus over the latitude band detailed above. This possible connection needs further attention in order to understand the meteorological and climatological factors related to the COVID-19 outbreak, and for anticipating the spatio-temporal distribution of possible future pandemics.", "doc_id": "n0c0928t"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Assessing the relationship between ground levels of ozone (O3) and nitrogen dioxide (NO2) with coronavirus (COVID-19) in Milan, Italy", "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.", "doc_id": "ksu2gjyb"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Prioritizing and Analyzing the Role of Climate and Urban Parameters in the Confirmed Cases of COVID-19 Based on Artificial Intelligence Applications", "abstract": "Nowadays, an infectious disease outbreak is considered one of the most destructive effects in the sustainable development process. The outbreak of new coronavirus (COVID-19) as an infectious disease showed that it has undesirable social, environmental, and economic impacts, and leads to serious challenges and threats. Additionally, investigating the prioritization parameters is of vital importance to reducing the negative impacts of this global crisis. Hence, the main aim of this study is to prioritize and analyze the role of certain environmental parameters. For this purpose, four cities in Italy were selected as a case study and some notable climate parameters-such as daily average temperature, relative humidity, wind speed-and an urban parameter, population density, were considered as input data set, with confirmed cases of COVID-19 being the output dataset. In this paper, two artificial intelligence techniques, including an artificial neural network (ANN) based on particle swarm optimization (PSO) algorithm and differential evolution (DE) algorithm, were used for prioritizing climate and urban parameters. The analysis is based on the feature selection process and then the obtained results from the proposed models compared to select the best one. Finally, the difference in cost function was about 0.0001 between the performances of the two models, hence, the two methods were not different in cost function, however, ANN-PSO was found to be better, because it reached to the desired precision level in lesser iterations than ANN-DE. In addition, the priority of two variables, urban parameter, and relative humidity, were the highest to predict the confirmed cases of COVID-19.", "doc_id": "nz5fqi0e"} {"topic_name": "coronavirus response to weather changes", "topic_id": "2", "title": "Susceptible supply limits the role of climate in the early SARS-CoV-2 pandemic", "abstract": "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.", "doc_id": "aiwxlxzt"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "T cells found in coronavirus patients 'bode well' for long-term immunity.", "abstract": "", "doc_id": "dqnhyqn0"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "A 219-mer CHO-expressing receptor-binding domain of SARS-CoV S protein induces potent immune responses and protective immunity.", "abstract": "Development of vaccines is essential for the prevention of future recurrences of severe acute respiratory syndrome (SARS), caused by the SARS coronavirus (SARS-CoV). The spike (S) protein, especially receptor-binding domain (RBD) of SARS-CoV, plays important roles in the prevention of SARS infection, and is thus an important component in SARS vaccine development. In this study, we expressed a 219-mer (residues 318-536) RBD protein in Chinese hamster ovary (CHO)-K1 cells (RBD219-CHO), and tested its immune responses and protective immunity in a mouse model. The results showed that this recombinant protein was correctly folded, being able to maintain intact conformation and authentic antigenicity. It could induce strong humoral and cellular immune responses and high titers of neutralizing antibodies in the vaccinated mice. RBD219-CHO protein elicited potent protective immunity that protected all vaccinated mice from SARS-CoV challenge. These results suggest that the recombinant RBD219-CHO protein has great potential for the development of an effective and safe SARS subunit vaccine.", "doc_id": "h1xzj01e"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "The perplexing question of trained immunity versus adaptive memory in COVID-19.", "abstract": "The wide spectrum of symptoms observed in COVID-19 appears to defy explanation. Apart from geographic limitation to people with prior exposure to other coronaviruses and air pollutants, inflammatory comordidities and older ages are also among the main factors of susceptibility to severe illness. The unusual epidemiological data pointed out in children and African territories have revealed new insights in host-pathogen interplay with more focus on epigenetic regulation of cognitive compartments belonging to innate immunity. Should trained immunity be proven to be involved in timely immune responsiveness against SARS-CoV-2 and that adaptive memory could be detrimental, both treatment regimens and vaccine design will tremendously change accordingly with more focus on upper respiratory tissue innate immunity to subdue this threat underway. This article is protected by copyright. All rights reserved.", "doc_id": "dayv5mup"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "The laboratory tests and host immunity of COVID-19 patients with different severity of illness.", "abstract": "BACKGROUND The Coronavirus Disease-2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak in China. The host immunity of COVID-19 patients is unknown. METHODS The routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission. RESULTS A total of 65 SARS-CoV-2-positive patients were classified as mild (n=30), severe (n=20), and extremely severe (n=15) illness. Many routine laboratory tests such as ferritin, lactate dehydrogenase and D-dimer were increased in severe and extremely severe patients. The absolute numbers of CD4+ T cells, CD8+ T cells and B cells were all gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4+ and CD8+ T cells were increased in severe and extremely severe patients compared with mild patients. The co-stimulatory molecule CD28 had opposite results. The percentage of natural regulatory T cells was decreased in extremely severe patients. The percentage of IFN-\u03b3 producing CD8+ T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-\u03b3 producing CD4+ T cells was increased in extremely severe patients. The IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients. CONCLUSIONS The number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4+ and CD8+ T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection.", "doc_id": "bbs7zocu"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "A phased lift of control: a practical strategy to achieve herd immunity against Covid-19 at the country level", "abstract": "Most countries are affected by the Covid-19 pandemic and experience rapidly increasing numbers of cases and deaths. Many have implemented nationwide stringent control to avoid overburdening the health care system. This paralyzes economic and social activities until the availability of a vaccine, which may take years. We propose an alternative exit strategy to develop herd immunity in a predictable and controllable way: a phased lift of control. This means that successive parts of the country (e.g. provinces) stop stringent control, and Covid-19-related IC admissions are distributed over the country as the whole. Importantly, vulnerable individuals need to be shielded until herd immunity has developed in their area. We explore the characteristics and duration of this strategy using a novel individual-based model for geographically stratified transmission of Covid-19 in a country. The model predicts that individuals will have to experience stringent control for about 14 months on average, but this duration may be significantly shortened by future developments (more IC beds, better drugs). Clearly, the strategy will have a profound impact on individuals and society, and should therefore be considered carefully by various other disciplines (e.g. health systems, ethics, economics) before actual implementation.", "doc_id": "f936bioj"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Can the protection be among us? Previous viral contacts and prevalent HLA alleles could be avoiding an even more disseminated COVID-19 pandemic.", "abstract": "Background: COVID-19 is bringing scenes of sci-fi movies into real life, and it seems to be far from over. Infected individuals exhibit variable severity, with no relation between the number of cases and mortality, suggesting the involvement of the populational genetic constitution and previous cross-reactive immune contacts in the individuals' disease outcome. Methods: A clustering approach was conducted to investigate the involvement of human MHC alleles with individuals' outcomes. HLA frequencies from affected countries were used to fuel the Hierarchical Clusterization Analysis. The formed groups were compared regarding their death rates. To prospect the T cell targets in SARS-CoV-2, and by consequence, the epitopes that are conferring cross-protection in the current pandemic, we modeled 3D structures of HLA-A*02:01 presenting immunogenic epitopes from SAR-CoV-1, recovered from Immune Epitope Database. These pMHC structures were also compared with models containing the corresponding SARS-CoV-2 epitope, with alphacoronavirus sequences, and with a panel of immunogenic pMHC structures contained in CrossTope. Findings: The combined use of HLA-B*07, HLA-B*44, HLA-DRB1*03, and HLADRB1*04 allowed the clustering of affected countries presenting similar death rates, based only on their allele frequencies. SARS-CoV HLA-A*02:01 epitopes were structurally investigated. It reveals molecular conservation between SARS-CoV-1 and SARS-CoV-2 peptides, enabling the use of formerly SARS-CoV-1 experimental epitopes to inspect actual targets that are conferring cross-protection. Alpha-CoVs and, impressively, viruses involved in human infections share fingerprints of immunogenicity with SARS-CoV peptides. Interpretation: Wide-scale HLA genotyping in COVID-19 patients shall improve prognosis prediction. Structural identification of previous triggers paves the way for herd immunity examination and wide spectrum vaccine development. Funding: This work was supported by the National Council for Scientific and Technological Development (CNPq) and National Council for the Improvement of Higher Education (CAPES) for their support", "doc_id": "in48pd8t"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Immunity Passports for SARS-CoV-2: an online experimental study of the impact of antibody test terminology on perceived risk and behaviour", "abstract": "Objective: To assess the impact of describing an antibody-positive test result using the terms Immunity and Passport or Certificate, alone or in combination, on perceived risk of becoming infected with SARS-CoV-2 and intention to continue protective behaviours. Design: 2 by 3 experimental design. Setting: Online with data collected between 28th April and 1st May 2020. Participants: 1,204 adults registered with a UK research panel. Intervention: Participants were randomised to receive one of six descriptions of an antibody test and results showing SARS-CoV-2 antibodies, differing in the terms used to describe the type of test (Immunity vs Antibody) and the test result (Passport vs Certificate vs Test). Main outcome measures: The primary outcome was the proportion of participants perceiving no risk of becoming infected with SARS-CoV-2 given an antibody positive test result. Other outcomes include intended changes to frequency of hand washing and physical distancing. Results: When using the term Immunity (vs Antibody), 19.1% of participants [95% CI: 16.1 to 22.5] (vs 9.8% [95% CI: 7.5 to 12.4]) perceived no risk of catching coronavirus at some point in the future given an antibody-positive test result (AOR: 2.91 [95% CI: 1.52 to 5.55]). Using the terms Passport or Certificate, as opposed to Test, had no significant effect (AOR: 1.24 [95% CI: 0.62 to 2.48] and AOR: 0.96 [95% CI: 0.47 to 1.99] respectively). There was no significant interaction between the effects of the test and result terminology. Across groups, perceiving no risk of infection was associated with an intention to wash hands less frequently (AOR: 2.32 [95% CI: 1.25 to 4.28]) but there was no significant association with intended avoidance of physical contact with others outside of the home (AOR: 1.37 [95% CI: 0.93 to 2.03]). Conclusions: Using the term Immunity (vs Antibody) to describe antibody tests for SARS-CoV-2 increases the proportion of people believing that an antibody-positive result means they have no risk of catching coronavirus in the future, a perception that may be associated with less frequent hand washing. The way antibody testing is described may have implications for the likely impact of testing on transmission rates.", "doc_id": "am3u7z76"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus.", "abstract": "The severe acute respiratory syndrome (SARS) outbreak of 2002 and 2003 occurred as a result of zoonotic transmission. Coronavirus (CoV) found in naturally infected palm civet (civet-CoV) represents the closest genetic relative to SARS-CoV, but the degree and the determinants of cross-neutralization among these viruses remain to be investigated. Studies indicate that the receptor binding domain (RBD) of the SARS-CoV spike (S) glycoprotein contains major determinants for viral entry and neutralization. We aim to characterize the impact of natural mutations within the RBDs of civet-CoVs on viral entry and cross-neutralization. In this study, the S glycoprotein genes were recovered from naturally infected civets in central China (Hubei province), extending the geographic distribution of civet-CoV beyond the southeastern province of Guangdong. Moreover, pseudoviruses generated in our laboratory with four civet S genes, each with a distinct RBD, infected cells expressing human receptor angiotensin-converting enzyme 2, but with 90 to 95% less efficiency compared to that of SARS-CoV. These four civet S genes were also constructed as DNA vaccines to immunize mice. Immunized sera elicited against most civet S glycoproteins displayed potent neutralizing activities against autologous viruses but were much less efficient (50% inhibitory concentration, 20- to 40-fold) at neutralizing SARS-CoV and vice versa. Convalescence-phase sera from humans were similarly ineffective against the dominant civet pseudovirus. Our findings suggest that the design of SARS vaccine should consider not only preventing the reemergence of SARS-CoV but also providing cross-protection, thus interrupting zoonotic transmission of a group of genetically divergent civet CoVs of broad geographic origin.", "doc_id": "q7zcqk2p"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Children's vaccines do not induce cross reactivity against SARS-CoV.", "abstract": "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.", "doc_id": "eo4ehcjv"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Antibodies to coronaviruses are higher in older compared with younger adults and binding antibodies are more sensitive than neutralizing antibodies in identifying coronavirus-associated illnesses", "abstract": "Human coronaviruses (HCoV) are common causes of respiratory illnesses (RI) despite preexisting humoral immunity. Sera were obtained near the onset of RI and 3 to 4 weeks later as part of a prospective study of 200 subjects evaluated for RI from 2009 to 2013. Antibodies against common HCoV strains were measured by enzyme-linked immunosorbent assay and neutralization assay comparing older adults with cardiopulmonary diseases (99 subjects) to younger, healthy adults (101 subjects). Virus shedding was detected in respiratory secretions by polymerase chain reaction. Of 43 HCoV-associated illnesses, 15 (35%) occurred in 14 older adults (aged ≥60 years) and 28 (65%) in 28 younger adults (aged 21-40 years). Binding and neutralizing antibodies were higher in older adults. Only 16 (35.7%) of RI with increases in binding antibodies also had increases in neutralizing antibodies to HCoV. Increases in binding antibodies with RI were more frequent than increased neutralizing antibodies and virus shedding, and more frequent in younger compared to older adults. Functional neutralizing antibodies were not stimulated as often as binding antibodies, explaining in part a susceptibility to reinfection with HCoV. Monitoring binding antibodies may be more sensitive for the serologic detection of HCoV infections.", "doc_id": "joapylf1"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "COVID-19 is milder in children possibly due to cross-immunity", "abstract": "", "doc_id": "es908m37"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "New IgM seroconversion and positive RT-PCR test after exposure to the virus in recovered COVID-19 patient", "abstract": "", "doc_id": "oecu6byi"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2", "abstract": "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.", "doc_id": "buwz6lu3"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "SARS-CoV-2 antibody testing-questions to be asked", "abstract": "Severe acute respiratory syndrome coronavirus 2 infection and development of coronavirus disease 2019 presents a major health care challenge of global dimensions. Laboratory diagnostics of infected patients, and the assessment of immunity against severe acute respiratory syndrome coronavirus 2, presents a major cornerstone in handling the pandemic. Currently, there is an increase in demand for antibody testing and a large number of tests are already marketed or are in the late stage of development. However, the interpretation of test results depends on many variables and factors, including sensitivity, specificity, potential cross-reactivity and cross-protectivity, the diagnostic value of antibodies of different isotypes, and the use of antibody testing in identification of acutely ill patients or in epidemiological settings. In this article, the recently established COVID-19 Task Force of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) addresses these issues on the basis of currently available data sets in this rapidly moving field.", "doc_id": "laobflfb"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Clinical, molecular, and epidemiological characterization of the SARS-CoV-2 virus and the Coronavirus Disease 2019 (COVID-19), a comprehensive literature review", "abstract": "Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least 7 coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms. Those that infect animals can evolve and become infectious to humans. Three recent examples of these viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19). COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 20 May 2020 show more than 5 million people had been infected with the virus, causing more than 330,000 deaths in over 210 countries worldwide. The large amount of information received daily relating to COVID-19 is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic. In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19).", "doc_id": "fs3kasu8"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract", "abstract": "The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.", "doc_id": "gb1weei2"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Long-term and herd immunity against SARS-CoV-2: implications from current and past knowledge", "abstract": "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.", "doc_id": "pcyscqux"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Multiplex detection and dynamics of IgG antibodies to SARS-CoV2 and the highly pathogenic human coronaviruses SARS-CoV and MERS-CoV", "abstract": "BACKGROUND: Knowledge of the COVID-19 epidemic extent and the level of herd immunity is urgently needed to help manage this pandemic. METHODS: We used a panel of 167 samples (77 pre-epidemic and 90 COVID-19 seroconverters) and SARS-CoV1, SARS-CoV2 and MERS-CoV Spike and/or Nucleopcapsid (NC) proteins to develop a high throughput multiplex screening assay to detect IgG antibodies in human plasma. Assay performances were determined by ROC curves analysis. A subset of the COVID-19+ samples (n = 36) were also tested by a commercial NC-based ELISA test and the results compared with those of the novel assay. RESULTS: On samples collected ≥14 days after symptoms onset, the accuracy of the assay is 100 % (95 % CI: 100-100) for the Spike antigen and 99.9 % (95 % CI:99.7-100) for NC. By logistic regression, we estimated that 50 % of the patients have seroconverted at 5.7 \u00b1 1.6; 5.7 \u00b1 1.8 and 7.9 \u00b1 1.0 days after symptoms onset against Spike, NC or both antigens, respectively and all have seroconverted two weeks after symptoms onset. IgG titration in a subset of samples showed that early phase samples present lower IgG titers than those from later phase. IgG to SARS-CoV2 NC cross-reacted at 100 % with SARS-CoV1 NC. Twenty-nine of the 36 (80.5 %) samples tested were positive by the commercial ELISA while 31/36 (86.1 %) were positive by the novel assay. CONCLUSIONS: Our assay is highly sensitive and specific for the detection of IgG antibodies to SARS-CoV2 proteins, suitable for high throughput epidemiological surveys. The novel assay is more sensitive than a commercial ELISA.", "doc_id": "ph6pxseu"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Will we see protection or reinfection in COVID-19?", "abstract": "", "doc_id": "9ieyw5fz"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Dissecting antibody-mediated protection against SARS-CoV-2", "abstract": "", "doc_id": "jkqjybm1"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2", "abstract": "Genetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen A [HLA-A], -B, and -C genes) may affect susceptibility to and severity of the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). We performed a comprehensive in silico analysis of viral peptide-MHC class I binding affinity across 145 HLA-A, -B, and -C genotypes for all SARS-CoV-2 peptides. We further explored the potential for cross-protective immunity conferred by prior exposure to four common human coronaviruses. The SARS-CoV-2 proteome was successfully sampled and was represented by a diversity of HLA alleles. However, we found that HLA-B*46:01 had the fewest predicted binding peptides for SARS-CoV-2, suggesting that individuals with this allele may be particularly vulnerable to COVID-19, as they were previously shown to be for SARS (M. Lin, H.-T. Tseng, J. A. Trejaut, H.-L. Lee, et al., BMC Med Genet 4:9, 2003, https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-4-9). Conversely, we found that HLA-B*15:03 showed the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting that it could enable cross-protective T-cell-based immunity. Finally, we reported global distributions of HLA types with potential epidemiological ramifications in the setting of the current pandemic.IMPORTANCE Individual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of severity of viral disease in the population. Following the development of a vaccine against SARS-CoV-2, the virus that causes COVID-19, individuals with high-risk HLA types could be prioritized for vaccination.", "doc_id": "90ryq775"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS", "abstract": "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.", "doc_id": "nacxjt2f"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Could BCG Vaccination Induce Protective Trained Immunity for SARS-CoV-2?", "abstract": "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.", "doc_id": "2d04geu3"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Development of passive immunity against SARS-CoV-2 for management of immunodeficient patients - a perspective", "abstract": "", "doc_id": "rirftuu9"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Grundlagen der Replikation und der Immunologie von SARS-CoV-2", "abstract": "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\u2011cell 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.", "doc_id": "neq2vqym"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "The immunity induced by recombinant spike proteins of SARS coronavirus in Balb/c mice", "abstract": "The immune effect of two recombinant protein fragments of spike protein in severe acute respiratory syndrome coronavirus (SARS CoV) was investigated in Balb/c mice. Two partial spike gene fragments S1 (322 1464 bp) and S2 (2170 2814 bp) of SARS coronavirus were amplified by RT-PCR, and cloned into pET-23a prokaryotic expression vector, then transformed into competent Escherichia E. coli BL21 (DE3)(pLysS) respectively. Recombinant proteins were expressed and purified by Ni(2+) immobilized metal ion affinity chromatography. The purified proteins mixed with complete Freund adjuvant were injected into Balb/c mice three times at a two-week interval. High titer antibody was detected in the serum of immunized Balb/c mice, and mice immunized with S1 protein produced high titer IgG1, IgG2a, IgG2b and IgG3, while those immunized with S2 protein produced high titer IgG1, IgG2a, but lower titer IgG2b and IgG3. Serum IFN-concentration was increased significantly but the concentrations of Il-2, IL-4 and IL-10 had no significant change. And a marked increase was observed in the number of spleen CD8+ T cells. The results showed that recombinant proteins of SARS coronavirus spike protein induced hormonal and cellular immune response in Balb/c mice.", "doc_id": "1udn20wo"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Immunodominant viral peptides as determinants of cross-reactivity in the immune system \u2013 Can we develop wide spectrum viral vaccines?", "abstract": "Summary When we look back to Edward Jenner vaccination of a young man in 1796, we cannot help thinking that he was both lucky and crazy. Crazy because he decided to test in a human being a hypothesis based mainly in the traditional belief that people who had acquired cowpox from the udders of a cow were thereafter resistant to smallpox, a quite devastating disease, and lucky because (even considering that he did not know this at that time) he succeeded to induce protection against a pathogen through the induction of an immune response directed against a different agent. Not only was he able to protect the young man but he took the first step towards the development of a vast new field, vaccination. It is acceptable to say that Jenner was lucky because he succeeded in promoting protection against smallpox using a cowpox virus and this induction of protection in a cross-reactive way is believed to be quite rare. Nevertheless, more and more examples of cross-reactive immune responses are being described and we are beginning to admit that cross-reactivity is far more common and important than we used to think. Here we review cross-reactivity in the immune system and the plasticity of T cell recognition. Based on the existence of T cell receptor promiscuous recognition and cross-recognition of conserved viral immunodominant epitopes, we propose two approaches to develop wide spectrum viral vaccines. The first one is based on the identification, characterization, and cloning of immunodominant viral epitopes able to stimulate responses against different viruses. The produced peptides could then be purified and serve as a basis for vaccine therapies. A second strategy is based on the identification of conserved patterns in immunodominant viral peptides and the production of synthetic peptides containing the amino acid residues necessary for MHC anchoring and TCR contact. Although we are still far from a complete knowledge of the cross-reactivity phenomenon in the immune system, the analysis of immunodominant viral epitopes and the identification of particular \u201cviral patterns\u201d seems to be important steps towards the development of wide spectrum viral vaccines.", "doc_id": "ae2x2wpg"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Coronavirus and PARP expression dysregulate the NAD Metabolome: a potentially actionable component of innate immunity", "abstract": "SARS-CoV-2 is a coronavirus (CoV) and cause of COVID-19, which is much more lethal in older people and those with comorbid conditions for unknown reasons. Innate immune responses to CoVs are initiated by recognition of double-stranded RNA and induction of interferon, which turns on a gene expression program that inhibits viral replication. Here we show that SARS-CoV-2 infection of cells, ferrets and a person strikingly dysregulates the NAD gene set by inducing a set of PARP family members that includes enzymes required for the innate immune response to CoVs. CoV infection also induces a severe attack on host cell NAD. Overexpression of one induced enzyme, PARP10, is sufficient to depress host NAD. Gene expression and pharmacological data suggest that boosting NAD through the nicotinamide and nicotinamide riboside kinase pathways may restore antiviral PARP functions to support innate immunity to CoVs, whereas PARP1,2 inhibition does not restore PARP10 activity.", "doc_id": "033phqmd"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Potential biases arising from epidemic dynamics in observational seroprotection studies", "abstract": "The extent and duration of immunity following SARS-CoV-2 infection are critical outstanding questions about the epidemiology of this novel virus, and studies are needed to evaluate the effects of serostatus on reinfection. Understanding the potential sources of bias and methods to alleviate biases in these studies is important for informing their design and analysis. Confounding by individual-level risk factors in observational studies like these is relatively well appreciated. Here, we show how geographic structure and the underlying, natural dynamics of epidemics can also induce noncausal associations. We take the approach of simulating serologic studies in the context of an uncontrolled or a controlled epidemic, under different assumptions about whether prior infection does or does not protect an individual against subsequent infection, and using various designs and analytic approaches to analyze the simulated data. We find that in studies assessing the efficacy of serostatus on future infection, comparing seropositive individuals to seronegative individuals with similar time-dependent patterns of exposure to infection, by stratifying or matching on geographic location and time of enrollment, is essential to prevent bias.", "doc_id": "ajcwapvt"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Anatomical features of anti-viral immunity in the respiratory tract", "abstract": "Abstract The mucosal surfaces of the lungs are a major portal of entry for virus infections and there are urgent needs for new vaccines that promote effective pulmonary immunity. However, we have only a rudimentary understanding of the requirements for effective cellular immunity in the respiratory tract. Recent studies have revealed that specialized cellular immune responses and lymphoid tissues are involved in the protection of distinct anatomical microenvironments of the respiratory tract, such as the large airways of the nose and the alveolar airspaces. This review discusses some of the anatomical features of anti-viral immunity in the respiratory tract including the role of local lymphoid tissues and the relationship between effector and memory T cells in the airways, the lung parenchyma, and lymphoid organs.", "doc_id": "qjximt34"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "DNA Vaccine Encoding Middle East Respiratory Syndrome Coronavirus S1 Protein Induces Protective Immune Responses in Mice", "abstract": "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-\u03b3 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.", "doc_id": "4ywrzyse"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "SARS-CoV-2, \u201ccommon cold\u201d coronaviruses\u2019 cross-reactivity and \u201cherd immunity\u201d: The razor of Ockham (1285-1347)?", "abstract": "", "doc_id": "uzhj4i1q"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Cross-sectional evaluation of humoral responses against SARS-CoV-2 Spike", "abstract": "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.", "doc_id": "xzl23c52"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses", "abstract": "Two zoonotic coronaviruses (CoV), SARS-CoV and MERS-CoV have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4(+) T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4(+) T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was interferon-\u03b3-dependent and required early induction of robust innate and virus-specific CD8(+) T cell responses. The conserved epitope was also recognized in SARS-CoV and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4(+) T cells targeting conserved epitopes may have broad applicability in the context of new CoV and other respiratory virus outbreaks.", "doc_id": "fj2rjmop"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Will children reveal their secret? The coronavirus dilemma", "abstract": "Epidemiological evidences show that SARS-CoV-2 infection in children is less frequent and severe than adults. Age-related ACE2 receptor expression, lymphocyte count and trained immunity might be the keystone to reveal children's secret.", "doc_id": "ia6d08j5"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2", "abstract": "Despite various levels of preventive measures, in 2020 many countries have suffered severely from the coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We show that population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups with low contact rates. We estimate that if R(0) = 2.5 in an age-structured community with mixing rates fitted to social activity then the disease-induced herd immunity level can be around 43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population. Our estimates should be interpreted as an illustration of how population heterogeneity affects herd immunity, rather than an exact value or even a best estimate.", "doc_id": "73oe5as9"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Respiratory virus-induced heterologous immunity: Part of the problem or part of the solution?", "abstract": "PURPOSE: To provide current knowledge on respiratory virus-induced heterologous immunity (HI) with a focus on humoral and cellular cross-reactivity. Adaptive heterologous immune responses have broad implications on infection, autoimmunity, allergy and transplant immunology. A better understanding of the mechanisms involved might ultimately open up possibilities for disease prevention, for example by vaccination. METHODS: A structured literature search was performed using Medline and PubMed to provide an overview of the current knowledge on respiratory-virus induced adaptive HI. RESULTS: In HI the immune response towards one antigen results in an alteration of the immune response towards a second antigen. We provide an overview of respiratory virus-induced HI, including viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (CoV) and influenza virus (IV). We discuss T cell receptor (TCR) and humoral cross-reactivity as mechanisms of HI involving those respiratory viruses. Topics covered include HI between respiratory viruses as well as between respiratory viruses and other pathogens. Newly developed vaccines which have the potential to provide protection against multiple virus strains are also discussed. Furthermore, respiratory viruses have been implicated in the development of autoimmune diseases, such as narcolepsy, Guillain\u2013Barr\u00e9 syndrome, type 1 diabetes or myocarditis. Finally, we discuss the role of respiratory viruses in asthma and the hygiene hypothesis, and review our recent findings on HI between IV and allergens, which leads to protection from experimental asthma. CONCLUSION: Respiratory-virus induced HI may have protective but also detrimental effects on the host. Respiratory viral infections contribute to asthma or autoimmune disease development, but on the other hand, a lack of microbial encounter is associated with an increasing number of allergic as well as autoimmune diseases. Future research might help identify the elements which determine a protective or detrimental outcome in HI-based mechanisms.", "doc_id": "4e2j89uy"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "Evaluating the promise of recombinant transmissible vaccines", "abstract": "Transmissible vaccines have the potential to revolutionize infectious disease control by reducing the vaccination effort required to protect a population against a disease. Recent efforts to develop transmissible vaccines focus on recombinant transmissible vaccine designs (RTVs) because they pose reduced risk if intra-host evolution causes the vaccine to revert to its vector form. However, the shared antigenicity of the vaccine and vector may confer vaccine-immunity to hosts infected with the vector, thwarting the ability of the vaccine to spread through the population. We build a mathematical model to test whether a RTV can facilitate disease management in instances where reversion is likely to introduce the vector into the population or when the vector organism is already established in the host population, and the vector and vaccine share perfect cross-immunity. Our results show that a RTV can autonomously eradicate a pathogen, or protect a population from pathogen invasion, when cross-immunity between vaccine and vector is absent. If cross-immunity between vaccine and vector exists, however, our results show that a RTV can substantially reduce the vaccination effort necessary to control or eradicate a pathogen only when continuously augmented with direct manual vaccination. These results demonstrate that estimating the extent of cross-immunity between vector and vaccine is a critical step in RTV design, and that herpesvirus vectors showing facile reinfection and weak cross-immunity are promising.", "doc_id": "6q92742u"} {"topic_name": "coronavirus immunity", "topic_id": "3", "title": "SARS-CoV2 coronavirus: So far polite with children. Debatable immunological and non-immunological evidence", "abstract": "Abstract The reasons for the relative resistance of children to certain infections such as that caused by coronavirus SARS- CoV2 are not yet fully clear. Deciphering these differences can provide important information about the pathogenesis of the disease. Regarding the SARS-CoV2 virus, children are at the same risk of infection as the general population of all ages, with the most serious cases being found in infants. However, it has been reported that the disease is much less frequent than in adults and that most cases are benign or moderate (even with high viral loads), provided there are no other risk factors or underlying diseases. It is not clear why they have lower morbidity and virtually no mortality. A series of findings, relationships and behavioral patterns between the infectious agent and the child host may account for the lower incidence and a greatly attenuated clinical presentation of the disease in children.", "doc_id": "hajvtzj9"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Acute respiratory distress syndrome-attributable mortality in critically ill patients with sepsis", "abstract": "PURPOSE: Previous studies assessing impact of acute respiratory distress syndrome (ARDS) on mortality have shown conflicting results. We sought to assess the independent association of ARDS with in-hospital mortality among intensive care unit (ICU) patients with sepsis. METHODS: We studied two prospective sepsis cohorts drawn from the Early Assessment of Renal and Lung Injury (EARLI; n = 474) and Validating Acute Lung Injury markers for Diagnosis (VALID; n = 337) cohorts. ARDS was defined by Berlin criteria. We used logistic regression to compare in-hospital mortality in patients with and without ARDS, controlling for baseline severity of illness. We also estimated attributable mortality, adjusted for illness severity by stratification. RESULTS: ARDS occurred in 195 EARLI patients (41%) and 99 VALID patients (29%). ARDS was independently associated with risk of hospital death in multivariate analysis, even after controlling for severity of illness, as measured by APACHE II (odds ratio [OR] 1.65 (95% confidence interval [CI] 1.02, 2.67), p = 0.04 in EARLI; OR 2.12 (CI 1.16, 3.92), p = 0.02 in VALID). Patients with severe ARDS (P/F < 100) primarily drove this relationship. The attributable mortality of ARDS was 27% (CI 14%, 37%) in EARLI and 37% (CI 10%, 51%) in VALID. ARDS was independently associated with ICU mortality, hospital length of stay (LOS), ICU LOS, and ventilator-free days. CONCLUSIONS: Development of ARDS among ICU patients with sepsis confers increased risk of ICU and in-hospital mortality in addition to other important outcomes. Clinical trials targeting patients with severe ARDS will be best poised to detect measurable differences in these outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06010-9) contains supplementary material, which is available to authorized users.", "doc_id": "omv6rkl1"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Infectious Atypical Pneumonia", "abstract": "Infectious atypical pneumonia, also known as severe acute respiratory syndrome (SARS), is an acute respiratory infectious disease caused by SARS coronavirus (SARS-CoV). Clinically, it is characterized by fever, headache, muscular soreness, fatigue, dry cough rarely with phlegm, and diarrhea. Most patients experience accompanying pneumonia. In severe cases, the conditions may develop into acute lung injury, acute respiratory distress syndrome (ARDS), or even multiple organ failure that causes death. In China, SARS has been legally listed as one of the class B infectious diseases but is managed as class A infectious diseases, like anthrax and human infection of avian influenza.", "doc_id": "7sy8e7hs"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Post-mortem examination of COVID19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction.", "abstract": "AIMS Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly evolved into a sweeping pandemic. While its major manifestation is in the respiratory tract, the general extent of organ involvement as well as microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID-19-associated organ alterations. METHODS This study reports 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. RESULTS The primary cause of death was respiratory failure with exudative diffuse alveolar damage with massive capillary congestion often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolisms (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 thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, 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 post-mortem 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 amongst these patients.", "doc_id": "sf0w0spq"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Covid-19: Death rate in England and Wales reaches record high because of covid-19.", "abstract": "", "doc_id": "2b8ei6g3"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Fatal Outcomes of COVID-19 in Patients with Severe Acute Kidney Injury.", "abstract": "The outcome of coronavirus disease 2019 (COVID-19) is associated with organ damage; however, the information about the relationship between acute kidney injury (AKI) and COVID-19 is still rare. We evaluated the clinical features and prognosis of COVID-19 patients with AKI according to the AKI severity. Medical data of hospitalized COVID-19 patients in two university-based hospitals during an outbreak in Daegu, South Korea, were retrospectively analyzed. AKI and its severity were defined according to the Acute Kidney Injury Network. Of the 164 hospitalized patients with COVID-19, 30 patients (18.3%) had AKI; 14, 4, and 12 patients had stage 1, 2, and 3, respectively. The median age was significantly higher in AKI patients than in non-AKI patients (75.5 vs. 67.0 years, p = 0.005). There were 17 deaths (56.7%) among AKI patients; 4 (28.6%), 1 (25.0%), and 12 (100.0%), respectively. In-hospital mortality was higher in AKI patients than in non-AKI patients (56.7% vs. 20.8%, p < 0.001). After adjusting for potential confounding factors, stage 3 AKI was associated with higher mortality than either non-AKI or stage 1 AKI (hazard ratio (HR) = 3.62 (95% confidence interval (CI) = 1.75-7.48), p = 0.001; HR = 15.65 (95% CI = 2.43-100.64), p = 0.004). Among the AKI patients, acute respiratory distress syndrome and low serum albumin on admission were considered independent risk factors for stage 3 AKI (both p < 0.05). Five patients with stage 3 AKI underwent dialysis and eventually died. In conclusion, COVID-19 patients with severe AKI had fatal outcomes.", "doc_id": "ez7fcgi2"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Covid-19: risk factors for severe disease and death.", "abstract": "", "doc_id": "jtui5j90"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "[Pathological changes of fatal coronavirus disease 2019 (COVID-19) in the lungs: report of 10 cases by postmortem needle autopsy].", "abstract": "Objectives: To observe the pulmonary changes with coronavirus disease 2019 (COVID-19) in postmortem needle specimens, to detect the presence of 2019 novel coronavirus(2019-nCoV) in the lung tissues, and to analyze the clinicopathological characteristics. Methods: For 10 decedents with 2019-nCoV infection in Wuhan, bilateral lungs underwent ultrasound-guided percutaneous multi-point puncture autopsy, and pulmonary pathological changes were described in routine hematoxylin-eosin staining (HE) slides. Electron microscopy was also performed. The reverse transcription polymerase chain reaction (RT-PCR) was employed to detect 2019-nCoV nucleic acid in lung tissue, and the pathological characteristics were demonstrated in combination with clinical data analysis. Results: Of the 10 deaths associated with COVID-19, 7 were male and 3 were female. The average age was 70 (39-87) years. Medical record showed that 7 patients had underlying diseases. The average course of disease was 30 (16-36) days. Nine cases showed fibrinous and suppurative exudation in the alveolar cavity accompanied by the formation of hyaline membrane, and fibroblastic proliferation of alveolar septum. Type \u2161 alveolar epithelial cells showed reactive hyperplasia and desquamation. Many macrophages accumulated in the alveolar cavity. Capillary hyaline thrombus and intravascular mixed thrombus were noted. In some cases, acute bronchiolitis with mucous membrane exfoliation, accumulation of bronchiolar secretions, and bronchiolar epithelial metaplasia occurred. In the cohort, a large number of bacteria (cocci) were detected in 1 case and a large number of fungi (yeast type) were detected in 1 case. Nine cases were positive for the nucleic acids of 2019-nCoV while one case remained negative by RT-PCR. Coronavirus particles were detected in the cytoplasm of type \u2161 alveolar epithelium. Conclusions: The pulmonary pathological changes of fatal COVID-19 are diffuse alveolar damage (DAD), mainly in the acute exudative stage and the organic proliferative stage. There are fibrinous exudate aggregation in alveolar cavity with hyaline membrane formation, fibroblastic proliferation in alveolar septum, and alveolar epithelial cell injuries with reactive hyperplasia and desquamation of type \u2161 alveolar epithelial cells. A large amount of neutrophils and monocytes infiltration is present in most cases and bacteria and fungi are detected in some cases, suggesting a serious bacterial or fungal infection secondary to the DAD.", "doc_id": "h5ky9y8v"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Clinical characteristics of 82 cases of death from COVID-19.", "abstract": "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.", "doc_id": "ls0x41h1"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Risk factors for myocardial injury and death in patients with COVID-19: insights from a cohort study with chest computed tomography.", "abstract": "AIMS Whether pulmonary artery (PA) dimension and coronary artery calcium (CAC) score, as assessed by chest computed tomography (CT), are associated with myocardial injury in patients with coronavirus disease 2019 (COVID-19) is not known. The aim of this study was to explore the risk factors for myocardial injury and death and to investigate whether myocardial injury has an independent association with all-cause mortality in patients with COVID-19. METHODS AND RESULTS This is a single-centre cohort study including consecutive patients with laboratory-confirmed COVID-19 undergoing chest CT on admission. Myocardial injury was defined as high-sensitivity troponin I > 20 ng/L on admission. A total of 332 patients with a median follow-up of 12 days were included. There were 68 (20.5%) deaths; 123 (37%) patients had myocardial injury. PA diameter was higher in patients with myocardial injury compared with patients without myocardial injury [29.0 (25th-75th percentile, 27-32) mm vs. 27.7 (25-30) mm, < 0.001). PA diameter was independently associated with an increased risk of myocardial injury [adjusted odds ratio 1.10, 95% confidence interval (CI) 1.02-1.19, P = 0.01] and death [adjusted hazard ratio (HR) 1.09, 95% CI 1.02-1.17, P = 0.01]. Compared with patients without myocardial injury, patients with myocardial injury had a lower prevalence of a CAC score of zero (25% vs. 55%, < 0.001); however, the CAC score did not emerge as a predictor of myocardial injury by multivariable logistic regression. Myocardial injury was independently associated with an increased risk of death by multivariable Cox regression (adjusted HR 2.25, 95% CI 1.27-3.96, P = 0.005). Older age, lower estimated glomerular filtration rate, and lower PaO/FiO ratio on admission were other independent predictors for both myocardial injury and death. CONCLUSIONS An increased PA diameter, as assessed by chest CT, is an independent risk factor for myocardial injury and mortality in patients with COVID-19. Myocardial injury is independently associated with an approximately two-fold increased risk of death. TRANSLATIONAL PERSPECTIVE The present study identifies myocardial injury as a clinically relevant independent risk factor for death in the short term in a population of hospitalized patients with laboratory-confirmed COVID-19 outside of China undergoing chest computed tomography for suspected pneumonia on admission.The study also provides novel insights into the risk factors for myocardial injury, showing that an increased pulmonary artery diameter, assessed by chest computed tomography, is an independent predictor of myocardial injury as well as of mortality, suggesting that pulmonary circulation dysfunction is a pivotal pathological event with cardiac implications in COVID-19.", "doc_id": "qhnqqae6"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Clinical and laboratory findings from patients with COVID-19 pneumonia in Babol North of Iran: a retrospective cohort study.", "abstract": "BACKGROUND In December, 2019, China, has experienced an outbreak of novel coronavirus disease 2019 (COVID-19). Coronavirus has now spread to all of the continents. We aimed to consider clinical characteristics, laboratory data of COVID-19 that provided more information for the research of this novel virus. METHODS We performed a retrospective cohort study on the clinical symptoms and laboratory findings of a series of the 100 confirmed patients with COVID-19. These patients were admitted to the hospitals affiliated to Babol University of Medical Sciences (Ayatollah Rohani, Shahid Beheshti and Yahyanejad hospitals) form 25 February 2020 to 12 March 2020. RESULTS Nineteen patients died during hospitalization and 81 were discharged. Non-survivor patients had a significantly higher C-reactive protein (CRP) (MD: 46.37, 95% CI: 20.84, 71.90; P= 0.001), white blood cells (WBCs) (MD: 3.10, 95% CI: 1.53, 4.67; P< 0.001) and lower lymphocyte (MD: -8.75, 95% CI: -12.62, -4.87; P< 0.001) compared to survivor patients Data analysis showed that comorbid conditions (aRR: 2.99, 95%CI: 1.09, 8.21, P= 0.034), higher CRP levels (aRR: 1.02, 95%CI: 1.01, 1.03, P= 0.044), and lower lymphocyte (aRR: 0.82, 95%CI: 0.73, 0.93, P= 0.003) were associated with increased risk of death. CONCLUSIONS Based on our findings, most non-survivors are elderly with comorbidities. Lymphopenia and increased levels of WBCs along with elevated CRP were associated with increased risk of death. Therefore, it is best to be regularly assessed these markers during treatment of COVID-19 patients.", "doc_id": "c3poqb7q"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "COVID-19: is fibrosis the killer?", "abstract": "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.", "doc_id": "b8bl5vq5"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19.", "abstract": "BACKGROUND Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19. METHODS We examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immunohistochemical analysis, micro-computed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression. RESULTS In patients who died from Covid-19-associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth - predominantly through a mechanism of intussusceptive angiogenesis - was 2.7 times as high as that in the lungs from patients with influenza (P<0.001). CONCLUSIONS In our small series, vascular angiogenesis distinguished the pulmonary pathobiology of Covid-19 from that of equally severe influenza virus infection. The universality and clinical implications of our observations require further research to define. (Funded by the National Institutes of Health and others.).", "doc_id": "8g8yc0tu"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "COVID-19 autopsy in people who died in community settings: the first series.", "abstract": "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.", "doc_id": "fnv2moum"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) - United States, February 12-March 16, 2020.", "abstract": "Globally, approximately 170,000 confirmed cases of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) have been reported, including an estimated 7,000 deaths in approximately 150 countries (1). On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic (2). Data from China have indicated that older adults, particularly those with serious underlying health conditions, are at higher risk for severe COVID-19-associated illness and death than are younger persons (3). Although the majority of reported COVID-19 cases in China were mild (81%), approximately 80% of deaths occurred among adults aged \u226560 years; only one (0.1%) death occurred in a person aged \u226419 years (3). In this report, COVID-19 cases in the United States that occurred during February 12-March 16, 2020 and severity of disease (hospitalization, admission to intensive care unit [ICU], and death) were analyzed by age group. As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities (4). Overall, 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths associated with COVID-19 were among adults aged \u226565 years with the highest percentage of severe outcomes among persons aged \u226585 years. In contrast, no ICU admissions or deaths were reported among persons aged \u226419 years. Similar to reports from other countries, this finding suggests that the risk for serious disease and death from COVID-19 is higher in older age groups.", "doc_id": "5y6gjl2t"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections", "abstract": "Background SARS-CoV-2 is the cause of an ongoing pandemic with a projected 100,000 to 240,000 U.S. deaths. To date, documentation of histopathologic features in fatal cases of COVID-19 has been limited due to small sample size and incomplete organ sampling. Methods Post-mortem examinations were performed on 12 fatal COVID-19 cases in Washington State during February-March 2020. Clinical and laboratory data were reviewed. Tissue examination of all major organs was performed by light microscopy and electron microscopy. The presence of viral RNA in sampled tissues was tested by RT-PCR. Results All 12 patients were older with significant preexisting comorbidities. The major pulmonary finding was diffuse alveolar damage in the acute and/or organizing phases with virus identified in type I and II pneumocytes by electron microscopy. The kidney demonstrated viral particles in the tubular epithelium, endothelium, and podocytes without significant inflammation. Viral particles were also observed in the trachea and large intestines. SARS-CoV-2 RNA was detected in the cardiac tissue of a patient with lymphocytic myocarditis. RT-PCR also detected viral RNA in the subcarinal lymph nodes, liver, spleen, and large intestines. Conclusion SARS-CoV-2 represents the third novel coronavirus to cause widespread human disease since 2002. Similar to SARS and MERS, the primary pathology was diffuse alveolar damage with virus located in the pneumocytes. However, other major organs including the heart and kidneys may be susceptible to viral replication and damage leading to increased mortality in those with disseminated disease. Understanding the pathology of SARS-CoV-2 will be essential to design effective therapies.", "doc_id": "0udqwhx8"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "A Case Report of Rapidly Lethal Acute Respiratory Distress Syndrome Secondary to Coronavirus Disease 2019 Viral Pneumonia", "abstract": "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", "doc_id": "q6wp6c08"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Early postmortem brain MRI findings in COVID-19 non-survivors", "abstract": "Importance: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuro-invasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). Brain magnetic resonance imaging (MRI) data in COVID-19 patients are scarce due to difficulties to obtain such examination in infected unstable patients during the COVID-19 outbreak. Objective: To investigate the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework. Design: Prospective, case series study with postmortem brain MRI obtained early (<24h) after death. Setting: Monocentric study. Participants: From 31/03/2020 to 24/04/2020, consecutive decedents who fulfilled the following inclusion criteria were included: death <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest computerized tomographic (CT) scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility. Main Outcome(s) and Measure(s): Signs of acute brain injury and MRI signal abnormalities along the olfactory tract and brainstem were searched independently by 3 neuroradiologists, then reviewed with neurologists and clinicians. Results: Among the 62 patients who died from COVID-19 during the inclusion period, 19 decedents fulfilled inclusion criteria. Subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES, one decedent), and nonspecific deep white matter changes (one decedent) were observed. Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality. Conclusions and Relevance: Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19 that might be triggered by the virus-induced endothelial disturbances. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. The absence of brainstem MRI abnormalities does not support a brain-related contribution to respiratory distress in COVID-19.", "doc_id": "wxwz7r7u"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Liver Chemistries in COVID-19 Patients with Survival or Death: A Meta-Analysis", "abstract": "Background and Aims: Although abnormal liver chemistries are linked to higher risk of death related to coronavirus disease (COVID-19), liver manifestations may be diverse and even confused. Thus, we performed a meta-analysis of published liver manifestations and described the liver damage in COVID-19 patients with death or survival. Methods: We searched PubMed, Google Scholar, medRxiv, bioRxiv, Cochrane Library, Embase, and three Chinese electronic databases through April 22, 2020. We analyzed pooled data on liver chemistries stratified by the main clinical outcome of COVID-19 using a fixed or random-effects model. Results: In the meta-analysis of 18 studies, which included a total of 2,862 patients, the pooled mean alanine aminotransferase (ALT) was 30.9 IU/L in the COVID-19 patients with death and 26.3 IU/L in the COVID-19 patients discharged alive (p < 0.0001). The pooled mean aspartate aminotransferase (AST) level was 45.3 IU/L in the COVID-19 patients with death while 30.1 IU/L in the patients discharged alive (p < 0.0001). Compared with the discharged alive cases, the dead cases tended to have lower albumin levels but longer prothrombin time, and international standardized ratio. Conclusions: In this meta-analysis, according to the main clinical outcome of COVID-19, we comprehensively described three patterns of liver impairment related to COVID-19, hepatocellular injury, cholestasis, and hepatocellular disfunction. Patients died from COVID-19 tend to have different liver chemistries from those are discharged alive. Close monitoring of liver chemistries provides an early warning against COVID-19 related death.", "doc_id": "4sxe7s03"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Accelerated hyaluronan concentration as the primary driver of morbidity and mortality in high-risk COVID-19 patients: with therapeutic introduction of an oral hyaluronan inhibitor in the prevention of \"Induced Hyaluronan Storm\" Syndrome", "abstract": "Background To date, more than 161,000 people have died from the coronavirus disease 2019 (COVID-19) yet the fundamental drivers of the morbidity and mortality remain uncertain. Clinicians worldwide appear to be at a loss to know how to prevent and treat the severe respiratory distress in these patients effectively. Consequently, the fundamental mechanisms leading to death in high-risk patients with COVID-19 need to be discovered and addressed with urgency. Despite a marked drop in frequency, the post-mortem autopsy remains an essential part of both discovering the cause of death in a particular individual, but also in advancing the science and treatment of disease, especially in the case of novel pathogens such as SARS-CoV-2[2]. The goal of an autopsy is to discover the cause of death (COD) using a macro/microscopic investigation. Traditionally, the intact organs are carefully removed, inspected, and weighed. Because lung weight is often affected by the cause of death and the last breath occurs very near if not at the moments of death, the evaluation of the lungs is one of the starting points of any COD investigation[3]. Method A comprehensive search was performed to systematically review all reported autopsy findings in COVID-19 patients in order to better understand the underlying disease mechanisms resulting in death. We then compared these findings with the results of a targeted literature review of hyaluronan in relationship to acute respiratory distress syndrome (ARDS). Results In total, data from 181 autopsies were identified. From this group, 6 autopsies of COVID-19 patients were selected for a detailed review and statistical analysis. The average lung weight of those who were determined to have died as a result of SARS-CoV-2 was 2196g-approximately 2.5x normal lung weight. Hyaline membranes were consistently identified on histologic sections. A review of the literature reveals that hyaluronan has been associated with the pathophysiology of ARDS since 1967. However, its key role in driving the morbidity and mortality of the condition has heretofore not been fully recognized. Conclusions We propose that the induced hyaluronan storm syndrome or IHS, is the model that best addresses the heretofore perplexing respiratory failure that is the proximal cause of death in a minority, but ever rising number, of patients. In addition to treating and preventing IHS in currently infected individuals now; an aggressive research effort should be undertaken to discover why the majority of individuals who are exposed to the virus are either minimally or asymptomatic, while a minority of high-risk individuals rapidly progress to respiratory failure and death. Keywords Systematic review; COVID-19; SARS-CoV-2; Hyaline Membrane; Hyaluronan; Acute Respiratory Distress Syndrome; ARDS; Autopsy; IHS; Induced Hyaluronan Storm Syndrome; COD; Cause of Death", "doc_id": "gsqzmuj5"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Comparison of the Clinical Implications among Two Different Nutritional Indices in Hospitalized Patients with COVID-19", "abstract": "Background: Coronavirus disease 2019 (COVID 19) is an emerging infectious disease.It was first reported in Wuhan, China, and then broke out on a large scale around the world.This study aimed to assess the clinical significance of two different nutritional indices in 245 patients with COVID 19. Methods: In this retrospective single center study, we finally included 245 consecutive patients who confirmed COVID 19 in Wuhan University Zhongnan Hospital from January 1 to February 29. Cases were classified as either discharged or dead. Demographic, clinical and laboratory datas were registered, two different nutritional indices were calculated: (i)the Controlling nutritional status (CONUT) score; (ii) prognostic nutritional index (PNI). We used univariate and multivariate logistic regression analysis to explore the relationship between nutritional indices and hospital death . Results: 212 of them were discharged and 33 of them died. In hospital mortality was signifcantly higher in the severe group of PNI than in the moderate and normal groups. It was also significantly worse in the severe CONUT group than in the moderate, mild , and normal CONUT groups. Multivariate logistic regression analysis showed the CONUT score (odds ratio3.371,95%CI (1.124 10.106), p = 0.030) and PNI(odds ratio 0.721,95% CI(0.581 0.896),P=0.003) were independent predictors of all cause death at an early stage; Multivariate logistic regression analysis also showed that the severe group of PNI was the independent risk predictor of in hospital death(odds ratio 24.225, 95% CI(2.147 273.327), p=0.010).The CONUT score cutoff value was 5.5 (56.00 and 80.81%; AUC 0.753; 95% CI(0.644 0.862);respectively).The PNI cutoff value was 40.58 (81.80 and 66.20%; AUC 0.778; 95% CI(0.686 0.809); respectively).We use PNI and the COUNT score to assess malnutrition, which can have a prognosis effect of COVID 19 patients. Conclusion:The CONUT score and PNI could be a reliable prognostic marker of all cause death in patients with COVID 19. Keywords: Coronavirus disease 2019; nutrition; indicies; prognosis", "doc_id": "nwh1842t"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Clinical characteristics of 25 death cases with COVID-19: A retrospective review of medical records in a single medical center, Wuhan, China", "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.", "doc_id": "8om7z5cc"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Analysis of Characteristics in Death Patients with COVID-19 Pneumonia without Underlying Diseases", "abstract": "", "doc_id": "6496homy"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Sudden cardiac death in COVID-19 patients, a report of three cases", "abstract": "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.", "doc_id": "u9omhsgu"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "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", "abstract": "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.", "doc_id": "j8rtwy6l"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Death from Covid-19 of 23 Health Care Workers in China", "abstract": "", "doc_id": "amuivx3s"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients", "abstract": "Higher rates of serious illness and death from coronavirus SARS-CoV-2 (COVID-19) infection among older people and those who have comorbidities suggest that age- and disease-related biological processes make such individuals more sensitive to environmental stress factors including infectious agents like coronavirus SARS-CoV-2. Specifically, impaired redox homeostasis and associated oxidative stress appear to be important biological processes that may account for increased individual susceptibility to diverse environmental insults. The aim of this Viewpoint is to justify (1) the crucial roles of glutathione in determining individual responsiveness to COVID-19 infection and disease pathogenesis and (2) the feasibility of using glutathione as a means for the treatment and prevention of COVID-19 illness. The hypothesis that glutathione deficiency is the most plausible explanation for serious manifestation and death in COVID-19 patients was proposed on the basis of an exhaustive literature analysis and observations. The hypothesis unravels the mysteries of epidemiological data on the risk factors determining serious manifestations of COVID-19 infection and the high risk of death and opens real opportunities for effective treatment and prevention of the disease.", "doc_id": "cd2mgrc7"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Covid-19: Death rate in England and Wales reaches record high because of covid-19", "abstract": "", "doc_id": "0vjvvgix"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Thrombocytopenia and its association with mortality in patients with COVID-19", "abstract": "BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes novel coronavirus disease 2019 (COVID-19), is spreading rapidly around the world. Thrombocytopenia in patients with COVID-19 has not been fully studied. OBJECTIVE: To describe thrombocytopenia in patients with COVID-19. METHODS: For each of 1476 consecutive patients with COVID-19 from Jinyintan Hospital, Wuhan, China, nadir platelet count during hospitalization was retrospectively collected and categorized into (0, 50], (50, 100], (100-150], or (150-) groups after taking the unit (\u00d7109 /L) away from the report of nadir platelet count. Nadir platelet counts and in-hospital mortality were analyzed. RESULTS: Among all patients, 238 (16.1%) patients were deceased and 306 (20.7%) had thrombocytopenia. Compared with survivors, non-survivors were older, were more likely to have thrombocytopenia, and had lower nadir platelet counts. The in-hospital mortality was 92.1%, 61.2%, 17.5%, and 4.7% for (0, 50], (50, 100], (100-150], and (150-) groups, respectively. With (150-) as the reference, nadir platelet counts of (100-150], (50, 100], and (0, 50] groups had a relative risk of 3.42 (95% confidence interval [CI] 2.36-4.96), 9.99 (95% CI 7.16-13.94), and 13.68 (95% CI 9.89-18.92), respectively. CONCLUSIONS: Thrombocytopenia is common in patients with COVID-19, and it is associated with increased risk of in-hospital mortality. The lower the platelet count, the higher the mortality becomes.", "doc_id": "s719vfak"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Fatal Outcomes of COVID-19 in Patients with Severe Acute Kidney Injury", "abstract": "The outcome of coronavirus disease 2019 (COVID-19) is associated with organ damage; however, the information about the relationship between acute kidney injury (AKI) and COVID-19 is still rare. We evaluated the clinical features and prognosis of COVID-19 patients with AKI according to the AKI severity. Medical data of hospitalized COVID-19 patients in two university-based hospitals during an outbreak in Daegu, South Korea, were retrospectively analyzed. AKI and its severity were defined according to the Acute Kidney Injury Network. Of the 164 hospitalized patients with COVID-19, 30 patients (18.3%) had AKI; 14, 4, and 12 patients had stage 1, 2, and 3, respectively. The median age was significantly higher in AKI patients than in non-AKI patients (75.5 vs. 67.0 years, p = 0.005). There were 17 deaths (56.7%) among AKI patients; 4 (28.6%), 1 (25.0%), and 12 (100.0%), respectively. In-hospital mortality was higher in AKI patients than in non-AKI patients (56.7% vs. 20.8%, p < 0.001). After adjusting for potential confounding factors, stage 3 AKI was associated with higher mortality than either non-AKI or stage 1 AKI (hazard ratio (HR) = 3.62 (95% confidence interval (CI) = 1.75-7.48), p = 0.001; HR = 15.65 (95% CI = 2.43-100.64), p = 0.004). Among the AKI patients, acute respiratory distress syndrome and low serum albumin on admission were considered independent risk factors for stage 3 AKI (both p < 0.05). Five patients with stage 3 AKI underwent dialysis and eventually died. In conclusion, COVID-19 patients with severe AKI had fatal outcomes.", "doc_id": "xo0cs4fd"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "COVID-19 infection may cause ketosis and ketoacidosis", "abstract": "The present study included 658 hospitalized patients with confirmed COVID-19. Forty-two (6.4%) out of 658 patients presented with ketosis on admission with no obvious fever or diarrhoea. They had a median (interquartile range [IQR]) age of 47.0 (38.0-70.3) years, and 16 (38.1%) were men. Patients with ketosis were younger (median age 47.0 vs. 58.0 years; P = 0.003) and had a greater prevalence of fatigue (31.0% vs. 10.6%; P < 0.001), diabetes (35.7% vs. 18.5%; P = 0.007) and digestive disorders (31.0% vs. 12.0%; P < 0.001). They had a longer median (IQR) length of hospital stay (19.0 [12.8-33.3] vs. 16.0 [10.0-24.0] days; P < 0.001) and a higher mortality rate (21.4% vs. 8.9%; P = 0.017). Three (20.0%) out of the 15 patients with diabetic ketosis developed acidosis, five patients (26.7%) with diabetic ketosis died, and one of these (25.0%) presented with acidosis. Two (7.4%) and four (14.3%) of the 27 non-diabetic ketotic patients developed severe acidosis and died, respectively, and one (25.0%) of these presented with acidosis. This suggests that COVID-19 infection caused ketosis or ketoacidosis, and induced diabetic ketoacidosis for those with diabetes. Ketosis increased the length of hospital stay and mortality. Meanwhile, diabetes increased the length of hospital stay for patients with ketosis but had no effect on their mortality.", "doc_id": "o0j2wexx"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "[Pathological changes of fatal coronavirus disease 2019 (COVID-19) in the lungs: report of 10 cases by postmortem needle autopsy]", "abstract": "Objectives: To observe the pulmonary changes with coronavirus disease 2019 (COVID-19) in postmortem needle specimens, to detect the presence of 2019 novel coronavirus(2019-nCoV) in the lung tissues, and to analyze the clinicopathological characteristics. Methods: For 10 decedents with 2019-nCoV infection in Wuhan, bilateral lungs underwent ultrasound-guided percutaneous multi-point puncture autopsy, and pulmonary pathological changes were described in routine hematoxylin-eosin staining (HE) slides. Electron microscopy was also performed. The reverse transcription polymerase chain reaction (RT-PCR) was employed to detect 2019-nCoV nucleic acid in lung tissue, and the pathological characteristics were demonstrated in combination with clinical data analysis. Results: Of the 10 deaths associated with COVID-19, 7 were male and 3 were female. The average age was 70 (39-87) years. Medical record showed that 7 patients had underlying diseases. The average course of disease was 30 (16-36) days. Nine cases showed fibrinous and suppurative exudation in the alveolar cavity accompanied by the formation of hyaline membrane, and fibroblastic proliferation of alveolar septum. Type \u00e2 \u00a1 alveolar epithelial cells showed reactive hyperplasia and desquamation. Many macrophages accumulated in the alveolar cavity. Capillary hyaline thrombus and intravascular mixed thrombus were noted. In some cases, acute bronchiolitis with mucous membrane exfoliation, accumulation of bronchiolar secretions, and bronchiolar epithelial metaplasia occurred. In the cohort, a large number of bacteria (cocci) were detected in 1 case and a large number of fungi (yeast type) were detected in 1 case. Nine cases were positive for the nucleic acids of 2019-nCoV while one case remained negative by RT-PCR. Coronavirus particles were detected in the cytoplasm of type \u00e2 \u00a1 alveolar epithelium. Conclusions: The pulmonary pathological changes of fatal COVID-19 are diffuse alveolar damage (DAD), mainly in the acute exudative stage and the organic proliferative stage. There are fibrinous exudate aggregation in alveolar cavity with hyaline membrane formation, fibroblastic proliferation in alveolar septum, and alveolar epithelial cell injuries with reactive hyperplasia and desquamation of type \u00e2 \u00a1 alveolar epithelial cells. A large amount of neutrophils and monocytes infiltration is present in most cases and bacteria and fungi are detected in some cases, suggesting a serious bacterial or fungal infection secondary to the DAD.", "doc_id": "tmkjkytb"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Assessing nitrogen dioxide (NO2) levels as a contributing factor to coronavirus (COVID-19) fatality", "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.", "doc_id": "agif48sg"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Clinical characteristics of 82 cases of death from COVID-19", "abstract": "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.", "doc_id": "jq0x08mw"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Symptom burden and clinical profile of COVID-19 deaths: a rapid systematic review and evidence summary", "abstract": "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.", "doc_id": "ndke01xy"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Association Between Hypoxemia and Mortality in Patients With COVID-19", "abstract": "OBJECTIVE: To identify markers associated with in-hospital death in patients with coronavirus disease 2019 (COVID-19)-associated pneumonia. PATIENTS AND METHODS: A retrospective cohort study was conducted of 140 patients with moderate to critical COVID-19-associated pneumonia requiring oxygen supplementation admitted to the hospital from January 28, 2020, through February 28, 2020, and followed up through March 13, 2020, in Union Hospital, Wuhan, China. Oxygen saturation (SpO2) and other measures were tested as predictors of in-hospital mortality in survival analysis. RESULTS: Of 140 patients with COVID-19-associated pneumonia, 72 (51.4%) were men, with a median age of 60 years. Patients with SpO2 values of 90% or less were older and were more likely to be men, to have hypertension, and to present with dyspnea than those with SpO2 values greater than 90%. Overall, 36 patients (25.7%) died during hospitalization after median 14-day follow-up. Higher SpO2 levels after oxygen supplementation were associated with reduced mortality independently of age and sex (hazard ratio per 1-U SpO2, 0.93; 95% CI, 0.91 to 0.95; P<.001). The SpO2 cutoff value of 90.5% yielded 84.6% sensitivity and 97.2% specificity for prediction of survival. Dyspnea was also independently associated with death in multivariable analysis (hazard ratio, 2.60; 95% CI, 1.24 to 5.43; P=.01). CONCLUSION: In this cohort of patients with COVID-19, hypoxemia was independently associated with in-hospital mortality. These results may help guide the clinical management of patients with severe COVID-19, particularly in settings requiring strategic allocation of limited critical care resources. TRIAL REGISTRATION: Chictr.org.cn Identifier: ChiCTR2000030852.", "doc_id": "yh9vunig"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Clinical and laboratory findings from patients with COVID-19 pneumonia in Babol North of Iran: a retrospective cohort study", "abstract": "BACKGROUND: In December, 2019, China, has experienced an outbreak of novel coronavirus disease 2019 (COVID-19). Coronavirus has now spread to all of the continents. We aimed to consider clinical characteristics, laboratory data of COVID-19 that provided more information for the research of this novel virus. METHODS: We performed a retrospective cohort study on the clinical symptoms and laboratory findings of a series of the 100 confirmed patients with COVID-19. These patients were admitted to the hospitals affiliated to Babol University of Medical Sciences (Ayatollah Rohani, Shahid Beheshti and Yahyanejad hospitals) form 25 February 2020 to 12 March 2020. RESULTS: Nineteen patients died during hospitalization and 81 were discharged. Non-survivor patients had a significantly higher C-reactive protein (CRP) (MD: 46.37, 95% CI: 20.84, 71.90; P= 0.001), white blood cells (WBCs) (MD: 3.10, 95% CI: 1.53, 4.67; P< 0.001) and lower lymphocyte (MD: -8.75, 95% CI: -12.62, -4.87; P< 0.001) compared to survivor patients Data analysis showed that comorbid conditions (aRR: 2.99, 95%CI: 1.09, 8.21, P= 0.034), higher CRP levels (aRR: 1.02, 95%CI: 1.01, 1.03, P= 0.044), and lower lymphocyte (aRR: 0.82, 95%CI: 0.73, 0.93, P= 0.003) were associated with increased risk of death. CONCLUSIONS: Based on our findings, most non-survivors are elderly with comorbidities. Lymphopenia and increased levels of WBCs along with elevated CRP were associated with increased risk of death. Therefore, it is best to be regularly assessed these markers during treatment of COVID-19 patients.", "doc_id": "e72ldtl4"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Acute complications and mortality in hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis", "abstract": "BACKGROUND: The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on clinically relevant outcomes in hospitalized patients with COVID-19. METHODS: MEDLINE, EMBASE, PubMed, and medRxiv were searched up to April 20, 2020, for studies including hospitalized symptomatic adult patients with laboratory-confirmed COVID-19. The primary outcomes were all-cause mortality and acute respiratory distress syndrome (ARDS). The secondary outcomes included acute cardiac or kidney injury, shock, coagulopathy, and venous thromboembolism. The main analysis was based on data from peer-reviewed studies. Summary estimates and the corresponding 95% prediction intervals (PIs) were obtained through meta-analyses. RESULTS: A total of 44 peer-reviewed studies with 14,866 COVID-19 patients were included. In general, risk of bias was high. All-cause mortality was 10% overall (95% PI, 2 to 39%; 1687/14203 patients; 43 studies), 34% in patients admitted to intensive care units (95% PI, 8 to 76%; 659/2368 patients; 10 studies), 83% in patients requiring invasive ventilation (95% PI, 1 to 100%; 180/220 patients; 6 studies), and 75% in patients who developed ARDS (95% PI, 35 to 94%; 339/455 patients; 11 studies). On average, ARDS occurred in 14% of patients (95% PI, 2 to 59%; 999/6322 patients; 23 studies), acute cardiac injury in 15% (95% PI, 5 to 38%; 452/2389 patients; 10 studies), venous thromboembolism in 15% (95% PI, 0 to 100%; patients; 3 studies), acute kidney injury in 6% (95% PI, 1 to 41%; 318/4682 patients; 15 studies), coagulopathy in 6% (95% PI, 1 to 39%; 223/3370 patients; 9 studies), and shock in 3% (95% PI, 0 to 61%; 203/4309 patients; 13 studies). CONCLUSIONS: Mortality was very high in critically ill patients based on very low-quality evidence due to striking heterogeneity and risk of bias. The incidence of clinically relevant outcomes was substantial, although reported by only one third of the studies suggesting considerable underreporting. TRIAL REGISTRATION: PROSPERO registration ID for this study is CRD42020177243 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=177243 ).", "doc_id": "8vokul5u"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Understanding pathways to death in patients with COVID-19", "abstract": "", "doc_id": "o6textzf"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "COVID-19: what if the brain had a role in causing the deaths?", "abstract": "", "doc_id": "nay6x9y1"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19", "abstract": "BACKGROUND: Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19. METHODS: We examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immunohistochemical analysis, micro-computed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression. RESULTS: In patients who died from Covid-19-associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth - predominantly through a mechanism of intussusceptive angiogenesis - was 2.7 times as high as that in the lungs from patients with influenza (P<0.001). CONCLUSIONS: In our small series, vascular angiogenesis distinguished the pulmonary pathobiology of Covid-19 from that of equally severe influenza virus infection. The universality and clinical implications of our observations require further research to define. (Funded by the National Institutes of Health and others.).", "doc_id": "5yt3gtml"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Todesf\u00e4lle in neun Regionen Italiens im Februar/M\u00e4rz 2020: \"Mortalit\u00e4ts-Exzess-Lupe\" f\u00fcr SARS-CoV-2/COVID-19-Epidemiologie in Deutschland./ [Deaths in nine regions of Italy in February/March 2020: \"Mortality Excess Loupe\" for SARS-CoV-2/COVID-19-Epidemiology in Germany]", "abstract": "Italy is particularly affected by SARS-CoV-2/COVID-19. Recently, Colombo and Impicciatore compared the deaths in 1084 selected municipalities between 21 February 2020 and 21 March 2020 with deaths in the same time period in 2015 to 2019. We extend analyses of data from the Italian National Institute of Statistics (ISTAT) and calculate SMRs for all causes of death in the nine selected regions of Italy, separately for men and women and summarized. We analyze the effect of covariables by Poisson modelling and discuss the limitations of the current elaborations. We conclude: In agreement with Colombo and Impicciatore, in the particular corona situation, this \"mortality excess loupe\" - assuming otherwise constant determinants of death - can be a virus-test-independent tool to determine mortality effects of SARS-CoV-2. The current \"loupe\" is focused on municipalities with increases of more than 20% deaths in March 2020 compared to the average deaths on the same days in 2015-2019. The time window of investigation could be opened before 21 February 2020 to detect masked increases in mortality before the first \"COVID-19 death\" was ascertained. The current \"loupe\" conveys pronounced mortality increases also in regions that were not considered to be corona hotspots. In this respect, even in the absence of representative virus test results, mortality data can be important indicators of the distribution or spread of a newly acting factor. Overall, it is advisable to carry out SMR analyses for Germany on a regular basis, differentiated by region, gender, age group and cause of death. Such analyses can contribute to the early detection and evaluation of the severity of a deadly pandemic (\"burden of disease\") as well as to monitoring the dynamic spread of a factor such as SARS-CoV-2. SMR analyses can also be used to assess and evaluate both desired and undesired effects of measures taken against SARS-CoV-2/COVID-19 - and possibly other epidemics or pandemics.", "doc_id": "4ishl6bj"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Gross and histopathological pulmonary findings in a COVID-19 associated death during self-isolation", "abstract": "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.", "doc_id": "b26j2sm4"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series", "abstract": "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.", "doc_id": "hfx418j6"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Kidney disease is associated with in-hospital death of patients with COVID-19", "abstract": "In December 2019, a coronavirus 2019 (COVID-19) disease outbreak occurred in Wuhan, Hubei Province, China, and rapidly spread to other areas worldwide. Although diffuse alveolar damage and acute respiratory failure were the main features, the involvement of other organs needs to be explored. Since information on kidney disease in patients with COVID-19 is limited, we determined the prevalence of acute kidney injury (AKI) in patients with COVID-19. Further, we evaluated the association between markers of abnormal kidney function and death in patients with COVID-19. This was a prospective cohort study of 701 patients with COVID-19 admitted in a tertiary teaching hospital that also encompassed three affiliates following this major outbreak in Wuhan in 2020 of whom 113 (16.1%) died in hospital. Median age of the patients was 63 years (interquartile range, 50-71), including 367 men and 334 women. On admission, 43.9% of patients had proteinuria and 26.7% had hematuria. The prevalence of elevated serum creatinine, elevated blood urea nitrogen and estimated glomerular filtration under 60 ml/min/1.73m2 were 14.4, 13.1 and 13.1%, respectively. During the study period, AKI occurred in 5.1% patients. Kaplan-Meier analysis demonstrated that patients with kidney disease had a significantly higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated baseline serum creatinine (hazard ratio: 2.10, 95% confidence interval: 1.36-3.26), elevated baseline blood urea nitrogen (3.97, 2.57-6.14), AKI stage 1 (1.90, 0.76-4.76), stage 2 (3.51, 1.49-8.26), stage 3 (4.38, 2.31-8.31), proteinuria 1+ (1.80, 0.81-4.00), 2+\u00e2\u0088\u00bc3+ (4.84, 2.00-11.70), and hematuria 1+ (2.99, 1.39-6.42), 2+\u00e2\u0088\u00bc3+ (5.56,2.58- 12.01) were independent risk factors for in-hospital death after adjusting for age, sex, disease severity, comorbidity and leukocyte count. Thus, our findings show the prevalence of kidney disease on admission and the development of AKI during hospitalization in patients with COVID-19 is high and is associated with in-hospital mortality. Hence, clinicians should increase their awareness of kidney disease in patients with severe COVID-19.", "doc_id": "4l1z09py"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Autopsy findings from the first known death from Severe Acute Respiratory Syndrome SARS-CoV-2 in Spain", "abstract": "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.", "doc_id": "y4t38b69"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "COVID-19 autopsy in people who died in community settings: the first series", "abstract": "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.", "doc_id": "85npeznw"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Sudden death due to acute pulmonary embolism in a young woman with COVID-19", "abstract": "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.", "doc_id": "qsamn8bk"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Dying with SARS-CoV-2 infection-an autopsy study of the first consecutive 80 cases in Hamburg, Germany", "abstract": "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.", "doc_id": "bkntg9y0"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Inside the lungs of COVID-19 disease", "abstract": "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.", "doc_id": "pdz6j4hv"} {"topic_name": "how do people die from the coronavirus", "topic_id": "4", "title": "Autopsy Findings and Venous Thromboembolism in Patients With COVID-19", "abstract": "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.", "doc_id": "mnta55wf"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry.", "abstract": "The type II transmembrane protease TMPRSS2 activates the spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) on the cell surface following receptor binding during viral entry into cells. In the absence of TMPRSS2, SARS-CoV achieves cell entry via an endosomal pathway in which cathepsin L may play an important role, i.e., the activation of spike protein fusogenicity. This study shows that a commercial serine protease inhibitor (camostat) partially blocked infection by SARS-CoV and human coronavirus NL63 (HCoV-NL63) in HeLa cells expressing the receptor angiotensin-converting enzyme 2 (ACE2) and TMPRSS2. Simultaneous treatment of the cells with camostat and EST [(23,25)trans-epoxysuccinyl-L-leucylamindo-3-methylbutane ethyl ester], a cathepsin inhibitor, efficiently prevented both cell entry and the multistep growth of SARS-CoV in human Calu-3 airway epithelial cells. This efficient inhibition could be attributed to the dual blockade of entry from the cell surface and through the endosomal pathway. These observations suggest camostat as a candidate antiviral drug to prevent or depress TMPRSS2-dependent infection by SARS-CoV.", "doc_id": "h06zxykb"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Suramin inhibits SARS-CoV-2 infection in cell culture by interfering with early steps of the replication cycle.", "abstract": "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 \u223c20 \u03bcM, 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.", "doc_id": "i3674z5x"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Structure-based design, synthesis, and biological evaluation of a series of novel and reversible inhibitors for the severe acute respiratory syndrome-coronavirus papain-like protease.", "abstract": "We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells. Upon the basis of the X-ray crystal structure of inhibitor 24-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2 (enzyme IC(50) = 0.46 microM; antiviral EC(50) = 6 microM). Interestingly, its methylamine derivative, 49, displayed good enzyme inhibitory potency (IC(50) = 1.3 microM) and the most potent SARS antiviral activity (EC(50) = 5.2 microM) in the series. We have carried out computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.", "doc_id": "mmqlwsye"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Current Drugs with Potential for Treatment of COVID-19: A Literature Review.", "abstract": "PURPOSE SARS-CoV-2 first emerged in China in December 2019 and rapidly spread worldwide. No vaccine or approved drug is available to eradicate the virus, however, some drugs that are indicated for other afflictions seems to be potentially beneficial to treat the infection albeit without unequivocal evidence. The aim of this article is to review the published background on the effectiveness of these drugs against COVID-19 Methods: A thorough literature search was conducted on recently published studies which have published between January 1 to March 25, 2020. PubMed, Google Scholar and Science Direct databases were searched Results: A total 22 articles were found eligible. 8 discuss about treatment outcomes from their applied drugs during treatment of COVID-19 patients, 4 report laboratory tests, one report animal trial and other 9 articles discuss recommendations and suggestions based on the treatment process and clinical outcomes of other diseases such as malaria, ebola, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The data and/or recommendations are categorized in 4 classes: (a) anti-viral and anti-inflammatory drugs, (b) anti-malaria drugs, (c) traditional Chinese drugs and (d) other treatments/drugs. CONCLUSION All examined treatments, although potentiality effective against COVID-19, need either appropriate drug development or clinical trial to be suitable for clinical use.", "doc_id": "er8qrkz3"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Immunogenicity and protective efficacy in mice and hamsters of a \u03b2-propiolactone inactivated whole virus SARS-CoV vaccine.", "abstract": "The immunogenicity and efficacy of \u03b2-propiolactone (BPL) inactivated whole virion SARS-CoV (WI-SARS) vaccine was evaluated in BALB/c mice and golden Syrian hamsters. The vaccine preparation was tested with or without adjuvants. Adjuvant Systems AS01(B) and AS03(A) were selected and tested for their capacity to elicit high humoral and cellular immune responses to WI-SARS vaccine. We evaluated the effect of vaccine dose and each adjuvant on immunogenicity and efficacy in mice, and the effect of vaccine dose with or without the AS01(B) adjuvant on the immunogenicity and efficacy in hamsters. Efficacy was evaluated by challenge with wild-type virus at early and late time points (4 and 18 wk post-vaccination). A single dose of vaccine with or without adjuvant was poorly immunogenic in mice; a second dose resulted in a significant boost in antibody levels, even in the absence of adjuvant. The use of adjuvants resulted in higher antibody titers, with the AS01(B)-adjuvanted vaccine being slightly more immunogenic than the AS03(A)-adjuvanted vaccine. Two doses of WI-SARS with and without Adjuvant Systems were highly efficacious in mice. In hamsters, two doses of WI-SARS with and without AS01(B) were immunogenic, and two doses of 2 \u03bcg of WI-SARS with and without the adjuvant provided complete protection from early challenge. Although antibody titers had declined in all groups of vaccinated hamsters 18 wk after the second dose, the vaccinated hamsters were still partially protected from wild-type virus challenge. Vaccine with adjuvant provided better protection than non-adjuvanted WI-SARS vaccine at this later time point. Enhanced disease was not observed in the lungs or liver of hamsters following SARS-CoV challenge, regardless of the level of serum neutralizing antibodies.", "doc_id": "2gsy750k"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Induction of interferon-gamma-inducible protein 10 by SARS-CoV infection, interferon alfacon 1 and interferon inducer in human bronchial epithelial Calu-3 cells and BALB/c mice.", "abstract": "BACKGROUND The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is poorly understood. Several mechanisms involving both direct effects on target cells and indirect effects via the immune system might exist. SARS-CoV has been shown in vitro to induce changes of cytokines and chemokines in various human and animal cells. We previously reported that interferon (IFN) alfacon-1 was more active against SARS-CoV infection in human bronchial epithelial Calu-3 cells than in African green monkey kidney epithelial cells on day 3 post-infection. METHODS In the current study, we first evaluated the efficacy of IFN-alfacon 1 in Calu-3 cells during the first 7 days of virus infection. We then used the two-antibody sandwich ELISA method to detect IFN-gamma-inducible protein 10 (IP-10). We further evaluated the efficacy of antivirals directed against SARS-CoV infection in BALB/c mice. RESULTS A potent, prolonged inhibition of SARS-CoV replication in Calu-3 cells with IFN-alfacon 1 was observed. Furthermore, IP-10, an IFN-inducible leukocyte chemoattractant, was detected in Calu-3 cells after SARS-CoV infection. Interestingly, IP-10 expression was shown to be significantly increased when SARS-CoV-infected Calu-3 cells were treated with IFN alfacon-1. IP-10 expression was detected in the lungs of SARS-CoV-infected BALB/c mice. Significantly high levels of mouse IP-10 in BALB/c mice was also detected when SARS-CoV-infected mice were treated with the interferon inducer, polyriboinosinic-polyribocytidylic acid stabilized with poly-L-lysine and carboxymethyl cellulose (poly IC:LC). Treatment with poly IC:LC by intranasal route were effective in protecting mice against a lethal infection with mouse-adapted SARS-CoV and reduced the viral lung titres. CONCLUSIONS Our data might provide an important insight into the mechanism of pathogenesis of SARS-CoV and these properties might be therapeutically advantageous.", "doc_id": "9aohx31y"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture.", "abstract": "Coronaviruses can cause respiratory and enteric disease in a wide variety of human and animal hosts. The 2003 outbreak of severe acute respiratory syndrome (SARS) first demonstrated the potentially lethal consequences of zoonotic coronavirus infections in humans. In 2012, a similar previously unknown coronavirus emerged, Middle East respiratory syndrome coronavirus (MERS-CoV), thus far causing over 650 laboratory-confirmed infections, with an unexplained steep rise in the number of cases being recorded over recent months. The human MERS fatality rate of \u223c 30% is alarmingly high, even though many deaths were associated with underlying medical conditions. Registered therapeutics for the treatment of coronavirus infections are not available. Moreover, the pace of drug development and registration for human use is generally incompatible with strategies to combat emerging infectious diseases. Therefore, we have screened a library of 348 FDA-approved drugs for anti-MERS-CoV activity in cell culture. If such compounds proved sufficiently potent, their efficacy might be directly assessed in MERS patients. We identified four compounds (chloroquine, chlorpromazine, loperamide, and lopinavir) inhibiting MERS-CoV replication in the low-micromolar range (50% effective concentrations [EC(50)s], 3 to 8 \u03bcM). Moreover, these compounds also inhibit the replication of SARS coronavirus and human coronavirus 229E. Although their protective activity (alone or in combination) remains to be assessed in animal models, our findings may offer a starting point for treatment of patients infected with zoonotic coronaviruses like MERS-CoV. Although they may not necessarily reduce viral replication to very low levels, a moderate viral load reduction may create a window during which to mount a protective immune response.", "doc_id": "02n30zc5"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner.", "abstract": "Although infection by SARS-CoV-2, the causative agent of coronavirus pneumonia disease (COVID-19), is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell fusion by targeting transmembrane serine protease 2 (TMPRSS2), and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (ACE2) and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an effective concentration (EC)50 around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. On the other hand, a significantly higher dose (EC50 around 30 mM) was required for VeroE6/TMPRSS2 cells, where the TMPRSS2-independent but cathepsin-dependent endosomal infection pathway likely predominates. Together, our study shows that nafamostat mesylate potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and also inhibits SARS-CoV-2 infection in vitro in a cell-type-dependent manner. These findings, together with accumulated clinical data regarding nafamostat's safety, make it a likely candidate drug to treat COVID-19.", "doc_id": "xge5hxel"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Generation of human bronchial organoids for SARS-CoV-2 research", "abstract": "Coronavirus disease 2019 (COVID-19) is a disease that causes fatal disorders including severe pneumonia. To develop a therapeutic drug for COVID-19, a model that can reproduce the viral life cycle and evaluate the drug efficacy of anti-viral drugs is essential. In this study, we established a method to generate human bronchial organoids (hBO) from commercially available cryopreserved human bronchial epithelial cells and examined whether they could be used as a model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research. Our hBO contain basal, club, ciliated, and goblet cells. Angiotensin-converting enzyme 2 (ACE2), which is a receptor for SARS-CoV-2, and transmembrane serine proteinase 2 (TMPRSS2), which is an essential serine protease for priming spike (S) protein of SARS-CoV-2, were highly expressed. After SARS-CoV-2 infection, not only the intracellular viral genome, but also progeny virus, cytotoxicity, pyknotic cells, and moderate increases of the type I interferon signal could be observed. Treatment with camostat, an inhibitor of TMPRSS2, reduced the viral copy number to 2% of the control group. Furthermore, the gene expression profile in SARS-CoV-2-infected hBO was obtained by performing RNA-seq analysis. In conclusion, we succeeded in generating hBO that can be used for SARS-CoV-2 research and COVID-19 drug discovery. Graphical abstract", "doc_id": "a6296nkd"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Inhibition of the replication of SARS-CoV-2 in human cells by the FDA-approved drug chlorpromazine", "abstract": "Urgent action is needed to fight the ongoing COVID-19 pandemic by reducing the number of infected people along with the infection contagiousness and severity. Chlorpromazine (CPZ), the prototype of typical antipsychotics from the phenothiazine group, is known to inhibit clathrin-mediated endocytosis and acts as an antiviral, in particular against SARS-CoV-1 and MERS-CoV. In this study, we describe the in vitro testing of CPZ against a SARS-CoV-2 isolate in monkey and human cells. We evidenced an antiviral activity against SARS-CoV-2 with an IC50 of \u223c10\u03bcM. Because of its high biodistribution in lung, saliva and brain, such IC50 measured in vitro may translate to CPZ dosage used in clinical routine. This extrapolation is in line with our observations of a higher prevalence of symptomatic and severe forms of COVID-19 infections among health care professionals compared to patients in psychiatric wards. These preclinical findings support the repurposing of CPZ, a largely used drug with mild side effects, in COVID-19 treatment.", "doc_id": "rvnvwe21"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "HTCC as a highly effective polymeric inhibitor of SARS-CoV-2 and MERS-CoV", "abstract": "The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the healthcare measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of previously developed by us HTCC compound (N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride), which may be used as potential inhibitor of currently circulating highly pathogenic coronaviruses \u2013 SARS-CoV-2 and MERS-CoV.", "doc_id": "86stuueg"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "The in vitro antiviral activity of the anti-hepatitis C virus (HCV) drugs daclatasvir and sofosbuvir against SARS-CoV-2", "abstract": "The infection by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes major public health concern and economic burden. Although clinically approved drugs have been repurposed to treat individuals with 2019 Coronavirus disease (COVID-19), the lack of safety studies and limited efficiency as well jeopardize clinical benefits. Daclatasvir and sofosbuvir (SFV) are clinically approved direct-acting antivirals (DAA) against hepatitis C virus (HCV), with satisfactory safety profile. In the HCV replicative cycle, daclatasvir and SFV target the viral enzymes NS5A and NS5B, respectively. NS5A is endowed with pleotropic activities, which overlap with several proteins from SARS-CoV-2. HCV NS5B and SARS-CoV-2 nsp12 are RNA polymerases that share homology in the nucleotide uptake channel. These characteristics of the HCV and SARS-CoV-2 motivated us to further study the activity of daclatasvir and SFV against the new coronavirus. Daclatasvir consistently inhibited the production of infectious SARS-CoV-2 virus particles in Vero cells, in the hepatoma cell line HuH-7 and in type II pneumocytes (Calu-3), with potencies of 0.8, 0.6 and 1.1 \u03bcM, respectively. Daclatasvir targeted early events during SARS-CoV-2 replication cycle and prevented the induction of IL-6 and TNF-\u03b1, inflammatory mediators associated with the cytokine storm typical of SARS-CoV-2 infection. Sofosbuvir, although inactive in Vero cells, displayed EC50 values of 6.2 and 9.5 \u03bcM in HuH-7 and Calu-3 cells, respectively. Our data point to additional antiviral candidates, in especial daclatasvir, among drugs overlooked for COVID-19, that could immediately enter clinical trials.", "doc_id": "7w19xxlq"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Rapid adaptation of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy", "abstract": "Coronavirus disease 2019 (COVID-19) threatens global public health and economy. In order to develop safe and effective vaccines, suitable animal models must be established. Here we report the rapid adaption of SARS-CoV-2 in BALB/c mice, based on which a convenient, economical and effective animal model was developed. Specifically, we found that mouse-adapted SARS-CoV-2 at passage 6 (MACSp6) efficiently infected both aged and young wild-type BALB/c mice, resulting in moderate pneumonia as well as inflammatory responses. The elevated infectivity of MACSp6 in mice could be attributed to the substitution of a key residue (N501Y) in the receptorbinding domain (RBD). Using this novel animal model, we further evaluated the in vivo protective efficacy of an RBD-based SARS-CoV-2 subunit vaccine, which elicited highly potent neutralizing antibodies and conferred full protection against SARS-CoV-2 MACSp6 challenge. This novel mouse model is convenient and effective in evaluating the in vivo protective efficacy of SARS-CoV-2 vaccine. Summary This study describes a unique mouse model for SARS-CoV-2 infection and confirms protective efficacy of a SARS-CoV-2 RBD subunit vaccine.", "doc_id": "gg0p6ct8"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication", "abstract": "The COVID-19 pandemic, attributed to the SARS-CoV-2 coronavirus infection, resulted in millions infected worldwide and an immediate need for antiviral treatments. The main protease (Mpro) in SARS-CoV-2 is a viable drug target because of its essential role in the cleavage of the virus polypeptide and subsequent viral replication. Feline infectious peritonitis, a fatal infection in cats caused by a coronavirus, was successfully treated previously with a dipeptide-based protease inhibitor. Here we show this drug, GC376, and its analog GC373, are effective inhibitors of the Mpro from both SARS-CoV and SARS-CoV-2 with IC50 values in the nanomolar range. Crystal structures of the SARS-CoV and SARS-CoV-2 Mpro with these inhibitors have a covalent modification of the nucleophilic Cys145. NMR analysis reveals that inhibition proceeds via reversible formation of a hemithioacetal. GC373 and GC376 are potent inhibitors of SARS-CoV-2 in cell culture, with EC50 values near one micromolar and little to no toxicity. These protease inhibitors are soluble, non-toxic, and bind reversibly. They are strong drug candidates for the treatment of human coronavirus infections because they have already been successful in animals (cats). The work here lays the framework for their use in human trials for the treatment of COVID-19.", "doc_id": "8agznchi"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "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", "abstract": "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.", "doc_id": "40fz5r90"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Suramin inhibits SARS-CoV-2 infection in cell culture by interfering with early steps of the replication cycle", "abstract": "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 \u223c20 \u00b5M, 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 showed that suramin acts on early steps of the replication cycle, possibly preventing 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 well-designed, properly controlled randomized clinical trials.", "doc_id": "r9dyt0n5"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "A Strategy to Treat COVID-19 Disease with Targeted Delivery of Inhalable Liposomal Hydroxychloroquine: A Non-clinical Pharmacokinetic Study", "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified pathogen causing coronavirus disease 2019 (COVID-19) pandemic. Hydroxychloroquine (HCQ), an antimalarial and anti-inflammatory drug, has been shown to inhibit SARS-CoV-2 infection in vitro and tested in clinical studies. However, lung concentration (6.7 \u00b5g/mL) to predict the in vivo antiviral efficacy might not be achievable with the currently proposed oral dosing regimen. Further, a high cumulative doses of HCQ may raise concerns of systemic toxicity, including cardiotoxicity. Here, we described a non-clinical study to investigate the pharmacokinetics of a novel formulation of liposomal HCQ administrated by intratracheal (IT) instillation in Sprague-Dawley (SD) rats which achieved 129.4 \u00b5g/g (Cmax) in the lung. Compared to unformulated HCQ administered intravenous (IV), liposomal HCQ with normalized dose showed higher (\u223c30-fold) lung exposure, longer (\u223c2.5-fold) half-life in lung, but lower blood exposure with \u223c20% of Cmax and 74% of AUC and lower heart exposure with 24% of Cmax and 58% of AUC. In conclusion, the pharmacokinetics results in an animal model demonstrate the proof of concept that inhalable liposomal HCQ may provide clinical benefit and serve as a potential treatment for COVID-19.", "doc_id": "4al9fv9g"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Favipiravir and severe acute respiratory syndrome coronavirus 2 in hamster model", "abstract": "There is a need for safe and effective antiviral molecules with which to combat COVID-19 pandemics. Recently, in vitro inhibitory activity of favipiravir against SARS-CoV-2 was reported. Here, we used a Syrian hamster model to explore the pharmacokinetics of this molecule and its in vivo efficacy against SARS-CoV-2. Results revealed that high doses (700-1400mg/kg/day) significantly reduced virus replication in the lungs accompanied by clinical alleviation of the disease. However, these high doses were associated with significant toxicity in hamsters. Favipiravir pharmacokinetics displayed non-linear increase in plasma exposure between the doses and good lung penetration. Analysis of viral genomes in vivo showed that favipiravir induced a mutagenic effect. Whilst the plasma trough concentrations observed in this study were comparable with those previously found during human clinical trials, this potential toxicity requires further investigation to assess whether a tolerable dosing regimen can be found in humans that effectively reduces virus replication.", "doc_id": "knpctp4p"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Multidrug treatment with nelfinavir and cepharanthine against COVID-19", "abstract": "Antiviral treatments targeting the emerging coronavirus disease 2019 (COVID-19) are urgently required. We screened a panel of already-approved drugs in a cell culture model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and identified two new antiviral agents: the HIV protease inhibitor Nelfinavir and the anti-inflammatory drug Cepharanthine. In silico modeling shows Nelfinavir binds the SARS-CoV-2 main protease consistent with its inhibition of viral replication, whilst Cepharanthine inhibits viral attachment and entry into cells. Consistent with their different modes of action, in vitro assays highlight a synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation. Mathematical modeling in vitro antiviral activity coupled with the known pharmacokinetics for these drugs predicts that Nelfinavir will facilitate viral clearance. Combining Nelfinavir/Cepharanthine enhanced their predicted efficacy to control viral proliferation, to ameliorate both the progression of disease and risk of transmission. In summary, this study identifies a new multidrug combination treatment for COVID-19.", "doc_id": "c6pbr3nn"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro", "abstract": "COVID-19 has become a global pandemic that threatens millions of people worldwide. There is an urgent call for developing effective drugs against the virus (SARS-CoV-2) causing this disease. The main protease of SARS-CoV-2, 3C-like protease (3CLpro), is highly conserved across coronaviruses and is essential for the maturation process of viral polyprotein. Scutellariae radix (Huangqin in Chinese), the root of Scutellaria baicalensis has been widely used in traditional Chinese medicine to treat viral infection related symptoms. The extracts of S. baicalensis have exhibited broad spectrum antiviral activities. We studied the anti-SARS-CoV-2 activity of S. baicalensis and its ingredient compounds. We found that the ethanol extract of S. baicalensis inhibits SARS-CoV-2 3CLpro activity in vitro and the replication of SARS-CoV-2 in Vero cells with an EC50 of 0.74 \u03bcg/ml. Among the major components of S. baicalensis, baicalein strongly inhibits SARS-CoV-2 3CLpro activity with an IC50 of 0.39 \u03bcM. We further identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CLpro activity at microM concentration. Our study demonstrates that the extract of S. baicalensis has effective anti-SARS-CoV-2 activity and baicalein and analogue compounds are strong SARS-CoV-2 3CLpro inhibitors.", "doc_id": "vy0mvzeb"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "In Vitro Inhibition of SARS-CoV-2 Infection by Bovine Lactoferrin", "abstract": "Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been posing a serious threat to public health worldwide as the causative agent of coronavirus disease 2019 (COVID-19). Now distributed in a pandemic pattern, this disease still lacks an effective drug treatment with low toxicity, leading pharmaceutical companies and research labs to work against time to find a candidate molecule to efficiently treat the affected patients. Due to the well-known broad-spectrum antimicrobial activity of the lactoferrin protein, we sought to verify whether its bovine form (bLf) would also be effective in vitro against SARS-CoV-2. Using an antiviral assay based on quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we found that bLf reduced progeny virus yield by up to \u223c84,6% in African green monkey kidney epithelial cells (Vero E6) and \u223c68,6% in adenocarcinomic human alveolar basal epithelial cells (A549) at 1 mg/mL, a concentration previously shown to have low cytotoxicity. Therefore, our preliminary data suggest that bLf has the potential to constitute a biochemical approach to fight the new coronavirus pandemic.", "doc_id": "irqdb024"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Dose-dependent response to infection with SARS-CoV-2 in the ferret model: evidence of protection to re-challenge", "abstract": "In December 2019 an outbreak of coronavirus disease (COVID-19) emerged in Wuhan, China. The causative agent was subsequently identified and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which rapidly spread worldwide causing a pandemic. Currently there are no licensed vaccines or therapeutics available against SARS-CoV-2 but numerous candidate vaccines are in development and repurposed drugs are being tested in the clinic. There is a vital need for authentic COVID-19 animal models to further our understanding of pathogenesis and viral spread in addition to pre-clinical evaluation of candidate interventions. Here we report a dose titration study of SARS-CoV-2 to determine the most suitable infectious dose to use in the ferret model. We show that a high (5\u00d7106 pfu) and medium (5\u00d7104 pfu) dose of SARS-CoV-2 induces consistent upper respiratory tract (URT) viral RNA shedding in both groups of six challenged animals, whilst a low dose (5\u00d7102 pfu) resulted in only one of six displaying signs of URT viral RNA replication. The URT shedding lasted up to 21 days in the high dose animals with intermittent positive signal from day 14. Sequential culls revealed distinct pathological signs of mild multifocal bronchopneumonia in approximately 5-15% of the lung, observed on day 3 in high and medium dosed animals, with presence of mild broncho-interstitial pneumonia on day 7 onwards. No obvious elevated temperature or signs of coughing or dyspnoea were observed although animals did present with a consistent post-viral fatigue lasting from day 9-14 in the medium and high dose groups. After virus shedding ceased, re-challenged ferrets were shown to be fully protected from acute lung pathology. The endpoints of URT viral RNA replication in addition to distinct lung pathology and post viral fatigue were observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease (as displayed by 80% of patients infected with SARS-CoV-2). In addition, intermittent viral shedding on days 14-21 parallel observations reported in a minority of clinical cases.", "doc_id": "08zf7161"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids", "abstract": "The current COVID-19 pandemic is caused by SARS-coronavirus 2 (SARS-CoV-2). There are currently no therapeutic options for mitigating this disease due to lack of a vaccine and limited knowledge of SARS-CoV-2 biology. As a result, there is an urgent need to create new disease models to study SARS-CoV-2 biology and to screen for therapeutics using human disease-relevant tissues. COVID-19 patients typically present with respiratory symptoms including cough, dyspnea, and respiratory distress, but nearly 25% of patients have gastrointestinal indications including anorexia, diarrhea, vomiting, and abdominal pain. Moreover, these symptoms are associated with worse COVID-19 outcomes1. Here, we report using human pluripotent stem cell-derived colonic organoids (hPSC-COs) to explore the permissiveness of colonic cell types to SARS-CoV-2 infection. Single cell RNA-seq and immunostaining showed that the putative viral entry receptor ACE2 is expressed in multiple hESC-derived colonic cell types, but highly enriched in enterocytes. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. We used hPSC-derived COs in a high throughput platform to screen 1280 FDA-approved drugs against viral infection. Mycophenolic acid and quinacrine dihydrochloride were found to block the infection of SARS-CoV-2 pseudo-entry virus in COs both in vitro and in vivo, and confirmed to block infection of SARS-CoV-2 virus. This study established both in vitro and in vivo organoid models to investigate infection of SARS-CoV-2 disease-relevant human colonic cell types and identified drugs that blocks SARS-CoV-2 infection, suitable for rapid clinical testing.", "doc_id": "97n1j0jj"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2", "abstract": "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.", "doc_id": "e9fjo7tl"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Antiviral activity of Glucosylceramide synthase inhibitors against SARS-CoV-2 and other RNA virus infections", "abstract": "The need for antiviral drugs is real and relevant. Broad spectrum antiviral drugs have a particular advantage when dealing with rapid disease outbreaks, such as the current COVID-19 pandemic. Since viruses are completely dependent on internal cell mechanisms, they must cross cell membranes during their lifecycle, creating a dependence on processes involving membrane dynamics. Thus, in this study we examined whether the synthesis of glycosphingolipids, biologically active components of cell membranes, can serve as an antiviral therapeutic target. We examined the antiviral effect of two specific inhibitors of GlucosylCeramide synthase (GCS); (i) Genz-123346, an analogue of the FDA-approved drug Cerdelga\u00ae, (ii) GENZ-667161, an analogue of venglustat which is currently under phase III clinical trials. We found that both GCS inhibitors inhibit the replication of four different enveloped RNA viruses of different genus, organ-target and transmission route: (i) Neuroinvasive Sindbis virus (SVNI), (ii) West Nile virus (WNV), (iii) Influenza A virus, and (iv) SARS-CoV-2. Moreover, GCS inhibitors significantly increase the survival rate of SVNI-infected mice. Our data suggest that GCS inhibitors can potentially serve as a broad-spectrum antiviral therapy and should be further examined in preclinical and clinical trial. Analogues of the specific compounds tested have already been studied clinically, implying they can be fast-tracked for public use. With the current COVID-19 pandemic, this may be particularly relevant to SARS-CoV-2 infection. One Sentence Summary An analogue of Cerdelga\u00ae, an FDA-approved drug, is effective against a broad range of RNA-viruses including the newly emerging SARS-CoV-2.", "doc_id": "2ejg2ngh"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Several FDA-approved drugs effectively inhibit SARS-CoV-2 infection in vitro", "abstract": "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 \u03bcM.", "doc_id": "4k7qymqd"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus.", "abstract": "A novel severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. We previously isolated and characterized SARS-CoV and SARS-CoV-like viruses from human and animals, respectively, suggesting that SARS could be transmitted from wild/farmed animals to humans. Comparison of the viral genomes indicated that sequence variation between animal and human isolates existed mainly in the spike (S) gene. We hypothesized that these variations may underlie a change of binding specificity of the S protein to the host cells, permitting viral transmission from animals to humans. Here we report that four 20-mer synthetic peptides (S protein fragments), designed to span these sequence variation hotspots, exhibited significant antiviral activities in a cell line. SARS-CoV infectivity was reduced over 10 000-fold through pre-incubation with two of these peptides, while it was completely inhibited in the presence of three peptides. Molecular modelling of the SARS-CoV peplomer suggests that three of these antiviral peptides map to the interfaces between the three monomers of the trimeric peplomer rather than the heptad repeat region from which short peptides are known to inhibit viral entry. Our results revealed novel regions in the spike protein that can be targeted to inhibit viral infection. The peptides identified in this study could be further developed into antiviral drugs.", "doc_id": "tfxarku1"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor.", "abstract": "A novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), has recently been identified as the causative agent of severe acute respiratory syndrome (SARS). SARS-CoV appears similar to other coronaviruses in both virion structure and genome organization. It is known for other coronaviruses that the spike (S) glycoprotein is required for both viral attachment to permissive cells and for fusion of the viral envelope with the host cell membrane. Here we describe the construction and expression of a soluble codon-optimized SARS-CoV S glycoprotein comprising the first 1,190 amino acids of the native S glycoprotein (S(1190)). The codon-optimized and native S glycoproteins exhibit similar molecular weight as determined by Western blot analysis, indicating that synthetic S glycoprotein is modified correctly in a mammalian expression system. S(1190) binds to the surface of Vero E6 cells, a cell permissive to infection, as demonstrated by fluorescence-activated cell sorter analysis, suggesting that S(1190) maintains the biologic activity present in native S glycoprotein. This interaction is blocked with serum obtained from recovering SARS patients, indicating that the binding is specific. In an effort to map the ligand-binding domain of the SARS-CoV S glycoprotein, carboxy- and amino-terminal truncations of the S(1190) glycoprotein were constructed. Amino acids 270 to 510 were the minimal receptor-binding region of the SARS-CoV S glycoprotein as determined by flow cytometry. We speculate that amino acids 1 to 510 of the SARS-CoV S glycoprotein represent a unique domain containing the receptor-binding site (amino acids 270 to 510), analogous to the S1 subunit of other coronavirus S glycoproteins.", "doc_id": "8pod36pz"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Structures of two coronavirus main proteases: implications for substrate binding and antiviral drug design.", "abstract": "Coronaviruses (CoVs) can infect humans and multiple species of animals, causing a wide spectrum of diseases. The coronavirus main protease (M(pro)), which plays a pivotal role in viral gene expression and replication through the proteolytic processing of replicase polyproteins, is an attractive target for anti-CoV drug design. In this study, the crystal structures of infectious bronchitis virus (IBV) M(pro) and a severe acute respiratory syndrome CoV (SARS-CoV) M(pro) mutant (H41A), in complex with an N-terminal autocleavage substrate, were individually determined to elucidate the structural flexibility and substrate binding of M(pro). A monomeric form of IBV M(pro) was identified for the first time in CoV M(pro) structures. A comparison of these two structures to other available M(pro) structures provides new insights for the design of substrate-based inhibitors targeting CoV M(pro)s. Furthermore, a Michael acceptor inhibitor (named N3) was cocrystallized with IBV M(pro) and was found to demonstrate in vitro inactivation of IBV M(pro) and potent antiviral activity against IBV in chicken embryos. This provides a feasible animal model for designing wide-spectrum inhibitors against CoV-associated diseases. The structure-based optimization of N3 has yielded two more efficacious lead compounds, N27 and H16, with potent inhibition against SARS-CoV M(pro).", "doc_id": "1a75s5l0"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Inactivated SARS-CoV vaccine prepared from whole virus induces a high level of neutralizing antibodies in BALB/c mice.", "abstract": "We tested the ability of inactivated SARS-CoV vaccine to induce neutralizing antibodies in BALB/c mice. The inactivated vaccine was prepared by SARS-CoV virus propagation in Vero cells, with subsequent beta-propiolactone inactivation and Sepharose 4FF column chromatography purification. One hundred forty BALB/c female mice were divided into seven groups of 20 mice each. Of the seven groups, three groups were inoculated with 0.1, 1, and 3 microg of the vaccine without adjuvant while three other groups were inoculated at the same three dosages of vaccine with aluminum hydroxide as adjuvant, respectively. The remaining group was set up as a blank control. Each mouse was inoculated twice at an interval of 3 weeks. One week after the second immunization, mice sera were collected to detect serum neutralizing antibodies. An assay for determining neutralizing antibody titers was developed. The results can be summarized as follows: (1) higher dosages of vaccine induced higher levels of neutralizing antibody titer; (2) the level of neutralizing antibodies induced by the inoculation with aluminum hydroxide adjuvant was slightly higher than that without adjuvant, but the difference was not statistically significant.", "doc_id": "7h2b1eku"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Protection from infection with severe acute respiratory syndrome coronavirus in a Chinese hamster model by equine neutralizing F(ab')2.", "abstract": "To warrant potential clinical testing, the equine anti-severe acute respiratory syndrome coronavirus (SARS-CoV) F(ab')(2) requires evaluation in as many animal models as possible. In this study, we established a new animal model, the Chinese hamster, susceptible to SARS-CoV infection. SARS-CoV could propagate effectively and sustain high levels for 1 wk in animal lungs. All animals were protected from SARS-CoV infection in preventive settings. Further, when used therapeutically this antibody led to an approximately 4-log(10) decrease in viral burden in infected animal lungs. The pathological changes in lungs correlated closely with the dose of antibody administered. The excellent preventive and therapeutic roles of equine anti-SARS-CoV F(ab')(2) in several animal models, including the novel Chinese hamster model described in this study, have provided exciting data concerning its potential clinical study.", "doc_id": "60516gav"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Baculovirus surface display of SARS coronavirus (SARS-CoV) spike protein and immunogenicity of the displayed protein in mice models.", "abstract": "The baculovirus surface display technique has provided an ideal tool to display foreign proteins with natural conformation, functions, and immunogenicity. In this work, we explored the application of this technique on SARS-associated coronavirus (SARS-CoV) spike (S) protein, and further analyzed the immunogenicity of displayed S protein. The entire ectodomain of S protein was fused between the gp64 signal peptide and the VSV-G membrane anchor and successfully displayed on the baculovirus surface. Subcutaneous injection with purified S-displayed baculoviruses without adjuvant elicited highly effective production of specific and neutralizing antibodies against S protein in mice. These results confirmed a successful surface display of S protein on baculoviruse, and suggested a potential role of S-displayed baculoviruses as a novel live virus-based vaccine candidate for SARS-CoV.", "doc_id": "4r6vh006"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "The aetiology of SARS: Koch's postulates fulfilled.", "abstract": "Proof that a newly identified coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV) is the primary cause of severe acute respiratory syndrome (SARS) came from a series of studies on experimentally infected cynomolgus macaques (Macaca fascicularis). SARS-CoV-infected macaques developed a disease comparable to SARS in humans; the virus was re-isolated from these animals and they developed SARS-CoV-specific antibodies. This completed the fulfilment of Koch's postulates, as modified by Rivers for viral diseases, for SARS-CoV as the aetiological agent of SARS. Besides the macaque model, a ferret and a cat model for SARS-CoV were also developed. These animal models allow comparative pathogenesis studies for SARS-CoV infections and testing of different intervention strategies. The first of these studies has shown that pegylated interferon-alpha, a drug approved for human use, limits SARS-CoV replication and lung damage in experimentally infected macaques. Finally, we argue that, given the worldwide nature of the socio-economic changes that have predisposed for the emergence of SARS and avian influenza in Southeast Asia, such changes herald the beginning of a global trend for which we are ill prepared.", "doc_id": "s4aisy2z"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Small molecules targeting severe acute respiratory syndrome human coronavirus.", "abstract": "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).", "doc_id": "biu8slfv"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "The FDA-approved gold drug auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells", "abstract": "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.", "doc_id": "d59dck5t"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Development of multi-specific humanized llama antibodies blocking SARS-CoV-2/ACE2 interaction with high affinity and avidity", "abstract": "Coronaviruses cause severe human viral diseases including SARS, MERS and COVID-19. Most recently SARS-CoV-2 virus (causing COVID-19) has led to a pandemic with no successful therapeutics. The SARS-CoV-2 infection relies on trimeric spike (S) proteins to facilitate virus entry into host cells by binding to ACE2 receptor on host cell membranes. Therefore, blocking this interaction with antibodies are promising agents against SARS-CoV-2. Here we describe using humanized llama antibody VHHs against SARS-CoV-2 that would overcome the limitations associated with polyclonal and monoclonal combination therapies. From two llama VHH libraries, unique humanized VHHs that bind to S protein and block the S/ACE2 interaction were identified. Furthermore, pairwise combination of VHHs showed synergistic blocking. Multi-specific antibodies with enhanced affinity and avidity, and improved S/ACE2 blocking are currently being developed using an in-silico approach that also fuses VHHs to Fc domains. Importantly, our current bi-specific antibody shows potent S/ACE2 blocking (KD - 0.25 nM, IC100 \u00e2\u0088\u00bc 36.7 nM, IC95 \u00e2\u0088\u00bc 12.2 nM, IC50 \u00e2\u0088\u00bc 1 nM) which is significantly better than individual monoclonal VHH-Fcs. Overall, this design would equip the VHH-Fcs multiple mechanisms of actions against SARS-CoV-2. Thus, we aim to contribute to the battle against COVID-19 by developing therapeutic antibodies as well as diagnostics.", "doc_id": "qbyz4uz5"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection", "abstract": "The recent emergence of the novel pathogenic SARS-coronavirus 2 (SARS-CoV-2) is responsible for a worldwide pandemic. Given the global health emergency, drug repositioning is the most reliable option to design an efficient therapy for infected patients without delay. The first step of the viral replication cycle [i.e. attachment to the surface of respiratory cells, mediated by the spike (S) viral protein] offers several potential therapeutic targets. The S protein uses the angiotension-converting enzyme-2 (ACE-2) receptor for entry, but also sialic acids linked to host cell surface gangliosides. Using a combination of structural and molecular modelling approaches, this study showed that chloroquine (CLQ), one of the drugs currently under investigation for SARS-CoV-2 treatment, binds sialic acids and gangliosides with high affinity. A new type of ganglioside-binding domain at the tip of the N-terminal domain of the SARS-CoV-2 S protein was identified. This domain (111-158), which is fully conserved among clinical isolates worldwide, may improve attachment of the virus to lipid rafts and facilitate contact with the ACE-2 receptor. This study showed that, in the presence of CLQ [or its more active derivative, hydroxychloroquine (CLQ-OH)], the viral S protein is no longer able to bind gangliosides. The identification of this new mechanism of action of CLQ and CLQ-OH supports the use of these repositioned drugs to cure patients infected with SARS-CoV-2. The in-silico approaches used in this study might also be used to assess the efficiency of a broad range of repositioned and/or innovative drug candidates before clinical evaluation.", "doc_id": "18yzwa2g"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "The anti-HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor of cell fusion caused by the SARSCoV-2 spike (S) glycoprotein warranting further evaluation as an antiviral against COVID-19 infections", "abstract": "Severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is the causative agent of the coronavirus disease-2019 (COVID-19) pandemic. Coronaviruses enter cells via fusion of the viral envelope with the plasma membrane and/or via fusion of the viral envelope with endosomal membranes after virion endocytosis. The spike (S) glycoprotein is a major determinant of virus infectivity. Herein, we show that the transient expression of the SARS CoV-2 S glycoprotein in Vero cells caused extensive cell fusion (formation of syncytia) in comparison to limited cell fusion caused by the SARS S glycoprotein. Both S glycoproteins were detected intracellularly and on transfected Vero cell surfaces. These results are in agreement with published pathology observations of extensive syncytia formation in lung tissues of patients with COVID-19. These results suggest that SARS CoV-2 is able to spread from cell-to-cell much more efficiently than SARS effectively avoiding extracellular neutralizing antibodies. A systematic screening of several drugs including cardiac glycosides and kinase inhibitors and inhibitors of human immunodeficiency virus (HIV) entry revealed that only the FDA-approved HIV protease inhibitor, nelfinavir mesylate (Viracept) drastically inhibited S-n- and S-o-mediated cell fusion with complete inhibition at a 10-\u00b5M concentration. In-silico docking experiments suggested the possibility that nelfinavir may bind inside the S trimer structure, proximal to the S2 amino terminus directly inhibiting S-n- and S-o-mediated membrane fusion. Also, it is possible that nelfinavir may act to inhibit S proteolytic processing within cells. These results warrant further investigations of the potential of nelfinavir mesylate to inhibit virus spread at early times after SARS CoV-2 symptoms appear.", "doc_id": "lzocumhd"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model", "abstract": "Countermeasures to prevent and treat COVID-19 are a global health priority. We enrolled a cohort of SARS-CoV-2-recovered participants, developed neutralization assays to interrogate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen over 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. We showed that passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters, as revealed by maintained weight and low lung viral titers in treated animals. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs define protective epitopes to guide vaccine design.", "doc_id": "gbffkame"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system", "abstract": "Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10 % depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50 % maximal effective concentrations (EC50) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC50 1.13-2.01 \u00b5M). Bexarotene demonstrated the highest Cmax:EC50 ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics.", "doc_id": "458smf3g"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "In Vitro and Animal Models for SARS-CoV-2 research", "abstract": "Basic research on SARS-CoV-2 is essential to understand its detailed pathophysiology and identify best drug targets. Models that can faithfully reproduce the viral life cycle and reproduce the pathology of COVID-19 are required. Here, we briefly review the cell lines, organoids, and animal models that are currently being used in COVID-19 research.", "doc_id": "qpim47hf"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Antiviral activities of mycophenolic acid and IMD-0354 against SARS-CoV-2", "abstract": "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 0.87\u00b5M, 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.", "doc_id": "fcxjt7qf"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Animal models of mechanisms of SARS-CoV-2 infection and COVID-19 pathology", "abstract": "The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 infections has led to substantial unmet need for treatments, many of which will require testing in appropriate animal models of this disease. Vaccine trials are already underway, but there remains an urgent need to find other therapeutic approaches to either target SARS-CoV-2 or the complications arising from viral infection, particularly the dysregulated immune response and systemic complications which have been associated with progression to severe COVID-19. At the time of writing, in vivo studies of SARS-CoV-2 infection have been described using macaques, cats, ferrets, hamsters, and transgenic mice expressing human angiotensin I converting enzyme 2 (ACE2). These infection models have already been useful for studies of transmission and immunity, but to date only partially model the mechanisms implicated in human severe COVID-19. There is therefore an urgent need for development of animal models for improved evaluation of efficacy of drugs identified as having potential in the treatment of severe COVID-19. These models need to recapitulate key mechanisms of COVID-19 severe acute respiratory distress syndrome and reproduce the immunopathology and systemic sequelae associated with this disease. Here, we review the current models of SARS-CoV-2 infection and COVID-19-related disease mechanisms and suggest ways in which animal models can be adapted to increase their usefulness in research into COVID-19 pathogenesis and for assessing potential treatments.", "doc_id": "y1b1vf1b"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "The search for a COVID-19 animal model", "abstract": "", "doc_id": "7st552bd"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection", "abstract": "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.", "doc_id": "frmc8bi5"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs", "abstract": "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.", "doc_id": "nyd1fhta"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Computational screening of antagonists against the SARS-CoV-2 (COVID-19) coronavirus by molecular docking", "abstract": "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.", "doc_id": "zqn6s0af"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner", "abstract": "Although infection by SARS-CoV-2, the causative agent of coronavirus pneumonia disease (COVID-19), is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell fusion by targeting transmembrane serine protease 2 (TMPRSS2), and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (ACE2) and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an effective concentration (EC)50 around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. On the other hand, a significantly higher dose (EC50 around 30 mM) was required for VeroE6/TMPRSS2 cells, where the TMPRSS2-independent but cathepsin-dependent endosomal infection pathway likely predominates. Together, our study shows that nafamostat mesylate potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and also inhibits SARS-CoV-2 infection in vitro in a cell-type-dependent manner. These findings, together with accumulated clinical data regarding nafamostat's safety, make it a likely candidate drug to treat COVID-19.", "doc_id": "z0h32jyu"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Ribavirin and interferon-\u03b2 synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines", "abstract": "Abstract Initial in vitro investigations demonstrated type I interferons (IFNs: IFN-\u03b1, IFN-\u03b2) to inhibit replication of SARS coronavirus (SARS-CoV), but found the nucleoside analogue ribavirin ineffective in Vero cells. In this report, ribavirin was shown to inhibit SARS-CoV replication in five different cell types of animal or human origin at therapeutically achievable concentrations. Since clinical anti-SARS-CoV activity of type I interferons or ribavirin is limited, we investigated the combination of IFN-\u03b2 and ribavirin. Determination of the virus yield indicated highly synergistic anti-SARS-CoV action of the combination suggesting the consideration of ribavirin plus IFN-\u03b2 for the treatment of SARS.", "doc_id": "wl83d6gs"} {"topic_name": "animal models of COVID-19", "topic_id": "5", "title": "Antiviral activities of type I interferons to SARS-CoV-2 infection", "abstract": "There is an urgent need to identify antivirals to curtail the COVID-19 pandemic. Herein, we report the sensitivity of SARS-CoV-2 to recombinant human interferons \u03b1 and \u03b2 (IFN\u03b1/\u03b2). Treatment with IFN-\u03b1 or IFN-\u03b2 at a concentration of 50 international units (IU) per milliliter reduces viral titers by 3.4 log or over 4 log, respectively, in Vero cells. The EC(50) of IFN-\u03b1 and IFN-\u03b2 treatment is 1.35 IU/ml and 0.76 IU/ml, respectively, in Vero cells. These results suggest that SARS-CoV-2 is more sensitive than many other human pathogenic viruses, including SARS-CoV. Overall, our results demonstrate the potential efficacy of human Type I IFN in suppressing SARS-CoV-2 infection, a finding which could inform future treatment options for COVID-19.", "doc_id": "si5o2hq0"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Comparison of Four Molecular In Vitro Diagnostic Assays for the Detection of SARS-CoV-2 in Nasopharyngeal Specimens.", "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel human coronavirus that causes coronavirus disease 2019 (COVID-19), was first discovered in December 2019 as the cause of an outbreak of pneumonia in the city of Wuhan, Hubei province, China. The clinical presentation of COVID-19 is fairly non-specific, and symptoms overlap with other seasonal respiratory infections concurrently circulating in the population. Furthermore, it is estimated that up to 80% of infected individuals experience mild symptoms or are asymptomatic, confounding efforts to reliably diagnose COVID-19 empirically. To support infection control measures, there is an urgent need for rapid and accurate molecular diagnostics to identify COVID-19 positive patients. In the present study, we have evaluated the analytical sensitivity and clinical performance of four SARS-CoV-2 molecular diagnostic assays granted Emergency Use Authorization by the FDA using nasopharyngeal swabs from symptomatic patients: the New York SARS-CoV-2 Real-time Reverse Transcriptase (RT)-PCR Diagnostic Panel (Modified CDC), the Simplexa COVID-19 Direct (Diasorin Molecular), GenMark ePlex SARS-CoV-2 assay (GenMark) and the Hologic Panther Fusion\u00ae SARS-CoV-2 assay (Hologic). This information is crucial for both laboratories and clinical teams, as decisions on which testing platform to implement are made.", "doc_id": "b0qtzzac"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Overcoming the bottleneck to widespread testing: A rapid review of nucleic acid testing approaches for COVID-19 detection.", "abstract": "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.", "doc_id": "b3wp314u"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Comparison of Commercially Available and Laboratory Developed Assays for in vitro Detection of SARS-CoV-2 in Clinical Laboratories.", "abstract": "Multiple laboratory developed tests and commercially available assays have emerged to meet diagnostic needs related to the SARS-CoV-2 pandemic. To date, there is limited comparison data for these different testing platforms. We compared the analytical performance of a laboratory developed test (LDT) developed in our clinical laboratory based on CDC primer sets and four commercially available, FDA emergency use authorized assays for SARS-CoV-2 (Cepheid, DiaSorin, Hologic Panther, and Roche Cobas) on a total of 169 nasopharyngeal swabs. The LDT and Cepheid Xpert Xpress SARS-CoV-2 assays were the most sensitive assays for SARS-CoV-2 with 100% agreement across specimens. The Hologic Panther Fusion, DiaSorin Simplexa, and Roche Cobas 6800 only failed to detect positive specimens near the limit of detection of our CDC-based LDT assay. All assays were 100% specific, using our CDC-based LDT as the gold standard. Our results provide initial test performance characteristics for SARS-CoV-2 RT-PCR and highlight the importance of having multiple viral detection testing platforms available in a public health emergency.", "doc_id": "8cppx8vs"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Covid-19: What is the UK's testing strategy?", "abstract": "", "doc_id": "aqbcq8rs"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Current practice and potential strategy in diagnosing COVID-19.", "abstract": "OBJECTIVE To summarize the current practice and potential strategy in diagnosing coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS PubMed, Web of Science were systematically searched using terms including \"COVID-19\", \"SARS-CoV-2\" and \"2019-nCoV\". After removing duplicates, we then identified articles, letters and commentaries regarding diagnosing COVID-19. RESULTS Here we summarized relatively mature diagnostic methods like nuclear acid test and computed tomography. Besides, new aspects regarding these detection methods like suitable specimens for nuclear acid test, possible use of 18F-FDG PET/CT were also reported. Especially, we also presented several novel techniques for diagnosing COVID-19 like lung ultrasound. CONCLUSIONS Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition) by National Health Commission is recommended to follow as it provides detailed diagnostic procedures using currently available tools. We suggest clinicians further explore the saliva's utility as a specimen for nuclear acid test and the use of lung ultrasound.", "doc_id": "7387fna7"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "A SARS-CoV-2 Coronavirus Nucleocapsid Antigen-Detecting Half-Strip Lateral Flow Assay Towards the Development of Point of Care Tests Using Commercially Available Reagents.", "abstract": "The SARS-CoV-2 pandemic has created an unprecedented need for rapid diagnostic testing to enable the efficient treatment and mitigation of COVID-19. The primary diagnostic tool currently employed is reverse transcription polymerase chain reaction (RT-PCR), which can have good sensitivity and excellent specificity. Unfortunately, implementation costs and logistical problems with reagents during the global SARS-CoV-2 pandemic have hindered its universal on demand adoption. Lateral flow assays (LFAs) represent a class of diagnostic that, if sufficiently clinically sensitive, may fill many of the gaps in the current RT-PCR testing regime, especially in low- and middle-income countries (LMICs). To date, many serology LFAs have been developed, though none meet the performance requirements necessary for diagnostic use cases, primarily due to the relatively long delay between infection and seroconversion. However, based on previously reported results from SARS-CoV-1, antigen-based SARS-CoV-2 assays may have significantly better clinical sensitivity than serology assays. To date, only a very small number of antigen-detecting LFAs have been developed. Development of a half-strip LFA is a useful first step in the development of any LFA format. In this paper we present a half-strip LFA using commercially available antibodies for the detection of SARS-CoV-2. We have tested this LFA in buffer and measured an LOD of 0.65 ng/ mL (95% CI of 0.53 to 0.77 ng/mL) ng/mL with recombinant antigen using an optical reader with sensitivity equivalent to a visual read. Further development, including evaluating the appropriate sample matrix, will be required for this assay approach to be made useful in a point of care setting, though this half-strip LFA may serve as a useful starting point for others developing similar tests.", "doc_id": "6drnriun"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Performance of Abbott ID NOW COVID-19 rapid nucleic acid amplification test in nasopharyngeal swabs transported in viral media and dry nasal swabs, in a New York City academic institution.", "abstract": "The recent emergence of the SARS-CoV-2 pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real time RT-PCR platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. Both platforms demonstrate comparable performance; however, the run times for each assay are 3.5 hours and 45 minutes, respectively. In search for a platform with shorter turnaround time, we sought to evaluate the recently released Abbott ID NOW COVID-19 assay which is capable of producing positive results in as little as 5 minutes. We present here the results of comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID NOW. Regardless of method of collection and sample type, Abbott ID NOW COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs.", "doc_id": "cc332omp"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Covid-19 mass testing facilities could end the epidemic rapidly.", "abstract": "", "doc_id": "1rsh59y3"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "A Single and Two-Stage, Closed-Tube, Molecular Test for the 2019 Novel Coronavirus (COVID-19) at Home, Clinic, and Points of Entry.", "abstract": "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.", "doc_id": "7fgjoqgb"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Evaluation of eleven rapid tests for detection of antibodies against SARS-CoV-2.", "abstract": "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.", "doc_id": "7ur8hr23"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Clinical Evaluation of Three Sample-To-Answer Platforms for the Detection of SARS-CoV-2.", "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread across the globe. As part of the worldwide response, many molecular diagnostic platforms have been granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) to identify SARS-CoV-2 positive patients. Our objective was to evaluate three sample-to-answer molecular diagnostic platforms (Cepheid Xpert\u00ae Xpress SARS-CoV-2 [Xpert Xpress], Abbott ID NOW\u2122 COVID-19 [ID NOW], GenMark ePlex\u00ae SARS-CoV-2 Test [ePlex]) to determine analytical sensitivity, clinical performance, and workflow for the detection of SARS-CoV-2 in nasopharyngeal swabs from 108 symptomatic patients. We found that the Xpert Xpress had the lowest limit of detection (100% detection at 100 copies/mL), followed by the ePlex (100% detection at 1,000 copies/mL), and the ID NOW (20,000 copies/mL). The Xpert Xpress also had highest positive percent agreement (PPA) when compared to our reference standard (98.3%) followed by the ePlex (91.4%) and ID now (87.7%). All three assays showed 100% negative percent agreement (NPA). In the workflow analysis, the ID NOW produced the most rapid time to result per specimen (\u223c17 minutes) as compared to the Xpert Xpress (\u223c46 minutes) and the ePlex (\u223c1.5 hours), but what the ID NOW gained in rapid results, it lost in analytical and clinical performance. The ePlex had the longest time to results and showed a slight improvement in PPA over the ID NOW. Information about the clinical and analytical performance of these assays, as well as workflow, will be critical in making informed and timely decisions on testing platform.", "doc_id": "54o9vjdl"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "INSIGHT: a scalable isothermal NASBA-based platform for COVID-19 diagnosis", "abstract": "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 \u00b5l 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.***", "doc_id": "66192ajk"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Pooling of Nasopharyngeal Swab Specimens for SARS-CoV-2 detection by RT-PCR", "abstract": "Systematic testing of large population groups by RT-PCR is mandatory to Covid-19 case identification and contact tracing in order to minimize the likelyhood of resurgence in contagion. Sample pooling for RT-PCR has been effectively used to detect community transmission of SARS CoV-2. Nevertheless, this procedure may decrease the sensitivity of RT-PCR assays due to specimen dilution. We evaluated the efficacy of this strategy for diagnosis of Covid-19 using a sensitive commercially-available RT-PCR targeting SARS CoV-2 E and RdRp genes in a single reaction. A total of 20 mini-pools containing either 5 (n=10) or 10 (n=10) nasopharyngeal exudates collected in universal transport medium were made, each of which including a unique positive NP specimen. Positive specimens yielding CT <32 for the E gene (6 out of 10) or <35.2 for the RdRP gene (7 out of 10) were detected in mini-pools of both sizes. In contrast, most NP samples displaying CTs > 35.8 for the E gene or 35.7 for the RdRP gene remained undetected in mini-pools of 5 specimens (3/4 and 2/3, respectively) or in mini-pools of 10 samples (4/4 and 3/3, respectively.", "doc_id": "csantx0k"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Immunochromatographic test for the detection of SARS-CoV-2 in saliva", "abstract": "We evaluated the rapid immunochromatographic test for SARS-CoV-2 antigen detection using 16 saliva specimens collected from 6 COVID-19 hospitalized patients, and detected N-antigen in 4 of 7 RT-PCR positive specimens. The POCT antigen test using saliva is highly considered to be a game-changer for COVID-19 diagnosis.", "doc_id": "ei5l6n8o"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Performance of Abbott ID NOW COVID-19 rapid nucleic acid amplification test in nasopharyngeal swabs transported in viral media and dry nasal swabs, in a New York City academic institution", "abstract": "The recent emergence of the SARS-CoV-2 pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real time RT-PCR platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. Both platforms demonstrate comparable performance; however, the run times for each assay are 3.5 hours and 45 minutes, respectively. In search for a platform with shorter turnaround time, we sought to evaluate the recently released Abbott ID NOW COVID-19 assay which is capable of producing positive results in as little as 5 minutes. We present here the results of comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID NOW. Regardless of method of collection and sample type, Abbott ID NOW COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs.", "doc_id": "918wd3ez"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Massive Multiplexing Can Deliver a $1 Test for COVID-19", "abstract": "The severe acute respiratory syndrome virus, SARS-CoV-2 (hereafter COVID-19), rapidly achieved global pandemic status, provoking large-scale screening programs in many nations. Their activation makes it imperative to identify methods that can deliver a diagnostic result at low cost. This paper describes an approach which employs sequence variation in the gene coding for its envelope protein as the basis for a scalable, inexpensive test for COVID-19. It achieves this by coupling a simple RNA extraction protocol with low-volume RT-PCR, followed by E-Gel screening and sequencing on high-throughput platforms to analyze 10,000 samples in a run. Slight modifications to the protocol could support screening programs for other known viruses and for viral discovery. Just as the $1,000 genome is transforming medicine, a $1 diagnostic test for viral and bacterial pathogens would represent a major advance for public health.", "doc_id": "dfz7e1pp"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "High-throughput extraction of SARS-CoV-2 RNA from nasopharyngeal swabs using solid-phase reverse immobilization beads", "abstract": "The ongoing pandemic of the novel coronavirus, SARS-CoV-2, has led to a global surge in laboratory testing for the virus. The gold standard approach to detecting an active viral infection is the use of RT-qPCR. This approach requires the isolation of viral RNA from respiratory specimens, such as nasopharyngeal swabs. We developed a method using a widely available lysis buffer coupled with solid-phase reverse immobilization (SPRI) beads to extract viral RNA from swabs collected in viral transport medium (VTM) which can be performed manually or on a Hamilton STAR liquid-handling robot. Using a WHO recommended, laboratory-developed RT-qPCR for SARS-CoV-2, we validated this method in a CAP-accredited laboratory, against the IVD-labelled bioM\u00e9rieux NucliSENS easyMAG automated extraction platform. Our method demonstrates a comparable sensitivity and specificity, making it suitable for large-scale testing and monitoring of suspected COVID-19 cases and healthcare workers. This is especially important as the world faces critical shortages of viral RNA extraction reagents for the existing commercial extraction systems.", "doc_id": "bx2xspbe"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "SARS-CoV-2 Detection Using an Isothermal Amplification Reaction and a Rapid, Inexpensive Protocol for Sample Inactivation and Purification", "abstract": "As the current SARS-CoV-2 pandemic spreads, the need for more diagnostic capabilities is great. In order to address this need, we have developed a highly sensitive RT-LAMP assay compatible with current reagents, that utilizes a colorimetric readout in as little as 30 minutes. In addition to this, we have developed an inexpensive pipeline to further increase sensitivity without requiring highly specialized equipment. A rapid inactivation protocol capable of inactivating virions, as well as endogenous nucleases, was also developed to increase sensitivity and sample stability. This protocol, combined with our RT-LAMP assay, has a sensitivity of at least 50 viral RNA copies per microliter in a sample. To further increase the sensitivity, a purification protocol compatible with this inactivation method was developed. The inactivation and purification protocol, combined with our RT-LAMP assay, brings the sensitivity to at least 1 viral RNA copy per microliter in a sample. We hope that this inactivation and purification pipeline, which costs approximately $0.07 per sample and which uses readily available reagents, will increase the availability of SARS-CoV-2 testing, as well as expand the settings in which this testing can be performed.", "doc_id": "8149l7tj"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "AI based Chest X-Ray (CXR) Scan Texture Analysis Algorithm for Digital Test of COVID-19 Patients", "abstract": "Chest Imaging in COVID-19 patient management is becoming an essential tool for controlling the pandemic that is gripping the international community. It is already indicated in patients with COVID-19 and worsening respiratory status. The rapid spread of the pandemic to all continents, albeit with a nonuniform community transmission, necessitates chest imaging for medical triage of patients presenting moderate-severe clinical COVID-19 features. This paper reports the development of innovative machine learning schemes for the analysis of Chest X-Ray (CXR) scan images of COVID-19 patients in almost real-time, demonstrating significantly high accuracy in identifying COVID-19 infection. The performance testing was conducted on a combined dataset comprising CXRs of positive COVID-19 patients, patients with various viral and bacterial infections, as well as persons with a clear chest. The test resulted in successfully distinguishing CXR COVID-19 infection from the other cases with an average accuracy of 94.43%, sensitivity 95% and specificity 93.86%.", "doc_id": "1zbe6t48"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "A rapid systematic review and case study on test, contact tracing, testing, and isolation policies for Covid-19 prevention and control", "abstract": "Objectives To conduct a rapid review on the efficacy and policy of contact tracing, testing, and isolation (TTI) in Covid-19 prevention and control, including a case study for their delivery. Method Research articles and reviews on the use of contact tracing, testing, self-isolation and quarantine for Covid-19 management published in English within 1 year (2019 to 28th May, 2020) were eligible to the review. We searched MEDLINE (PubMed), Cochrane Library, SCOPUS and JSTOR with search terms included \"contact tracing\" or \"testing\" or \"self-isolation\" or \"quarantine\" in the title in combination with \"Covid-19\" or \"COVID-19\" or \"coronavirus\" in the title or abstract. Studies not associated with TTI or Covid-19 or being solely commentary were excluded. A narrative synthesis with a tabulation system was used to analyse studies for their diverse research designs, methods, and implications. Information for the case study was obtained from the Centers for Disease Control Taiwan. Results Among the 160 initial publications, 30 eligible studies are included in the review. Included studies applied various designs: experiments, clinical studies, Government Documents, systematic reviews, observational studies, surveys, practice guidelines, technical reports. A case study on TTI delivery is summarised based on policy and procedures in Taiwan. Conclusions The information included in the review may inform the TTI program in the UK.", "doc_id": "2sq8g01x"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Self-Collected Oral Fluid and Nasal Swabs Demonstrate Comparable Sensitivity to Clinician Collected Nasopharyngeal Swabs for Covid-19 Detection", "abstract": "Background: Currently, there is a pandemic caused by the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes Covid-19. We wanted to compare specimen types and collection methods to explore if a simpler to collect specimen type could expand access to testing. Methods: We recruited individuals recently tested for SARS-CoV-2 infection through a testing program (drive-through). In homes of participants, we assessed the performance of self-collected oral fluid swab specimens with and without clinician supervision, clinician-supervised self-collected mid-turbinate (nasal) swab specimens, and clinician-collected nasopharyngeal swab specimens. We tested specimens with a validated reverse transcription-quantitative polymerase chain reaction assay for the detection of SARS-CoV-2 and measured cycle threshold values. Symptom status and date of onset of symptoms was also recorded for each participant. Results: We recruited 45 participants. The median age of study participant was 42 years old (Interquartile range, 31 to 52 years). Of the participants, 29 had at least one specimen test positive for SARS-CoV-2. Of those, 21 (73%) of 29 reported active symptoms. By specimen type and home-based collection method, clinician-supervised self-collected oral fluid swab specimens detected 26 (90%) of 29 infected individuals, clinician-supervised self-collected nasal swab specimens detected 23 (85%) of 27, clinician-collected posterior nasopharyngeal swab specimens detected 23 (79%) of 29, and unmonitored self-collected oral fluid swab specimens detected 19 (66%) of 29. Despite nasopharyngeal swabs being considered the gold standard, 4 participants tested negative by clinician-collected nasopharyngeal swab and positive by the 3 other specimen types. Additionally, false negative results by each sample type were seen to generally not overlap. Conclusions: Supervised self-collected oral fluid and nasal swab specimens performed similarly to, if not better than clinician-collected nasopharyngeal swab specimens for the detection of SARS-CoV-2 infection. No sample type captured all SARS-CoV-2 infections, suggesting potential heterogeneity in the distribution of viral load in different parts of the respiratory tract between individuals. Supervised self-collection performed comparably to clinician collection and would allow for rapid expansion of testing capacity in the United States by reducing the need for trained healthcare workers, reducing exposure of healthcare workers, and reducing the amount of PPE (personal protective equipment) being used for testing during a critical shortage.", "doc_id": "0u7j42i2"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Rapid Molecular Detection of SARS-CoV-2 (COVID-19) Virus RNA Using Colorimetric LAMP", "abstract": "The ability to detect an infectious agent in a widespread epidemic is crucial to the success of quarantine efforts in addition to sensitive and accurate screening of potential cases of infection from patients in a clinical setting. Enabling testing outside of sophisticated laboratories broadens the scope of control and surveillance efforts, but also requires robust and simple methods that can be used without expensive instrumentation. Here we report a method to identify SARS-CoV-2 (COVID-19) virus RNA from purified RNA or cell lysis using loop-mediated isothermal amplification (LAMP) using a visual, colorimetric detection. This test was additionally verified using RNA samples purified from respiratory swabs collected from COVID-19 patients in Wuhan, China with equivalent performance to a commercial RT-qPCR test while requiring only heating and visual inspection. This simple and sensitive method provides an opportunity to facilitate virus detection in the field without a requirement for complex diagnostic infrastructure.", "doc_id": "cv3qgno3"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Diagnostic accuracy of a host response point-of-care test for identifying COVID-19", "abstract": "Rationale Management of the COVID-19 pandemic is hampered by long delays associated with centralised laboratory PCR testing. In hospitals this leads to poor patient flow and nosocomial transmission and rapid, accurate diagnostic tests are urgently required. The FebriDx is a point-of-care test that detects an antiviral host response protein in finger prick blood within 10 minutes, but its accuracy for the detection of COVID-19 is unknown. Objectives To evaluate the diagnostic accuracy of FebriDx in hospitalised patients during the first wave of the pandemic. Methods Measures of diagnostic accuracy were calculated based on FebriDx results compared to the reference standard of PCR, and stratified by duration of symptoms. A multivariable predictive model was developed and underwent internal validation. Results FebriDx was performed on 251 patients and gave a valid result in 248. 118 of 248 (48%) were PCR positive for COVID-19. Sensitivity of FebriDx for the identification of COVID-19 was 93% (110/118; 95% CI 87 to 97%) and specificity was 86% (112/130; 95%CI 79 to 92%). Positive and negative likelihood ratios were 6.73 (95%CI 4.37 to 10.37) and 0.08 (95%CI 0.04 to 0.15) respectively. In the multivariate model diagnosis of COVID-19 was not significantly influenced by clinical symptoms and signs, and FebriDx accuracy was not improved by restricting testing to those with duration of symptoms of less than seven days. Conclusions During the first wave of the pandemic, FebriDx had high sensitivity for the identification of COVID-19 in hospitalised adults and could be deployed as a front door triage tool.", "doc_id": "8lhzgqfr"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Sensitivity and specificity of a rapid test for assessment of exposure to SARS-CoV-2 in a community-based setting in Brazil", "abstract": "Background: While the recommended laboratory diagnosis of COVID-19 is a molecular based assay, population-based studies to determine the prevalence of COVID-19 usually use serological assays. Objective: To evaluate the sensitivity and specificity of a rapid diagnostic test for COVID-19 compared to quantitative reverse transcription polymerase chain reaction (qRT-PCR). Methods: We evaluated the sensitivity using a panel of finger prick blood samples from participants >18 years of age that had been tested for COVID-19 by qRT-PCR. For assessing specificity, we used serum samples from the 1982 Pelotas (Brazil) Birth Cohort participants collected in 2012 with no exposure to SARS-CoV-2. Results: The sensitivity of the test was 77.1% (95% CI 66.6 - 85.6), based upon 83 subjects who had tested positive for qRT-PCR at least 10 days before the rapid diagnostic test (RDT). Based upon 100 sera samples, specificity was 98.0% (95% CI 92.9 - 99.8). There was substantial agreement (Kappa score 0.76) between the qRT-PCR results and the RDT. Interpretation. The validation results are well in line with previous assessments of the test, and confirm that it is sufficiently precise for epidemiological studies aimed at monitoring levels and trends of the COVID-19 pandemic.", "doc_id": "2siuovme"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Saliva Sample as a Non-Invasive Specimen for the Diagnosis of Coronavirus Disease-2019 (COVID-19): a Cross-Sectional Study", "abstract": "Objectives. Amid the increasing number of global pandemic coronavirus disease 2019 (COVID-19) cases, there is a need for a quick and easy method to obtain a non-invasive sample for the detection of this novel coronavirus 2019 (SARS-CoV-2). We aimed to investigate the potential use of saliva samples as a non-invasive tool for the diagnosis of COVID-19. Methods. From 27 March to 4 April, 2020, we prospectively collected saliva samples and a standard nasopharyngeal and throat swab in persons seeking care at an acute respiratory infection clinic in a university hospital during the outbreak of COVID-19. Real-time polymerase chain reaction (RT-PCR) was performed, and the results of the two specimens were compared. Results. Two-hundred pairs of the samples were collected. Sixty-nine (34.5%) patients were male, and the median (interquartile) age was 36 (28-48) years. Using nasopharyngeal and throat swab RT-PCR as the reference standard, the prevalence of COVID-19 diagnosed by nasopharyngeal and throat swab RT-PCR was 9.5%. The sensitivity and specificity of the saliva sample RT-PCR were 84.2% [95% confidence interval (CI) 79.2%-89.3%], and 98.9% (95% CI 97.5-100.3%), respectively. An analysis of the agreement between the two specimens demonstrated 97.5% observed agreement (kappa coefficient 0.851, 95% CI 0.723-0.979; p <0.001). Conclusions. Saliva specimens can be used for the diagnosis of COVID-19. The collection method is non-invasive, and non-aerosol generating. Using a saliva sample as a specimen for the detection of SARS-CoV-2 could facilitate the diagnosis of the disease, which is one of the strategies that helps in controlling the epidemic.", "doc_id": "0bbzo9cp"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Combination of Antibody based rapid diagnostic tests used in an algorithm may improve their performance in SARS CoV-2 diagnosis.", "abstract": "Background: Globally response to the SARS-CoV-2 pandemic is highly limited by diagnostic methods. Currently, World Health Organization (WHO) recommends the use of molecular assays for confirmation of SARS-CoV-2 infection which are highly expensive and require specialized laboratory equipment. This is a limitation in mass testing and in low resource settings. SARS CoV-2 IgG/IgM antibody tests have had poor diagnostic performance that do not guarantee their use in diagnostics. In this study we demonstrate a concept of using a combination of RDTs in an algorithm to improve their performance for diagnostics. Method: Eighty six (86) EDTA whole blood samples were collected from SARS-CoV-2 positive cases admitted at Masaka and Mbarara Regional Referral Hospitals in Uganda. These were categorized from day when confirmed positive as follows; category A (0-3 days, 10 samples), category B (4-7 days, 20 samples), Category C (8-17 days, 11 samples) and Category D (18-28 days, 20 samples). Plasma was prepared, transported to the testing laboratory and stored at -200C prior to testing. A total of 13 RDTS were tested following manufacturers instructions. Data was entered in Microsoft Excel exported to STATA for computation of sensitivity and specificity. We computed for all possible combinations of 2 of the 13 RDTS (13C2) that were evaluated in parallel algorithm. Results: The individual sensitives of the RDTs ranged between 74% and 18% and there was a general increasing trend across the categories with days since PCR confirmation. A total of 78 possible combinations of the RDTs to be used in parallel was computated. The combinations of the 2 RDTS improved the sensitivities to 90%. Discussion: We demonstrate that use of RDTs in combinations can improve their overall sensitivity. This approach when used on a wider range of combination of RDTs may yield combinations that can give sensitivities that are of diagnostics relevance in mass testing and low resource setting.", "doc_id": "bqgm1e1x"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Recommendations for sample pooling on the Cepheid GeneXpert\u00ae system using the Cepheid Xpert\u00ae Xpress SARS-CoV-2 assay", "abstract": "The coronavirus disease 2019 (Covid-19) pandemic, caused by SARS-CoV-2, has resulted in a global testing supply shortage. In response, pooled testing has emerged as a promising strategy that can immediately increase testing capacity. Here, we provide support for the adoption of sample pooling with the point-of-care Cepheid Xpert\u00ae Xpress SARS-CoV-2 molecular assay. Corroborating previous findings, the Xpert\u00ae Xpress SARS-CoV-2 assay limit of detection was comparable to central laboratory reverse-transcription quantitative PCR tests with observed SARS-CoV-2 detection below 100 copies/mL. The Xpert\u00ae Xpress assay detected SARS-CoV-2 after samples with minimum viral loads of 461 copies/mL were diluted into six sample pools. Based on these data, we recommend the adoption of pooled testing with the Xpert\u00ae Xpress SARS-CoV-2 assay where warranted by population public health needs. The suggested number of samples per pool, or pooling depth, is unique for each point-of-care test site and should be determined by assessing positive test rates. To statistically determine appropriate pooling depth, we have calculated the pooling efficiency for numerous combinations of pool sizes and test rates. This information is included as a supplemental dataset that we encourage public health authorities to use as a guide to make recommendations that will maximize testing capacity and resource conservation.", "doc_id": "ati4ym9b"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Evaluation of performance of two SARS-CoV-2 Rapid whole-blood finger-stick IgM-IgGCombined Antibody Tests", "abstract": "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.", "doc_id": "85b4lwh3"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Pooled RNA sample reverse transcriptase real time PCR assay for SARS CoV-2 infection: a reliable, faster and economical method.", "abstract": "Background: Corona virus disease 2019 (COVID-19) which initially started as a cluster of pneumonia cases in the Wuhan city of China has now become a full blown pandemic. Timely diagnosis of COVID-19 is the key in containing the pandemic and breaking the chain of In low and middle income countries availability of testing kits has become the major bottle neck in testing. Novel methods like pooling of samples are the need of the hour. Method: Extracted RNA samples were randomly placed in pools of 8 on a 96 well plate. Both individual RNA (ID) and pooled RNA RT-qPCR for the screening E gene were done in the same plate and the positivity for the E gene was seen. Results: The present study demonstrated that pool testing with 8 RNA samples can easily detect even up to a single positive sample with Ct value as high as 38. The present study also showed that the results of pool testing is not affected by number of positive samples in a pool. Conclusion: Pooling of 8 RNA samples can reduce the time and expense by one eighth, and can help expand diagnostic capabilities, especially during constrained supply of reagents and PCR kits for the diagnosis of SARS-CoV-2 infection.", "doc_id": "467ypllv"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Comparison of Cepheid Xpert Xpress and Abbott ID Now to Roche cobas for the Rapid Detection of SARS-CoV-2", "abstract": "The SARS-CoV-2 pandemic has created an urgent and unprecedented need for rapid large-scale diagnostic testing to inform timely patient management. This study compared two recently-authorized rapid tests, Cepheid Xpert Xpress SARS-CoV-2 and Abbott ID Now SARS-CoV-2 to the Roche cobas SARS-CoV-2 assay. A total of 113 nasopharyngeal swabs were tested, including 88 positives spanning the full range of observed Ct values on the cobas assay. Compared to cobas, the overall positive agreement was 73.9% with ID Now and 98.9% with Xpert. Negative agreement was 100% and 92.0% for ID Now and Xpert, respectively. Both ID Now and Xpert showed 100% positive agreement for medium and high viral concentrations (Ct value <30). However, for Ct values >30, positive agreement was 34.3% for ID Now and 97.1% for Xpert. These findings highlight an important limitation of ID Now for specimens collected in viral or universal transport media with low viral concentrations. Further studies are needed to evaluate the performance of ID Now for direct swabs.", "doc_id": "2qynwc0a"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "iSCAN: An RT-LAMP-coupled CRISPR-Cas12 module for rapid, sensitive detection of SARS-CoV-2", "abstract": "The COVID-19 pandemic caused by SARS-CoV-2 affects all aspects of human life. Detection platforms that are efficient, rapid, accurate, specific, sensitive, and user friendly are urgently needed to manage and control the spread of SARS-CoV-2. RT-qPCR based methods are the gold standard for SARS-CoV-2 detection. However, these methods require trained personnel, sophisticated infrastructure, and a long turnaround time, thereby limiting their usefulness. Reverse transcription-loop-mediated isothermal amplification (RT-LAMP), a one-step nucleic acid amplification method conducted at a single temperature, has been used for colorimetric virus detection. CRISPR-Cas12 and CRISPR-Cas13 systems, which possess collateral activity against ssDNA and RNA, respectively, have also been harnessed for virus detection. Here, we built an efficient, rapid, specific, sensitive, user-friendly SARS-CoV-2 detection module that combines the robust virus amplification of RT-LAMP with the specific detection ability of SARS-CoV-2 by CRISPR-Cas12. Furthermore, we combined the RT-LAMP-CRISPR-Cas12 module with lateral flow cells to enable highly efficient point-of-care SARS-CoV-2 detection. Our iSCAN SARS-CoV-2 detection module, which exhibits the critical features of a robust molecular diagnostic device, should facilitate the effective management and control of COVID-19.", "doc_id": "1d0i10o7"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Noisy Pooled PCR for Virus Testing", "abstract": "Fast testing can help mitigate the coronavirus disease 2019 (COVID-19) pandemic. Despite their accuracy for single sample analysis, infectious diseases diagnostic tools, like RT-PCR, require substantial resources to test large populations. We develop a scalable approach for determining the viral status of pooled patient samples. Our approach converts group testing to a linear inverse problem, where false positives and negatives are interpreted as generated by a noisy communication channel, and a message passing algorithm estimates the illness status of patients. Numerical results reveal that our approach estimates patient illness using fewer pooled measurements than existing noisy group testing algorithms. Our approach can easily be extended to various applications, including where false negatives must be minimized. Finally, in a Utopian world we would have collaborated with RT-PCR experts; it is difficult to form such connections during a pandemic. We welcome new collaborators to reach out and help improve this work!", "doc_id": "8kccpd4x"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Evaluation on the diagnostic efficiency of different methods in detecting COVID-19.", "abstract": "Objective: To evaluate the diagnostic efficiency of different methods in detecting COVID-19 to provide preliminary evidence on choosing favourable method for COVID-19 detection. Methods: PubMed, Web of Science and Embase databases were searched for identifing eligible articles. All data were calculated utilizing Meta Disc 1.4, Revman 5.3.2 and Stata 12. The diagnostic efficiency was assessed via these indicators including summary sensitivity and specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curve (sROC) and calculate the AUC. Results: 18 articles (3648 cases) were included. The results showed no significant threshold exist. EPlex: pooled sensitivity was 0.94; specificity was 1.0; PLR was 90.91; NLR was 0.07; DOR was 1409.49; AUC=0.9979, Q*=0.9840. Panther Fusion: pooled sensitivity was 0.99; specificity was 0.98; PLR was 42.46; NLR was 0.02; DOR was 2300.38; AUC=0.9970, Q*=0.9799. Simplexa: pooled sensitivity was 1.0; specificity was 0.97; PLR was 26.67; NLR was 0.01; DOR was 3100.93; AUC=0.9970, Q*=0.9800. Cobas: pooled sensitivity was 0.99; specificity was 0.96; PLR was 37.82; NLR was 0.02; DOR was 3754.05; AUC=0.9973, Q*=0.9810. RT-LAMP: pooled sensitivity was 0.98; specificity was 0.99; PLR was 36.22; NLR was 0.04; DOR was 751.24; AUC=0.9905, Q*=0.9596. Xpert Xpress: pooled sensitivity was 0.99; specificity was 0.97; PLR was 27.44; NLR was 0.01; DOR was 3488.15; AUC=0.9977, Q*=0.9829. Conclusions: These methods (ePlex, Panther Fusion, Simplexa, Cobas, RT-LAMP and Xpert Xpress) bear higher sensitivity and specificity, and might be efficient methods complement to the gold standard.", "doc_id": "16crg3k8"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "A new role for Biofoundries in rapid prototyping, development, and validation of automated clinical diagnostic tests for SARS-CoV-2", "abstract": "The SARS-CoV-2 pandemic has shown how the rapid rise in demand for patient and community sample testing, required for tracing and containing a highly infectious disease, has quickly overwhelmed testing capability globally. With most diagnostic infrastructure dependent on specialised instruments, their exclusive reagent supplies quickly become bottlenecks in times of peak demand, creating an urgent need for novel approaches to boost testing capacity. We address this challenge by refocusing the full synthetic biology stack available at the London Biofoundry onto the development of alternative patient sample testing pipelines. We present a reagent-agnostic automated SARS-CoV-2 testing platform that can be quickly deployed and scaled, and that accepts a diverse range of reagents. Using an in-house-generated, open-source, MS2-virus-like-particle-SARS-CoV-2 standard, we validate RNA extraction and RT-qPCR workflows as well as two novel detection assays based on CRISPR-Cas and Loop-mediated isothermal Amplification (LAMP) approaches. In collaboration with an NHS diagnostic testing lab, we report the performance of the overall workflow and benchmark SARS-CoV-2 detection in patient samples via RT-qPCR, CRISPR-Cas, and LAMP against clinical test sets. The validated RNA extraction and RT-qPCR platform has been installed in NHS diagnostic labs and now contributes to increased patient sample processing in the UK while we continue to refine and develop novel high-throughput diagnostic methods. Finally, our workflows and protocols can be quickly implemented and adapted by members of the Global Biofoundry Alliance and the wider scientific and medical diagnostics community.", "doc_id": "9h7kulwn"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "A SIMPLE COLORIMETRIC MOLECULAR DETECTION OF NOVEL CORONAVIRUS (COVID-19), AN ESSENTIAL DIAGNOSTIC TOOL FOR PANDEMIC SCREENING", "abstract": "The recent outbreak of the newly emerged novel coronavirus (SARS-CoV-2) presents a big challenge for public health laboratories as virus isolates are not available while there is an increasing evidence that the epidemic is more widespread than initially thought, as well as spreading internationally across borders through travellers does already happen warranting a methodology for the rapid detection of the infection to control SARS-CoV-2. Aim: We intended to develop and deploy a robust and rapid diagnostic methodology using LAMP assay for use in point of care settings to detect SARS-COV-2 infection. Methodology: In the present study, we have developed a validated rapid diagnostic procedure to detect SARS-CoV-2 using LAMP assay, its design relying on isothermal amplification of the nucleic acids of the SARS-CoV-2. Results: The LAMP assay developed detects SARS-CoV-2 infection rapidly with high sensitivity and reliability. The data generated by LAMP assay were comparable and at par with the data generated by real-time PCR method. Conclusion: The present study demonstrates that the LAMP assay developed was a rapid, reliable, sensitive and cost effective method to detect SARS-CoV-2 infection in a point of care as well as in laboratory settings.", "doc_id": "5n1847is"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Head-to-head comparison of four antigen-based rapid detection tests for the diagnosis of SARS-CoV-2 in respiratory samples", "abstract": "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\u2019 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\u201371.9), 16.7% (CI95% 10.0\u201326.5), and 85.0% (CI95% 75.6\u201391.2), 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.", "doc_id": "3taykdr1"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Comparison of Four Molecular In Vitro Diagnostic Assays for the Detection of SARS-CoV-2 in Nasopharyngeal Specimens", "abstract": "The novel human coronavirus SARS-CoV-2 was first discovered in the city of Wuhan, Hubei province, China, causing an outbreak of pneumonia in January 2020. As of April 10, 2020, the virus has rapidly disseminated to over 200 countries and territories, causing more than 1.6 million confirmed cases of COVID-19 and 97,000 deaths worldwide. The clinical presentation of COVID-19 is fairly non-specific, and symptoms overlap with other seasonal respiratory infections concurrently circulating in the population. Further, it is estimated that up to 80% of infected individuals experience mild symptoms or are asymptomatic, confounding efforts to reliably diagnose COVID-19 empirically. To support infection control measures, there is an urgent need for rapid and accurate molecular diagnostics to identify COVID-19 positive patients. In the present study, we have evaluated the analytical sensitivity and clinical performance of four SARS-CoV-2 molecular diagnostic assays granted Emergency Use Authorization by the FDA using nasopharyngeal swabs from symptomatic patients. This information is crucial for both laboratories and clinical teams, as decisions on which testing platform to implement are made.", "doc_id": "2bf3xzni"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Rapid, sensitive, full genome sequencing of Severe Acute Respiratory Syndrome Virus Coronavirus 2 (SARS-CoV-2)", "abstract": "SARS-CoV-2 recently emerged, resulting a global pandemic. Rapid genomic information is critical to understanding transmission and pathogenesis. Here, we describe validated protocols for generating high-quality full-length genomes from primary samples. The first employs multiplex RT-PCR followed by MinION or MiSeq sequencing. The second uses singleplex, nested RT-PCR and Sanger sequencing.", "doc_id": "6ucdibzh"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Laboratory capability for molecular detection and confirmation of novel coronavirus in Europe, November 2012.", "abstract": "A rapid survey by the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) Regional Office for Europe ascertained the availability of national reference laboratory testing for a recently detected novel coronavirus as of 28 November 2012. Screening by internal quality controlled upE-RT-PCR assay was available in 23/46 of responding countries in the WHO European Region, of which 19/30 in European Union (EU) and European Economic Area (EEA) countries. Confirmation of positive screened samples by either ORF1b - RT-PCR, or other target RT-PCR assays with sequence analysis or whole-genome sequence analysis was available in 22/46 responding countries of which 18/30 in EU/EEA countries.", "doc_id": "63tcubi9"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "The Appropriate Use of Testing for COVID-19", "abstract": "Many public officials are calling for increased testing for the 2019 novel coronavirus disease (COVID-19), and some governments have taken extraordinary measures to increase the availability of testing. However, little has been published about the sensitivity and specificity of the reverse transcriptase-polymerase chain reaction (RT-PCR) nasopharyngeal swabs that are commonly used for testing. This narrative review evaluates the literature regarding the accuracy of these tests, and makes recommendations based on this literature. In brief, a negative RT-PCR nasopharyngeal swab test is insufficient to rule out COVID-19. Thus, over-reliance on the results of the test may be dangerous, and the push for widespread testing may be overstated.", "doc_id": "a038jilw"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Loop mediated isothermal amplification (LAMP) assays as a rapid diagnostic for COVID-19", "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 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.", "doc_id": "ax8qn0ci"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Combining PCR and CT testing for COVID", "abstract": "We analyze the effect of using a screening CT-scan for evaluation of potential COVID-19 infections in order to isolate and perform contact tracing based upon a viral pneumonia diagnosis. RT-PCR is then used for continued isolation based upon a COVID diagnosis. Both the low false negative rates and rapid results of CT-scans lead to dramatically reduced transmission. The reduction in cases after 60 days with widespread use of CT-scan screening compared to PCR by itself is as high as $50\\times$, and the reduction of effective reproduction rate $R(t)$ is $0.20$. Our results imply that much more rapid extinction of COVID is possible by combining social distancing with CT-scans and contact tracing.", "doc_id": "aryiusq4"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Diagnostic testing for SARS-CoV-2", "abstract": "", "doc_id": "awm9ja23"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Novel One-Step Single-Tube Nested Quantitative Real-Time PCR Assay for Highly Sensitive Detection of SARS-CoV-2", "abstract": "Coronavirus disease 2019 (COVID-19) has become a public health emergency. The reverse transcriptase real-time quantitative PCR (qRT-PCR) test is currently considered as the gold standard in the laboratory for the etiological detection of COVID-19. However, qRT-PCR results could be false-negative due to the inadequate sensitivity of qRT-PCR. In this study, we have developed and evaluated a novel one-step single-tube nested quantitative real-time PCR (OSN-qRT-PCR) assay for the highly sensitive detection of SARS-CoV-2 targeting the ORF1ab and N genes. The sensitivity of the OSN-qRT-PCR assay was 1 copy/reaction and 10-fold higher than that of the commercial qRT-PCR kit (10 copies/reaction). The clinical performance of the OSN-qRT-PCR assay was evaluated using 181 clinical samples. Among them, 14 qRT-PCR-negative samples (7 had no repetitive results and 7 had no cycle threshold (CT) values) were detected by OSN-qRT-PCR. Moreover, the 7 qRT-PCR-positives in the qRT-PCR gray zone (CT values of ORF1ab ranged from 37.48 to 39.07, and CT values of N ranged from 37.34 to 38.75) were out of the gray zone and thus were deemed to be positive by OSN-qRT-PCR, indicating that the positivity of these samples is confirmative. Compared to the qRT-PCR kit, the OSN-qRT-PCR assay revealed higher sensitivity and specificity, showing better suitability to clinical applications for the detection of SARS-CoV-2 in patients with low viral load.", "doc_id": "a4fc19q5"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Trends and Innovations in Biosensors for COVID-19 Mass Testing", "abstract": "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.", "doc_id": "d5d10lwr"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Laboratory information system requirements to manage the COVID-19 pandemic: a report from the Belgian national reference testing center", "abstract": "OBJECTIVE: To describe the development, implementation and requirements of laboratory information system (LIS) functionality to manage test ordering, registration, sample flow, and result reporting during the COVID-19 pandemic. CONTEXT AND SETTING: Our large (>12,000,000 tests/year) academic hospital laboratory is the Belgian National Reference Center (NRC) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. We performed a moving total of > 25,000 SARS-CoV-2 PCR tests in parallel to standard routine testing since the start of the outbreak. A LIS implementation team dedicated to develop tools to remove the bottlenecks, primarily situated in the pre- and post-analytical phase, was established early in the crisis. RESULTS: We outline the design, implementation and requirements of LIS functionality related to managing increased test demand during the COVID-19 crisis, including tools for test ordering, standardized order sets integrated into a computerized provider order entry module, notifications on shipping requirements, automated triaging based on digital metadata forms, and the establishment of databases with contact details of other laboratories and primary care physicians to enable automated reporting. We also describe our approach to data mining and reporting of actionable daily summary statistics to governing bodies and other policymakers. DISCUSSION: Rapidly developed, agile extendable LIS functionality and its meaningful use alleviates the administrative burden on laboratory personnel and improves turn-around-time of SARS-CoV-2 testing. It will be important to maintain an environment that is conducive for the rapid adoption of meaningful LIS tools post-COVID crisis.", "doc_id": "3b06j75h"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Development of a rapid test kit for SARS-CoV-2: an example of product design", "abstract": "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.", "doc_id": "52pw2vwx"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Development of a reverse transcription-loop-mediated isothermal amplification as a rapid early-detection method for novel SARS-CoV-2", "abstract": "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\u00e2\u0080 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.", "doc_id": "77jpm4o0"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Multi-center evaluation of cepheid xpert\u00ae xpress SARS-CoV-2 point-of-care test during the SARS-CoV-2 pandemic", "abstract": "BACKGROUND: With the outbreak of SARS-CoV-2, rapid diagnostics are paramount to contain the current pandemic. The routinely used realtime RT-PCR is sensitive, specific and able to process large batches of samples. However, turnaround time is long and in cases where fast obtained results are critical, molecular point of care tests (POCT) can be an alternative. Here we report on a multicenter evaluation of the Cepheid Xpert Xpress SARS-CoV-2 point-of-care test. STUDY DESIGN: The Xpert Xpress SARS-CoV-2 assay was evaluated against the routine in-house real-time RT-PCR assays in three medical microbiology laboratories in The Netherlands. A sensitivity and specificity panel was tested consisting of a dilution series of SARS-CoV-2 and ten samples containing SARS-CoV-2 and a range of other seasonal respiratory viruses. Additionally, 58 samples of patients positive for SARS-CoV-2 with different viral loads and 30 tested negative samples in all three Dutch laboratories using an in-house RT-PCR, were evaluated using Cepheids Xpert Xpress SARS-CoV-2 cartridges. RESULTS: Xpert Xpress SARS-CoV-2 point of care test showed equal performance compared to routine in-house testing with a limit of detection (LOD) of 8.26 copies/mL. Other seasonal respiratory viruses were not detected. In clinical samples Xpert Xpress SARS-CoV-2 reaches an agreement of 100 % compared to all in-house RT-PCRs CONCLUSION: Cepheids GeneXpert Xpert Xpress SARS-CoV-2 is a valuable addition for laboratories in situations where rapid and accurate diagnostics are of the essence.", "doc_id": "4nq2ok89"} {"topic_name": "coronavirus test rapid testing", "topic_id": "6", "title": "Point-of-Care Diagnostic Tests for Detecting SARS-CoV-2 Antibodies: A Systematic Review and Meta-Analysis of Real-World Data", "abstract": "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.", "doc_id": "4ipuy7su"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Antibody epitope repertoire analysis enables rapid antigen discovery and multiplex serology", "abstract": "The detection of pathogen-specific antibodies remains a cornerstone of clinical diagnostics. Yet, many test exhibit undesirable performance or are completely lacking. Given this, we developed serum epitope repertoire analysis (SERA), a method to rapidly discover conserved, pathogen-specific antigens and their epitopes, and applied it to develop an assay for Chagas disease caused by the protozoan parasite Trypanosoma cruzi. Antibody binding peptide motifs were identified from 28 Chagas repertoires using a bacterial display random 12-mer peptide library and next-generation sequencing (NGS). Thirty-three motifs were selected and mapped to candidate Chagas antigens. In a blinded validation set (n = 72), 30/30 Chagas were positive, 30/30 non-Chagas were negative, and 1/12 Leishmania sp. was positive. After unblinding, a Leishmania cross-reactive epitope was identified and removed from the panel. The Chagas assay exhibited 100% sensitivity (30/30) and specificity (90/90) in a second blinded validation set including individuals with other parasitic infections. Amongst additional epitope repertoires with unknown Chagas serostatus, assay specificity was 99.8% (998/1000). Thus, the Chagas assay achieved a combined sensitivity and specificity equivalent or superior to diagnostic algorithms that rely on three separate tests to achieve high specificity. NGS-based serology via SERA provides an effective approach to discover antigenic epitopes and develop high performance multiplex serological assays.", "doc_id": "equnyib7"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Immunity to infection", "abstract": "", "doc_id": "g861k4st"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "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", "abstract": "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.", "doc_id": "0te5ybjv"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "SARS-CoV-2 serology: Test, test, test, but interpret with caution!", "abstract": "SARS-CoV-2 serological tests are a subject of intense interest and have the potential to significantly enhance the diagnostic capability of healthcare services in the current pandemic. However, as with all novel assays, significant validation is required to understand the clinical relevance of results.We present the first study to assess clinician interpretation of SARS-CoV-2 serology scenarios. We identify common key assumptions regarding patient infectivity and protection that are not currently supported by the SARS-CoV-2 evidence base. In this rapidly developing field, we therefore strongly recommend serological assay results are accompanied by clear interpretive support from laboratory and infectious diseases specialists.", "doc_id": "djlrtuvy"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Performance Characteristics of Four High-Throughput Immunoassays for Detection of IgG Antibodies against SARS-CoV-2.", "abstract": "The role of serologic testing for SARS-CoV-2, both in the clinical and public health settings, will continue to evolve as we gain increasing insight into our immune response to the virus. Here, we evaluated four high throughput serologic tests for detection of anti-SARS-CoV-2 IgG antibodies, including assays from Abbott Laboratories (Abbott Park, IL), Epitope Diagnostics Inc. (San Diego, CA), Euroimmun (Lubeck, Germany), and Ortho-Clinical Diagnostics (Rochester, NY), using a panel of serially collected serum samples (N=224) from 56 patients with confirmed COVID-19, healthy donor sera from 2018 and a cross-reactivity serum panel collected in early 2020. Sensitivity of the Abbott, Epitope, Euroimmun and Ortho-Clinical IgG assays in convalescent serum samples collected more than 14 days post symptom onset or initial positive RT-PCR result was 92.9% (78/84), 88.1% (74/84), 97.6% (82/84) and 98.8% (83/84), respectively. Among unique convalescent patients, sensitivity of the Abbott, Epitope, Euroimmun and Ortho-Clinical anti-SARS-CoV-2 IgG assays was 97.3% (36/37), 73% (27/37), 94.6% (35/37) and 97.3% (36/37), respectively. Overall assay specificity and positive predictive values based on a 5% prevalence rate are 99.6%/92.8%, 99.6%/90.6%, 98.0%/71.2% and 99.6%/92.5%, respectively, for the Abbott, Epitope, Euroimmun and Ortho-Clinical IgG assays. In conclusion, we show high sensitivity in convalescent sera and high specificity for the Abbott, Euroimmun and Ortho-Clinical anti-SARS-CoV-2 IgG assays. With the unprecedented influx of commercially available serologic tests for detection of antibodies against SARS-CoV-2, it remains imperative that laboratories thoroughly evaluate such assays for accuracy prior to implementation.", "doc_id": "9khsgtz3"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Covid-19: Antibody tests will not be rolled out in UK until at least May, MPs hear.", "abstract": "", "doc_id": "5fkvbtjc"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Efficacy of Serology Testing in Predicting Reinfection in Patients with SARS-CoV-2.", "abstract": "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.", "doc_id": "g1dij8ty"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "The researchers taking a gamble with antibody tests for coronavirus.", "abstract": "", "doc_id": "1tc0i21c"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Seroepidemiologic Study Designs for Determining SARS-COV-2 Transmission and Immunity.", "abstract": "Serologic studies are crucial for clarifying dynamics of the coronavirus disease pandemic. Past work on serologic studies (e.g., during influenza pandemics) has made relevant contributions, but specific conditions of the current situation require adaptation. Although detection of antibodies to measure exposure, immunity, or both seems straightforward conceptually, numerous challenges exist in terms of sample collection, what the presence of antibodies actually means, and appropriate analysis and interpretation to account for test accuracy and sampling biases. Successful deployment of serologic studies depends on type and performance of serologic tests, population studied, use of adequate study designs, and appropriate analysis and interpretation of data. We highlight key questions that serologic studies can help answer at different times, review strengths and limitations of different assay types and study designs, and discuss methods for rapid sharing and analysis of serologic data to determine global transmission of severe acute respiratory syndrome coronavirus 2.", "doc_id": "91pb9nq3"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "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.", "abstract": "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.", "doc_id": "82iy2prw"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies up to 25 April 2020 and public health implications.", "abstract": "We reviewed the diagnostic accuracy of SARS-CoV-2 serological tests. Random-effects models yielded a summary sensitivity of 82% for IgM, and 85% for IgG and total antibodies. For specificity, the pooled estimate were 98% for IgM and 99% for IgG and total antibodies. In populations with \u2264 5% of seroconverted individuals, unless the assays have perfect (i.e. 100%) specificity, the positive predictive value would be \u2264 88%. Serological tests should be used for prevalence surveys only in hard-hit areas.", "doc_id": "95v0nfme"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "[Sensitivity, specificity, predictive values in serological Covid-19 tests].", "abstract": "", "doc_id": "ck8boz7i"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "[Effect of heat inactivation of blood samples on the efficacy of three detection methods of SARS-CoV-2 antibodies].", "abstract": "OBJECTIVE To evaluate the effects of heat inactivation of blood samples at 56\u2103 for 30 min on the results of SARS-CoV-2 antibody detection using different methods. METHODS This retrospective study was conducted in 11 patients with established diagnosis of COVID-19 and 10 patients with diseases other than COVID- 19 in our hospital. We collected samples of serum, plasma and whole blood from each patient between February, 12 and 18, 2020, and with a double- blind design, the samples were examined for SARS-CoV-2 antibodies before and after heat inactivation at 56 \u2103 for 30 min. In all the samples, the total SARS-CoV-2 antibodies were detected using immunochromatography, and the IgM antibodies were detected using fluorescence immunochromatography; the IgM and IgG antibodies in the serum and plasma samples detected with chemiluminescence immunoassay. We compared the detection results and analyzed the correlation of semi-quantitative detection results of IgM and IgG antibodies before and after heat inactivation of the samples. RESULTS With immuno-chromatography, the coincidence rate of the total SARS-CoV-2 antibody detection before and after heat inactivation of the serum and plasma samples was 90.0% in COVID-19 cases and 100.0% in the negative cases, resulting in a total coincidence rate 95.2%; for the whole blood samples, the total coincidence rates of the total SARS-CoV-2 antibodies were 100.0%. For detection of IgM antibodies in the serum, plasma and whole blood samples using fluorescence immunochromatography, the coincidence rates in SARS-CoV-2-positive and negative cases and the total coincidence rate before and after inactivation were 100.0%, 0 and 47.6%, respectively. For detection of serum IgM and IgG antibodies and plasma IgG antibodies with chemiluminescence immunoassay, the coincidence rates in SARS-CoV-2-positive and negative cases and the total coincidence rate before and after inactivation were all 100.0%, and the total coincidence rate of plasma IgM antibodies was 95.2%. Pearson correlation analysis of the semi-quantitative results of IgM and IgG detection in the serum and plasma samples showed a correlation coefficient of 0.9999 (95%CI: 0.9998-1.000, P < 0.001) between the results before and after sample inactivation. CONCLUSIONS Heat inactivation of blood samples at 56 \u2103 for 30 min does not obviously affect the results of immunochromatography and chemiluminescent immunoassay for detection of SARS-COV-2 antibodies but can reduce the risk of infection for the operators. Heat-inactivated samples can not be used in fluorescence immunochromatography for SARS-CoV-2 antibody detection.", "doc_id": "ekytw2io"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays", "abstract": "Introduction Commercially available SARS-CoV-2 serological assays based on different viral antigens have been approved for the qualitative determination of anti-SARS-CoV-2 antibodies. However, there is limited published data associating the results from commercial assays with neutralizing antibodies. Methods 67 specimens from 48 patients with PCR-confirmed COVID-19 and a positive result by the Roche Elecsys SARS-CoV-2, Abbott SARS-CoV-2 IgG, or EUROIMMUN SARS-CoV-2 IgG assays and 5 control specimens were analyzed for the presence of neutralizing antibodies to SARS-CoV-2. Correlation, concordance, positive percent agreement (PPA), and negative percent agreement (NPA) were calculated at several cutoffs. Results were compared in patients categorized by clinical outcomes. Results The correlation between SARS-CoV-2 neutralizing titer (EC50) and the Roche, Abbott, and EUROIMMUN assays was 0.29, 0.47, and 0.46 respectively. At an EC50 of 1:32, the concordance kappa with Roche was 0.49 (95% CI; 0.23-0.75), with Abbott was 0.52 (0.28-0.77), and with EUROIMMUN was 0.61 (0.4-0.82). At the same neutralizing titer, the PPA and NPA for the Roche was 100% (94-100) & 56% (30-80); Abbott was 96% (88-99) & 69% (44-86); and EUROIMMUN was 91% (80-96) & 81% (57-93) for distinguishing neutralizing antibodies. Patients who died, were intubated, or had a cardiac injury from COVID-19 infection had significantly higher neutralizing titers relative to those with mild symptoms. Conclusion COVID-19 patients generate an antibody response to multiple viral proteins such that the calibrator ratios on the Roche, Abbott, and EUROIMMUN assays are all associated with SARS-CoV-2 neutralization. Nevertheless, commercial serological assays have poor NPA for SARS-CoV-2 neutralization, making them imperfect proxies for neutralization.", "doc_id": "38bz0acw"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Clinical validation and performance evaluation of the automated Vitros Total Anti-SARS-CoV-2 Antibodies assay for screening of serostatus in COVID-19", "abstract": "Objectives: Evaluation of serostatus against SARS-CoV-2 has emerged as an important tool in identification of exposure to COVID-19. We report on the validation of the Vitros Anti-SARS-CoV-2 Total (CoV2T) assay for qualitative serological testing of SARS-CoV-2 antibodies. Methods: We performed validation studies according to COLA guidelines, using samples previously tested for SARS-CoV-2 by RT-PCR. We evaluated precision, analytical interferences, and cross-reactivity with other viral infections. We also evaluated concordance with molecular and other serological testing, and evaluated seroconversion. Results: The Vitros CoV2T assay exhibited acceptable precision, was resistant to analytical interference, and did not exhibit cross-reactivity with samples positive for other respiratory viruses. The CoV2T assay exhibited 100% negative predictive agreement (56/56) and 71% positive predictive agreement (56/79) with RT-PCR across all patient samples, and was concordant with other serological assays. Concordance with RT-PCR was 97% > 7 days after symptom onset. Conclusions: The Vitros CoV2T assay was successfully validated in our laboratory. We anticipate it will be a useful tool in screening for exposure to SARS-CoV-2, however, the use of the CoV2T and other serological assays in clinical management of COVID-19 patients is yet unknown, and must be evaluated in future studies.", "doc_id": "3hsptk9x"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Indication for SARS-CoV-2 serology: first month follow-up", "abstract": "SARS-CoV-2 detection is mainly performed by RT-PCR but recently serological tests were made available. A first one month follow-up of the SARS-CoV-2 serology records was performed in our laboratory to precise the diversity and proportion of the SARS-CoV-2 serology test indications and to identify new valid indications (meningoencephalitis, vasculitis, etc)", "doc_id": "8fuj9td2"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Clinical Sensitivity and Interpretation of PCR and Serological COVID-19 Diagnostics for Patients Presenting to the Hospital", "abstract": "Introduction: The diagnosis of COVID-19 requires integration of clinical and laboratory data. SARS-CoV-2 diagnostic assays play a central role in diagnosis and have fixed technical performance metrics. Interpretation becomes challenging because the clinical sensitivity changes as the virus clears and the immune response emerges. Our goal was to examine the clinical sensitivity of two most common SARS-CoV-2 diagnostic test modalities, polymerase chain reaction (PCR) and serology, over the disease course to provide insight into their clinical interpretation in patients presenting to the hospital. Methods: A single-center, retrospective study. To derive clinical sensitivity of PCR, we identified 209 PCR-positive SARS-CoV-2 patients with multiple PCR test results (624 total PCR tests) and calculated daily sensitivity from date of symptom onset or first positive test. To calculate daily clinical sensitivity by serology, we utilized 157 PCR-positive patients with a total of 197 specimens tested by enzyme-linked immunosorbent assay for IgM, IgG, and IgA anti-SARS-CoV-2 antibodies. Results: Clinical sensitivity of PCR decreased with days post symptom onset with >90% clinical sensitivity during the first 5 days after symptom onset, 70-71% from days 9-11, and 30% at day 21. In contrast, serological sensitivity increased with days post symptom onset with >50% of patients seropositive by at least one antibody isotype after day 7, >80% after day 12, and 100% by day 21. Conclusion: PCR and serology are complimentary modalities that require time-dependent interpretation. Superimposition of sensitivities over time indicate that serology can function as a reliable diagnostic aid indicating recent or prior infection.", "doc_id": "g0fam0fm"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Evaluation of ELISA tests for the qualitative determination of IgG, IgM and IgA to SARS-CoV-2", "abstract": "Serological assays for anti-SARS-CoV-2 antibodies are now of critical importance to support diagnosis, guide epidemiological intervention, and understand immune response to natural infection and vaccine administration. We developed and validated new anti-SARS-CoV-2 IgG, IgM and IgA ELISA tests (ENZY-WELL SARS-CoV-2 ELISA, DIESSE Diagnostica Senese S.p.a.) based on whole-virus antigens. We used a total of 553 serum samples including samples from COVID-19 suspected and confirmed cases, healthy donors, and patients positive for other infections or autoimmune conditions. Overall, the assays showed good concordance with the indirect immunofluorescence reference test in terms of sensitivity and specificity. Especially for IgG and IgA, we observed high sensitivity (92.5 and 93.6%, respectively); specificity was high (>96%) for all antibody types ELISAs. In addition, sensitivity was linked to the days from symptoms onset (DSO) due to the seroconversion window, and for ENZY-WELL SARS-CoV-2 IgG and IgA ELISAs resulted 100% in those samples collected after 10 and 12 DSO, respectively. The results showed that ENZY-WELL SARS-CoV-2 ELISAs may represent a valid option for both diagnostic and epidemiological purposes, covering all different antibody types developed in SARS-CoV-2 immune response.", "doc_id": "0w7tq79d"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "A how-to-guide to building a robust SARS-CoV-2 testing program at a university-based health system", "abstract": "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.", "doc_id": "23q7c15b"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Seroprevalence of antibodies against SARS-CoV-2 among public community and health-care workers in Alzintan City of Libya", "abstract": "Abstract A study was conducted to determine the seroprevalence of antibodies against SARS-CoV-2 among public community and health care workers in Alzintan City, Libya. During the period from 2/4/2020 to 18/5/2020, a total of 219 blood samples were collected and analyzed for the presence of antibodies against SARS-CoV-2. Collection of samples were divided in two categories; random samples from public community and samples from health care workers belong to two Governmental hospitals and one private clinic. One Step Novel Coronavirus (COVID-19) IgM/IgG Antibody Test was used. Out of the 219 samples tested, 6 (2.74%) samples were seropositive for SARS-CoV-2. All health-care workers were tested negative. All positive cases were females and 5 of them aged between 44 to 75 years and one aged 32 years. The prevalence in young females ([\u2264]40 years) was 1.4% in total young females tested in the study and 1.75% in young females taken from public community. The prevalence in older females aged ( 40 years), was 11.1% in total females tested and 13.9% in females taken from public community. In conclusion, the preliminary investigation of SARS-CoV-2 revealed considerable prevalence in Alzintan City although the disease seems to be in its mild form. Active surveillance studies with high number of samples using both virological and serological tests are in urgent need.", "doc_id": "b7dxkgo8"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Reliability of serological tests for COVID-19: Comparison of three immunochromatography test kits for SARS-CoV-2 antibodies.", "abstract": "Background: Several immunochromatographic serological test kits have been developed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies, but their relative performance and potential clinical utility is unclear. Methods: Three commercially available serological test kits were evaluated using 99 serum samples collected from 29 patients diagnosed with coronavirus disease 2019 (COVID-19). Results: The IgM antibody-positive rates of the three serological test kits for samples taken at the early stage of the disease (0-6 days after onset) were 19.0%, 23.8%, and 19.0%, respectively. The IgM antibody-positive rates over the entire period were 21.2%, 60.6%, and 15.2%, respectively. The IgG antibody-positive rates for samples taken after 13 days of onset were 100.0%, 97.6%, and 97.6%, respectively. Conclusion: There were large differences among the results of the three test kits. Only few cases showed positive results for IgM in the early stage of disease and the IgM antibody-positive rates over the entire period were low, suggesting that the kits used in this study were unsuitable for diagnosis of COVID-19. The IgG antibody was positive in almost all samples after 13 days of onset, suggesting that it may be useful for determining infections in the recent past.", "doc_id": "fn9t38as"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Joint Detection of Serum IgM/IgG Antibody is An Important Key to Clinical Diagnosis of SARS-COV-2 Infection", "abstract": "Background: This study was aimed to investigate the application of SARS- COV-2 IgM and IgG antibodies in diagnosis of COVID-19 infection. Method: This study enrolled a total of 178 patients at Huangshi Central Hospital from January to February, 2020. Among them, 68 patients were SARS-COV-2 infected confirmed with nucleic acid test (NAT) and CT imaging. 9 patients were in the suspected group (NAT negative) with fever and other respiratory symptoms. 101 patients were in the control group with other diseases and negative to SARS-COV-2 infection. After serum samples were collected, SARS-COV-2 IgG and IgM antibodies were tested by chemiluminescence immunoassay (CLIA) for all patients. Results: The specificity of serum IgM and IgG antibodies to SARS-COV-2 were 99.01% (100/101) and 96.04% (97/101) respectively, and the sensitivity were 88.24% (60/68) and 97.06% (66/68) respectively. The combined detection rate of SARS-COV-2 IgM and IgG antibodies were 98.53% (67/68). Conclusion: Combined detection of serum SARS-COV-2 IgM and IgG antibodies had better sensitivity compared with single IgM or IgG test, which can be used as an important diagnostic tool for SARS-COV-2 infection and a screening tool of potential SARS-COV-2 carriers in clinics, hospitals and accredited scientific laboratory.", "doc_id": "60vmohgq"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Comparative assessment of multiple COVID-19 serological technologies supports continued evaluation of point-of-care lateral flow assays in hospital and community healthcare settings", "abstract": "There is a clear requirement for an accurate SARS-CoV-2 antibody test, both as a complement to existing diagnostic capabilities and for determining community seroprevalence. We therefore evaluated the performance of a variety of antibody testing technologies and their potential as diagnostic tools. A highly specific in-house ELISA was developed for the detection of anti-spike (S), -receptor binding domain (RBD) and -nucleocapsid (N) antibodies and used for the cross-comparison of ten commercial serological assays - a chemiluminescence-based platform, two ELISAs and seven colloidal gold lateral flow immunoassays (LFIAs) - on an identical panel of 110 SARS-CoV-2-positive samples and 50 pre-pandemic negatives. There was a wide variation in the performance of the different platforms, with specificity ranging from 82% to 100%, and overall sensitivity from 60.9% to 87.3%. However, the head to head comparison of multiple serodiagnostic assays on identical sample sets revealed that performance is highly dependent on the time of sampling, with sensitivities of over 95% seen in several tests when assessing samples from more than 20 days post onset of symptoms. Furthermore, these analyses identified clear outlying samples that were negative in all tests, but were later shown to be from individuals with mildest disease presentation. Rigorous comparison of antibody testing platforms will inform the deployment of point of care technologies in healthcare settings and their use in the monitoring of SARS-CoV-2 infections.", "doc_id": "c2bwky6e"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Evaluation of the performance of SARS-CoV-2 serological tools and their positioning in COVID-19 diagnostic strategies", "abstract": "Rapid and accurate diagnosis is crucial for successful outbreak containment. During the current coronavirus disease 2019 (COVID-19) public health emergency, the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis is the detection of viral RNA by reverse transcription (RT)-PCR. Additional diagnostic methods enabling the detection of current or past SARS-CoV-2 infection would be highly beneficial to ensure the timely diagnosis of all infected and recovered patients. Here, we investigated several serological tools, i.e., two immunochromatographic lateral flow assays (LFA-1 (Biosynex COVID-19 BSS) and LFA-2 (COVID-19 Sign IgM/IgG)) and two enzyme-linked immunosorbent assays (ELISAs) detecting IgA (ELISA-1 Euroimmun), IgM (ELISA-2 EDI) and/or IgG (ELISA-1 and ELISA-2) based on well-characterized panels of serum samples from patients and healthcare workers with PCR-confirmed COVID-19 and from SARS-CoV-2-negative patients. A total of 272 serum samples were used, including 62 serum samples from hospitalized patients (panel 1 and panel 3), 143 serum samples from healthcare workers (panel 2) diagnosed with COVID-19 and 67 serum samples from negative controls. Diagnostic performances of each assay were assessed according to days after symptom onset (dso) and the antigenic format used by manufacturers. We found overall sensitivities ranging from 69% to 93% on panels 1 and 2 and specificities ranging from 83% to 98%. The clinical sensitivity varied greatly according to the panel tested and the dso. The assays we tested showed poor mutual agreement. A thorough selection of serological assays for the detection of ongoing or past infections is advisable.", "doc_id": "chuaqnl2"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "A preliminary study on analytical performance of serological assay for SARS-CoV-2 IgM/IgG and application in clinical practice", "abstract": "Objective: To investigate the performance of serological test and dynamics of serum antibody with the progress of SARS-CoV-2 infections. Methods: A total of 419 patients were enrolled including 19 confirmed cases and 400 patients from fever clinics. Their serial serum samples collected during the hospitalization were menstruated for IgM and IgG against SARS-CoV-2 using gold immunochromatographic assay and chemiluminescence immunoassay. We investigated whether thermal inactivation could affect the results of antibody detection. The dynamics of antibodies with the disease progress and false positive factors for antibody testing were also analyzed. Results: The positive rate of IgG detection was 91.67% and 83.33% using two CLIA, respectively. However, the IgM positive rate was dramatically declined might due to the lack of blood samples at early stages of the disease. The chemiluminescence immunoassay had a favorable but narrow linear range. Our work showed increased IgG values in serums from virus-negative patients and four negative samples were IgG weak-positive after thermal incubation. Our data showed the specificity of viral N+S proteins was higher than single antigen. Unlike generally thought that IgM appeared earlier than IgG, there is no certain chronological order of IgM and IgG seroconversion in COVID-19 patients. It was difficult to detect antibodies in asymptomatic patients suggesting that their low viral loads were not enough to cause immune response. Analysis of common interferent in three IgG false-positive patients, such as rheumatoid factor, proved that false positives were not caused by these interfering substances and antigenic cross-reaction. Conclusions: Viral serological test is an effective means for SARS-CoV-2 infect detection using both chemiluminescence immunoassay and gold immunochromatographic assay. Chemiluminescence immunoassay against multi-antigens has obvious advantages but still need improve in reducing false positives.", "doc_id": "bboi6l69"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "SARS-CoV-2-specific antibody detection for sero-epidemiology: a multiplex analysis approach accounting for accurate seroprevalence", "abstract": "Background The COVID-19 pandemic demands detailed understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population. Methods Spike protein subunits S1 and RBD, and Nucleoprotein were coupled to distinct microspheres. Sera collected before the emergence of SARS-CoV-2 (N=224), and of non-SARS-CoV-2 influenza-like illness (N=184), and laboratory-confirmed cases of SARS-CoV-2 infection (N=115) with various severity of COVID-19 were tested for SARS-CoV-2-specific concentrations of IgG. Results Our assay discriminated SARS-CoV-2-induced antibodies and those induced by other viruses. The assay obtained a specificity between 95.1 and 99.0% with a sensitivity ranging from 83.6-95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to non-hospitalized cases. Conclusions The bead-based serological assay for quantitation of SARS-CoV-2-specific antibodies proved to be robust and can be conducted in many laboratories. Finally, we demonstrated that testing of antibodies against different antigens increases sensitivity and specificity compared to single antigen-specific IgG determination.", "doc_id": "0beno5o5"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Validation of a commercially available SARS-CoV-2 serological Immunoassay", "abstract": "Aims: To validate the diagnostic accuracy of a Euroimmun SARS-CoV-2 IgG and IgA immunoassay for COVID-19 disease. Methods: In this unmatched (1:1) case-control validation study, we used sera of 181 laboratory-confirmed SARS-CoV-2 cases and 176 negative controls collected before the emergence of SARS-CoV-2. Diagnostic accuracy of the immunoassay was assessed against a whole spike protein-based recombinant immunofluorescence assay (rIFA) by receiver operating characteristic (ROC) analyses. Discrepant cases between ELISA and rIFA were further tested by pseudo-neutralization assay. Results: COVID-19 patients were more likely to be male and older than controls, and 50.3% of them were hospitalized. ROC curve analyses indicated that IgG and IgA had a high diagnostic accuracy with AUCs of 0.992 (95% Confidence Interval [95%CI]: 0.986-0.996) and 0.977 (95%CI: 0.963-0.990), respectively. IgG assays outperformed IgA assays (p=0.008). Considering optimized cut-offs taking the 15% inter-assay imprecision assessed into account, an IgG ratio cut-off > 1.5 displayed a 100% specificity (95%CI: 98-100) and a 100% positive predictive value (95%CI: 97-100). A 0.5 cut-off displayed a 97% sensitivity (95%CI: 93-99) and a 97% negative predictive value (95%CI: 93-99). Adopting these thresholds, rather than those of the manufacturer, improved assay performance, leaving 12% of IgG ratios ranging between 0.5-1.5 as indeterminate. Conclusions: The Euroimmun assay displays a nearly optimal diagnostic accuracy using IgG against SARS-CoV-2 in a samples of patients, without any obvious gains from considering IgA serology. The optimized cut-offs are fit for rule-in and rule-out purposes, allowing determination of whether individuals have been exposed to SARS-CoV-2 or not in our study population. They should however not be considered as a surrogate of protection at this stage.", "doc_id": "0dgmfeak"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Correlation of ELISA based with random access serologic immunoassays for identifying adaptive immune response to SARS-CoV-2", "abstract": "Public health emergency of SARS-CoV-2 has facilitated diagnostic testing as a related medical countermeasure against COVID-19 outbreak. Numerous serologic antibody tests have become available through an expedited federal emergency use only process. This paper highlights the analytical characteristic of an ELISA based assay by AnshLabs and three random access immunoassay (RAIA) by DiaSorin, Roche, and Abbott that have been approved for emergency use authorization (EUA), at a tertiary academic center in a low disease-prevalence area. The AnshLabs gave higher estimates of sero-prevalence, over the three RAIA methods. For positive results, AnshLabs had 93.3% and 100% concordance with DiaSorin or Abbott and Roche respectively. For negative results, AnshLabs had 69.7% and 73.0% concordance with DiaSorin and Roche or Abbott respectively. All discrepant samples that were positive by AnshLabs and negative by RAIA tested positive by all-in-one step SARS-CoV-2 Total (COV2T) assay performed on the automated Siemens Advia Centaur XPT analyzer. None of these methods, however, are useful in early diagnosis of SARSCoV- 2.", "doc_id": "4vr4cm1s"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Estimating Force of Infection from Serologic Surveys with Imperfect Tests", "abstract": "The force of infection, or the rate at which susceptible individuals become infected, is an important public health measure for assessing the extent of outbreaks and the impact of control programs. Here we present methods for estimating force of infection from serological surveys of infections which produce lasting immunity, taking into account imperfections in the test used, and uncertainty in such imperfections. The methods cover both single serological surveys, in which age is a proxy for time at risk, and repeat surveys in the same people, in which the force of infection is estimated more directly. Fixed values can be used for the sensitivity and specificity of the tests, or existing methods for belief elicitation can be used to include uncertainty in these values. The latter may be applicable, for example, when the specificity of a test depends on co-circulating pathogens, which may not have been well characterized in the setting of interest. We illustrate the methods using data from two published serological studies of dengue.", "doc_id": "7w3mvhqa"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Rapid response flow cytometric assay for the detection of antibody responses to SARS-CoV-2", "abstract": "SARS-CoV-2 has emerged as a previously unknown zoonotic coronavirus that spread worldwide causing a serious pandemic. While reliable nucleic acid-based diagnostic assays were rapidly available, there exists only a limited number of validated serological assays. Here, we evaluated a novel flow cytometric approach based on antigen-expressing HEK 293T cells to assess spike-specific IgG and IgM antibody responses. Analyses of 201 pre-COVID-19 sera proved a high assay specificity in comparison to commercially available CLIA and ELISA systems, while also revealing the highest sensitivity in specimens from PCR-confirmed SARS-CoV-2 infected patients. Additionally, a soluble Angiotensin-Converting-Enzyme 2 (ACE-2) variant was established as external standard to quantify spike-specific antibody responses on different assay platforms. In conclusion, our newly established flow cytometric assay allows sensitive and quantitative detection of SARS-CoV-2-specific antibodies, which can be easily adopted in different laboratories and does not rely on external supply of assay kits.", "doc_id": "2r9jlejw"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Laboratory diagnosis of SARS.", "abstract": "The emergence of new viral infections of man requires the development of robust diagnostic tests that can be applied in the differential diagnosis of acute illness, or to determine past exposure, so as to establish the true burden of disease. Since the recognition in April 2003 of the severe acute respiratory syndrome coronavirus (SARS-CoV) as the causative agent of severe acute respiratory syndrome (SARS), enormous efforts have been applied to develop molecular and serological tests for SARS which can assist rapid detection of cases, accurate diagnosis of illness and the application of control measures. International progress in the laboratory diagnosis of SARS-CoV infection during acute illness has led to internationally agreed World Health Organization criteria for the confirmation of SARS. Developments in the dissection of the human immune response to SARS indicate that serological tests on convalescent sera are essential to confirm SARS infection, given the sub-optimal predictive value of molecular detection tests performed during acute SARS illness.", "doc_id": "7ayg3typ"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay reveals high sensitivity of the nucleocapsid protein in acute-phase sera of severe acute respiratory syndrome patients.", "abstract": "Accurate and timely diagnosis of severe acute respiratory syndrome coronavirus (SARS-CoV) infection is a critical step in preventing another global outbreak. In this study, 829 serum specimens were collected from 643 patients initially reported to be infected with SARS-CoV. The sera were tested for the N protein of SARS-CoV by using an antigen capture enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibodies against the N protein of SARS-CoV and compared to 197 control serum samples from healthy donors and non-SARS febrile patients. The results of the N protein detection analysis were directly related to the serological analysis data. From 27 SARS patients who tested positive with the neutralization test, 100% of the 24 sera collected from 1 to 10 days after the onset of symptoms were positive for the N protein. N protein was not detected beyond day 11 in this group. The positive rates of N protein for sera collected at 1 to 5, 6 to 10, 11 to 15, and 16 to 20 days after the onset of symptoms for 414 samples from 298 serologically confirmed patients were 92.9, 69.8, 36.4, and 21.1%, respectively. For 294 sera from 248 serological test-negative patients, the rates were 25.6, 16.7, 9.3, and 0%, respectively. The N protein was not detected in 66 patients with cases of what was initially suspected to be SARS but serologically proven to be negative for SARS and in 197 serum samples from healthy donors and non-SARS febrile patients. The specificity of the assay was 100%. Furthermore, of 16 sera collected from four patients during the SARS recurrence in Guangzhou, 5 sera collected from 7 to 9 days after the onset of symptoms were positive for the N protein. N protein detection exhibited a high positive rate, 96 to 100%, between day 3 and day 5 after the onset of symptoms for 27 neutralization test-positive SARS patients and 298 serologically confirmed patients. The N protein detection rate continually decreased beginning with day 10, and N protein was not detected beyond day 19 after the onset of symptoms. In conclusion, an antigen capture ELISA reveals a high N protein detection rate in acute-phase sera of patients with SARS, which makes it useful for early diagnosis of SARS.", "doc_id": "8e8h7bo3"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Use of antibody avidity assays for diagnosis of severe acute respiratory syndrome coronavirus infection.", "abstract": "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.", "doc_id": "4rbtif2y"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Specific serology for emerging human coronaviruses by protein microarray.", "abstract": "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.", "doc_id": "79bzd4nl"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Detection of specific antibodies to severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein for serodiagnosis of SARS coronavirus pneumonia.", "abstract": "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.", "doc_id": "b1qnfl41"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Laboratory Tests for COVID-19: A Review of Peer-Reviewed Publications and Implications for Clinical UIse.", "abstract": "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.", "doc_id": "ey34e59f"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "[Rapid point-of-care serology testing for sars-cov-2].", "abstract": "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.", "doc_id": "91872v0l"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Use of viral lysate antigen combined with recombinant protein in Western immunoblot assay as confirmatory test for serodiagnosis of severe acute respiratory syndrome.", "abstract": "A Western immunoblot assay for confirmatory serodiagnosis of severe acute respiratory syndrome (SARS) was developed utilizing viral lysate antigens combined with a recombinant nucleocapsid protein, GST-N (glutathione S-transferase-nucleocapsid) of the SARS coronavirus (SARS-CoV). The viral lysate antigens were separated by electrophoresis and transblotted onto nitrocellulose membranes. The resultant membrane was subsequently added with the GST-N recombinant protein at a specific location. The positions of bands corresponding to some of the structural proteins immobilized on the membrane were then located and verified with mouse or rabbit antisera specific to the respective proteins. The Western immunoblot assay was able to detect antibodies to SARS-CoV in all 40 serum specimens from SARS patients and differentiate the SARS-positive samples from those of the healthy donor or non-SARS patient controls (150 samples) when set criteria were followed. In addition, when the immunoblot was used to test samples considered falsely positive by an in-house-developed SARS-specific enzyme-linked immunosorbent assay, band patterns different from those with samples from SARS patients were obtained.", "doc_id": "bkp5pvir"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Comparison of serologic assays for measurement of antibody response to coronavirus in cats.", "abstract": "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.", "doc_id": "8g5s381b"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Detection of coronavirus 229E antibody by indirect hemagglutination.", "abstract": "Tannic-acid treated sheep erythrocytes (fresh or glutaraldehyde preserved) were sensitized with 229E antigens from human embryonic lung (RU-1) cell cultures. Indirect hemagglutination (IHA) antigen titers in 229E-infected cell cultures paralleled virus infectivity and complement fixation (CF) antigen titers. The identity of the IHA antigen was confirmed by testing extracts from inoculated and control cell cultures for ability to inhibit IHA. Also, significant increases in IHA antibody were demonstrated with acute and convalescent serum pairs from patients with proven 229E infections. A comparison of IHA, neutralization and CF titers for 229E antibodies was made on human sera drawn from different populations. The IHA and neutralization results were in agreement on 93% of the 129 sera found to be positive by at least one of three tests. The number of antibody titers detected by the CF test was insufficient to permit comparison. Hyperimmune sera from animals immunized with OC 43 did not react with 229E by IHA. Also no increase in IHA antibody was demonstrated with acute and convalescent serum pairs from patients with seroconversions to OC 43. These findings suggest that the IHA test provides (i) a rapid and sensitive method for serodiagnosis of 229E infections and (ii) a simple and inexpensive method for seroepidemiological studies.", "doc_id": "cy10ei1c"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "The value of hospital personnel serological screening in an integrated COVID-19 infection prevention and control strategy", "abstract": "", "doc_id": "2sytrto5"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Antik\u00f6rpertests bei COVID-19 - Was uns die Ergebnisse sagen./ [Antibody tests for COVID-19: What the results tell us]", "abstract": "INTRODUCTION: In the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the detection of virus-specific antibodies (AB) will play an increasing role. The presence or absence of such antibodies can potentially lead to considerations regarding immunity and infection. ISSUE: How reliable are inferences from positive or negative test results regarding the actual presence of SARS-CoV-2 specific antibodies? METHODS: Calculation of the probability that, depending on the pretest probability (prevalence of SARS-CoV-2 infection) and test properties, antibodies are present or absent in the case of positive or negative test results. RESULTS: Sensitivity and specificity of different SARS-CoV-2 AB test systems vary between 53 % and 94 % and between 91 % and 99.5 %, respectively. When using a test with high test quality, the positive predictive value (PPV) is 42 % and 7 9%, respectively, with a pre-test probability of 1 % to 5 %, as can currently be assumed for the general population in Austria or Germany. For persons with an increased pre-test probability of 20 %, e. g. persons from high-risk professions, the PPW is 95 %, with a pre-test probability of 80 % the PPW is almost 100 %. The negative predictive value (NPV) is at least 99.7 % for persons with a low pre-test probability of up to 5 % and 79.1 % for persons with a pre-test probability of 80 %. When using test systems with lower sensitivity and specificity, the reliability of the results decreases considerably. The PPV is 5.9 % with a pre-test probability of 1 %. CONCLUSIONS: A sufficiently high sensitivity and specificity are prerequisites for the application of antibody test systems. Positive test results are often false if the pre-test probability is low. Depending on the assumed prevalence of a SARS-CoV-2 infection, there are substantial differences in the significance of a concrete test result for the respective affected persons.", "doc_id": "4bdn6xje"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Covid-19: Antibody tests will not be rolled out in UK until at least May, MPs hear", "abstract": "", "doc_id": "7agfi6ao"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019", "abstract": "OBJECTIVE: To investigate the diagnostic value of serological testing and dynamic variance of serum antibody in coronavirus disease 2019 (COVID-19). METHODS: This study retrospectively included 43 patients with a laboratory-confirmed infection and 33 patients with a suspected infection, in whom the disease was eventually excluded. The IgM/IgG titer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was measured by chemiluminescence immunoassay analysis. RESULTS: Compared to molecular detection, the sensitivities of serum IgM and IgG antibodies to diagnose COVID-19 were 48.1% and 88.9%, and the specificities were 100% and 90.9%, respectively.In the COVID-19 group, the IgM-positive rate increased slightly at first and then decreased over time; in contrast, the IgG-positive rate increased to 100% and was higher than IgM at all times. The IgM-positive rate and titer were not significantly different before and after conversion to virus-negative. The IgG-positive rate was up to 90% and not significantly different before and after conversion to virus-negative. However, the median IgG titer after conversion to virus-negative was double that before, and the difference was significant. CONCLUSIONS: Viral serological testing is an effective means of diagnosis for SARS-CoV-2 infection. The positive rate and titer variance of IgG are higher than those of IgM in COVID-19.", "doc_id": "5ig5upot"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study", "abstract": "BACKGROUND: Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level. METHODS: 35\u00e2\u0080\u0088883 households were selected from municipal rolls using two-stage random sampling stratified by province and municipality size, with all residents invited to participate. From April 27 to May 11, 2020, 61\u00e2\u0080\u0088075 participants (75\u00b71% of all contacted individuals within selected households) answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors, received a point-of-care antibody test, and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay. Prevalences of IgG antibodies were adjusted using sampling weights and post-stratification to allow for differences in non-response rates based on age group, sex, and census-tract income. Using results for both tests, we calculated a seroprevalence range maximising either specificity (positive for both tests) or sensitivity (positive for either test). FINDINGS: Seroprevalence was 5\u00b70% (95% CI 4\u00b77-5\u00b74) by the point-of-care test and 4\u00b76% (4\u00b73-5\u00b70) by immunoassay, with a specificity-sensitivity range of 3\u00b77% (3\u00b73-4\u00b70; both tests positive) to 6\u00b72% (5\u00b78-6\u00b76; either test positive), with no differences by sex and lower seroprevalence in children younger than 10 years (<3\u00b71% by the point-of-care test). There was substantial geographical variability, with higher prevalence around Madrid (>10%) and lower in coastal areas (<3%). Seroprevalence among 195 participants with positive PCR more than 14 days before the study visit ranged from 87\u00b76% (81\u00b71-92\u00b71; both tests positive) to 91\u00b78% (86\u00b73-95\u00b73; either test positive). In 7273 individuals with anosmia or at least three symptoms, seroprevalence ranged from 15\u00b73% (13\u00b78-16\u00b78) to 19\u00b73% (17\u00b77-21\u00b70). Around a third of seropositive participants were asymptomatic, ranging from 21\u00b79% (19\u00b71-24\u00b79) to 35\u00b78% (33\u00b71-38\u00b75). Only 19\u00b75% (16\u00b73-23\u00b72) of symptomatic participants who were seropositive by both the point-of-care test and immunoassay reported a previous PCR test. INTERPRETATION: The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial proportion of people with symptoms compatible with COVID-19 did not have a PCR test and at least a third of infections determined by serology were asymptomatic. These results emphasise the need for maintaining public health measures to avoid a new epidemic wave. FUNDING: Spanish Ministry of Health, Institute of Health Carlos III, and Spanish National Health System.", "doc_id": "d8ddjzon"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Comparison of four new commercial serologic assays for determination of SARS-CoV-2 IgG", "abstract": "BACKGROUND: Facing the ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need for serological assays identifying individuals with past coronavirus disease 2019 (COVID-19). STUDY DESIGN: Our study is the first to compare four new commercially available assays using 75 sera from patients tested positive or negative by SARS-CoV-2 PCR: the anti SARS-CoV-2 ELISA (IgG) (Euroimmun, Germany), the EDI New Coronavirus COVID-19 IgG ELISA, (Epitope diagnostics (EDI), USA), the recomWell SARS-CoV-2 IgG ELISA (Mikrogen, Germany), and the SARS-CoV-2 Virachip IgG (Viramed, Germany). RESULTS: We found a sensitivity of 86.4 %, 100 %, 86.4 %, and 77.3 % and a specificity of 96,2 %, 88,7 %, 100 %, and 100 % for the Euroimmun assay, the EDI assay, the Mikrogen assay, and the Viramed assay, respectively. CONCLUSIONS: Commercially available SARS-CoV-2 IgG assays have a sufficient specificity and sensitivity for identifying individuals with past SARS-CoV-2 infection.", "doc_id": "7e79o2gy"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Serology assays to manage COVID-19", "abstract": "", "doc_id": "31qbazhh"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients", "abstract": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by PCR testing of symptomatic patients for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the spike protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV-specific antibodies in people. Here we use a large panel of human sera (63 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate RBD's performance as an antigen for reliable detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs. We observed a strong correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-CoV-2 neutralizing antibodies in people.", "doc_id": "4cqjqwk9"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Analysis of the diagnostic value of serum specific antibody testing for coronavirus disease 2019", "abstract": "The coronavirus disease 2019 (COVID-19) pandemic has spread to various regions worldwide. As of 27 April 2020, according to real-time statistics released by the World Health Organization, there have been 84,341 confirmed cases and 4,643 deaths in China, with more than 2,979,484 confirmed cases and 206,450 deaths outside China. The detection of antibodies produced during the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become an important laboratory method for the diagnosis of COVID-19. However, at present, little research on these specific antibodies has been conducted. In this study, retrospective analysis was used to explore the dynamic changes of serum IgM and IgG antibody and factors affecting diagnostic efficacy, so as to provide a theoretical basis for clinical diagnosis and treatment. This article is protected by copyright. All rights reserved.", "doc_id": "40txr2du"} {"topic_name": "serological tests for coronavirus", "topic_id": "7", "title": "Comparison of test performance of commercial anti-SARS-CoV-2 immunoassays in serum and plasma samples", "abstract": "BACKGROUND: For epidemiologic, social and economic reasons, assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prevalence and immunity are important to adapt decisions to current demands. Hence, immunoassays for detection of anti-SARS-CoV-2 antibodies are introduced rapidly without requiring FDA emergency use authorization approval. Thus, evaluation of test performance predominantly relies on laboratories. This study aimed to evaluate the test performance of recently launched commercial immunoassays in serum and plasma samples. METHODS: 51 serum samples from 26 patients with confirmed SARS-CoV-2 infection after end of quarantine and 25 control patients were analyzed using anti-SARS-CoV-2 IgG immunoassays from Roche, Euroimmun and Epitope to assess diagnostic sensitivity and specificity. 20 matching pairs of serum and plasma samples were included to analyze comparability between different specimens. RESULTS: Overall, a diagnostic sensitivity of 92.3%, 96.2-100% and 100% with a respective diagnostic specificity of 100%, 100% and 84-86% for the immunoassays from Roche, Euroimmun and Epitope were determined. In total, 84-96 % of samples were correctly classified as negative and 92.3-95.2% as positive. The level of concordance between plasma- and serum-based testing diverged between the assays (Epitope r2=0.97; Euroimmun r2=0.91; Roche r2=0.76). CONCLUSIONS: The immunoassays from Euroimmun and Roche revealed a higher specificity than the Epitope assay without a substantial drop of diagnostic sensitivity. Significant differences between plasma- and serum-based testing highlights the need for determination of appropriate cut-offs per specimen type. Hence, there is an urgent need for test harmonization and establishment of quality standards for an appropriate use of COVID-19 serological tests.", "doc_id": "bis8m5f0"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "COVID-19-New Insights on a Rapidly Changing Epidemic.", "abstract": "", "doc_id": "63aoc5vp"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "COVID-19 Fatality Rate and Performed Swabs in Italy: a Misleading Perception.", "abstract": "BACKGROUND CoronaVirus Disease 2019 (COVID-19) fatality rate in Italy is controversial and is largely affecting discussion on the impact of containment measures that are straining the world's social and economic fabric, such as large-scale use of isolation and quarantine, closing borders, imposing limits on public gatherings, and implementing nationwide lockdowns. OBJECTIVE The scientific community, citizens, politicians and mass media are arguing over data that seem to suggest that Italy has a significantly higher number of COVID-19-related deaths than in the rest of the world. Moreover, Italian citizens have a misleading perception related to the number of actually performed swab tests. Citizens and mass media denounce that the coverage obtained by COVID-19 swab testing in Italy is not in line with other countries all over the world. METHODS In this paper, we try to clarify, with a set of statistical analysis conducted world-wide, both aspects by highlighting the actual numbers and by comparing them with the official data available. RESULTS The analysis clearly shows that the Italian COVID-19 fatality and mortality rate are in line with the official world scenario, and these findings are true also for the number of COVID-19 swabs performed in Italy and in Lombardy Region. CONCLUSIONS Up-to-date analysis of this type may simplify the understanding of the pandemic evolution. CLINICALTRIAL", "doc_id": "8esaz4or"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Covid-19: \"Illogical\" lack of testing is causing healthy staff to self-isolate, BMA chief warns.", "abstract": "", "doc_id": "5tpbb765"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Underestimation of COVID-19 cases in Japan: an analysis of RT-PCR testing for COVID-19 among 47 prefectures in Japan.", "abstract": "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.", "doc_id": "7gmacx72"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Transmission in Latent Period Causes A Large Number of Infected People in the United States", "abstract": "By April 29, 2020, the cumulative number of confirmed cases in the United States has exceeded one million, becoming the country with the most serious pandemic in the world. It is urgent to analyze the real situation and follow-up trend of the epidemic in the United States. The proposed model divides the time period into two different phases, before and after March 21, 2020. The results show that the basic reproduction number in the early period of propagation in the United States is estimated to be 4.06 (95% CI: 1.86-6.73) based on the confirmed cases data ranging from January 21, 2020 to March 21, 2020. The normalized contributions to R_0 for three different categories of communicators were estimated, including the numbers of the latent population (in incubation period) L, the documented infectious population Id, and the undocumented infectious population Iu. The results show that L contributes 16.17% (95% CI: 12.86% - 21.60%) to R_0, Id contributes 55.13% (95% CI: 43.15% - 63.97%), and Iu contributes 28.70% (95% CI: 19.29% - 40.07%) to R0. The metapopulation network was used to simulate the true spread of COVID-19 in the United States, and the Bayesian inference was applied to estimate the key parameters including the rate of the number of the susceptibles and the infected beta, the infection ratio between undocumented and documented transmission 1, the infection ratio between latent and documented transmission 2, the proportion of confirmed cases in the infectious population x, and the duration of latent period (incubation period) TL . From the analysis of phase one, 1 was estimated to be 0.40 (95% CI: 0.17 - 0.54), 2 was estimated to be 0.06 (95% CI: 0.02 - 0.11), x was estimated to be 0.70 (95% CI: 0.55 - 0.78), T_L was estimated to be 8.41 (95% CI: 6.64 - 9.42). As of April 13, 2020, it was estimated that only 45% (95% CI: 35% - 73%) of symptom onset cases in the United States have been documnented. The infectivity of undocumented infectious population was 0.59 (95% CI: 0.21 - 0.70) of that of the documented infectious population, while that of the latent population was 0.19 (95% CI: 0.11 - 0.27) of that of the documented infectious population. The incubation period of COVID-19 was estimated to be 10.69 days (95% CI: 10.02 - 11.74). We estimated that if the current control interventions are continued, the pandemic situation in the United States is likely to keep climbing up, and the cumulative number of confirmed cases is expected to reach more than 1.7 million in July and continue to grow. We also performed component analysis and sensitivity analysis, researching the compositions of the people with COVID-19, and considering that there is only a random time delay between the number of patients in the incubation period and the actual number of patients.", "doc_id": "nkrwyq89"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "COVID-19: Recovering estimates of the infected fatality rate during an ongoing pandemic through partial data", "abstract": "In an ongoing epidemic, the case fatality rate is not a reliable estimate of a disease's severity. This is particularly so when a large share of asymptomatic or pauci-symptomatic patients escape testing, or when overwhelmed healthcare systems are forced to limit testing further to severe cases only. By leveraging data on COVID-19, we propose a novel way to estimate a disease's infected fatality rate, the true lethality of the disease, in the presence of sparse and partial information. We show that this is feasible when the disease has turned into a pandemic and data comes from a large number of countries, or regions within countries, as long as testing strategies vary sufficiently. For Italy, our method estimates an IFR of 1.1% (95% CI: 0.2% - 2.1%), which is strongly in line with other methods. At the global level, our method estimates an IFR of 1.6% (95% CI: 1.1% - 2.1%). This method also allows us to show that the IFR varies according to each country's age structure and healthcare capacity.", "doc_id": "a1c7bfr4"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "COVID-19 Spread in India: Dynamics, Modeling, and Future Projections", "abstract": "COVID-19 is an extremely infectious disease with a relatively large virus incubation period in the affected people who may be asymptomatic. Therefore, to reduce the transmission of this pathogen, several countries have taken many intervention measures. In this paper, we show that the impact of these measures in India is different from several other countries. It is shown that an early lockdown in late March 2020 changed the initial exponential growth curve of COVID-19 to a linear one, but a surge in the number of cases from late April 2020 brought India back to a quadratic trajectory. A regional analysis shows the disparate impact of the intervention in different states. It is further shown that the number of reported infections correlates with the number of tests, and therefore regions with limited diagnostics resources may not have a realistic estimate of the virus spread. This insufficiency of diagnostic test data is also reflected in an increasing positivity rate for India nearly 2.5 months after the lockdown, inconsistent with the trends observed for other geographical regions. Nonetheless, future projections are made using different epidemiological models based on the available data, and a comparative study is presented. In the absence of a reliable estimate of the true number of infections, these projections will have a limited accuracy: with that limitation, the most optimistic prediction suggests a continuing virus transmission through September 2020.", "doc_id": "qk5z84xd"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Reconciling early-outbreak estimates of the basic reproductive number and its uncertainty: framework and applications to the novel coronavirus (SARS-CoV-2) outbreak", "abstract": "A novel coronavirus (SARS-CoV-2) has recently emerged as a global threat. As the epidemic progresses, many disease modelers have focused on estimating the basic reproductive number Ro -- the average number of secondary cases caused by a primary case in an otherwise susceptible population. The modeling approaches and resulting estimates of Ro vary widely, despite relying on similar data sources. Here, we present a novel statistical framework for comparing and combining different estimates of Ro across a wide range of models by decomposing the basic reproductive number into three key quantities: the exponential growth rate $r$, the mean generation interval $\\bar G$, and the generation-interval dispersion $\\kappa$. We then apply our framework to early estimates of Ro for the SARS-CoV-2 outbreak. We show that many early Ro estimates are overly confident. Our results emphasize the importance of propagating uncertainties in all components of Ro, including the shape of the generation-interval distribution, in efforts to estimate Ro at the outset of an epidemic.", "doc_id": "p5aj5k2g"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Maybe not an overreaction", "abstract": "", "doc_id": "3imi635m"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Multi-parametric disease dynamics study and analysis of the COVID-19 epidemic and implementation of population-wide intrusions: The Indian perspective", "abstract": "The outbreak of COVID-19 had spread at a deadly rate since its onset at Wuhan, China and is now spread across 216 countries and has affected more than 6 million people all over the world. The global response throughout the world has been primarily the implementation of lockdown measures, testing and contact tracing to minimise the spread of the disease. The aim of the present study was to predict the COVID-19 prevalence and disease progression rate in Indian scenario in order to provide an analysis that can shed light on comprehending the trends of the outbreak and outline an impression of the epidemiological stage for each state of a diverse country like India. In addition, the forecast of COVID-19 incidence trends of these states can help take safety measures and policy design for this epidemic in the days to come. In order to achieve the same, we have utilized an approach where we test modelling choices of the spatially unambiguous kind, proposed by the wave of infections spreading from the initial slow progression to a higher curve. We have estimated the parameters of an individual state using factors like population density and mobility. The findings can also be used to strategize the testing and quarantine processes to manipulate the spread of the disease in the future. This is especially important for a country like India that has several limitations about healthcare infrastructure, diversity in socioeconomic status, high population density, housing conditions, health care coverage that can be important determinants for the overall impact of the pandemic. The results of our 5-phase model depict a projection of the state wise infections/disease over time. The model can generate live graphs as per the change in the data values as the values are automatically being fetched from the crowd-sourced database.", "doc_id": "g8pu6x4c"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Covid-19 prevalence estimation by random sampling in the wider population - Optimal sample pooling under varying assumptions about true prevalence", "abstract": "The number of confirmed Covid-19 cases in a population is used as a coarse measurement for the burden of disease. However, this number depends heavily on the sampling intensity and the various test criteria used in different jurisdictions. A wide range of sources indicate that a large fraction of cases go undetected. Estimates of the true prevalence of Covid-19 can be made by random sampling in the wider population. Here we use simulations to explore confidence intervals of prevalence estimates under different sampling intensities and degrees of sample pooling.", "doc_id": "zbax2vk7"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Reconstructing the global dynamics of under-ascertained COVID-19 cases and infections", "abstract": "Background: Asymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures. Methods: Using reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever >= to 37.5C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the case fatality ratio (CFR) as an assumed baseline. We then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment. Results: We estimate that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.38% (Bangladesh) to 99.6% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6th July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 17.8 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. Despite low case detection in some countries, our results that adjust for this still suggest that all countries have had only a small fraction of their populations infected as of July 2020. Conclusions: We found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each country's population infected with SARS-CoV-2 worldwide is generally low.", "doc_id": "no0xh7t0"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "A novel comprehensive metric to assess COVID-19 testing outcomes: Effects of geography, government, and policy response", "abstract": "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.", "doc_id": "6ed3two6"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Early trends for SARS-CoV-2 infection in central and north Texas and impact on other circulating respiratory viruses", "abstract": "Introduction: Rapid diagnosis and isolation are key to containing the rapid spread of a pandemic agent like SARS-CoV-2, which has spread globally since its initial outbreak in Wuhan province in China. SARS-CoV-2 is novel to most parts of the world including USA and the effect on normally prevalent viruses is just becoming apparent. We present our initial data on the prevalence of respiratory viruses in the month of March, 2020. Methods: This is a retrospective cohort study post launching of SARS-CoV-2 testing at BSWH, Temple TX. Testing for SARS-CoV-2 was performed by real-time RT-PCR assay and results were shared with State public health officials for immediate interventions. Results: More than 3500 tests were performed during the first two weeks of testing for SARS-CoV-2 and identified 168 (4.7%) positive patients. Sixty-two (3.2%) of the 1,912 ambulatory patients and 106 (6.3%) of the 1,659 ED/inpatients were tested positive. Higher rate of infection (6.9%) were noted in the patients belonging to age group 25-34 years and least number of positive cases were noted in <25 years old (2%) group. The TX State county specific patient demographic information was shared with respective public health departments for epidemiological interventions. Incidentally, this study showed that there was a sudden decrease in the occurrence of other infections due to seasonal viruses, perhaps due to increased epidemiological awareness, about SARS-CoV-2, among general public. Authors would also like to share a small study on SARS-CoV-2 serological assay for the detection of IgG antibodies. Conclusions: This study was intended to provide an initial experience of dealing with a pandemic and the role of laboratories in crisis management. Epidemiological interventions depend on timely availability of accurate diagnostic tests and throughput capacity of such systems during large outbreaks like SARS-CoV-2.", "doc_id": "5fz8ef4f"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Bayesian nowcasting with adjustment for delayed and incomplete reporting to estimate COVID-19 infections in the United States", "abstract": "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.", "doc_id": "bge7btzz"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Is tracking and modeling Covid-19 infection dynamics for Bangladesh using daily data feasible?", "abstract": "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.", "doc_id": "ettclw13"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "COVID-19: The unreasonable effectiveness of simple models", "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.", "doc_id": "nda1toup"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Time Course of COVID-19 epidemic in Algeria: Retrospective estimate of the actual burden", "abstract": "Since December 2019, the five continents have been incrementally invaded by SARS-CoV-2. Africa is the last and least affected to date. However, Algeria is among the first countries affected since February 25, 2020. In order to benefit from its experience in the least affected countries, this study aims to describe the current situation of the epidemic and then retrospectively estimate its real burden. As a first part of the study, we described the indicators of the epidemic as; the cumulative and daily reported cases and deaths, and we computed the R0 evolution. Secondly, we used the New York City cases-fatality rate standardized by Algerian age structure, to retrospectively estimate the actual burden. We found that reported cases are in a clear diminution, but, the epidemic epicentre is moving from Blida to other cities. We noted a clear peak in daily cases-fatality from March 30, to April 17, 2020, Fig. 3, due to underestimating the actual infections of the first 25 days. Since May 8, 2020, the daily R0 is around one, Fig. 4. Moreover, we noticed 31% reduction of its mean value from 1,41 to 0,97 between the last two months. The Algerian Age-Standardized Infection Fatality Rate we found is 0,88%. Based on that, we demonstrated that only 1,5% of actual infections were detected and reported before March 30, and 20% after March 31, Fig. 5. Therefore, the actual infections burden is currently five times higher than reported. At the end, we found that at least 0,2 % of the population have been infected until May 27. Consequently, the acquired herd immunity to date is therefore not sufficient to avoid a second wave. We believe that, the under estimation of the actual burden of the epidemic is probably due to the lack of testing capacities, however, all the indicators show that the situation is currently controlled. This requires more vigilance for the next weeks during the gradual easing of the preventive measures.", "doc_id": "pymowl6n"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Testing for tracing or testing just for treating? A comparative analysis between strategies to face COVID-19 pandemic.", "abstract": "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.", "doc_id": "rjzther1"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Estimation of SARS-CoV-2 Infection Prevalence in Santa Clara County", "abstract": "To reliably estimate the demand on regional health systems and perform public health planning, it is necessary to have a good estimate of the prevalence of infection with SARS-CoV-2 (the virus that causes COVID-19) in the population. In the absence of wide-spread testing, we provide one approach to infer prevalence based on the assumption that the fraction of true infections needing hospitalization is fixed and that all hospitalized cases of COVID-19 in Santa Clara are identified. Our goal is to estimate the prevalence of SARS-CoV-2 infections, i.e. the true number of people currently infected with the virus, divided by the total population size. Our analysis suggests that as of March 17, 2020, there are 6,500 infections (0.34% of the population) of SARS-CoV-2 in Santa Clara County. Based on adjusting the parameters of our model to be optimistic (respectively pessimistic), the number of infections would be 1,400 (resp. 26,000), corresponding to a prevalence of 0.08% (resp. 1.36%). If the shelter-in-place led to R0 < 1, we would expect the number of infections to remain about constant for the next few weeks. However, even if this were true, we expect to continue to see an increase in hospitalized cases of COVID-19 in the short term due to the fact that infection of SARS-CoV-2 on March 17th can lead to hospitalizations up to 14 days later.", "doc_id": "6vt60348"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "COVID-19 Antibody Seroprevalence in Santa Clara County, California", "abstract": "Background Addressing COVID-19 is a pressing health and social concern. To date, many epidemic projections and policies addressing COVID-19 have been designed without seroprevalence data to inform epidemic parameters. We measured the seroprevalence of antibodies to SARS-CoV-2 in Santa Clara County. Methods On 4/3-4/4, 2020, we tested county residents for antibodies to SARS-CoV-2 using a lateral flow immunoassay. Participants were recruited using Facebook ads targeting a representative sample of the county by demographic and geographic characteristics. We report the prevalence of antibodies to SARS-CoV-2 in a sample of 3,330 people, adjusting for zip code, sex, and race/ethnicity. We also adjust for test performance characteristics using 3 different estimates: (i) the test manufacturer's data, (ii) a sample of 37 positive and 30 negative controls tested at Stanford, and (iii) a combination of both. Results The unadjusted prevalence of antibodies to SARS-CoV-2 in Santa Clara County was 1.5% (exact binomial 95CI 1.11-1.97%), and the population-weighted prevalence was 2.81% (95CI 2.24-3.37%). Under the three scenarios for test performance characteristics, the population prevalence of COVID-19 in Santa Clara ranged from 2.49% (95CI 1.80-3.17%) to 4.16% (2.58-5.70%). These prevalence estimates represent a range between 48,000 and 81,000 people infected in Santa Clara County by early April, 50-85-fold more than the number of confirmed cases. Conclusions The population prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that the infection is much more widespread than indicated by the number of confirmed cases. Population prevalence estimates can now be used to calibrate epidemic and mortality projections.", "doc_id": "zpv5f8pr"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "New blood tests for antibodies could show true scale of coronavirus pandemic", "abstract": "How many COVID-19 cases have gone undetected? And are those who had mild cases of the disease\u2014perhaps so mild they dismissed it as a cold or allergies\u2014immune to new infections? If so, they could slow the spread of the burgeoning pandemic Labs and companies around the world have raced to develop antibody tests, and a few have been used in small studies and received commercial approval, including several from China But so far, large-scale data from such tests\u2014for example showing what fraction of people in the hard-hit city of Wuhan, China, might now be immune\u2014is still lacking or at least not public Scientists hope that will soon change as more tests become available", "doc_id": "ecxji8x8"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Substantial underestimation of SARS-CoV-2 infection in the United States due to incomplete testing and imperfect test accuracy", "abstract": "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.", "doc_id": "ehcikhnw"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "On the true numbers of COVID-19 infections: behind the available data", "abstract": "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.", "doc_id": "o66rchhw"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Estimation of Undetected Covid-19 Infections in India", "abstract": "Background and Objectives: While the number of detected COVID-19 infections are widely available, an understanding of the extent of undetected COVID- 19 cases is urgently needed for an effective tackling of the pandemic and as a guide to lifting the lockdown. The aim of this work is to estimate and predict the true number of COVID-19 (detected and undetected) infections in India for short to medium forecast horizons. In particular, using publicly available COVID-19 infection data upto 16th April 2020, we predict the true number of infections in India during and upto the end of the formal lockdown period (21st April 2020). Methods: The high death rate observed in most COVID-19 hit countries is suspected to be a function of the undetected infections existing in the population. An estimate of the age weighted infection fatality rate (IFR) of the disease of 0.41%, specifically calculated by taking into account the age structure of Indian population, is already available in the literature. In addition, the recorded case fatality rate (CFR= 0.70%) of Kerala, the only state in India to report single digit new infections over the second week of April, is used as a second estimate of the IFR. These estimates are used to formulate a relationship between deaths recorded and the true number of infections. The estimated undetected and detected cases time series based on these two IFR estimates are then used to fit a discrete time multivariate infection model to predict the total infections at the end of the formal lockdown period. Results: In two consecutive fortnights during the lockdown, it was noted that the rise in detected infections has decreased by 2.7 times. For an IFR of 0.41%, the rise in undetected infections decreased by 3.2 times and the predicted number of total infections in India is 3.14 lakhs. While for an IFR of 0.70%, the rise in undetected cases decreased by 3.3 times and the total number of infections predicted on 21st April is 1.75 lakhs. Interpretation and Conclusions: The behaviour of the undetected cases over time effectively illustrates the effects of lockdown and increased testing. From our estimates, it is found that the lockdown has brought down the undetected to detected cases ratio, and has consequently dampened the increase in the number of total cases. However, even though the rate of rise in total infections has fallen, the lifting of the lockdown should be done keeping in mind that 1.75 to 3 lakhs undetected cases will already exist in the population on 21st April.", "doc_id": "t4d2ibng"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "The usefulness of SARS-CoV-2 test positive proportion as a surveillance tool", "abstract": "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.", "doc_id": "ole70vk0"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Estimating the global spread of COVID-19", "abstract": "Limited and inconsistent testing and differences in age distribution, health care resources, social distancing, and policies have caused large variations in the extent and dynamics of the COVID-19 pandemic across nations, complicating the estimation of prevalence, the infection fatality rate (IFR), and other factors important to care providers and policymakers. Using data for all 84 countries with reliable testing data (spanning 4.75 billion people) we develop a dynamic epidemiological model integrating data on cases, deaths, excess mortality and other factors to estimate how asymptomatic transmission, disease acuity, hospitalization, and behavioral and policy responses to risk condition prevalence and IFR across nations and over time. For these nations we estimate IFR averages 0.68% (0.64%-0.7%). Cases and deaths through June 18, 2020 are estimated to be 11.8 and 1.48 times official reports, respectively, at 88.5 (85-95.3) million and 600 (586-622) thousand. Prevalence and IFR vary substantially, e.g., Ecuador (18%; 0.61%), Chile (15.5%; 0.57%), Mexico (8.8%; 0.69%), Iran (7.9%; 0.44%), USA (5.3%; 0.99%), UK (5.2%; 1.59%), Iceland (1.65%, 0.56%), New Zealand (0.1%, 0.64%), but all nations remain well below the level needed for herd immunity. By alerting the public earlier and reducing contacts, extensive testing when the pandemic was declared could have averted 35.3 (32.7-42.7) million cases and 197 (171-232) thousand deaths. However, future outcomes are less dependent on testing and more contingent on the willingness of communities and governments to reduce transmission. Absent breakthroughs in treatment or vaccination and with mildly improved responses we project 249 (186-586) million cases and 1.75 (1.40-3.67) million deaths in the 84 countries by Spring 2021.", "doc_id": "837qlk8y"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Estimating the true (population) infection rate for COVID-19: A Backcasting Approach with Monte Carlo Methods", "abstract": "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.", "doc_id": "vq7k0gma"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Application of pooled testing in screening and estimating the prevalence of Covid-19", "abstract": "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.", "doc_id": "dbzpcy5v"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Coronavirus cases have dropped sharply in South Korea. What\u2019s the secret to its success?", "abstract": "Europe is now the epicenter of the COVID-19 pandemic Case counts and deaths are soaring in Italy, Spain, France, and Germany, and many countries have imposed lockdowns and closed borders Meanwhile, the United States, hampered by a fiasco with delayed and faulty test kits, is just guessing at its COVID-19 burden, though experts believe it is on the same trajectory as countries in Europe", "doc_id": "722hm18k"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "The Mathematics of Testing with Application to Prevalence of COVID-19", "abstract": "We formulate three basic assumptions that should ideally guide any well-designed COVID-19 prevalence study. We provide, on the basis of these assumptions alone, a full derivation of mathematical formulas required for statistical analysis of testing data. In particular, we express the disease prevalence in a population through those for its homogeneous subpopulations. Although some of these formulas are routinely employed in prevalence studies, the study design often contravenes the assumptions upon which these formulas vitally depend. We also designed a natural prevalence estimator from the testing data and studied some of its properties. The results are equally valid for diseases other than COVID-19 as well as in non-epidemiological settings.", "doc_id": "39jcr69r"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "SCALE19: A scalable and cost-efficient method for testing Covid-19 based on hierarchical group testing", "abstract": "Containment of Covid-19 requires an extensive testing of the affected population. Some propose global testing to effectively contain Covid-19. Current tests for Covid-19 are administered individually. These tests for Covid-19 are expensive and are limited due to the lack of resources and time. We propose a simple and efficient group testing method for Covid-19. We propose a group testing method where test subjects are grouped and tested. Depending on the result of the group test, subsequent sub groups are formed and tested recursively based on a quartery search algorithm. We designed and built an evaluation model that simulates test subject population, infected test subjects according to available Covid-19 statistics, and the group testing processes in SCALE19. We considered several population models including USA and the world. Our results show that we can significantly reduce the required number of tests up to 89% without sacrificing the accuracy of the individual test of the entire population. For USA, up to 280 million tests can be reduced from the total US population of 331 million and it would be equivalent saving of $28 billion assuming a cost of $100 per test. For the world, 6.96 billion tests can be reduced from the total population of 7.8 billion and it would be equivalent to saving $696 billion. We propose SCALE19 can significantly reduce the total required number of tests compared to individual tests of the entire population. We believe SCALE19 is efficient and simple to be deployed in containment of Covid-19.", "doc_id": "1bhv9snq"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Extrapolation of Infection Data for the CoVid-19 Virus and Estimate of the Pandemic Time Scale.", "abstract": "Predictions about the further development of the Corona pandemic are widely diverging. Here, a simple yet powerful algorithm is introduced for extrapolating infection rate and number of total infections from available data. The calculation predicts that under present conditions the infection rate in Germany will culminate in a few weeks and decrease to low values by mid-June 2020. Total number of infections will reach several 100,000 though.", "doc_id": "kcx8cnco"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Bayesian modeling of COVID-19 cases with a correction to account for under-reported cases", "abstract": "The novel of COVID-19 disease started in late 2019 making the worldwide governments came across a high number of critical and death cases, beyond constant fear of the collapse in their health systems. Since the beginning of the pandemic, researchers and authorities are mainly concerned with carrying out quantitative studies (modeling and predictions) overcoming the scarcity of tests that lead us to under- reporting cases. To address these issues, we introduce a Bayesian approach to the SIR model with correction for under-reporting in the analysis of COVID-19 cases in Brazil. The proposed model was enforced to obtain estimates of important quantities such as the reproductive rate and the average infection period, along with the more likely date when the pandemic peak may occur. Several under-reporting scenarios were considered in the simulation study, showing how impacting is the lack of information in the modeling.", "doc_id": "orh8fd1c"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Is reporting many cases of COVID-19 in Iran due to strength or weakness of iran\u2019s health system?", "abstract": "", "doc_id": "ezfm64j9"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Influenza-Negative Influenza-Like Illness (fnILI) Z-Score as a Proxy for Incidence and Mortality of COVID-19", "abstract": "Though ideal for determining the burden of disease, SARS-CoV2 test shortages preclude its implementation as a robust surveillance system in the US. We correlated the use of the derivative influenza-negative influenza-like illness (fnILI) z-score from the CDC as a proxy for incident cases and disease-specific deaths. For every unit increase of fnILI z-score, the number of cases increased by 70.2 (95%CI[5.1,135.3]) and number of deaths increased by 2.1 (95%CI[1.0,3.2]). FnILI data may serve as an accurate outcome measurement to track the spread of the and allow for informed and timely decision-making on public health interventions.", "doc_id": "6g7mijbz"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "\u2018These are answers we need.\u2019 WHO plans global study to discover true extent of coronavirus infections", "abstract": "In an effort to understand how many people have been infected with the new coronavirus, the World Health Organization (WHO) is planning a coordinated study to test blood samples for the presence of antibodies to the virus Called Solidarity II, the program, which will involve more than half a dozen countries around the globe, will launch in the coming days, says Maria Van Kerkhove, who is helping coordinate WHO\u2019s COVID-19 response Knowing the true number of cases\u2014including mild ones\u2014will help pin down the prevalence and mortality rate of COVID-19 in different age groups It will also help policymakers decide how long shutdowns and quarantines should last \u201cThese are answers we need, and we need the right answers to drive policy,\u201d WHO\u2019s executive director for health emergencies, Michael Ryan, told a press briefing on 27 March", "doc_id": "0klg8yvs"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Using viral genomics to estimate undetected infections and extent of superspreading events for COVID-19", "abstract": "Asymptomatic infections and limited testing capacity have led to under-reporting of SARS-CoV-2 cases. This has hampered the ability to ascertain true infection numbers, evaluate the effectiveness of surveillance strategies, determine transmission dynamics, and estimate reproductive numbers. Leveraging both viral genomic and time series case data offers methods to estimate these parameters. Using a Bayesian inference framework to fit a branching process model to viral phylogeny and time series case data, we estimated time-varying reproductive numbers and their variance, the total numbers of infected individuals, the probability of case detection over time, and the estimated time to detection of an outbreak for 12 locations in Europe, China, and the United States. The median percentage of undetected infections ranged from 13% in New York to 92% in Shanghai, China, with the length of local transmission prior to two cases being detected ranging from 11 days (95% CI: 4-21) in California to 37 days (9-100) in Minnesota. The probability of detection was as low as 1% at the start of local epidemics, increasing as the number of reported cases increased exponentially. The precision of estimates increased with the number of full-length viral genomes in a location. The viral phylogeny was informative of the variance in the reproductive number with the 32% most infectious individuals contributing 80% of total transmission events. This is the first study that incorporates both the viral genomes and time series case data in the estimation of undetected COVID-19 infections. Our findings suggest the presence of undetected infections broadly and that superspreading events are contributing less to observed dynamics than during the SARS epidemic in 2003. This genomics-informed modeling approach could estimate in near real-time critical surveillance metrics to inform ongoing COVID-19 response efforts.", "doc_id": "1jf2zz5q"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "The true case fatality of COVID19: An analytical solution", "abstract": "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.", "doc_id": "2zf9rmbf"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Estimate of COVID-19 case prevalence in India based on surveillance data of patients with severe acute respiratory illness", "abstract": "In absence of extensive testing for SARS-CoV-2, true prevalence of COVID-19 cases in India remain unknown. In this study, a conservative estimate of prevalence of COVID-19 is calculated based on the age wise COVID-19 positivity rate among patients with severe respiratory illness as reported by Indian Council of Medical Research. Calculations in the study estimates a cumulative number of 17151 COVID-19 positive cases by the end of April 2, 2020.", "doc_id": "0gikppdh"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Disentangling Increased Testing From Covid-19 Epidemic Spread", "abstract": "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.", "doc_id": "l7jme343"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Using early data to estimate the actual infection fatality ratio from COVID-19 in France", "abstract": "Background. The number of screening tests carried out in France and the methodology used to target the patients tested do not allow for a direct computation of the actual number of cases and the infection fatality ratio (IFR). The main objective was to estimate the actual number of people infected with COVID-19 during the observation window in France and to deduce the IFR. Methods. We develop a 'mechanistic-statistical' approach coupling a SIR epidemiological model describing the unobserved epidemiological dynamics, a probabilistic model describing the data acquisition process and a statistical inference method. Results. The actual number of infected cases in France is probably higher than the observations: we find here a factor x 8 (95%-CI: 5-12) which leads to an IFR in France of 0.5% (95%-CI: 0.3-0.8) based on hospital death counting data. Adjusting for the number of deaths in nursing homes, we obtain an IFR of 0.8% (95%-CI: 0.45-1.25). Conclusions. This IFR is consistent with previous findings in China (0.66%) and in the UK (0.9%) and lower than the value previously computed on the Diamond Princess cruse ship data (1.3%).", "doc_id": "dqg8fkca"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Basic prediction methodology for covid-19: estimation and sensitivity considerations", "abstract": "The purpose of the present paper is to present simple estimation and prediction methods for basic quantities in an emerging epidemic like the ongoing covid-10 pandemic. The simple methods have the advantage that relations between basic quantities become more transparent, thus shedding light to which quantities have biggest impact on predictions, with the additional conclusion that uncertainties in these quantities carry over to high uncertainty also in predictions. A simple non-parametric prediction method for future cumulative case fatalities, as well as future cumulative incidence of infections (assuming a given infection fatality risk f), is presented. The method uses cumulative reported case fatalities up to present time as input data. It is also described how the introduction of preventive measures of a given magnitude \u03c1 will affect the two incidence predictions, using basic theory of epidemic models. This methodology is then reversed, thus enabling estimation of the preventive magnitude \u03c1, and of the resulting effective reproduction number RE. However, the effects of preventive measures only start affecting case fatalities some 3-4 weeks later, so estimates are only available after this time has elapsed. The methodology is applicable in the early stage of an outbreak, before, say, 10% of the community have been infected. Beside giving simple estimation and prediction tools for an ongoing epidemic, another important conclusion lies in the observation that the two quantities f (infection fatality risk) and \u03c1 (the magnitude of preventive measures) have very big impact on predictions. Further, both of these quantities currently have very high uncertainty: current estimates of f lie in the range 0.2% up to 2% ([9], [7]), and the overall effect of several combined preventive measures is clearly very uncertain. The two main findings from the paper are hence that, a) any prediction containing f, and/or some preventive measures, contain a large amount of uncertainty (which is usually not acknowledged well enough), and b) obtaining more accurate estimates of in particular f, should be highly prioritized. Seroprevalence testing of random samples in a community where the epidemic has ended are urgently needed.", "doc_id": "hsgzkpg4"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Testing for COVID-19: a few points to remember.", "abstract": "Diagnostic approaches to COVID-19 include clinical history, PCR tests for the presence of SARS-CoV-2 virus and detection of antibodies. By combining these three approaches, the seroprevalence of anti-SARS-CoV-2 antibodies can be examined in healthcare teams. The aim of the study was to examine the seroprevalence of anti-SARS-CoV-2 antibodies in a population of healthcare professionals 6 - 8 weeks after the first COVID-19 case was detected in the Czech Republic. A total of 269 subjects were enrolled in the study (187 women, 82 men) with a median age of 45.9 years (21 - 71 years). We used a questionnaire to ascertain travel history and clinical signs of any respiratory tract infection. Blood samples were collected, and IgG levels were analysed in all samples. The level of IgA antibodies was analysed in those positive for IgG. PCR testing was performed in cases testing positive for presence of antibodies. The enzyme-linked immunosorbent assay (ELISA) test system for SARS-CoV-2 from Euroimmun (Germany) was used to analyse immunoglobulin levels. 17 % of the tested cohort reported symptoms compatible with COVID-19 and 35.8 % reported history of international travel. There were 5 subjects positive IgG cases (of 269; 1.85 %), and one IgA positive and IgG borderline positive subject (0.37 %). There was only one PCR positive subject. Anti SARS-CoV-2 antibodies were thus detected in 2.22% of participating health professionals. This article shows the pitfalls of the testing methods and highlights the necessity of using a correct testing algorithm, considering the character of the tested population and the expected low prevalence.", "doc_id": "6gar1zyl"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Counting Coronavirus Disease 2019 (COVID-19) Cases: Case Definitions, Screened Populations and Testing Techniques Matter.", "abstract": "While counting cases of disease appears straightforward, there are issues to consider when enumerating disease counts during an epidemic. For example, for Coronavirus Disease-2019 (COVID-19), how is a case defined? Hubei province in China changed its case definition twice in a fortnight-from laboratory-confirmed cases to clinically-confirmed cases without laboratory tests, and back to laboratory-confirmed cases. This caused confusion in the reported number of cases. If a confirmed case requires laboratory testing, what is the population who are laboratory-tested? Due to limited laboratory testing capacity in the early phase of an emerging epidemic, only \"suspected cases\" are laboratory-tested in most countries. This will result in underdiagnosis of confirmed cases and also raises the question: how is a \"suspect case\" defined? With the passage of time and increased capability to perform laboratory tests, more people can be screened and the number of confirmed cases will increase. What are the technical considerations of laboratory testing? This includes specimen collection (variable collection methods), samples collected (upper or lower respiratory tract biospecimens), time of collection in relation to course of disease, different laboratory test methods and kits (not all of which may be standardised or approved by authorities such as the Food and Drug Administration). Are approved laboratory facilities and trained manpower available, and how are test results interpreted and false-negatives excluded? These issues will affect the accuracy of disease counts, which in turn will have implications on how we mount an appropriate response to the outbreak.", "doc_id": "63ihwrpe"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Are official confirmed cases and fatalities counts good enough to study the COVID-19 pandemic dynamics? A critical assessment through the case of Italy", "abstract": "As the COVID-19 outbreak is developing the two most frequently reported statistics seem to be the raw confirmed case and case fatalities counts. Focusing on Italy, one of the hardest hit countries, we look at how these two values could be put in perspective to reflect the dynamics of the virus spread. In particular, we find that merely considering the confirmed case counts would be very misleading. The number of daily tests grows, while the daily fraction of confirmed cases to total tests has a change point. It (depending on region) generally increases with strong fluctuations till (around, depending on region) 15th-22nd March and then decreases linearly after. Combined with the increasing trend of daily performed tests, the raw confirmed case counts are not representative of the situation and are confounded with the sampling effort. This we observe when regressing on time the logged fraction of positive tests and for comparison the logged raw confirmed count. Hence, calibrating model parameters for this virus's dynamics should not be done based only on confirmed case counts (without rescaling by the number of tests), but take also fatalities and hospitalization count under consideration as variables not prone to be distorted by testing efforts. Furthermore, reporting statistics on the national level does not say much about the dynamics of the disease, which are taking place at the regional level. These findings are based on the official data of total death counts up to 15th April 2020 released by ISTAT and up to 10th May 2020 for the number of cases. In this work we do not fit models but we rather investigate whether this task is possible at all. This work also informs about a new tool to collect and harmonize official statistics coming from different sources in the form of a package for the R statistical environment and presents the COVID-19 Data Hub.", "doc_id": "58b7m1b8"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Estimating the COVID-19 infection rate: Anatomy of an inference problem", "abstract": "As a consequence of missing data on tests for infection and imperfect accuracy of tests, reported rates of cumulative population infection by the SARS CoV-2 virus are lower than actual rates of infection. Hence, reported rates of severe illness conditional on infection are higher than actual rates. Understanding the time path of the COVID-19 pandemic has been hampered by the absence of bounds on infection rates that are credible and informative. This paper explains the logical problem of bounding these rates and reports illustrative findings, using data from Illinois, New York, and Italy. We combine the data with assumptions on the infection rate in the untested population and on the accuracy of the tests that appear credible in the current context. We find that the infection rate might be substantially higher than reported. We also find that the infection fatality rate in Illinois, New York, and Italy is substantially lower than reported.", "doc_id": "8wg27hcu"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Test, test, test for COVID-19 antibodies: the importance of sensitivity, specificity and predictive powers", "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests of varying specificity and sensitivity are now available. For informing individuals whether they have had coronavirus disease 2019 (COVID-19), they need to be very accurate. For measuring population prevalence of past infection, the numbers of false positives and negatives need to be roughly equal. With a series of worked examples for a notional population of 100,000 people, we show that even test systems with a high specificity can yield a large number of false positive results, especially where the population prevalence is low. For example, at a true population prevalence of 5%, using a test with 99% sensitivity and specificity, 16% of positive results will be false and thus 950 people will be incorrectly informed they have had the infection. Further confirmatory testing may be needed. Giving false reassurance on which personal or societal decisions might be based could be harmful for individuals, undermine public confidence and foster further outbreaks.", "doc_id": "hzi3kvw5"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "Covid-19 pandemic by the \"real-time\" monitoring: the Tunisian case and lessons for global epidemics in the context of 3PM strategies", "abstract": "Covid-19 is neither the first nor the last viral epidemic which societies around the world are, were and will be affected by. Which lessons should be taken from the current pandemic situation? The Covid-19 disease is still not well characterised, and many research teams all over the world are working on prediction of the epidemic scenario, protective measures to populations and sub-populations, therapeutic and vaccination issues, amongst others. Contextually, countries with currently low numbers of Covid-19-infected individuals such as Tunisia are intended to take lessons from those countries which already reached the exponential phase of the infection distribution as well as from those which have the exponential phase behind them and record a minor number of new cases such as China. To this end, in Tunisia, the pandemic wave has started with a significant delay compared with Europe, the main economic partner of the country. In this paper, we do analyse the current pandemic situation in this country by studying the infection evolution and considering potential protective strategies to prevent a pandemic scenario. The model is predictive based on a large number of undetected Covid-19 cases that is particularly true for some country regions such as Sfax. Infection distribution and mortality rate analysis demonstrate a highly heterogeneous picture over the country. Qualitative and quantitative comparative analysis leads to a conclusion that the reliable \"real-time\" monitoring based on the randomised laboratory tests is the optimal predictive strategy to create the most effective evidence-based preventive measures. In contrast, lack of tests may lead to incorrect political decisions causing either unnecessary over-protection of the population that is risky for a long-term economic recession, or under-protection of the population leading to a post-containment pandemic rebound. Recommendations are provided in the context of advanced predictive, preventive and personalised (3P) medical approach.", "doc_id": "fls35tpb"} {"topic_name": "coronavirus under reporting", "topic_id": "8", "title": "How Reliable are Test Numbers for Revealing the COVID-19 Ground Truth and Applying Interventions?", "abstract": "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.", "doc_id": "7bvsf5dk"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "SARS back in Canada", "abstract": "", "doc_id": "n97bfo0j"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Canada and COVID-19: learning from SARS", "abstract": "", "doc_id": "c7cd91pg"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Market Area Delineation for Airports to Predict the Spread of Infectious Disease", "abstract": "Air travel facilitates the international spread of infectious disease. While global air travel data represent the volume of travel between airports, identifying which airport an infected individual might use, or where a disease might spread after an infected passenger deplanes, remains a largely unexplored area of research and public health practice. This gap can be addressed by estimating airport catchment areas. This research aims to determine how existing market area delineation techniques estimate airport catchments differently, and which techniques are best suited to anticipate where infectious diseases may spread. Multiple techniques were tested for airports in the Province of Ontario, Canada: circular buffers, drive-time buffers, Thiessen polygons, and the Huff model, with multiple variations tested for some techniques. The results were compared qualitatively and quantitatively based on spatial patterns as well as area and population of each catchment area. There were notable differences, specifically between deterministic and probabilistic approaches. Deterministic techniques may only be suitable if all airports in a study area are similar in terms of attractiveness. The probabilistic Huff model appeared to produce more realistic results because it accounted for variation in airport attractiveness. Additionally, the Huff model requires few inputs and therefore would be efficient to execute in situations where time, resources, and data are limited.", "doc_id": "6apsd91c"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Risk of a second wave of Covid-19 infections: using artificial intelligence to investigate stringency of physical distancing policies in North America.", "abstract": "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.", "doc_id": "6ar58ea6"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Baseline characteristics and outcomes of patients with COVID-19 admitted to intensive care units in Vancouver, Canada: a case series.", "abstract": "BACKGROUND Pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with high intensive care unit (ICU) mortality. We aimed to describe the clinical characteristics and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19) in a Canadian setting. METHODS We conducted a retrospective case series of critically ill patients with laboratory-confirmed SARS-CoV-2 infection consecutively admitted to 1 of 6 ICUs in Metro Vancouver, British Columbia, Canada, between Feb. 21 and Apr. 14, 2020. Demographic, management and outcome data were collected by review of patient charts and electronic medical records. RESULTS Between Feb. 21 and Apr. 14, 2020, 117 patients were admitted to the ICU with a confirmed diagnosis of COVID-19. The median age was 69 (interquartile range [IQR] 60-75) years, and 38 (32.5%) were female. At least 1 comorbidity was present in 86 (73.5%) patients. Invasive mechanical ventilation was required in 74 (63.2%) patients. The duration of mechanical ventilation was 13.5 (IQR 8-22) days overall and 11 (IQR 6-16) days for patients successfully discharged from the ICU. Tocilizumab was administered to 4 patients and hydroxychloroquine to 1 patient. As of May 5, 2020, a total of 18 (15.4%) patients had died, 12 (10.3%) remained in the ICU, 16 (13.7%) were discharged from the ICU but remained in hospital, and 71 (60.7%) were discharged home. INTERPRETATION In our setting, mortality in critically ill patients with COVID-19 admitted to the ICU was lower than in previously published studies. These data suggest that the prognosis associated with critical illness due to COVID-19 may not be as poor as previously reported.", "doc_id": "dw2kljya"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Laboratory-confirmed COVID-19 in children and youth in Canada, January 15-April 27, 2020.", "abstract": "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.", "doc_id": "xzoleks8"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Communication, transparency key as Canada faces new coronavirus threat.", "abstract": "", "doc_id": "0ujw0gak"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Open access epidemiologic data and an interactive dashboard to monitor the COVID-19 outbreak in Canada.", "abstract": "", "doc_id": "6a6m7ye5"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Projecting demand for critical care beds during COVID-19 outbreaks in Canada.", "abstract": "BACKGROUND Increasing numbers of coronavirus disease 2019 (COVID-19) cases in Canada may create substantial demand for hospital admission and critical care. We evaluated the extent to which self-isolation of mildly ill people delays the peak of outbreaks and reduces the need for this care in each Canadian province. METHODS We developed a computational model and simulated scenarios for COVID-19 outbreaks within each province. Using estimates of COVID-19 characteristics, we projected the hospital and intensive care unit (ICU) bed requirements without self-isolation, assuming an average number of 2.5 secondary cases, and compared scenarios in which different proportions of mildly ill people practised self-isolation 24 hours after symptom onset. RESULTS Without self-isolation, the peak of outbreaks would occur in the first half of June, and an average of 569 ICU bed days per 10 000 population would be needed. When 20% of cases practised self-isolation, the peak was delayed by 2-4 weeks, and ICU bed requirement was reduced by 23.5% compared with no self-isolation. Increasing self-isolation to 40% reduced ICU use by 53.6% and delayed the peak of infection by an additional 2-4 weeks. Assuming current ICU bed occupancy rates above 80% and self-isolation of 40%, demand would still exceed available (unoccupied) ICU bed capacity. INTERPRETATION At the peak of COVID-19 outbreaks, the need for ICU beds will exceed the total number of ICU beds even with self-isolation at 40%. Our results show the coming challenge for the health care system in Canada and the potential role of self-isolation in reducing demand for hospital-based and ICU care.", "doc_id": "9ffvdgon"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Temporal estimates of case-fatality rate for COVID-19 outbreaks in Canada and the United States.", "abstract": "BACKGROUND Estimates of the casefatality rate (CFR) associated with coronavirus disease 2019 (COVID-19) vary widely in different population settings. We sought to estimate and compare the COVID-19 CFR in Canada and the United States while adjusting for 2 potential biases in crude CFR. METHODS We used the daily incidence of confirmed COVID-19 cases and deaths in Canada and the US from Jan. 31 to Apr. 22, 2020. We applied a statistical method to minimize bias in the crude CFR by accounting for the survival interval as the lag time between disease onset and death, while considering reporting rates of COVID-19 cases less than 50% (95% confidence interval 10%-50%). RESULTS Using data for confirmed cases in Canada, we estimated the crude CFR to be 4.9% on Apr. 22, 2020, and the adjusted CFR to be 5.5% (credible interval [CrI] 4.9%-6.4%). After we accounted for various reporting rates less than 50%, the adjusted CFR was estimated at 1.6% (CrI 0.7%-3.1%). The US crude CFR was estimated to be 5.4% on Apr. 20, 2020, with an adjusted CFR of 6.1% (CrI 5.4%-6.9%). With reporting rates of less than 50%, the adjusted CFR for the US was 1.78 (CrI 0.8%-3.6%). INTERPRETATION Our estimates suggest that, if the reporting rate is less than 50%, the adjusted CFR of COVID-19 in Canada is likely to be less than 2%. The CFR estimates for the US were higher than those for Canada, but the adjusted CFR still remained below 2%. Quantification of case reporting can provide a more accurate measure of the virulence and disease burden of severe acute respiratory syndrome coronavirus 2.", "doc_id": "glah2z2m"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Healthcare Worker COVID-19 Cases in Ontario, Canada: A Cross-sectional Study", "abstract": "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.", "doc_id": "4rutnzbu"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Sex-specific differences in COVID-19 testing, cases and outcomes: a population-wide study in Ontario, Canada", "abstract": "In this population-wide study in Ontario, Canada we report on all 194,372 unique residents who received testing for SARS-CoV-2 between January 23, 2020 and April 28, 2020. We found that while more women than men were tested for SARS-CoV-2, men had a higher rate of laboratory-confirmed COVID-19 infection, hospitalization, ICU admission and death. These findings were consistent even with age adjustment, suggesting that the observed differences in outcomes between women and men were not explained by age or systematic differences in testing by sex. Instead, they may be due to sex-based immunological or other gendered differences, such as higher rates of smoking leading to cardiovascular disease.", "doc_id": "n6oofe3i"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Association Between Nursing Home Crowding and COVID-19 Infection and Mortality in Ontario, Canada", "abstract": "", "doc_id": "q1ib25xr"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Estimated surge in hospitalization and intensive care due to the novel coronavirus pandemic in the Greater Toronto Area, Canada: a mathematical modeling study with application at two local area hospitals", "abstract": "Background: A hospital-level pandemic response involves anticipating local surge in healthcare needs. Methods: We developed a mechanistic transmission model to simulate a range of scenarios of COVID-19 spread in the Greater Toronto Area. We estimated healthcare needs against 2019 daily admissions using healthcare administrative data, and applied outputs to hospital-specific data on catchment, capacity, and baseline non-COVID admissions to estimate potential surge by day 90 at two hospitals (St. Michael\u0092s Hospital [SMH] and St. Joseph\u0092s Health Centre [SJHC]). We examined fast/large, default, and slow/small epidemics, wherein the default scenario (R0 2.4) resembled the early trajectory in the GTA. Results: Without further interventions, even a slow/small epidemic exceeded the city\u0092s daily ICU capacity for patients without COVID-19. In a pessimistic default scenario, for SMH and SJHC to remain below their non-ICU bed capacity, they would need to reduce non-COVID inpatient care by 70% and 58% respectively. SMH would need to create 86 new ICU beds, while SJHC would need to reduce its ICU beds for non-COVID care by 72%. Uncertainty in local epidemiological features was more influential than uncertainty in clinical severity. If physical distancing reduces contacts by 20%, maximizing the diagnostic capacity or syndromic diagnoses at the community-level could avoid a surge at each hospital. Interpretation: As distribution of the city\u0092s surge varies across hospitals over time, efforts are needed to plan and redistribute ICU care to where demand is expected. Hospital-level surge is based on community-level transmission, with community-level strategies key to mitigating each hospital\u0092s surge. Keywords: COVID-19, pandemic preparedness, mathematical model, transmission model", "doc_id": "nbn3wox6"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Determinants of self-reported symptoms and testing for COVID-19 in Canada using a nationally representative survey", "abstract": "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.", "doc_id": "u54kja4g"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Reduced COVID-19-Related Critical Illness and Death, and High Risk of Epidemic Resurgence, After Physical Distancing in Ontario, Canada", "abstract": "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.", "doc_id": "bp2ilntr"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "New Epidemiological Model Suggestions Revealing Size of Epidemics Based on the COVID-19 Pandemic Example: Wavelength Models", "abstract": "The main purpose of the study is to introduce the wavelength models developed to measure the size of outbreaks based on the COVID-19 example. In this way, the wavelengths of the outbreaks can be calculated, ensuring that the outbreaks are valid, reliable and easy to follow at the national and international level. Wavelength models consist of approved case, death, recovered case and net wavelength models. Thus, the size of the outbreak can be measured both individually and as a whole. COVID-19 cases of 181 countries were used to demonstrate the application of the models. The prominent findings in the applied wavelength models are as follows: the countries with the highest case wavelength are USA, Italy, Spain and Germany, respectively. However, Italy ranks first in the death wavelength, followed by Spain, the USA and France. On the other hand, China has taken the first place in the recovered case wavelength. This country was followed by Spain and Germany and Italy, respectively. Based on all these wavelength models mentioned, net wavelength lengths are calculated. According to the net wavelengths obtained, Canada ranked first, followed by United Kingdom, the USA and the Netherlands, respectively.", "doc_id": "3mmo1x2n"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "MERS-CoV- Low risk to Canadians.", "abstract": "Middle East respiratory syndrome - Coronavirus (MERS-CoV) -- is a novel coronavirus that has caused a number of community-acquired cases and health care associated outbreaks in Saudi Arabia and the United Arab Emirates (UAE) as well as sporadic cases in other countries, especially in the Middle East. The evidence to date links MERS-CoV cases with exposure to camels, including camel products or to probable or confirmed human cases of MERS-CoV. It typically presents as an acute respiratory illness and is associated with a 35% mortality rate. Based on available information at this time, the current risk to Canadians for acquiring MERS-CoV infections is considered low. However, the International Health Regulations Committee concerning MERS-CoV has cautioned that the upsurge of cases seen this past spring (2014) may be predictive of an increase in cases related to the Hajj - an annual pilgrimage to Mecca in Saudi Arabia that took place in early October 2014. Although the overall risk is low, the Public Health Agency of Canada and its National Microbiology Laboratory (NML) in close collaboration with provincial and territorial partners, the Canadian Public Health Laboratory Network (CPHLN) and infection prevention and control experts have developed a number of preparedness guidance documents and protocols to address the risk of an imported case of MERS-CoV in Canada.", "doc_id": "per78v5q"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Impact of COVID-19 on Canadian medical oncologists and cancer care: Canadian Association of Medical Oncologists survey report", "abstract": "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\u00e2\u0096 cancer prognosis and anticipated benefit from treatment,\u00e2\u0096 risk of treatment toxicity during scarce health care access, and\u00e2\u0096 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.", "doc_id": "y8ntig41"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Risk of a second wave of Covid-19 infections: using artificial intelligence to investigate stringency of physical distancing policies in North America", "abstract": "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.", "doc_id": "1mxgmhik"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Health-related concerns and precautions during the COVID-19 pandemic: A comparison of Canadians with and without underlying health conditions", "abstract": "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.", "doc_id": "in2edn29"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "The Impact of Coronavirus Disease 2019 Pandemic on U.S. and Canadian PICUs", "abstract": "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.", "doc_id": "nd1gecxg"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Risk for COVID-19 Resurgence Related to Duration and Effectiveness of Physical Distancing in Ontario, Canada", "abstract": "", "doc_id": "281pj442"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Diagnosis and Management of First Case of COVID-19 in Canada: Lessons applied from SARS", "abstract": "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.", "doc_id": "h9ovovhk"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Post-Discharge Cardiac Care in the Era of Coronavirus 2019: How Should We Prepare?", "abstract": "The novel coronavirus 2019 disease (COVID-19) pandemic has placed intense pressure on health care organizations around the world. Among other concerns, there has been an increasing recognition of common and deleterious cardiovascular effects of COVID-19 based on preliminary studies. Furthermore, patients with preexisting cardiac disease are likely to experience a more severe disease course with COVID-19. As case numbers continue to increase exponentially, a surge in the number of patients with new or comorbid cardiovascular disease will translate into more frequent and, in some cases, prolonged rehabilitation needs after acute hospitalization. This report describes the current status of post-discharge cardiac care in Canada and provides suggestions regarding steps that policymakers and health care organizations can take to prepare for the COVID-19 pandemic.", "doc_id": "ryh7cqwn"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Baseline characteristics and outcomes of patients with COVID-19 admitted to intensive care units in Vancouver, Canada: a case series", "abstract": "BACKGROUND: Pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with high intensive care unit (ICU) mortality. We aimed to describe the clinical characteristics and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19) in a Canadian setting. METHODS: We conducted a retrospective case series of critically ill patients with laboratory-confirmed SARS-CoV-2 infection consecutively admitted to 1 of 6 ICUs in Metro Vancouver, British Columbia, Canada, between Feb. 21 and Apr. 14, 2020. Demographic, management and outcome data were collected by review of patient charts and electronic medical records. RESULTS: Between Feb. 21 and Apr. 14, 2020, 117 patients were admitted to the ICU with a confirmed diagnosis of COVID-19. The median age was 69 (interquartile range [IQR] 60-75) years, and 38 (32.5%) were female. At least 1 comorbidity was present in 86 (73.5%) patients. Invasive mechanical ventilation was required in 74 (63.2%) patients. The duration of mechanical ventilation was 13.5 (IQR 8-22) days overall and 11 (IQR 6-16) days for patients successfully discharged from the ICU. Tocilizumab was administered to 4 patients and hydroxychloroquine to 1 patient. As of May 5, 2020, a total of 18 (15.4%) patients had died, 12 (10.3%) remained in the ICU, 16 (13.7%) were discharged from the ICU but remained in hospital, and 71 (60.7%) were discharged home. INTERPRETATION: In our setting, mortality in critically ill patients with COVID-19 admitted to the ICU was lower than in previously published studies. These data suggest that the prognosis associated with critical illness due to COVID-19 may not be as poor as previously reported.", "doc_id": "7g12596l"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Laboratory-confirmed COVID-19 in children and youth in Canada, January 15-April 27, 2020", "abstract": "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.", "doc_id": "bvujapf5"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "First imported case of 2019 novel coronavirus in Canada, presenting as mild pneumonia", "abstract": "", "doc_id": "cietpenq"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "It can be dangerous to take epidemic curves of COVID-19 at face value", "abstract": "During an epidemic with a new virus, we depend on modelling to plan the response: but how good are the data? The aim of our work was to better understand the impact of misclassification errors in identification of true cases of COVID-19 on epidemic curves. Data originated from Alberta, Canada (available on 28 May 2020). There is presently no information of sensitivity (Sn) and specificity (Sp) of laboratory tests used in Canada for the causal agent for COVID-19. Therefore, we examined best attainable performance in other jurisdictions and similar viruses. This suggested perfect Sp and Sn 60-95%. We used these values to re-calculate epidemic curves to visualize the potential bias due to imperfect testing. If the sensitivity improved, the observed and adjusted epidemic curves likely fall within 95% confidence intervals of the observed counts. However, bias in shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60-70% range. These issues are minor early in the epidemic, but hundreds of undiagnosed cases are likely later on. It is therefore hazardous to judge progress of the epidemic based on observed epidemic curves unless quality of testing is better understood.", "doc_id": "hsr2ue28"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Open access epidemiologic data and an interactive dashboard to monitor the COVID-19 outbreak in Canada", "abstract": "", "doc_id": "ep79lg0p"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Estimation of COVID-19-induced depletion of hospital resources in Ontario, Canada", "abstract": "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.", "doc_id": "h6g65f9w"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Severity of coronavirus respiratory tract infections in adults admitted to acute care in Toronto, Ontario", "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.", "doc_id": "i8bw7ut9"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Real-time forecasts and risk assessment of novel coronavirus (COVID-19) cases: A data-driven analysis", "abstract": "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.", "doc_id": "d9f8lbr6"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Predicting turning point, duration and attack rate of COVID-19 outbreaks in major Western countries", "abstract": "In this paper, we employed a segmented Poisson model to analyze the available daily new cases data of the COVID-19 outbreaks in the six Western countries of the Group of Seven, namely, Canada, France, Germany, Italy, UK and USA. We incorporated the governments' interventions (stay-at-home advises/orders, lockdowns, quarantines and social distancing) against COVID-19 into consideration. Our analysis allowed us to make a statistical prediction on the turning point (the time that the daily new cases peak), the duration (the period that the outbreak lasts) and the attack rate (the percentage of the total population that will be infected over the course of the outbreak) for these countries.", "doc_id": "1da6ackj"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Projecting demand for critical care beds during COVID-19 outbreaks in Canada", "abstract": "BACKGROUND: Increasing numbers of coronavirus disease 2019 (COVID-19) cases in Canada may create substantial demand for hospital admission and critical care. We evaluated the extent to which self-isolation of mildly ill people delays the peak of outbreaks and reduces the need for this care in each Canadian province. METHODS: We developed a computational model and simulated scenarios for COVID-19 outbreaks within each province. Using estimates of COVID-19 characteristics, we projected the hospital and intensive care unit (ICU) bed requirements without self-isolation, assuming an average number of 2.5 secondary cases, and compared scenarios in which different proportions of mildly ill people practised self-isolation 24 hours after symptom onset. RESULTS: Without self-isolation, the peak of outbreaks would occur in the first half of June, and an average of 569 ICU bed days per 10 000 population would be needed. When 20% of cases practised self-isolation, the peak was delayed by 2-4 weeks, and ICU bed requirement was reduced by 23.5% compared with no self-isolation. Increasing self-isolation to 40% reduced ICU use by 53.6% and delayed the peak of infection by an additional 2-4 weeks. Assuming current ICU bed occupancy rates above 80% and self-isolation of 40%, demand would still exceed available (unoccupied) ICU bed capacity. INTERPRETATION: At the peak of COVID-19 outbreaks, the need for ICU beds will exceed the total number of ICU beds even with self-isolation at 40%. Our results show the coming challenge for the health care system in Canada and the potential role of self-isolation in reducing demand for hospital-based and ICU care.", "doc_id": "ezirpmbd"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Quantification of Tomographic Patterns associated with COVID-19 from Chest CT", "abstract": "Purpose: To present a method that automatically segments and quantifies abnormal CT patterns commonly present in coronavirus disease 2019 (COVID-19), namely ground glass opacities and consolidations. Materials and Methods: In this retrospective study, the proposed method takes as input a non-contrasted chest CT and segments the lesions, lungs, and lobes in three dimensions, based on a dataset of 9749 chest CT volumes. The method outputs two combined measures of the severity of lung and lobe involvement, quantifying both the extent of COVID-19 abnormalities and presence of high opacities, based on deep learning and deep reinforcement learning. The first measure of (PO, PHO) is global, while the second of (LSS, LHOS) is lobewise. Evaluation of the algorithm is reported on CTs of 200 participants (100 COVID-19 confirmed patients and 100 healthy controls) from institutions from Canada, Europe and the United States collected between 2002-Present (April, 2020). Ground truth is established by manual annotations of lesions, lungs, and lobes. Correlation and regression analyses were performed to compare the prediction to the ground truth. Results: Pearson correlation coefficient between method prediction and ground truth for COVID-19 cases was calculated as 0.92 for PO (P<.001), 0.97 for PHO(P<.001), 0.91 for LSS (P<.001), 0.90 for LHOS (P<.001). 98 of 100 healthy controls had a predicted PO of less than 1%, 2 had between 1-2%. Automated processing time to compute the severity scores was 10 seconds per case compared to 30 minutes required for manual annotations. Conclusion: A new method segments regions of CT abnormalities associated with COVID-19 and computes (PO, PHO), as well as (LSS, LHOS) severity scores.", "doc_id": "4dnzjeyp"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Air pollution in Ontario, Canada during the COVID-19 State of Emergency", "abstract": "In March of 2020, the province of Ontario declared a State of Emergency (SOE) to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19). This disruption to the economy provided an opportunity to measure change in air pollution when the population spends more time at home with fewer trips. Hourly air pollution observations were obtained for fine particulate matter, nitrogen dioxide, nitrogen oxides and ozone from the Ontario air monitoring network for 2020 and the previous five years. The analysis is focused on a five-week period during the SOE with a previous five-week period used as a control. Fine particulate matter did not show any significant reductions during the SOE. Ozone concentrations at 12 of the 32 monitors were lower than any of the previous five-years; however, four locations were above average. Average ozone concentrations were 1 ppb lower during the SOE, but this ranged at individual monitors from 1.5 ppb above to 4.2 ppb below long-term conditions. Nitrogen dioxide and nitrogen oxides demonstrated a reduction across Ontario, and both pollutants displayed their lowest concentrations for 22 of 29 monitors. Individual monitors ranged from 1 ppb (nitrogen dioxide) and 5 ppb (nitrogen oxides) above average to 4.5 (nitrogen dioxide) and 7.1 ppb (nitrogen oxides) below average. Overall, both nitrogen dioxide and nitrogen oxides demonstrated a reduction across Ontario in response to the COVID-19 SOE, ozone concentrations suggested a possible reduction, and fine particulate matter has not varied from historic concentrations.", "doc_id": "ltnnjx0x"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Temporal estimates of case-fatality rate for COVID-19 outbreaks in Canada and the United States", "abstract": "BACKGROUND: Estimates of the case-fatality rate (CFR) associated with coronavirus disease 2019 (COVID-19) vary widely in different population settings. We sought to estimate and compare the COVID-19 CFR in Canada and the United States while adjusting for 2 potential biases in crude CFR. METHODS: We used the daily incidence of confirmed COVID-19 cases and deaths in Canada and the US from Jan. 31 to Apr. 22, 2020. We applied a statistical method to minimize bias in the crude CFR by accounting for the survival interval as the lag time between disease onset and death, while considering reporting rates of COVID-19 cases less than 50% (95% confidence interval 10%-50%). RESULTS: Using data for confirmed cases in Canada, we estimated the crude CFR to be 4.9% on Apr. 22, 2020, and the adjusted CFR to be 5.5% (credible interval [CrI] 4.9%-6.4%). After we accounted for various reporting rates less than 50%, the adjusted CFR was estimated at 1.6% (CrI 0.7%-3.1%). The US crude CFR was estimated to be 5.4% on Apr. 20, 2020, with an adjusted CFR of 6.1% (CrI 5.4%-6.9%). With reporting rates of less than 50%, the adjusted CFR for the US was 1.78 (CrI 0.8%-3.6%). INTERPRETATION: Our estimates suggest that, if the reporting rate is less than 50%, the adjusted CFR of COVID-19 in Canada is likely to be less than 2%. The CFR estimates for the US were higher than those for Canada, but the adjusted CFR still remained below 2%. Quantification of case reporting can provide a more accurate measure of the virulence and disease burden of severe acute respiratory syndrome coronavirus 2.", "doc_id": "9hbgn66l"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Using Machine Learning to Estimate Unobserved COVID-19 Infections in North America", "abstract": "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.", "doc_id": "mdt11ba5"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Real-time Forecast of Multiphase Outbreak", "abstract": "We used a single equation with discrete phases to fit the daily cumulative case data from the 2003 severe acute respiratory syndrome outbreak in Toronto. This model enabled us to estimate turning points and case numbers during the 2 phases of this outbreak. The 3 estimated turning points are March 25, April 27, and May 24. The estimated case number during the first phase of the outbreak between February 23 and April 26 is 140.53 (95% confidence interval [CI] 115.88\u2013165.17) if we use the data from February 23 to April 4; and 249 (95% CI: 246.67\u2013251.25) at the end of the second phase on June 12 if we use the data from April 28 to June 4. The second phase can be detected by using case data just 3 days past the beginning of the phase, while the first and third turning points can be identified only \u224810 days afterwards. Our modeling procedure provides insights into ongoing outbreaks that may facilitate real-time public health responses.", "doc_id": "h6cfru7u"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Canada needs to rapidly escalate public health interventions for its COVID-19 mitigation strategies", "abstract": "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\u20134 days.", "doc_id": "vwwt70mo"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Estimating the Maximum Capacity of COVID-19 Cases Manageable per Day Given a Health Care System's Constrained Resources", "abstract": "", "doc_id": "sdf2cw4g"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Projecting the demand for ventilators at the peak of the COVID-19 outbreak in the USA", "abstract": "", "doc_id": "aj1cod3x"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Human Coronavirus NL63 Infection in Canada", "abstract": "The isolation of human coronavirus NL63 (HCoV-NL63) in The Netherlands raised questions about its contribution to respiratory illness. In this study, a total of 525 respiratory specimens, collected in Canada primarily during the winter months of 2001\u20132002, were tested for HCoV-NL63; 19 tested positive for HCoV-NL63, demonstrating virus activity during January\u2013March 2002. Patients with HCoV-NL63 were 1 month-100 years old (median age, 37 years). The main clinical presentations were fever (15/19), sore throat (5/19), and cough (9/19), and 4 patients were hospitalized. These results provide evidence for the worldwide distribution of HCoV-NL63.", "doc_id": "nalulzfo"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "Communication in the Toronto critical care community: important lessons learned during SARS", "abstract": "The SARS outbreak in 2003 pushed Toronto's health care system to its limits. Staffing shortages, transmission of SARS within the ICU, and the influx of critically ill SARS patients were some unique challenges to the delivery of critical care. Communication strategies were a key component in the critical care response to SARS. Regular teleconference calls, web-based training and education, and the rapid coordination of research studies were some of the initiatives developed within the Toronto critical care community during the SARS outbreak. Other critical care communities should consider their communication strategies in advance of similar events.", "doc_id": "8wlxkflg"} {"topic_name": "coronavirus in Canada", "topic_id": "9", "title": "COVID-19: Pandemic Risk, Resilience and Possibilities for Aging Research", "abstract": "The COVID-19 global crisis is reshaping Canadian society in unexpected and profound ways. The significantly higher morbidity and mortality risks by age suggest that this is largely a \u201cgero-pandemic,\u201d which has thrust the field of aging onto center stage. This editorial emphasizes that vulnerable older adults are also those most affected by COVID-19 in terms of infection risk, negative health effects, and the potential deleterious outcomes on a range of social, psychological, and economic contexts \u2013 from ageism to social isolation. We also contend that the pathogenic analysis of this pandemic needs to be balanced with a salutogenic approach that examines the positive adaptation of people, systems and society, termed COVID-19 resilience. This begs the question: how and why do some older adults and communities adapt and thrive better than others? This examination will lead to the identification and response to research and data gaps, challenges, and innovative opportunities as we plan for a future in which COVID-19 has become another endemic infection in the growing list of emerging and re-emerging pathogens.", "doc_id": "no8y1ior"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Mandatory Social Distancing Associated With Increased Doubling Time: An Example Using Hyperlocal Data", "abstract": "", "doc_id": "ljpd7flk"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "No Place Like Home: A Cross-National Assessment of the Efficacy of Social Distancing during the COVID-19 Pandemic.", "abstract": "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 (\u03b2) 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 \u03b2 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", "doc_id": "3nanf73b"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Timing of Community Mitigation and Changes in Reported COVID-19 and Community Mobility - Four U.S. Metropolitan Areas, February 26-April 1, 2020.", "abstract": "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.", "doc_id": "16t5rs6j"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Social distancing: A non-pharmacological intervention for COVID-19.", "abstract": "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.", "doc_id": "3cke9x69"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Strong Social Distancing Measures In The United States Reduced The COVID-19 Growth Rate.", "abstract": "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.].", "doc_id": "ereh4ub8"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Social distancing, population density, and spread of COVID-19 in England: a longitudinal study.", "abstract": "BACKGROUND The UK government introduced social distancing measures between 16-22 March 2020, aiming to slow down transmission of COVID-19. AIM To explore the spreading of COVID-19 in relation to population density after the introduction of social distancing measures. DESIGN & SETTING Longitudinal design with 5-weekly COVID-19 incidence rates per 100 000 people for 149 English Upper Tier Local Authorities (UTLAs), between 16 March and 19 April 2020. METHOD Multivariable multilevel model to analyse weekly incidence rates per 100 000 people; time was level-1 unit and UTLA level-2 unit. Population density was divided into quartiles. The model included an interaction between week and population density. Potential confounders were percentage aged \u226565, percentage non-white British, and percentage in two highest classes of the National Statistics Socioeconomic Classification. Co-variates were male life expectancy at birth, and COVID-19 prevalence rate per 100 000 people on March 15. Confounders and co-variates were standardised around the mean. RESULTS Incidence rates per 100 000 people peaked in the week of March 30-April 5, showing higher adjusted incidence rate per 100 000 people (46.2; 95% confidence interval [CI] = 40.6 to 51.8) in most densely populated ULTAs (quartile 4) than in less densely populated ULTAs (quartile 1: 33.3, 95% CI = 27.4 to 37.2; quartile 2: 35.9, 95% CI = 31.6 to 40.1). Thereafter, incidence rate dropped in the most densely populated ULTAs resulting in rate of 22.4 (95% CI = 16.9 to 28.0) in the week of April 13-19; this was lower than in quartiles 1, 2, and 3, respectively 31.4 (95% CI = 26.5 to 36.3), 34.2 (95% CI = 29.9 to 38.5), and 43.2 (95% CI = 39.0 to 47.4). CONCLUSION After the introduction of social distancing measures, the incidence rates per 100 000 people dropped stronger in most densely populated ULTAs.", "doc_id": "qrhzum9v"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Evaluating the Effectiveness of Social Distancing Interventions to Delay or Flatten the Epidemic Curve of Coronavirus Disease.", "abstract": "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.", "doc_id": "x9zg7ulr"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Effects of Proactive Social Distancing on COVID-19 Outbreaks in 58 Cities, China.", "abstract": "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.", "doc_id": "maxvppn8"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Vertical social distancing policy is ineffective to contain the COVID-19 pandemic.", "abstract": "Considering numerical simulations, this study shows that the so-called vertical social distancing health policy is ineffective to contain the COVID-19 pandemic. We present the SEIR-Net model, for a network of social group interactions, as a development of the classic mathematical model of SEIR epidemics (Susceptible-Exposed-Infected (symptomatic and asymptomatic)-Removed). In the SEIR-Net model, we can simulate social contacts between groups divided by age groups and analyze different strategies of social distancing. In the vertical distancing policy, only older people are distanced, whereas in the horizontal distancing policy all age groups adhere to social distancing. These two scenarios are compared to a control scenario in which no intervention is made to distance people. The vertical distancing scenario is almost as bad as the control, both in terms of people infected and in the acceleration of cases. On the other hand, horizontal distancing, if applied with the same intensity in all age groups, significantly reduces the total infected people \"flattening the disease growth curve\". Our analysis considers the city of Belo Horizonte, Minas Gerais State, Brazil, but similar conclusions apply to other cities as well. Code implementation of the model in R-language is provided in the supplementary material.", "doc_id": "raojr7o4"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Estimates of regional infectivity of COVID-19 in the United Kingdom following imposition of social distancing measures", "abstract": "We describe regional variation in the reproduction number of SARS-CoV-2 infections observed using publicly reported data in the UK, with a view to understanding both if there are clear hot spots in viral spread in the country, or if there are any clear spatial patterns. We estimate that the viral replication number remains slightly above 1 overall but that its trend is to decrease, based on case data up to the 8 April. This suggests the peak of the first wave of COVID-19 patients is imminent. We find that there is significant regional variation in different regions of the UK and that this is changing over time. Within England currently the reproductive ratio is lowest in the Midlands (1.11 95% CI 1.07; 1.14), and highest in the North East of England (1.38 95% CI 1.33-1.42). It remains unclear whether the overall reduction in the reproductive number is a result of social distancing measures, due to the long and variable time delays between infection and positive detection of cases. As we move forwards, if we are to prevent further outbreaks, it is critical that we can both reduce the time taken for detection and improve our ability to predict the regional spread of outbreaks", "doc_id": "fqvrlrv0"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Sustaining Social Distancing Policies to Prevent a Dangerous Second Peak of COVID-19 Outbreak", "abstract": "Governments around the world have enacted strict social distancing policies in order to slow the spread of COVID-19. The next step is figuring out when to relax these restrictions and to what degree. Our results predict potentially disastrous implications of ending these policies too soon, based on projections made from a Susceptible-Exposed-Infectious-Removed (SEIR) epidemic model. Even when infection rates appear to be slowing down or decreasing, prematurely returning to \"business as usual\" produces a severe second peak far worse than the first. Furthermore, such a second peak is made more likely when very severe restrictions are initially enacted. Only an appropriately measured and committed set of restrictions can appropriately control COVID-19 outbreak levels.", "doc_id": "j1ma6r50"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Are we #stayinghome to Flatten the Curve?", "abstract": "The recent spread of COVID-19 across the U.S. led to concerted efforts by states to ``flatten the curve\" through the adoption of stay-at-home mandates that encourage individuals to reduce travel and maintain social distance and indeed using data on travel activity we find that residents start reducing mobility early in most states. Combining data on changes in travel activity with COVID-19 health outcomes and variation in state policy adoption, we characterize the direct impact of stay-at-home mandates on mobility and social distancing and link these behavioral changes to health benefits. We find evidence of dramatic declines in mobility nationwide prior to the adoption of statewide mandates. Despite these early reductions, we find that statewide stay-at-home policies induced \"mandate effects\" of between 4.1 and 5.9 percentage point declines relative to pre-COVID-19 levels for the first four states to introduce such policies. These effects persist when considering all states' mandates and alternate estimation strategies that account for states' differences in travel behavior prior to policy adoption. Using previous changes in mobility, we find significant effects on current mortality, with 1% reductions in visits to non-essential businesses weeks prior being associated with 9.2 fewer deaths per 100 million per day, corresponding with over 74,000 lives saved nationwide and resulting economic benefits between $249-$745 billion for observed behavioral changes in March and April. Observed reductions in mobility indeed contribute to flattening the curve and reduce the strain on the medical system during those two months. Our findings provide evidence that statewide stay-at-home ordinances induce additional social distancing, and ultimately attenuate the negative health consequences of COVID-19, revealing themselves as important policy tools in the fight against pandemic. Further, substantial reductions in mobility prior to state-level policies convey important policy implications.", "doc_id": "4lgy9te8"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Public health interventions in India slowed the spread of COVID-19 epidemic dynamics", "abstract": "Background The government of India implemented social distancing interventions to contain the COVID-19 epidemic. However, effects on epidemic dynamics are yet to be understood. Methods Rates of laboratory-confirmed COVID-19 infections per day and effective reproduction number (Rt) were estimated for 4 periods (Pre-lockdown and Lockdown Phases 1 to 3) according to nationally implemented phased interventions. Adoption of these interventions was estimated using Google mobility data. Estimates at the national level and for 12 Indian states most affected by COVID-19 are presented. Findings Daily case rates ranged from 0.03 to 30.05/10 million people across 4 discrete periods in India. From May 4-17, 2020, the National Capital Territory (NCT) of Delhi had the highest case rate (222/10 million people/day), whereas Kerala had the lowest (2.18/10 million/day). Average Rt was 1.99 (95% CI 1.93-2.06) for India; it ranged from 1.38 to 2.78, decreasing over time. Median mobility in India decreased in all contact domains, with the lowest being 21% in retail/recreation (95% CI 13-46%), except home which increased to 129% (95% CI 117-132%) compared to the 100% baseline value. Interpretation The Indian government imposed strict contact mitigation, followed by a phased relaxation, which slowed the spread of COVID-19 epidemic progression in India. The identified daily COVID-19 case rates and Rt will aid national and state governments in formulating ongoing COVID-19 containment plans. Furthermore, these findings may inform COVID-19 public health policy in developing countries with similar settings to India. Funding Non-funded.", "doc_id": "nney9kuq"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Impact of social distancing measures for preventing coronavirus disease 2019 : A systematic review and meta-analysis protocol", "abstract": "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.", "doc_id": "3mwx9s5x"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Estimating the effect of physical distancing on the COVID-19 pandemic using an urban mobility index", "abstract": "Governments around the world are implementing population-wide physical distancing measures in an effort to control transmission of COVID-19, but metrics to evaluate their effectiveness are not readily available. We used a publicly available mobility index based on the relative frequency of trips planned in a popular transit application to evaluate the effect of physical distancing on infection growth rates and reproductive number in 34 states and countries. We found that a 10% decrease in relative mobility in the 2nd week of March was associated with a 11.8% relative decrease (exp(\u03b2) = 0.882; 95% CI: 0.822, 0.946) in the average daily growth rate in the fourth week of March and a change in the instantaneous reproductive number of -0.054 (95% CI: 0.097, -0.011) in the same period. Our analysis demonstrates that decreases in urban mobility were predictive of declines in epidemic growth at national or sub-national scales. Mobility metrics offer an appealing method to calibrate population-level physical distancing policy and implementation.", "doc_id": "radi0wlh"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Full lockdown policies in Western Europe countries have no evident impacts on the COVID-19 epidemic.", "abstract": "This phenomenological study assesses the impacts of full lockdown strategies applied in Italy, France, Spain and United Kingdom, on the slowdown of the 2020 COVID-19 outbreak. Comparing the trajectory of the epidemic before and after the lockdown, we find no evidence of any discontinuity in the growth rate, doubling time, and reproduction number trends. Extrapolating pre-lockdown growth rate trends, we provide estimates of the death toll in the absence of any lockdown policies, and show that these strategies might not have saved any life in western Europe. We also show that neighboring countries applying less restrictive social distancing measures (as opposed to police-enforced home containment) experience a very similar time evolution of the epidemic.", "doc_id": "fmgj3noh"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Orthogonal Functions for Evaluating Social Distancing Impact on CoVID-19 Spread", "abstract": "Early CoVID-19 growth often obeys: N{t}=N/Iexp[+K/ot], with K/o=[(ln2)/(t/dbl)], where t/dbl is the pandemic doubling time, prior to society-wide Social Distancing. Previously, we modeled Social Distancing with t/dbl as a linear function of time, where N[t]=1exp[+K/A t/(1+ gamma/o t)] is used here. Additional parameters besides {K/o,gamma/o} are needed to better model different rho[t]=dN[t]/dt shapes. Thus, a new Orthogonal Function Model [OFM] is developed here using these orthogonal function series: N(Z) = sum[m=0,M/F] g/m L/m(Z) exp[-Z] , R(Z) = sum[m=0,M/F] c/m L/m(Z) exp[-Z] , where N(Z) and Z[t] form an implicit N[t]=N(Z[t]) function, giving: G/o = [K/A / gamma/o ] , Z[t] = +[ G/o / (1+ gamma/ot) ] , rho[t] = [ gamma/o / G/o ] (Z^2) R(Z) , with L/m(Z) being the Laguerre Polynomials. At large M/F values, nearly arbitrary functions for N[t] and rho[t]=dN[t]/dt can be accommodated. How to determine {K/A, gamma/o} and the {g/m; m=(0,+M/F)} constants from any given N(Z) dataset is derived, with rho[t] set by: c/(M/F - k) = sum[m=0,k] g/m . The bing.com USA CoVID-19 data was analyzed using M/F=(0,1,2) in the OFM. All results agreed to within about 10 percent, showing model robustness. Averaging over all these predictions gives the following overall estimates for the number of USA CoVID-19 cases at the pandemic end: = 5,009,677 (+/-) 269,450 (data to 5/3/20), and = 4,422,803 (+/-) 162,580 (data to 6/7/20), which compares the pre- and post-early May bing.com revisions. The CoVID-19 pandemic in Italy was examined next. The M/F=2 limit was inadequate to model the Italy rho[t] pandemic tail. Thus, regions with a quick CoVID-19 pandemic shutoff may have additional Social Distancing factors operating, beyond what can be easily modeled by just progressively lengthening pandemic doubling times (with 13 Figures).", "doc_id": "1exyjhj0"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Enacting national social distancing policies corresponds with dramatic reduction in COVID19 infection rates", "abstract": "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.", "doc_id": "vdrd74nz"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Estimating the impact of physical distancing measures in containing COVID-19: an empirical analysis", "abstract": "Background Epidemic modelling studies predict that physical distancing is critical in containing COVID-19. However, few empirical studies have validated this finding. Our study evaluates the effectiveness of different physical distancing measures in controlling viral transmission. Methods We identified three distinct physical distancing measures with varying intensity and implemented at different times - international travel controls, restrictions on mass gatherings, and lockdown-type measures - based on the Oxford COVID-19 Government Response Tracker. We also estimated the time-varying reproduction number (Rt) for 142 countries and tracked Rt temporally for two weeks following the 100th reported case in each country. We regressed Rt on the physical distancing measures and other control variables (income, population density, age structure, and temperature) and performed several robustness checks to validate our findings. Findings Complete travel bans and all forms of lockdown-type measures have been effective in reducing average Rt over the 14 days following the 100th case. Recommended stay-at-home advisories and partial lockdowns are as effective as complete lockdowns in outbreak control. However, these measures have to be implemented early to be effective. Lockdown-type measures should be instituted two weeks before the 100th case and travel bans about a week before detection of the first case. Interpretation A combination of physical distancing measures, if implemented early, can be effective in containing COVID-19 - tight border controls to limit importation of cases, encouraging physical distancing, moderately stringent measures such as working from home, and a full lockdown in the case of a probable uncontrolled outbreak.", "doc_id": "ldeqvajo"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Modelling the impact of control measures against the COVID-19 pandemic in Viet Nam", "abstract": "Objectives: Health care system of many countries are facing a surging burden of COVID-19. Although Vietnam has successfully controlled the COVID-19 pandemic to date, there is a sign of initial community transmission. An estimate of possible scenarios to prepare health resources in the future is needed. We used modelling methods to estimate impacts of mitigation measures on the COVID-19 pandemic in Vietnam. Methods: SEIR model built in the COVIDSIM1.1 tool was adopted using available data for estimation. The herd immunization scenario was with no intervention implemented. Other scenarios consisted of isolation and social distancing at different levels (25%, 50%, 75% and 10%, 20%, 30%, respectively). Outcomes include epidemic apex, daily new and cumulative cases, deaths, hospitalized patients and ICU beds needed. Results: By April 8, 2020, there would be 465 infected cases with COVID-19 in Viet Nam, of those 50% were detected. Cumulatively, there would be 1,400 cases and 30 deaths by end of 2020, if 75% of cases was detected and isolated, and 30% of social distancing could be maintained. The most effective intervention scenario is the detection and isolation of 75% infected cases and reduction of 10% social contacts. This will require an expansion of testing capacity at health facilities and in the community, posing a challenge to identify high-risk groups to prioritized testing. Conclusions: In a localized epidemic setting, the expansion of testing should be the key measure to control the epidemic. Social distancing plays a significant role to prevent further transmission to the community.", "doc_id": "0k6r5q1t"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Instantaneous R calculation for COVID-19 epidemic in Brazil", "abstract": "COVID-19 pandemic represents a major challenge to health systems of all countries. Brazilian regions habe been showing marked di[ff]erences in onset and number of cases. Health authorities instituted widespread social distancing and lockdown measures but their implementation has also varied. The authors used data on con[fi]rmed cases of COVID-19 in Brazil and its states to calculate the value of instantaneous reproduction number at these regions. The results show a reduction of instantaneous reproduction number with time, probably due to social distancing measures put in place in the last weeks by brazillian authorities. It seems logical to maintain restrictions to social contact until the epidemic peak has occurred in Brazil.", "doc_id": "o5cmhvy3"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Modelling the potential impact of social distancing on the COVID-19 epidemic in South Africa", "abstract": "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.", "doc_id": "q5xc4m3j"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "SHELTER IN PLACE ORDER CONTAINED COVID-19 GROWTH RATE IN GREECE", "abstract": "Background: The Greek authorities implemented the strong social distancing measures within the first few weeks after the first confirmed case of the virus to curtail the COVID-19 growth rate. Objectives: To estimate the effect of the two-stage strong social distancing measures, the closure of all non-essential shopping centers and businesses on March 16 and the shelter in place orders (SIPOs) on March 23 on the COVID-19 growth rate in Greece Methods: We obtained data on COVID-19 cases in Greece from February 26th through May 4th from publicly available sources. An interrupted time-series regression analysis was used to estimate the effect of the measures on the exponential growth of confirmed COVID-19 cases, controlling for the number of daily testing, and weekly fixed-effects. Results: The growth rate of the COVID-19 cases in the pre-policies implementation period was positive as expected (p=0.003). Based on the estimates of the interrupted time-series, our results indicate that the SIPO on March 23 significantly slowed the growth rate of COVID-19 in Greece (p=0.04). However, we did not find evidence on the effectiveness of standalone and partial measures such as the non-essential business closures implemented on March 16 on the COVID-19 spread reduction. Discussion: The combined social distancing measures implemented by the Greek authorities within the first few weeks after the first confirmed case of the virus reduced the COVID-19 growth rate. These findings provide evidence and highlight the effectiveness of these measures to flatten the curve and to slow the spread of the virus.", "doc_id": "tkajjrri"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Effects of social distancing on the spreading of COVID-19 inferred from mobile phone data", "abstract": "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.", "doc_id": "gz18sxzc"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Social Distancing Has Merely Stabilized COVID-19 in the US", "abstract": "Social distancing measures, with varying degrees of restriction, have been imposed around the world in order to stem the spread of COVID-19. 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.", "doc_id": "all7ocnd"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "A single holiday was the turning point of the COVID-19 policy of Israel", "abstract": "Background: The impact of COVID-19 has been profound, and the public health challenge seem to be the most serious regarding respiratory viruses since the 1918 H1N1 influenza pandemic. In the absence of effective vaccine or biomedical treatment, the basic rules of public health measures have not changed, namely public distancing. Methods: We analyzed epidemiological investigation reports during the first month of the outbreak in Israel. In addition, we present a deterministic compartment model and simulations of several scenarios emphasizing quarantine and isolation policies given their efficiency. Results: We identify an abrupt change from controlled epidemic regime to an exponential growth (R_0= 2.19) in light of the actual policy-makers decisions and public behavior in Israel. Our analysis show that before the abrupt change, the new cases trend was due to returning citizens infected abroad. The abrupt change followed a holiday in which social distancing was clearly inefficient and many public gatherings were held. We further discuss three different modeled scenarios of quarantine efficiency: high-, medium-, and low-efficiency. Conclusions: Israel early lessons show that there is no allowance to compromise with the directive of social distancing. Even before the onset of the pandemic in Israel, fine-tuned but determined early decisions were taken by policy makers to monitor flight arrivals from Covid-19 affected regions and to limit public gatherings. Our analysis show that one particular holiday has shifted the occurrence curve from controlled regime to exponential growth. Therefore, even a short lapse in public responsiveness can have a dramatic effect.", "doc_id": "32hjzdum"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Flattening the curve and the effect of atypical events on mitigation measures in Mexico: a modeling perspective", "abstract": "On 23 and 30 March 2020 the Mexican Federal government implemented social distancing measures to mitigate the COVID-19 epidemic. We use a mathematical model to explore atypical transmission events within the confinement period, triggered by the timing and strength of short time perturbations of social distancing. We show that social distancing measures were successful in achieving a significant reduction of the effective contact rate in the early weeks of the intervention. However, \"flattening the curve\" had an undesirable effect, since the epidemic peak was delayed too far, almost to the government preset day for lifting restrictions (01 June 2020). If the peak indeed occurs in late May or early June, then the events of children's day and mother's day may either generate a later peak (worst case scenario), a long plateau with relatively constant but high incidence (middle case scenario) or the same peak date as in the original baseline epidemic curve, but with a post-peak interval of slower decay.", "doc_id": "9azl5nl8"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Analyzing the World-Wide Impact of Public Health Interventions on the Transmission Dynamics of COVID-19", "abstract": "We analyze changes in the reproduction number, R, of COVID-19 in response to public health interventions. Our results indicate that public health measures undertaken in China reduced R from 1.5 in January to 0.4 in mid-March 2020. They also suggest, however, the limitations of isolation, quarantine, and large-scale attempts to limit travel. While the world-wide reproduction number briefly dropped below 1 as China implemented extensive public health measures, the introduction of the virus to other nations swiftly led to an increasing world-wide average value of R. In Italy, the nation hardest-hit following China, social distancing measures brought the local value of R down from 3.71 to 2.51. Nonetheless, the value of R in Italy persisted at levels well above 1, allowing for ongoing transmission. By mid-March 2020, as COVID-19 spread in areas without extensive public health interventions in place, the world-wide value of R increased to a level similar to that of late January.", "doc_id": "tc02pxt9"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Estimates of the ongoing need for social distancing and control measures post-\"lockdown\" from trajectories of COVID-19 cases and mortality.", "abstract": "By 21st April 2020 COVID_19 had caused more than 2m cases across more than 200 countries. The majority of countries with significant outbreaks introduced social distancing or \"lockdown\" measures to reduce viral transmission. The key question now in many countries is when, how, and to what extent these measures can be lifted. By fitting regression models to publically available data on daily numbers of newly-confirmed cases and mortality, trajectories, doubling times and reproduction number (R0) were estimated both before and under the control measures. These data ran up to 21st April 2020, and covered 67 countries that had provided sufficient data for modelling. The estimates of R0, before lockdown, based on these data were broadly consistent with those previously published at between 2.0 and 3.7 in the countries with the largest number of cases available for analysis (USA, Italy, Spain, France and UK). There was little evidence to suggest that the restrictions had reduced R far below 1 in many places, with Spain having the most rapid reductions - R0 0.71 (95%CI 0.65-0.78) based on cases and 0.81 (95%CI 0.77-0.85) based on mortality. Intermittent lockdown has been proposed as a means of controlling the outbreak while allowing periods of increase freedom and economic activity. These data suggest that few countries could have even one week per month unrestricted without seeing resurgence of the epidemic. Similarly, restoring 20% of the activity that has been prevented by the lockdowns looks difficult to reconcile with preventing the resurgence of the disease in most countries.", "doc_id": "nf6v5dya"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Act early, save lives: managing COVID-19 in Greece", "abstract": "Abstract Objectives: To assess the impact of the implemented social distancing interventions (SD) in Greece. Study Design: A dynamic, discrete time, stochastic individual-based model was developed to simulate COVID-19 transmission. Methods: We fit the transmission model to the observed trends in deaths and ICU beds use. Results: If Greece had not implemented the SD measures, the healthcare system would have been overwhelmed between 30 March and 4 of April. Additionally, the SD interventions averted 4360 deaths and prevent the healthcare system from overwhelmed. Conclusions: The fast reflexes of the Greek government limit the burden of the Covid-19 outbreak.", "doc_id": "7mbvxx1n"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Transmission of SARS-CoV-2 in Georgia, USA, 2020", "abstract": "Objective: SARS-CoV-2 has significantly impacted Georgia, USA including two major hotspots, Metro Atlanta and Dougherty County in southwestern Georgia. With government deliberations about relaxing social distancing measures, it is important to understand the trajectory of the epidemic in the state of Georgia. Methods: We collected daily cumulative incidence of confirmed COVID-19 cases in Georgia. We estimated the reproductive number (Re) of the COVID-19 epidemic on April 18 and May 2 by characterizing the initial growth phase of the epidemic using the generalized-growth model. Results: The data presents a sub-exponential growth pattern in the cumulative incidence curves. On April 18, 2020, Re was estimated as 1.20 (95% CI: 1.10, 1.20) for the state of Georgia, 1.10 (95% CI: 1.00, 1.20) for Dougherty County, and 1.20 (95% CI: 1.10, 1.20) for Metro Atlanta. Extending our analysis to May 2, 2020, Re estimates decreased to 1.10 (95% CI: 1.10, 1.10) for the state of Georgia, 1.00 (95% CI: 1.00, 1.10) for Dougherty County, and 1.10 (95% CI: 1.10, 1.10) for Metro Atlanta. Conclusions: Transmission appeared to be decreasing after the implementation of social distancing measures. However, these results should be interpreted with caution when considering relaxing control measures due to low testing rates.", "doc_id": "e2v9o6oa"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Diminishing Marginal Benefit of Social Distancing in Balancing COVID-19 Medical Demand-to-Supply", "abstract": "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/", "doc_id": "rzh7ja6a"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "COVID-19 outbreak response: a first assessment of mobility changes in Italy following national lockdown", "abstract": "Italy is currently experiencing the largest COVID-19 outbreak in Europe so far, with more than 100,000 confirmed cases. Following the identification of the first infections, on February 21, 2020, national authorities have put in place an increasing number of restrictions aimed at containing the outbreak and delaying the epidemic peak. Since March 12, the whole country is under lockdown. Here we provide the first quantitative assessment of the impact of such measures on the mobility and the spatial proximity of Italians, through the analysis of a large-scale dataset on de-identified, geo-located smartphone users. With respect to pre-outbreak averages, we estimate a reduction of 50% of the total trips between Italian provinces, following the lockdown. In the same week, the average users' radius of gyration has declined by about 50% and the average degree of the users' proximity network has dropped by 47% at national level.", "doc_id": "sgkuqcq6"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Insufficient social distancing may be related to a future COVID-19 outbreak in Ijui-Brazil: Predictions of further social interventions.", "abstract": "The coronavirus disease that initiates in 2019 (COVID-19) has proven to be highly contagious since it became pandemic quickly and nowadays presents higher transmission rates worldwide, including small Brazilian cities, as Ijui. Located in the northwestern of the State of Rio Grande do Sul (RS) with 83,475 inhabitants, Ijui was selected to receive a population-based survey divided into four steps separated by 15 days each that involved 1,750 subjects. Subjects were tested for the presence of antibodies against coronavirus (SARS CoV-2) and answered questions about social distance adherence, daily routine, comorbidities, and sociodemographic characteristics. In parallel, the local government registered the official COVID-19 cases in Ijui. In this study, we demonstrated the levels of social distancing adherence and the beginning of COVID-19 community transmission in Ijui and showed some predictions for cases, hospitalization, and deaths. We concluded that the insufficient social distancing registered in the population-based study might be related to the rapid increase of COVID-19 cases in Ijui. Our study predicts a closer outbreak of community infection of COVID-19, which could be avoided or attenuated if the levels of the social distancing in the population increase in the next weeks.", "doc_id": "0w8i7l7v"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Evaluating the Efficacy of Stay-At-Home Orders: Does Timing Matter?", "abstract": "BACKGROUND: The many economic, psychological, and social consequences of pandemics and social distancing measures create an urgent need to determine the efficacy of non-pharmaceutical interventions (NPIs), and especially those considered most stringent, such as stay-at-home and self-isolation mandates. This study focuses specifically on the efficacy of stay-at-home orders, both nationally and internationally, in the control of COVID-19. METHODS: We conducted an observational analysis from April to May 2020 and included countries and US states with known stay-at-home orders. Our primary exposure was the time between the date of the first reported case of COVID-19 to an implemented stay-at-home mandate for each region. Our primary outcomes were the time from the first reported case to the highest number of daily cases and daily deaths. We conducted simple linear regression analyses, controlling for the case rate of the outbreak. RESULTS: For US states and countries, a larger number of days between the first reported case and stay-at-home mandates was associated with a longer time to reach the peak daily case and death counts. The largest effect was among regions classified as the latest 10% to implement a mandate, which in the US, predicted an extra 35.3 days to the peak number of cases (95 % CI: 18.2, 52.5), and 38.3 days to the peak number of deaths (95 % CI: 23.6, 53.0). CONCLUSIONS: Our study supports the potential beneficial effect of earlier stay-at-home mandates, by shortening the time to peak case and death counts for US states and countries. Regions in which mandates were implemented late experienced a prolonged duration to reaching both peak daily case and death counts.", "doc_id": "mnt12ot2"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "COVID-19 related social distancing measures and reduction in city mobility", "abstract": "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.", "doc_id": "71b6ai77"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "SOCRATES: An online tool leveraging a social contact data sharing initiative to assess mitigation strategies for COVID-19", "abstract": "Objective: Establishing a social contact data sharing initiative and an interactive tool to assess mitigation strategies for COVID-19. Results: We organized data sharing of published social contact surveys via online repositories and formatting guidelines. We analyzed this social contact data in terms of weighted social contact matrices, next generation matrices, relative incidence and R0. We incorporated location-specific isolation measures (e.g. school closure or telework) and capture their effect on transmission dynamics. All methods have been implemented in an online application based on R Shiny and applied to COVID-19 with age-specific susceptibility and infectiousness. Using our online tool with the available social contact data, we illustrate that social distancing could have a considerable impact on reducing transmission for COVID-19. The effect itself depends on assumptions made about disease-specific characteristics and the choice of intervention(s). Keywords: social contact data, user interface, transmission dynamics, infectious diseases, epidemics, social distancing, behavioral changes, data sharing initiative, open-source, COVID-19", "doc_id": "hs38s0vc"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Is the impact of social distancing on coronavirus growth rates effective across different settings? A non-parametric and local regression approach to test and compare the growth rate", "abstract": "Epidemiologists use mathematical models to predict epidemic trends, and these results are inherently uncertain when parameters are unknown or changing. In other contexts, such as climate, modellers use multi-model ensembles to inform their decision-making: when forecasts align, modellers can be more certain. This paper looks at a sub-set of alternative epidemiological models that focus on the growth rate, and it cautions against relying on the method proposed in (Pike & Saini, 2020): relying on the data for China to calculate future trajectories is likely to be subject to overfitting, a common problem in financial and economic modelling. This paper finds, surprisingly, that the data for China are double-exponential, not exponential; and that different countries are showing a range of different trajectories. The paper proposes using non-parametric and local regression methods to support epidemiologists and policymakers in assessing the relative effectiveness of social distancing policies. All works contained herein are provided free to use worldwide by the author under CC BY 2.0.", "doc_id": "sg5uwuqc"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "The effect of non-pharmaceutical interventions (NPIs) on the spread of COVID-19 pandemic in Japan: A modeling study", "abstract": "Non-pharmaceutical interventions (NPIs) are founded to be effective to delay epidemic spread and to reduce the number of patients. Moderate NPIs took in Japan seemed to have reduced the COVID-19 patients and to lower death rates, thus, effects of those NPIs are worthy of investigation. We used open source data and divided the data into three periods: Jan 22 to Feb 25 (Period I), Feb 26 to Apr 6 (Period II), and Apr 7 to May 14 (Period III). We developed the SIRD model and applied the Monte Carlo Simulation to estimate a combination of optimal results, including the peak of infected cases, the peak date, and R0. For Period I, the estimated peak infected cases were smaller than the observed ones, the peak date was earlier than the observed one, and the R0 was about 4.66. For the other two periods, the estimated cases were more, and the peak dates were earlier than the observed ones. The R0 was 2.50 in Period II, and 1.79 in Period III. NPIs took in Japan might have reduced more than 50% of the daily contacts per people compared to that before COVID-19. Owing to the effects of NPIs, the Japanese society had avoided collapse of medical service. Nevertheless, the capacity of daily RT-PCR may have restricted the reported confirmed cases.", "doc_id": "80bn2wgd"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Analysis and Prediction of the COVID-19 outbreak in Pakistan", "abstract": "In this study, we estimate the severity of the COVID-19 outbreak in Pakistan prior to and after lockdown restrictions were eased. We also project the epidemic curve considering realistic quarantine, social distancing, and possible medication scenarios. We use a deterministic epidemic model that includes asymptomatic, quarantined, isolated, and medicated population compartments for our analysis. We calculate the basic reproduction number R0 for the pre and post lockdown periods, noting that during this time, no medication was available. The pre-lock down the value of R0 is estimated to be 1.07, and the post lockdown value is estimated to be 1.86. We use this analysis to project the epidemic curve for a variety of lockdown, social distancing, and medication scenarios. We note that if no substantial efforts are made to contain the epidemic, it will peak in mid of September, with the maximum projected active cases being close to 700,000. In a realistic, best-case scenario, we project that the epidemic peaks in early to mid-July with the maximum active cases being around 120000.We note that social distancing measures and medication, if available, will help flatten the curve, however without the reintroduction of further lockdown, it would be very difficult to bring R0 below 1. Our study strongly supports the recent WHO recommendation of reintroducing lockdowns to control the epidemic.", "doc_id": "3dx6deei"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Evaluation of Turkish social distancing measures on the spread of COVID-19", "abstract": "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.", "doc_id": "uwix8ftr"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "The nexus of travel restriction, air pollution and COVID-19 infection: Investigation from a megacity of the southern China", "abstract": "To control and prevent the spread of COVID-19, generalized social distancing measures, such as traffic control and travel restriction acted in China. Previous studies indicated that the traffic conditions had significant influence on the air quality, and which was related to the respiratory diseases. This study aimed to reveal the nexus of travel restriction, air pollution and COVID-19. Shenzhen, one of the top 4 megacities in China was considered as the study area, statistical analysis methods, including linear/nonlinear regression and bivariate correlation was conducted to evaluate the relationship of the traffic and passenger population, travel intensity, NO2, PM10, PM2.5 and the number of COVID-19 confirmed cases. The results suggested that traffic control and travel restriction had a significant correlation with the number of COVID-19 confirmed cases, which shown negative correlation with the traffic intensity of the city, NO2, PM10 and PM2.5 show significant positive correlation with the traffic intensity, traffic control and travel restriction would slow down and prevent the spread of the viruses at the outbreak period. Different study scale might results in different results, thus the research focused on the nexus of traffic control and travel restriction, air pollution and COVID-19 should been enhanced in future, and differentiated epidemic control and prevention measures should be considered according to the different situation of cities as well as countries.", "doc_id": "tarb3zxk"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "COVID-19 Control Strategies and Intervention Effects in Resource Limited Settings: A Modeling Study", "abstract": "Background Many countries with weaker health systems are struggling to put together a coherent strategy against the COVID-19 epidemic. We explored COVID-19 control strategies that could offer the greatest benefit in resource limited settings. Methods Using an age-structured SEIR model, we explored the effects of COVID-19 control interventions--a lockdown, physical distancing measures, and active case finding (testing and isolation, contact tracing and quarantine)-- implemented individually and in combination to control a hypothetical COVID-19 epidemic in Kathmandu (population 2.6 million), Nepal. Results A month-long lockdown that is currently in place in Nepal will delay peak demand for hospital beds by 36 days, as compared to a base scenario of no interventions (peak demand at 108 days (IQR 97-119); a 2 month long lockdown will delay it by 74 days, without any difference in annual mortality, or healthcare demand volume. Year-long physical distancing measures will reduce peak demand to 36% (IQR 23%-46%) and annual morality to 67% (IQR 48%-77%) of base scenario. Following a month long lockdown with ongoing physical distancing measures and an active case finding intervention that detects 5% of the daily infection burden could reduce projected morality and peak demand by more than 99%. Interpretation Limited resources settings are best served by a combination of early and aggressive case finding with ongoing physical distancing measures to control the COVID-19 epidemic. A lockdown may be helpful until combination interventions can be put in place but is unlikely to reduce annual mortality or healthcare demand.", "doc_id": "8w22yn1i"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "A sub-national analysis of the rate of transmission of COVID-19 in Italy", "abstract": "Italy was the first European country to experience sustained local transmission of COVID-19. As of 1st May 2020, the Italian health authorities reported 28,238 deaths nationally. To control the epidemic, the Italian government implemented a suite of non-pharmaceutical interventions (NPIs), including school and university closures, social distancing and full lockdown involving banning of public gatherings and non essential movement. In this report, we model the effect of NPIs on transmission using data on average mobility. We estimate that the average reproduction number (a measure of transmission intensity) is currently below one for all Italian regions, and significantly so for the majority of the regions. Despite the large number of deaths, the proportion of population that has been infected by SARS-CoV-2 (the attack rate) is far from the herd immunity threshold in all Italian regions, with the highest attack rate observed in Lombardy (13.18% [10.66%-16.70%]). Italy is set to relax the currently implemented NPIs from 4th May 2020. Given the control achieved by NPIs, we consider three scenarios for the next 8 weeks: a scenario in which mobility remains the same as during the lockdown, a scenario in which mobility returns to pre-lockdown levels by 20%, and a scenario in which mobility returns to pre-lockdown levels by 40%. The scenarios explored assume that mobility is scaled evenly across all dimensions, that behaviour stays the same as before NPIs were implemented, that no pharmaceutical interventions are introduced, and it does not include transmission reduction from contact tracing, testing and the isolation of confirmed or suspected cases. New interventions, such as enhanced testing and contact tracing are going to be introduced and will likely contribute to reductions in transmission; therefore our estimates should be viewed as pessimistic projections. We find that, in the absence of additional interventions, even a 20% return to pre-lockdown mobility could lead to a resurgence in the number of deaths far greater than experienced in the current wave in several regions. Future increases in the number of deaths will lag behind the increase in transmission intensity and so a second wave will not be immediately apparent from just monitoring of the daily number of deaths. Our results suggest that SARS-CoV-2 transmission as well as mobility should be closely monitored in the next weeks and months. To compensate for the increase in mobility that will occur due to the relaxation of the currently implemented NPIs, adherence to the recommended social distancing measures alongside enhanced community surveillance including swab testing, contact tracing and the early isolation of infections are of paramount importance to reduce the risk of resurgence in transmission.", "doc_id": "32lau54s"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Impact of control strategies on COVID-19 pandemic and the SIR model based forecasting in Bangladesh.", "abstract": "COVID-19 is transmitting worldwide drastically and infected nearly two and half million of people sofar. Till date 2144 cases of COVID-19 is confirmed in Bangladesh till 18th April though the stage-3/4 transmission is not validated yet. To project the final infection numbers in Bangladesh we used the SIR mathematical model. We also tried to demonstrate the impact of control strategies like social distancing on the COVID-19 transmission. Due to large population and socio-economic characteristics, we assumed 60% social distancing and lockdown can be possible. Assuming that, the predicated final size of infections will be 3782558 on the 92th day from the first infections. To estimate the impact of social distancing we assumed eight different scenarios, the predicted results confirmed the positive impact of this type of control strategies suggesting that by strict social distancing and lockdown, COVID-19 infection can be under control and then the infection cases will steadily decrease down to zero.", "doc_id": "le2eifv8"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Modeling the Transmission of Respiratory Infectious Diseases in Mass Transportation Systems", "abstract": "Mass transportation is one of the areas that are badly hit by respiratory infectious disease outbreaks due to moderate to high exposure risk to pathogens brought about by the interaction among commuters. Here, we formulate agent-based models that simulate the spread of a respiratory infectious disease in a train wagon in the Manila Light Rail Transit System, and in a 49-seater public utility bus. We consider preventive measures such as implementation of social distancing, and limitation of interaction or movement among the commuters to investigate how these measures will inhibit disease transmission. We also consider the effect of protective gears and practices, crowd density, and prevalence of disease in the community on the possible number of newly-infected individuals. Our simulations show that (i) individuals must have protection with more than 90% effectiveness to inhibit transmission of the disease; (ii) social or physical distancing by more than 1m distance reduces the risk of being infected; (iii) minimizing movement or interaction with other passengers reduces the risk of transmission by 50%; (iv) passenger capacity should be less than 10-50% of the maximum seating capacity to reduce the number of infections depending on the level of imposed social distancing and passenger interaction; (v) vehicles with greater number of occupied seating capacity generate higher number of infections but vehicles with smaller dimensions have faster disease transmissions; and (vi) ideal set-up for a 24-seater train wagon (49-seater bus) is to allow a maximum of 12 (24) passengers, with little to no interaction among passengers, with social distancing of more than 1m distance apart, and each person has a protection with 90% effectiveness as much as possible. These results can aid policy makers in determining optimal strategies to minimize infections while maintaining transportation services during pandemics or disease outbreaks.", "doc_id": "n3rdxn2a"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Reacting to outbreaks at neighboring localities", "abstract": "We study the dynamics of epidemics in a networked metapopulation model. In each subpopulation, representing a locality, disease propagates according to a modified susceptible-exposed-infected-recovered (SEIR) dynamics. We assume that individuals reduce their number of contacts as a function of the weighted sum of cumulative number of cases within the locality and in neighboring localities. The susceptible and exposed (pre-symptomatic and infectious) individuals are allowed to travel between localities undetected. To investigate the combined effects of mobility and contact reduction on disease progression within interconnected localities, we consider a scenario with two localities where disease originates in one and is exported to the neighboring locality via travel of undetected pre-symptomatic individuals. We associate the behavior change at the disease-importing locality due to the outbreak size at the origin with the level of preparedness of the locality. Our results show that restricting mobility is valuable if the importing locality is increasing its level of preparedness with respect to the outbreak size at the origin. Moreover, increased levels of preparedness can yield lower total outbreak size by further reducing the outbreak size at the importing locality, even when the response at the origin is weak. Our results highlight that public health decisions on social distancing at localities with less severe outbreaks should strongly account for potential impact of neighbouring localities with a poor response to the outbreak rather than localities with successful responses.", "doc_id": "ceehbhcb"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Evaluating the effectiveness of social distancing interventions against COVID-19", "abstract": "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.", "doc_id": "0a49okho"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Optimal Control applied to a SEIR model of 2019-nCoV with social distancing", "abstract": "Does the implementation of social distancing measures have merit in controlling the spread of the novel coronavirus? In this study, we develop a mathematical model to explore the effect of social distancing on new disease infections. Mathematical analyses of our model indicate that successful eradication of the disease is strongly dependent on the chosen preventive measure. Numerical computations of the model solution demonstrate that the ability to flatten the curve becomes easier as social distancing is strictly enforced. Based on our model, we also formulate an optimal control problem and solve it using Pontryagin's Maximum Principle and an efficient numerical iterative method. Our numerical results of an optimal 2019-nCoV treatment protocol that yields a minimum disease burden from this disease indicates that social distancing is vitally important.", "doc_id": "qm2qvcwk"} {"topic_name": "coronavirus social distancing impact", "topic_id": "10", "title": "Assessing the effect of global travel and contact reductions to mitigate the COVID-19 pandemic and resurgence", "abstract": "Travel and physical distancing interventions have been implemented across the World to mitigate the COVID-19 pandemic, but studies are needed to quantify the effectiveness of these measures across regions and time. Timely population mobility data were obtained to measure travel and contact reductions in 135 countries or territories. During the 10 weeks of March 22 - May 30, 2020, domestic travel in study regions has dramatically reduced to a median of 59% (interquartile range [IQR] 43% - 73%) of normal levels seen before the outbreak, with international travel down to 26% (IQR 12% - 35%). If these travel and physical distancing interventions had not been deployed across the World, the cumulative number of cases might have shown a 97-fold (IQR 79 - 116) increase, as of May 31, 2020. However, effectiveness differed by the duration and intensity of interventions and relaxation scenarios, with variations in case severity seen across populations, regions, and seasons.", "doc_id": "5bj2fn7g"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Clinical Ethical Challenges in the Covid-19 Crisis in South Africa", "abstract": "", "doc_id": "7o3qhfk3"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Organising a COVID-19 Triage Unit: a Swiss Perspective.", "abstract": "BACKGROUND With the rapid global spread of the acute respiratory syndrome coronavirus 2, urgent health-care measures have been implemented. We describe the organizational process in setting up a coronavirus disease 2019 triage unit in a Swiss tertiary care hospital. METHODS Our triage unit was set-up outside of the main hospital building and consists of three areas: 1. Pre-triage, 2. Triage, and 3. Triage plus. The Pre-triage check-points identify any potential COVID-19-infected patients and re-direct them to the main Triage area where trained medical staff screen which patients undergo diagnostic testing. If testing is indicated, nasopharyngeal swabs are performed. If patients require further investigations, they are referred to Triage plus. At this stage, patients are then discharged home after additional testing or admitted to the hospital for management. OBSERVATIONS A total of 1,265 patients were screened between March 10th 2020 and April 12th 2020 at our Triage unit. Of these, 112 (8.9%) tested positive. 73 (65%) of the positively-tested patients were female and 39 (35%) were male. The mean age for all patients was 43.8 years (SD 16.3 years). Distinguishing between genders, mean age for females was 41.1 (SD 16.5) and mean age for males was 48.6 (SD 14.9), with females being significantly younger than males (p<0.001). CONCLUSION Our triage unit was set-up as part of a large-scale restructuring process. Current challenges include low sensitivity for test results as well as limited staff and resources. We hope that our experience will help other health care institutions develop similar triage systems.", "doc_id": "lom4jdcj"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "COVID-19: Management.", "abstract": "Coronavirus disease (COVID-19) has grasped the world including Pakistan. Clinical features of this disease are variable, ranging from asymptomatic to critical disease. In this unprecedented global war, the Pakistan Chest Society has written a guideline for quick review for the specialists providing care to suspected or confirmed patients. This review highlights the approach to a patient with COVID-19, including definition of the various syndromes of the disease, the abnormal laboratory parameters and outlines the therapeutic measures which are currently under investigation.", "doc_id": "7d3s6jo0"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Use of Radiographic Features in COVID-19 Diagnosis: Challenges and Perspectives.", "abstract": "The rapid surge and wide-spread of the coronavirus disease-2019 (COVID-19) overshadows the entire medical industries worldwide. The stringent medical resources hinder the diagnostic capacity globally, while 84 thousands of new cases confirmed within a single day of 14 April 2020. Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) with is the current first-line diagnosis, but the false-negative rate remains concerned. Radiographic technologies and tools, including Computed tomography (CT) and Chest X-ray (CXR), were applied for initial screening and follow-up, from which provides detail diagnosis with specific pathologic features for staging and treatment arrangement. Although the radiographic imaging is found less sensitive, numerous CT-positive patients were not screened out by RT-PCR initially and later confirmed as COVID-19 positive. Besides, the shortage of sampling kits and the longer turn-over time of PCR examinations in some areas were noticed due to logistic issues and healthcare burden. In this review, we will discuss the challenges and the future perspectives of using radiographic modalities for COVID-19 diagnosis in view of securing human lives amid the crisis.", "doc_id": "th7o8toc"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Reorganising the pandemic triage processes to ethically maximise individuals' best interests.", "abstract": "PURPOSE To provide a revised definition, process and purpose of triage to maximise the number of patients receiving intensive care during a crisis. METHODS Based on the ethical principle of virtue ethics and the underlying goal of providing individual patients with treatment according to their best interests, the methodology of triage is reassessed and revised. RESULTS The decision making processes regarding treatment decisions during a pandemic are redefined and new methods of intensive care provision recommended as well as recommending the use of a 'ranking' system for patients excluded from intensive care, defining the role of non-intensive care specialists, and applying two types of triage as 'organisational triage' and 'treatment triage' based on the demand for intensive care. CONCLUSION Using a different underlying ethical basis upon which to plan for a pandemic crisis could maximise the number of patients receiving intensive care based on individual patients' best interests.", "doc_id": "whwkv4ne"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Management Considerations for the Surgical Treatment of Colorectal Cancer During the Global Covid-19 Pandemic.", "abstract": "OBJECTIVE The COVID-19 pandemic requires to conscientiously weigh \"timely surgical intervention\" for colorectal cancer against efforts to conserve hospital resources and protect patients and health care providers. SUMMARY BACKGROUND DATA Professional societies provided ad-hoc guidance at the outset of the COVID-19 pandemic on deferral of surgical and perioperative interventions, but these lack specific parameters to determine the optimal timing of surgery. METHODS Using the GRADE system, published evidence was analyzed to generate weighted statements for stage, site, acuity of presentation and hospital setting to specify when surgery should be pursued, the time and duration of oncologically acceptable delays, and when to utilize non-surgical modalities to bridge the waiting period. RESULTS Colorectal cancer surgeries - prioritized as emergency, urgent with (a) imminent emergency or (b) oncologically urgent, or elective - were matched against the phases of the pandemic. Surgery in COVID-19 positive patients must be avoided. Emergent and imminent emergent cases should mostly proceed unless resources are exhausted. Standard practices allow for postponement of elective cases and deferral to nonsurgical modalities of stage II/III rectal and metastatic colorectal cancer. Oncologically urgent cases may be delayed for 6(-12) weeks without jeopardizing oncological outcomes. Outside established principles, administration of nonsurgical modalities is not justified and increases the vulnerability of patients. CONCLUSION The COVID-19 pandemic has stressed already limited health care resources and forced rationing, triage and prioritization of care in general, specifically of surgical interventions. Established guidelines allow for modifications of optimal timing and type of surgery for colorectal cancer during an unrelated pandemic.", "doc_id": "j3n1etkr"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "[COVID-19 Triage: Who is an inpatient? The Essen triage model].", "abstract": "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.", "doc_id": "hrqwt37s"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "The formation and design of the TRIAGE study--baseline data on 6005 consecutive patients admitted to hospital from the emergency department.", "abstract": "BACKGROUND Patient crowding in emergency departments (ED) is a common challenge and associated with worsened outcome for the patients. Previous studies on biomarkers in the ED setting has focused on identification of high risk patients, and and the ability to use biomarkers to identify low-risk patients has only been sparsely examined. The broader aims of the TRIAGE study are to develop methods to identify low-risk patients appropriate for early ED discharge by combining information from a wide range of new inflammatory biomarkers and vital signs, the present baseline article aims to describe the formation of the TRIAGE database and characteristize the included patients. METHODS We included consecutive patients \u2265 17 years admitted to hospital after triage staging in the ED. Blood samples for a biobank were collected and plasma stored in a freezer (-80 \u00b0C). Triage was done by a trained nurse using the Danish Emergency Proces Triage (DEPT) which categorizes patients as green (not urgent), yellow (urgent), orange (emergent) or red (rescusitation). Presenting complaints, admission diagnoses, comorbidities, length of stay, and 'events' during admission (any of 20 predefined definitive treatments that necessitates in-hospital care), vital signs and routine laboratory tests taken in the ED were aslo included in the database. RESULTS Between September 5(th) 2013 and December 6(th) 2013, 6005 patients were included in the database and the biobank (94.1 % of all admissions). Of these, 1978 (32.9 %) were categorized as green, 2386 (39.7 %) yellow, 1616 (26.9 %) orange and 25 (0.4 %) red. Median age was 62 years (IQR 46-76), 49.8 % were male and median length of stay was 1 day (IQR 0-4). No events were found in 2658 (44.2 %) and 158 (2.6 %) were admitted to intensive or intermediate-intensive care unit and 219 (3.6 %) died within 30 days. A higher triage acuity level was associated with numerous events, including acute surgery, endovascular intervention, i.v. treatment, cardiac arrest, stroke, admission to intensive care, hospital transfer, and mortality within 30 days (p < 0.001). CONCLUSION The TRIAGE database has been completed and includes data and blood samples from 6005 unselected consecutive hospitalized patients. More than 40 % experienced no events and were therefore potentially unnecessary hospital admissions.", "doc_id": "1nkpmw5a"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Extracorporeal Membrane Oxygenation for Pediatric Patients With Coronavirus Disease 2019-Related Illness.", "abstract": "OBJECTIVE To describe current hospital guidelines and the opinions of extracorporeal membrane oxygenation leaders at U.S. children's hospitals concerning the use of extracorporeal membrane oxygenation for coronavirus disease 2019-positive pediatric patients. DESIGN Confidential, self-administered questionnaire. SETTING One hundred twenty-seven U.S. pediatric extracorporeal membrane oxygenation centers. SUBJECTS Extracorporeal membrane oxygenation center program directors and coordinators. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS In March 2020, a survey was sent to 127 pediatric extracorporeal membrane oxygenation centers asking them to report their current hospital extracorporeal membrane oxygenation guidelines for coronavirus disease 2019-positive patients. Respondents were also asked their opinion on three ethical dilemmas including: prioritization of children over adults for extracorporeal membrane oxygenation use, institution of do-not-resuscitate orders, and the use of extracorporeal cardiopulmonary resuscitation for coronavirus disease 2019-positive patients. Forty-seven extracorporeal membrane oxygenation centers had enacted guidelines including 46 (100%) that offer venovenous-extracorporeal membrane oxygenation and 42 (89%) that offer venoarterial-extracorporeal membrane oxygenation for coronavirus disease 2019-positive pediatric patients. Forty-four centers (94%) stated that the indications for extracorporeal membrane oxygenation candidacy in coronavirus disease 2019 disease were similar to those used in other viral illnesses, such as respiratory syncytial virus or influenza. Most program directors (98%) did not endorse that children hospitalized with coronavirus disease 2019 should be made do-not-resuscitate and had variable opinions on whether children should be given higher priority over adults when rationing extracorporeal membrane oxygenation. Over half of program directors (60%) did not support the use of extracorporeal cardiopulmonary resuscitation for coronavirus disease 2019. CONCLUSIONS The majority of pediatric extracorporeal membrane oxygenation centers have proactively established guidelines for the use of extracorporeal membrane oxygenation for coronavirus disease 2019-related illnesses. Further work is needed to help guide the fair allocation of extracorporeal membrane oxygenation resources and to determine the appropriateness of extracorporeal cardiopulmonary resuscitation.", "doc_id": "f7ylxcog"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Immersion in an emergency department triage center during the Covid-19 outbreak: first report of the Li\u00e8ge University hospital experience.", "abstract": "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 Li\u00e8ge 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.", "doc_id": "gyghpk64"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Response of a comprehensive cancer center to the COVID-19 pandemic: the experience of the Fondazione IRCCS-Istituto Nazionale dei Tumori di Milano.", "abstract": "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.", "doc_id": "r4r1a6fd"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Simple, fast and affordable triaging pathway for COVID-19.", "abstract": "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.", "doc_id": "ba5x3ysq"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Analysis and suggestions for the preview and triage screening of children with suspected COVID-19 outside the epidemic area of Hubei Province", "abstract": "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.", "doc_id": "macqp9k1"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "\u201cDaily Work in the Fever Clinics of Wuhan Union Hospital During the Novel Coronavirus Pneumonia Epidemic: A Special Spring Festival in Wuhan, China\u201dExtracorporeal Membrane Oxygenation for Pediatric Patients With Coronavirus Disease 2019\u2013Related Illness", "abstract": "Objective: To describe current hospital guidelines and the opinions of extracorporeal membrane oxygenation leaders at U S children\u2019s hospitals concerning the use of extracorporeal membrane oxygenation for coronavirus disease 2019\u2013positive pediatric patients Design: Confidential, self-administered questionnaire Setting: One hundred twenty-seven U S pediatric extracorporeal membrane oxygenation centers Subjects: Extracorporeal membrane oxygenation center program directors and coordinators Interventions: None Measurements and Main Results: In March 2020, a survey was sent to 127 pediatric extracorporeal membrane oxygenation centers asking them to report their current hospital extracorporeal membrane oxygenation guidelines for coronavirus disease 2019\u2013positive patients Respondents were also asked their opinion on three ethical dilemmas including: prioritization of children over adults for extracorporeal membrane oxygenation use, institution of do-not-resuscitate orders, and the use of extracorporeal cardiopulmonary resuscitation for coronavirus disease 2019\u2013positive patients Forty-seven extracorporeal membrane oxygenation centers had enacted guidelines including 46 (100%) that offer venovenous-extracorporeal membrane oxygenation and 42 (89%) that offer venoarterial-extracorporeal membrane oxygenation for coronavirus disease 2019\u2013positive pediatric patients Forty-four centers (94%) stated that the indications for extracorporeal membrane oxygenation candidacy in coronavirus disease 2019 disease were similar to those used in other viral illnesses, such as respiratory syncytial virus or influenza Most program directors (98%) did not endorse that children hospitalized with coronavirus disease 2019 should be made do-not-resuscitate and had variable opinions on whether children should be given higher priority over adults when rationing extracorporeal membrane oxygenation Over half of program directors (60%) did not support the use of extracorporeal cardiopulmonary resuscitation for coronavirus disease 2019 Conclusions: The majority of pediatric extracorporeal membrane oxygenation centers have proactively established guidelines for the use of extracorporeal membrane oxygenation for coronavirus disease 2019\u2013related illnesses Further work is needed to help guide the fair allocation of extracorporeal membrane oxygenation resources and to determine the appropriateness of extracorporeal cardiopulmonary resuscitation Drs MacGregor and Antiel are co-first authors Supplemental digital content is available for this article Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal\u2019s website (http://journals lww com/pccmjournal) The authors have disclosed that they do not have any potential conflicts of interest For information regarding this article, E-mail: baddr@wustl edu \u00a92020The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies", "doc_id": "q2xjx56v"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Predicting individual risk for COVID19 complications using EMR data", "abstract": "Background: The global pandemic of COVID-19 has challenged healthcare organizations and caused numerous deaths and hospitalizations worldwide. The need for data-based decision support tools for many aspects of controlling and treating the disease is evident but has been hampered by the scarcity of real-world reliable data. Here we describe two approaches: a. the use of an existing EMR-based model for predicting complications due to influenza combined with available epidemiological data to create a model that identifies individuals at high risk to develop complications due to COVID-19 and b. a preliminary model that is trained using existing real world COVID-19 data. Methods: We have utilized the computerized data of Maccabi Healthcare Services a 2.3 million member state-mandated health organization in Israel. The age and sex matched matrix used for training the XGBoost ILI-based model included, circa 690,000 rows and 900 features. The available dataset for COVID-based model included a total 2137 SARS-CoV-2 positive individuals who were either not hospitalized (n=1658), or hospitalized and marked as mild (n=332), or as having moderate (n=83) or severe (n=64) complications. Findings: The AUC of our models and the priors on the 2137 COVID-19 patients for predicting moderate and severe complications as cases and all other as controls, the AUC for the ILI-based model was 0.852[0.824-0.879] for the COVID19-based model - 0.872[0.847-0.879].. Interpretation: These models can effectively identify patients at high-risk for complication, thus allowing optimization of resources and more focused follow up and early triage these patients if once symptoms worsen.", "doc_id": "lir8ht2i"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "DERIVATION OF A SCORE TO PREDICT ADMISSION TO INTENSIVE CARE UNIT IN PATIENTS WITH COVID-19: THE ABC-GOALS SCORE", "abstract": "Background. COVID-19 pandemic poses a burden on hospital resources and intensive care unit (ICU) occupation. The study aimed to derive a scoring system that, assessed upon patient first-contact evaluation, predicts the need for admission to ICU. Methods. All consecutive patients admitted to a COVID-19 reference center were prospectively assessed. Patients were segregated into a group that required admission to ICU during their hospitalization and a group that never required ICU admission and was already discharged from hospitalization. Three models including clinical, laboratory and imaging findings were derived by logistic regression analysis and internally validated. A score, defined as the ABC-GOALS score was created by assigning values based on the variables weighted odd ratios. Results. The study comprised 329 patients, 115 (35%) required ICU admission and 214 (65%) were hospitalized and discharged from general wards. The clinical prediction model (ABC-GOALSc) included sex, obesity, the Charlson comorbidity index, dyspnea, arterial pressure and respiratory rate at triage evaluation. The clinical plus laboratory model (ABC-GOALScl) added serum albumin, glucose, lactate dehydrogenase and S/F ratio to the clinical model. The model that included imaging (ABC-GOALSclx) added the CT scan finding of >50% lung involvement. All three models outperformed other pneumonia-specific scores with area under the curve of 0.79 (0.74-0.83), 0.86 (0.82-0.90) and 0.88 (0.84-0.92) for the clinical, laboratory and imaging model, respectively. Conclusion. The ABC-GOALS score is a tool to evaluate patients with COVID-19 at admission to the emergency department that allows to timely predict their risk of admission to an ICU and may help optimize healthcare capacities.", "doc_id": "w9aaalgo"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Development of a severity of disease score and classification model by machine learning for hospitalized COVID-19 patients", "abstract": "BACKGROUND: Efficient and early triage of hospitalized Covid-19 patients to detect those with higher risk of severe disease is essential for appropriate case management. METHODS: We trained, validated, and externally tested a machine-learning model to early identify patients who will die or require mechanical ventilation during hospitalization from clinical and laboratory features obtained at admission. A development cohort with 918 Covid-19 patients was used for training and internal validation, and 352 patients from another hospital were used for external testing. Performance of the model was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity and specificity. RESULTS: A total of 363 of 918 (39.5%) and 128 of 352 (36.4%) Covid-19 patients from the development and external testing cohort, respectively, required mechanical ventilation or died during hospitalization. In the development cohort, the model obtained an AUC of 0.85 (95% confidence interval [CI], 0.82 to 0.87) for predicting severity of disease progression. Variables ranked according to their contribution to the model were the peripheral blood oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio, age, estimated glomerular filtration rate, procalcitonin, C-reactive protein, updated Charlson comorbidity index and lymphocytes. In the external testing cohort, the model performed an AUC of 0.83 (95% CI, 0.81 to 0.85). This model is deployed in an open source calculator, in which Covid-19 patients at admission are individually stratified as being at high or non-high risk for severe disease progression. CONCLUSIONS: This machine-learning model, applied at hospital admission, predicts risk of severe disease progression in Covid-19 patients.", "doc_id": "msuks2jn"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Derivation and validation of a prognostic model for predicting in-hospital mortality in patients admitted with COVID-19 in Wuhan, China: the PLANS (Platelet Lymphocyte Age Neutrophil Sex) model", "abstract": "OBJECTIVE To develop and validate a prognostic model for in-hospital mortality in COVID-19 patients using routinely collected demographic and clinical characteristics. DESIGN Multicenter, retrospective cohort study. SETTING Jinyintan Hospital, Union Hospital, and Tongji Hosptial in Wuhan, China. PARTICIPANTS A pooled derivation cohort of 1008 COVID-19 patients from Jinyintan Hospital, Union Hospital in Wuhan and an external validation cohort of 1031 patients from Tongji Hospital in Wuhan, China. MAIN OUTCOME MEASURES Outcome of interest was in-hospital mortality, treating discharged alive from hospital as the competing event. Fine-Gray models, using backward elimination for inclusion of predictor variables and allowing non-linear effects of continuous variables, were used to derive a prognostic model for predicting in-hospital mortality among COVID-19 patients. Internal validation was implemented to check model overfitting using bootstrap approach. External validation to a separate hospital was implemented to evaluate the generalizability of the model. RESULTS The derivation cohort was a case-mix of mild-to-severe hospitalized COVID-19 patients (n=1008, 43.6% females, median age 55). The final model (PLANS), including five predictor variables of platelet count, lymphocyte count, age, neutrophil count, and sex, had an excellent predictive performance (optimism-adjusted C-index: 0.85, 95% CI: 0.83 to 0.87; averaged calibration slope: 0.95, 95% CI: 0.82 to 1.08). Internal validation showed little overfitting. External validation using an independent cohort (n=1031, 47.8% female, median age 63) demonstrated excellent predictive performance (C-index: 0.87, 95% CI: 0.85 to 0.89; calibration slope: 1.02, 95% CI: 0.92 to 1.12). The averaged predicted survival curves were close to the observed survival curves across patients with different risk profiles. CONCLUSIONS The PLANS model based on the five routinely collected demographic and clinical characteristics (platelet count, lymphocyte count, age, neutrophil count, and sex) showed excellent discriminative and calibration accuracy in predicting in-hospital mortality in COVID-19 patients. This prognostic model would assist clinicians in better triaging patients and allocating healthcare resources to reduce COVID-19 fatality.", "doc_id": "wbc2z5wt"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Triage of Acute Ischemic Stroke in Confirmed COVID-19: Large Vessel Occlusion Associated With Coronavirus Infection", "abstract": "The outbreak of COVID-19 has posed a significant challenge to global healthcare. Acute stroke care requires rapid bedside attendance, imaging, and intervention. However, for acute stroke patients who have a diagnosis of or are under investigation for COVID-19, the concern for nosocomial transmission moderates operational procedures for acute stroke care. We present our experience with an in-hospital stroke code called on a COVID-19-positive patient with a left middle cerebral artery syndrome and the challenges faced for timely examination, imaging, and decision to intervene. The outlook for the ongoing COVID-19 pandemic necessitates the development of protocols to sustain timely and effective acute stroke care while mitigating healthcare-associated transmission.", "doc_id": "4t4gr0jz"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "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", "abstract": "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.", "doc_id": "blqpb9a1"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Triage tool for suspected COVID-19 patients in the emergency room: AIFELL score", "abstract": "Clinical prediction scores support the assessment of patients in the emergency setting to determine the need for further diagnostic and therapeutic steps. During the current COVID-19 pandemic, physicians in emergency rooms (ER) of many hospitals have a considerably higher patient load and need to decide within a short time frame whom to hospitalize. Based on our clinical experiences in dealing with COVID-19 patients at the University Hospital Zurich, we created a triage score with the acronym AIFELL consisting of clinical, radiological and laboratory findings. The score was then evaluated in a retrospective analysis of 122 consecutive patients with suspected COVID-19 from March until mid-April 2020. Descriptive statistics, Student's t-test, ANOVA and Scheffe's post hoc analysis confirmed the diagnostic power of the score. The results suggest that the AIFELL score has potential as a triage tool in the ER setting intended to select probable COVID-19 cases for hospitalization in spontaneously presenting or referred patients with acute respiratory symptoms.", "doc_id": "xzidr8dv"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Hospital-based autonomous pre-clinical screening of COVID-19: An emergency triage using a vital signs recording system, Paris-Ile de France region.", "abstract": "The COVID-19 pandemic has had a dramatic toll worldwide on the populations but also has been essentially supported by the existing public health system, particularly hospital-based emergency wards and intensive care units. In France, the first cases were identified on the 24th of January 2020. The first epidemic sprout emerged in the Eastern part of the country and spread in two weeks towards the center to the Paris-region where it peaked on the 14th of April 2020. In Paris and the region around it, the intensity of the epidemic has increased significantly to have a strong impact on all public and private hospital systems in a few weeks. During France's 2020 COVID-19 epidemic, a private hospital went into a major organizational change of its Emergency Department which mainly included the use of a Telemedicine Booth for vitals automatic recording during triage procedures. The present study describes the organizational scheme adopted by the hospital and discusses the data of 1,844 patients that attended the facility over a month. While among them, 766 patients were engaged in an automated triage process supported by a Telemedicine Booth. Patients' clinical characteristics are comparable to those found in international literature during the COVID-19 pandemic. The use of the Telemedicine Booth as a screening process facilitated patients' flow. It usefully participated in the patient rapid orientation, relieving the hospital emergency department, actively contributes in a safe and secure environment highly trusted by the hospital staff and health workers. To our knowledge, the Telemedicine Booth use as a screening process during an epidemic constitutes the first contribution to such an innovative approach.", "doc_id": "8mtqlcoi"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "On the Front (Phone) Lines: Results of a COVID-19 Hotline in Northeast Ohio", "abstract": "ABSTRACT Importance: Severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the associated coronavirus disease of 2019 (COVID-19) have presented immense challenges for health care systems. Many regions have struggled to adapt to disruptions to health care practice and employ systems that effectively manage the demand for services. Objective: To examine the effectiveness of the first five weeks of a 24/7 physician-staffed COVID-19 hotline. Design: Cohort study using electronic health records. Setting: A single large health care system in Northeast Ohio. Participants: During 5 weeks of operation, 10,112 patients called the hotline (callers) and were evaluated by a registered nurse (RN) using standardized protocols. Of these, 4,213 (42%) were referred for a physician telehealth visit (telehealth patients). The mean age of callers was 42 years. 67% were female, 51% white, and 46% were on Medicaid or uninsured. Intervention: Physician telehealth visits for COVID-19. Main Outcomes and Measures: We describe clinical diagnosis, patient characteristics (age, sex race/ethnicity, smoking status, insurance status), and visit disposition. We use logistic regression to evaluate associations between patient characteristics, visit disposition and subsequent emergency department use, hospitalization, and SARS-Cov-2 PCR testing. Results: Common caller concerns included cough, fever, and shortness of breath. Most telehealth patients (79%) were advised to self-isolate at home, 14% were determined to be unlikely to have COVID-19, 3% were advised to seek emergency care, and 4% had miscellaneous other dispositions. A total of 287 (7%) patients had a subsequent ED visit, and 44 (1%) were hospitalized with a COVID-19 diagnosis. Of the callers, 482 (5%) had a COVID-19 test reported with 69 (14%) testing positive. Among patients advised to stay at home, 83% had no further face-to-face visits. In multivariable results, only a physician recommendation to seek emergency care was associated with emergency room use (OR=4.73, 95%CI 1.37-16.39, p=.014). Only older age was associated with having a positive test result. Conclusions and Relevance: Robust, physician-directed telehealth services can meet a wide range of needs during the acute phase of a pandemic, conserving scarce resources such as personal protective equipment and testing supplies and preventing the spread of infections to patients and health care workers.", "doc_id": "p8we6mrm"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Low albumin levels are associated with poorer outcomes in a case series of COVID-19 patients in Spain: a retrospective cohort study", "abstract": "OBJECTIVE To describe the clinical characteristics and epidemiological features of severe (non-ICU) and critically patients (ICU) with COVID-19 at triage, prior hospitalization, in one of the main hospitals in The Balearic Islands health care system. DESIGN Retrospective observational study SETTING Son Llatzer University Hospital in Palma de Mallorca (Spain) PARTICIPANTS Among a cohort of 52 hospitalized patients as of 31 March 2020, 48 with complete demographic information and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test, were analyzed. Data were collected between March 15th, 2020, and March 31th 2020, inclusive of these dates. MAIN OUTCOMES Clinical, vital signs and routine laboratory outcomes at the time of hospitalization, including symptoms reported prior to hospitalization. Demographics and baseline comorbidities were also collected. Mortality was reported at the end of the study. RESULTS 48 patients (27 non-ICU and 21 ICU) resident in Mallorca, Spain (mean age, 66 years, [range, 33-88 years]; 67% males) with positive SARS-CoV-2 infection were analyzed. There were no differences in age or sex among groups (p >.05). Initial symptoms included fever (100%), coughing (85%), dyspnea (76%), diarrhea (42%) and asthenia (21%). The majority of patients in this case series were hospitalized because of low SpO2 (SpO2 below 90%) and presentation of bilateral pneumonia (94%) at triage. ICU patients had a higher prevalence of dyspnea compared to non-ICU patients (95% vs 61%, p = .022). Acute respiratory syndrome (ARDS) was presented in 100% of the ICU-patients. All the patients included in the study required oxygen therapy. ICU-patients had lymphopenia as well as hypoalbuminemia. Inflammatory markers such as lactate dehydrogenase (LDH), C-reactive protein (CRP), and procalcitonin were significantly higher in ICU patients compared to non-ICU (p < .001).Lower albumin levels were associated with poor prognosis measured as longer hospital length (r= -0.472, p <.001) and mortality (r= -0.424, p=.003). Interestingly we also found, that MCV was lower among of those patients who died (p=.0002). As of April 28, 2020, 10 patients (8 ICU and 2 non-ICU) had died (21% mortality) and while 100% of the non-ICU patients had been discharged, 33% of ICU patients still remained hospitalized (5 in ICU and 2 had been transferred to ward). CONCLUSION Critically ill patients with COVID-19 present lymphopenia, hypoalbuminemia as well high levels of inflammation. Lower levels of albumin were associated with poorer outcomes in COVID-19 patients. Albumin might be of importance because of its association with disease severity in patients infected with SARS-CoV-2.", "doc_id": "t2tvo083"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Simple triage scoring system predicting death and the need for critical care resources for use during epidemics.", "abstract": "OBJECTIVES In the event of pandemic influenza, the number of critically ill victims will likely overwhelm critical care capacity. To date, no standardized method for allocating scarce resources when the number of patients in need far exceeds capacity exists. We sought to derive and validate such a triage scheme. DESIGN : Retrospective analysis of prospectively collected data. SETTING Emergency departments of two urban tertiary care hospitals. PATIENTS Three separate cohorts of emergency department patients with suspected infection, comprising a total of 5,133 patients. INTERVENTIONS None. MEASUREMENTS A triage decision rule for use in an epidemic was developed using only those vital signs and patient characteristics that were readily available at initial presentation to the emergency department. The triage schema was derived from a cohort at center 1, validated on a second cohort from center 1, and then validated on a third cohort of patients from center 2. The primary outcome for the analysis was in-hospital mortality. Secondary outcomes were intensive care unit admission and use of mechanical ventilation. MAIN RESULTS Multiple logistic regression demonstrated the following as independent predictors of death: a) age of >65 yrs, b) altered mental status, c) respiratory rate of >30 breaths/min, d) low oxygen saturation, and e) shock index of >1 (heart rate > blood pressure). This model had an area under the receiver operating characteristic curve of 0.80 in the derivation set and 0.74 and 0.76 in the validation sets. When converted to a simple rule assigning 1 point per covariate, the discrimination of the model remained essentially unchanged. The model was equally effective at predicting need for intensive care unit admission and mechanical ventilation. CONCLUSIONS If, as expected, patient demand far exceeds the capability to provide critical care services in an epidemic, a fair and just system to allocate limited resources will be essential. The triage rule we have developed can serve as an initial guide for such a process.", "doc_id": "lgq1awcl"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Critical care triaging in the shadow of COVID-19: Ethics considerations.", "abstract": "Since the World Health Organization declared coronavirus disease 2019 (COVID-19) a Public Health Emergency of International Concern, COVID-19 infection and the associated mortality have increased exponentially, globally. South Africa (SA) is no exception. Concerns abound over whether SA's healthcare system can withstand a demand for care that is disproportionate to current resources, both in the state and private health sectors. While healthcare professionals in SA have become resilient and adept at making difficult decisions in the face of resource limitations, a surge in COVID-19 cases could place a severe strain on the country's critical care services and necessitate unprecedented rationing decisions. This could occur at two critical points: access to ventilation, and withdrawal of intensive care in non- responsive or deteriorating cases. The ethical dimensions of decision-making at both junctures merit urgent consideration.", "doc_id": "r1gbtbhn"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Salivary gland disease in the era of COVID-19 pandemic", "abstract": "Coronavirus disease 2019 (COVID-19) pandemic forced significant changes in current approach to outpatient evaluation of common otolaryngology complaints as hospitals around the world are trying to limit the spread of the virus and to preserve health care resources. These changes raise a lot of questions regarding patient triage and treatment decisions in clinical situations when it is unclear if the workup and management can be postponed. In this communication, we present our approach to evaluation and triage of new patients with complaints concerning for salivary gland disease.", "doc_id": "iwpfxb1v"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Triaging moderate COVID-19 and other viral pneumonias from routine blood tests", "abstract": "The COVID-19 is sweeping the world with deadly consequences. Its contagious nature and clinical similarity to other pneumonias make separating subjects contracted with COVID-19 and non-COVID-19 viral pneumonia a priority and a challenge. However, COVID-19 testing has been greatly limited by the availability and cost of existing methods, even in developed countries like the US. Intrigued by the wide availability of routine blood tests, we propose to leverage them for COVID-19 testing using the power of machine learning. Two proven-robust machine learning model families, random forests (RFs) and support vector machines (SVMs), are employed to tackle the challenge. Trained on blood data from 208 moderate COVID-19 subjects and 86 subjects with non-COVID-19 moderate viral pneumonia, the best result is obtained in an SVM-based classifier with an accuracy of 84%, a sensitivity of 88%, a specificity of 80%, and a precision of 92%. The results are found explainable from both machine learning and medical perspectives. A privacy-protected web portal is set up to help medical personnel in their practice and the trained models are released for developers to further build other applications. We hope our results can help the world fight this pandemic and welcome clinical verification of our approach on larger populations.", "doc_id": "qikmhoo4"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "[Diagnosis and clinical management of 2019 novel coronavirus infection: an operational recommendation of Peking Union Medical College Hospital (V2.0)]", "abstract": "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.", "doc_id": "lqxtvaug"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Primary stratification and identification of suspected Corona virus disease 2019 (COVID-19) from clinical perspective by a simple scoring proposal", "abstract": "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.", "doc_id": "lfxne39o"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Revised Triage and Surveillance Protocols for Temporary Emergency Department Closures in Tertiary Hospitals as a Response to COVID-19 Crisis in Daegu Metropolitan City", "abstract": "BACKGROUND: When an emergency-care patient is diagnosed with an emerging infectious disease, hospitals in Korea may temporarily close their emergency departments (EDs) to prevent nosocomial transmission. Since February 2020, multiple, consecutive ED closures have occurred due to the coronavirus disease 2019 (COVID-19) crisis in Daegu. However, sudden ED closures are in contravention of laws for the provision of emergency medical care that enable the public to avail prompt, appropriate, and 24-hour emergency medical care. Therefore, this study ascertained the vulnerability of the ED at tertiary hospitals in Daegu with regard to the current standards. A revised triage and surveillance protocol has been proposed to tackle the current crisis. METHODS: This study was retrospectively conducted at 6 level 1 or 2 EDs in a metropolitan city where ED closure due to COVID-19 occurred from February 18 to March 26, 2020. The present status of ED closure and patient characteristics and findings from chest radiography and laboratory investigations were assessed. Based on the experience from repeated ED closures and the modified systems that are currently used in EDs, revised triage and surveillance protocols have been developed and proposed. RESULTS: During the study period, 6 level 1 or 2 emergency rooms included in the study were shut down 27 times for 769 hours. Thirty-one confirmed COVID-19 cases, of whom 7 died, were associated with the incidence of ED closure. Typical patient presentation with respiratory symptoms of COVID-19 was seen in less than 50% of patients, whereas abnormal findings on chest imaging investigations were detected in 93.5% of the study population. The chest radiography facility, resuscitation rooms, and triage area were moved to locations outside the ED, and a new surveillance protocol was applied to determine the factors warranting quarantine, including symptoms, chest radiographic findings, and exposure to a source of infection. The incidence of ED closures decreased after the implementation of the revised triage and surveillance protocols. CONCLUSION: Triage screening by emergency physicians and surveillance protocols with an externally located chest imaging facility were effective in the early isolation of COVID-19 patients. In future outbreaks of emerging infectious diseases, efforts should be focused toward the provision of continued ED treatment with the implementation of revised triage and surveillance protocols.", "doc_id": "5tw93oq1"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Rapid De-Escalation and Triaging Patients in Community-Based Palliative Care", "abstract": "CONTEXT: The coronavirus disease 2019 (COVID-19) pandemic created a rapid and unprecedented shift in our medical system. Medical providers, teams, and organizations have needed to shift their visits away from face-to-face visits and toward telehealth (both by phone and through video). Palliative care teams who practice in the community setting are faced with a difficult task: How do we actively triage the most urgent visits while keeping our vulnerable patients safe from the pandemic? MEASURES: The following are recommendations created by the Palo Alto Medical Foundation Palliative Care and Support Services team to help triage and coordinate for timely, safe, and effective palliative care in the community and outpatient setting during the ongoing COVID-19 pandemic. Patients are initially triaged based on location followed by acuity. Interdisciplinary care is implemented using strict infection control guidelines in the setting of limited personal protective equipment resources. We implement thorough screening for COVID-19 symptoms at multiple levels before a patient is seen by a designated provider. CONCLUSIONS/LESSONS LEARNED: We recommend active triaging, communication, and frequent screening for COVID-19 symptoms for palliative care patients been evaluated in the community setting. An understanding of infection risk, mutual consent between designated providers, patients, and their families are crucial to maintaining safety while delivering community-based palliative care during the COVID-19 pandemic.", "doc_id": "eazqdlds"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in Wuhan, China", "abstract": "OBJECTIVE: In December 2019, coronavirus disease (COVID-19) emerged in Wuhan. However, the characteristics and risk factors associated with disease severity, unimprovement and mortality are unclear and our objective is to throw some light on these. METHODS: All consecutive patients diagnosed with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 11 to February 6, 2020, were enrolled in this retrospective cohort study. RESULTS: A total of 663 COVID-19 patients were included in this study. Among these, 247 (37.3%) had at least one kind of chronic disease; 0.5% of the patients (n = 3) were diagnosed with mild COVID-19, while 37.8% (251/663), 47.5% (315/663), and 14.2% (94/663) were in moderate, severe, and critical conditions, respectively. In our hospital, during follow-up 251 of 663 patients (37.9%) improved and 25 patients died, a mortality rate of 3.77%. Older patients (>60 years old) and those with chronic diseases were prone to have a severe to critical COVID-19 condition, to show unimprovement, and to die (p <0.001, <0.001). Multivariate logistic regression analysis identified being male (OR = 0.486, 95%CI 0.311-0.758; p 0.001), having a severe COVID-19 condition (OR = 0.129, 95%CI 0.082-0.201; p <0.001), expectoration (OR = 1.796, 95%CI 1.062-3.036; p 0.029), muscle ache (OR = 0.309, 95%CI 0.153-0.626; p 0.001), and decreased albumin (OR = 1.929, 95%CI 1.199-3.104; p 0.007) as being associated with unimprovement in COVID-19 patients. CONCLUSION: Male sex, a severe COVID-19 condition, expectoration, muscle ache, and decreased albumin were independent risk factors which influence the improvement of COVID-19 patients.", "doc_id": "nwbr5wpf"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Proposed Modifications in the 6-minutue Walk Test for Potential Application in Patients with mild Coronavirus Disease 2019 (COVID-19): A Step to Optimize Triage Guidelines", "abstract": "", "doc_id": "ss8yikca"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Organizing a COVID-19 triage unit: a Swiss perspective", "abstract": "Background: With the rapid global spread of the acute respiratory syndrome coronavirus 2, urgent health-care measures have been implemented. We describe the organizational process in setting up a coronavirus disease 2019 triage unit in a Swiss tertiary care hospital. Methods: Our triage unit was set-up outside of the main hospital building and consists of three areas: 1. Pre-triage, 2. Triage, and 3. Triage plus. The Pre-triage check-points identify any potential COVID-19-infected patients and re-direct them to the main Triage area where trained medical staff screen which patients undergo diagnostic testing. If testing is indicated, nasopharyngeal swabs are performed. If patients require further investigations, they are referred to Triage plus. At this stage, patients are then discharged home after additional testing or admitted to the hospital for management. Observations: A total of 1265 patients were screened between 10 March 2020 and 12 April 2020 at our Triage unit. Of these, 112 (8.9%) tested positive. 73 (65%) of the positively-tested patients were female and 39 (35%) were male. The mean age for all patients was 43.8 years (SD 16.3 years). Distinguishing between genders, mean age for females was 41.1 (SD 16.5) and mean age for males was 48.6 (SD 14.9), with females being significantly younger than males (p < 0.001). Conclusion: Our triage unit was set-up as part of a large-scale restructuring process. Current challenges include low sensitivity for test results as well as limited staff and resources. We hope that our experience will help other health care institutions develop similar triage systems.", "doc_id": "holb6bk3"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Luchtwegklachten in tijden van corona./ [Respiratory complaints in the time of COVID-19]", "abstract": "The current guidelines for diagnosis and treatment of primary respiratory infections are still useful during the COVID-19 epidemic.Telephone triage of patients with respiratory complaints aims to identify patients with complications or an increased risk of complications.There are no indications to test for SARS-CoV-2 virus in general practice.During this COVID-19 epidemic, protective clothing is recommended in all physical contacts with patients with respiratory complaints.There is no reason to be cautious about using NSAIDs in patients suspected of COVID-19.Amoxicillin is first choice treatment for respiratory infections during the COVID-19 epidemic; there is lack of evidence to support azithromycin as a first choice.Respiratory rate > 24 / min or saturation <92-94% indicate imminent respiratory decompensation and may be reasons for referral.", "doc_id": "1cpk2p9g"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Risk factors for adverse clinical outcomes with COVID-19 in China: a multicenter, retrospective, observational study", "abstract": "Background: The risk factors for adverse events of Coronavirus Disease-19 (COVID-19) have not been well described. We aimed to explore the predictive value of clinical, laboratory and CT imaging characteristics on admission for short-term outcomes of COVID-19 patients. Methods: This multicenter, retrospective, observation study enrolled 703 laboratory-confirmed COVID-19 patients admitted to 16 tertiary hospitals from 8 provinces in China between January 10, 2020 and March 13, 2020. Demographic, clinical, laboratory data, CT imaging findings on admission and clinical outcomes were collected and compared. The primary endpoint was in-hospital death, the secondary endpoints were composite clinical adverse outcomes including in-hospital death, admission to intensive care unit (ICU) and requiring invasive mechanical ventilation support (IMV). Multivariable Cox regression, Kaplan-Meier plots and log-rank test were used to explore risk factors related to in-hospital death and in-hospital adverse outcomes. Results: Of 703 patients, 55 (8%) developed adverse outcomes (including 33 deceased), 648 (92%) discharged without any adverse outcome. Multivariable regression analysis showed risk factors associated with in-hospital death included ≥ 2 comorbidities (hazard ratio [HR], 6.734; 95% CI; 3.239-14.003, p < 0.001), leukocytosis (HR, 9.639; 95% CI, 4.572-20.321, p < 0.001), lymphopenia (HR, 4.579; 95% CI, 1.334-15.715, p = 0.016) and CT severity score > 14 (HR, 2.915; 95% CI, 1.376-6.177, p = 0.005) on admission, while older age (HR, 2.231; 95% CI, 1.124-4.427, p = 0.022), ≥ 2 comorbidities (HR, 4.778; 95% CI; 2.451-9.315, p < 0.001), leukocytosis (HR, 6.349; 95% CI; 3.330-12.108, p < 0.001), lymphopenia (HR, 3.014; 95% CI; 1.356-6.697, p = 0.007) and CT severity score > 14 (HR, 1.946; 95% CI; 1.095-3.459, p = 0.023) were associated with increased odds of composite adverse outcomes. Conclusion: The risk factors of older age, multiple comorbidities, leukocytosis, lymphopenia and higher CT severity score could help clinicians identify patients with potential adverse events.", "doc_id": "7hxojh6f"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study", "abstract": "BACKGROUND: COVID-19 has spread globally. Epidemiological susceptibility to COVID-19 has been reported in patients with cancer. We aimed to systematically characterise clinical features and determine risk factors of COVID-19 disease severity for patients with cancer and COVID-19. METHODS: In this multicentre, retrospective, cohort study, we included all adult patients (aged ≥18 years) with any type of malignant solid tumours and haematological malignancy who were admitted to nine hospitals in Wuhan, China, with laboratory-confirmed COVID-19 between Jan 13 and March 18, 2020. Enrolled patients were statistically matched (2:1) with patients admitted with COVID-19 who did not have cancer with propensity score on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, illness severity, and clinical interventions were compared between patients with COVID-19 with or without cancer as well as between patients with cancer with non-severe or severe COVID-19. COVID-19 disease severity was defined on admission on the basis of the WHO guidelines. Univariable and multivariable logistic regression, adjusted for age, sex, comorbidities, cancer type, tumour stage, and antitumour treatments, were used to explore risk factors associated with COVID-19 disease severity. This study was registered in the Chinese Clinical Trial Register, ChiCTR2000030807. FINDINGS: Between Jan 13 and March 18, 2020, 13\u00e2\u0080\u0088077 patients with COVID-19 were admitted to the nine hospitals in Wuhan and 232 patients with cancer and 519 statistically matched patients without cancer were enrolled. Median follow-up was 29 days (IQR 22-38) in patients with cancer and 27 days (20-35) in patients without cancer. Patients with cancer were more likely to have severe COVID-19 than patients without cancer (148 [64%] of 232 vs 166 [32%] of 519; odds ratio [OR] 3\u00b761 [95% CI 2\u00b759-5\u00b704]; p<0\u00b70001). Risk factors previously reported in patients without cancer, such as older age; elevated interleukin 6, procalcitonin, and D-dimer; and reduced lymphocytes were validated in patients with cancer. We also identified advanced tumour stage (OR 2\u00b760, 95% CI 1\u00b705-6\u00b743; p=0\u00b7039), elevated tumour necrosis factor α (1\u00b722, 1\u00b701-1\u00b747; p=0\u00b7037), elevated N-terminal pro-B-type natriuretic peptide (1\u00b765, 1\u00b703-2\u00b778; p=0\u00b7032), reduced CD4+ T cells (0\u00b784, 0\u00b771-0\u00b798; p=0\u00b7031), and reduced albumin-globulin ratio (0\u00b712, 0\u00b702-0\u00b777; p=0\u00b7024) as risk factors of COVID-19 severity in patients with cancer. INTERPRETATION: Patients with cancer and COVID-19 were more likely to deteriorate into severe illness than those without cancer. The risk factors identified here could be helpful for early clinical surveillance of disease progression in patients with cancer who present with COVID-19. FUNDING: China National Natural Science Foundation.", "doc_id": "3m9rwl3z"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Policies and Guidelines for COVID-19 Preparedness: Experiences from the University of Washington", "abstract": "The Coronavirus Disease 2019 (COVID-19) pandemic initially presented in the United States in the greater Seattle area, and has rapidly progressed across the nation in the past 2 months, with the United States having the highest number of cases in the world. Radiology departments play a critical role in policy and guideline development both for the department and for the institutions, specifically in planning diagnostic screening, triage, and management of patients. In addition, radiology workflows, volumes and access must be optimized in preparation for the expected COVID-19 patient surges. This article discusses the processes that have been implemented at the University of Washington in managing the COVID-19 pandemic as well in preparing for patient surges, which may provide important guidance for other radiology departments who are in the early stages of preparation and management.", "doc_id": "v9zrivd3"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "The ultrasound guided triage: a new tool for prehospital management of COVID-19 pandemic", "abstract": "", "doc_id": "dzi2ze0a"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Ethics in the Covid-19 emergency: Examining rationing decisions", "abstract": "Early last month, the Italian Society of Anaesthesia was forced to publish the above guideline (1) for the country's hospitals. Besides the rising cases of infection, the doctors realised that patients required up to 15-20 days of intensive care as the disease progressed (2). In the face of medical resource scarcities, the guideline established that everyone could not be saved from the coronavirus. And a massive death toll ensued.", "doc_id": "toe6sl0l"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Rapid design and implementation of an integrated patient self-triage and self-scheduling tool for COVID-19", "abstract": "OBJECTIVE: To rapidly deploy a digital patient-facing self-triage and self-scheduling tool in a large academic health system to address the COVID-19 pandemic. MATERIALS AND METHODS: We created a patient portal-based COVID-19 self-triage and self-scheduling tool and made it available to all primary care patients at the University of California, San Francisco Health, a large academic health system. Asymptomatic patients were asked about exposure history and were then provided relevant information. Symptomatic patients were triaged into 1 of 4 categories-emergent, urgent, nonurgent, or self-care-and then connected with the appropriate level of care via direct scheduling or telephone hotline. RESULTS: This self-triage and self-scheduling tool was designed and implemented in under 2 weeks. During the first 16 days of use, it was completed 1129 times by 950 unique patients. Of completed sessions, 315 (28%) were by asymptomatic patients, and 814 (72%) were by symptomatic patients. Symptomatic patient triage dispositions were as follows: 193 emergent (24%), 193 urgent (24%), 99 nonurgent (12%), 329 self-care (40%). Sensitivity for detecting emergency-level care was 87.5% (95% CI 61.7-98.5%). DISCUSSION: This self-triage and self-scheduling tool has been widely used by patients and is being rapidly expanded to other populations and health systems. The tool has recommended emergency-level care with high sensitivity, and decreased triage time for patients with less severe illness. The data suggests it also prevents unnecessary triage messages, phone calls, and in-person visits. CONCLUSION: Patient self-triage tools integrated into electronic health record systems have the potential to greatly improve triage efficiency and prevent unnecessary visits during the COVID-19 pandemic.", "doc_id": "myyr9rci"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "The role of triage in the prevention and control of COVID-19", "abstract": "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.", "doc_id": "jv3xx09f"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "The good, the bad and the ugly: pandemic priority decisions and triage", "abstract": "In this analysis we discuss the change in criteria for triage of patients during three different phases of a pandemic like COVID-19, seen from the critical care point of view. Availability of critical care beds has become a hot topic, and in many countries, we have seen a huge increase in the provision of temporary intensive care bed capacity. However, there is a limit where the hospitals may run out of resources to provide critical care, which is heavily dependent on trained staff, just-in-time supply chains for clinical consumables and drugs and advanced equipment. In the first (good) phase, we can still do clinical prioritisation and decision-making as usual, based on the need for intensive care and prognostication: what are the odds for a good result with regard to survival and quality of life. In the next (bad phase), the resources are mostly available, but the system is stressed by many patients arriving over a short time period and auxiliary beds in different places in the hospital being used. We may have to abandon admittance of patients with doubtful prognosis. In the last (ugly) phase, usual medical triage and priority setting may not be sufficient to decrease inflow and there may not be enough intensive care unit beds available. In this phase different criteria must be applied using a utilitarian approach for triage. We argue that this is an important transition where society, and not physicians, must provide guidance to support triage that is no longer based on medical priorities alone.", "doc_id": "dvmv5u5j"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "A novel risk score to predict diagnosis with coronavirus disease 2019 (COVID-19) in suspected patients: A retrospective, multicenter, and observational study", "abstract": "The aim of the study was to explore a novel risk score to predict diagnosis with COVID-19 among all suspected patients at admission. This was a retrospective, multicenter, and observational study. The clinical data of all suspected patients were analyzed. Independent risk factors were identified via multivariate logistic regression analysis. Finally, 336 confirmed COVID-19 patients and 139 control patients were included. We found nine independent risk factors for diagnosis with COVID-19 at admission to hospital: epidemiological exposure histories (OR:13.32; 95%CI, 6.39-27.75), weakness/fatigue (OR:4.51, 95%CI, 1.70-11.96), heart rate less than 100 beat/minutes (OR:3.80, 95%CI, 2.00-7.22), bilateral pneumonia (OR:3.60, 95%CI, 1.83-7.10), neutrophil count less than equal to 6.3 \u00d7 109 /L (OR: 6.77, 95%CI, 2.52-18.19), eosinophil count less than equal to 0.02 \u00d7 109 /L (OR:3.14, 95%CI, 1.58-6.22), glucose more than equal to 6 mmol/L (OR:2.43, 95%CI, 1.04-5.66), D-dimer ≥ 0.5 mg/L (OR:3.49, 95%CI, 1.22-9.96), and C-reactive protein less than 5 mg/L (OR:3.83, 95%CI, 1.86-7.92). As for the performance of this risk score, a cut-off value of 20 (specificity: 0.866; sensitivity: 0.813) was identified to predict COVID-19 according to reciever operator characteristic curve and the area under the curve was 0.921 (95%CI: 0.896-0.945; P < .01). We designed a novel risk score which might have a promising predictive capacity for diagnosis with COVID-19 among suspected patients.", "doc_id": "4gajban9"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations", "abstract": "As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill.", "doc_id": "t55od92g"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Triage of patients with COVID-19", "abstract": "", "doc_id": "hym5giqi"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Enhancing the triage and cohort of patients in public primary care clinics in response to the coronavirus disease 2019 (COVID-19) in Hong Kong: an experience from a hospital cluster", "abstract": "", "doc_id": "5m1i4zip"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Updating the diagnostic criteria of COVID-19 \"suspected case\" and \"confirmed case\" is necessary", "abstract": "On 6 February 2020, our team had published a rapid advice guideline for diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infection, and this guideline provided our experience and make well reference for fighting against this pandemic worldwide. However, the coronavirus disease 2019 (COVID-19) is a new disease, our awareness and knowledge are gradually increasing based on the ongoing research findings and clinical practice experience; hence, the strategies of diagnosis and treatment are also continually updated. In this letter, we answered one comment on our guideline and provided the newest diagnostic criteria of \"suspected case\" and \"confirmed case\" according to the latest Diagnosis and Treatment Guidelines for COVID-19 (seventh version) that issued by the National Health Committee of the People's Republic of China.", "doc_id": "lzw5h7x5"} {"topic_name": "coronavirus hospital rationing", "topic_id": "11", "title": "Extracorporeal Membrane Oxygenation for Pediatric Patients With Coronavirus Disease 2019-Related Illness", "abstract": "OBJECTIVE: To describe current hospital guidelines and the opinions of extracorporeal membrane oxygenation leaders at U.S. children's hospitals concerning the use of extracorporeal membrane oxygenation for coronavirus disease 2019-positive pediatric patients. DESIGN: Confidential, self-administered questionnaire. SETTING: One hundred twenty-seven U.S. pediatric extracorporeal membrane oxygenation centers. SUBJECTS: Extracorporeal membrane oxygenation center program directors and coordinators. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In March 2020, a survey was sent to 127 pediatric extracorporeal membrane oxygenation centers asking them to report their current hospital extracorporeal membrane oxygenation guidelines for coronavirus disease 2019-positive patients. Respondents were also asked their opinion on three ethical dilemmas including: prioritization of children over adults for extracorporeal membrane oxygenation use, institution of do-not-resuscitate orders, and the use of extracorporeal cardiopulmonary resuscitation for coronavirus disease 2019-positive patients. Forty-seven extracorporeal membrane oxygenation centers had enacted guidelines including 46 (100%) that offer venovenous-extracorporeal membrane oxygenation and 42 (89%) that offer venoarterial-extracorporeal membrane oxygenation for coronavirus disease 2019-positive pediatric patients. Forty-four centers (94%) stated that the indications for extracorporeal membrane oxygenation candidacy in coronavirus disease 2019 disease were similar to those used in other viral illnesses, such as respiratory syncytial virus or influenza. Most program directors (98%) did not endorse that children hospitalized with coronavirus disease 2019 should be made do-not-resuscitate and had variable opinions on whether children should be given higher priority over adults when rationing extracorporeal membrane oxygenation. Over half of program directors (60%) did not support the use of extracorporeal cardiopulmonary resuscitation for coronavirus disease 2019. CONCLUSIONS: The majority of pediatric extracorporeal membrane oxygenation centers have proactively established guidelines for the use of extracorporeal membrane oxygenation for coronavirus disease 2019-related illnesses. Further work is needed to help guide the fair allocation of extracorporeal membrane oxygenation resources and to determine the appropriateness of extracorporeal cardiopulmonary resuscitation.", "doc_id": "34v1w16g"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Prevention of respiratory outbreaks in the rehabilitation setting", "abstract": "BACKGROUND: Respiratory viral (RV) outbreaks in rehabilitation facilities can jeopardise patient safety, interfere with patient rehabilitation goals and cause unit closures that impede patient flow in referring facilities. PROBLEM: Despite education about infection prevention practices, frequent RV outbreaks were declared each year at our rehabilitation facility. METHODS: Before and after study design. The primary outcome was the number of bed closure days due to outbreak per overall bed days. Process measures included delays in initiation of transmission-based precautions, RV testing and reporting of staff to occupational health and safety (OHS). Balancing measures included the number of isolation days and staff missed work hours. INTERVENTIONS: Based on comprehensive analysis of prior outbreaks, the following changes were implemented: (1) clear criteria for initiation of transmission-based precautions, (2) communication to visitors to avoid visitation if infectious symptoms were present, (3) exemption of staff absences if documented due to infectious illness, (4) development of an electronic programme providing guidance to staff about whether they should be excluded from work due to infectious illness. RESULTS: The number of bed closure days due to outbreak per overall bed days dropped from 2.8% to 0.5% during the intervention season and sustained at 0.6% during the postintervention season (p<0.001). There were fewer delays in initiation of droplet and contact precautions (28.8% to 15.5%, p=0.005) and collection of RV testing (42.9% to 20.3%, p<0.001), better reporting to OHS (9 vs 28.8 reports per 100 employees; p<0.001) and fewer isolation days (7.8% vs 7.3%; p=0.02) without a significant increase in missed work hours per 100 hours worked (4.0 vs 3.9; p=0.12). CONCLUSION: This Quality Improvement study highlights the process changes that can prevent respiratory outbreaks in the rehabilitation setting.", "doc_id": "25dcnext"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Updated rapid risk assessment from ECDC on the outbreak of COVID-19: increased transmission globally", "abstract": "", "doc_id": "bd7whqxf"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Background Information: Isolation Routines", "abstract": "The isolation of patients with suspected or documented infections\u2014to not spread to others\u2014has been discussed for hundreds of years. Guidelines are many, methods are different, attitudes show vide variations, routines and procedures are still changing, regulations by law may be absent, and some healthcare professionals may be afraid of adverse outcomes of isolation [1\u201344]. Microbes that are spread in the environment, on the hands and equipment are invisible. The invisible agent does not call on attention before the infection; clinical disease, hospital infection or nosocomial infection is a factum that can be registered [23, 28, 29, 35\u201337]. How to stop the transmission is often \u201cto believe and not believe\u201d in infection control.", "doc_id": "0ai8chbu"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Infection Control and the Need for Family-/Child-Centered Care", "abstract": "Patient- and family-centered care (FCC) has become central to the delivery of medical care over the last 20 years and has been shown to improve patient outcomes. Infection control practices have the potential to greatly influence family centeredness and care providers, and hospital personnel must consider the potential impacts of isolation and the use of personal protective equipment (PPE). Approaching infection control with the perspective of FCC requires balancing patient safety and overall patient well-being. In this chapter, authors consider infection control and the benefits of FCC, family and sibling visitation, the use of playrooms, animals in healthcare settings including animal-assisted interventions, the potential adverse effects of infection control practices, and strategies to mitigate these impacts.", "doc_id": "5rj49l14"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "CDC updates quarantine rules", "abstract": "", "doc_id": "7k05aoya"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Surge Capacity", "abstract": "", "doc_id": "y1fwisjg"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Disaster Mitigation", "abstract": "", "doc_id": "uhrciaiz"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Chemical, Biologic, and Nuclear Quarantine", "abstract": "", "doc_id": "1sn3jl9z"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "An outbreak of Severe Acute Respiratory Syndrome in a nursing home: Lessons to learn", "abstract": "Hong Kong experienced an epidemic of Severe Acute Respiratory Syndrome (SARS) from March to June 2003. Nursing homes were a potential area of cross\u2010infection because of the crowded living space, substandard environmental hygiene, inadequate ventilation, low working staff to resident ratio, and staff who lacked knowledge of infection control. The mortality in elderly SARS patients was high because of their atypical presentations, their multiple comorbidities, and that they are more susceptible to the side\u2010effects of treatment. The community geriatric assessment team need to work closely with the hospitals and the primary health care system to provide surveillance of the disease, infection control, and management of sub\u2010acute clinical problems, in order to reduce unnecessary hospital admissions in nursing home residents during an epidemic outbreak.", "doc_id": "isgv7sm4"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Home-based exercise note in Covid-19 quarantine situation for office workers: A commentary.", "abstract": "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.", "doc_id": "tg02icy0"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Delivering healthcare remotely to cardiovascular patients during COVID-19: A rapid review of the evidence.", "abstract": "BACKGROUND Although attention is focused on addressing the acute situation created by the COVID-19 illness, it is imperative to continue our efforts to prevent cardiovascular morbidity and mortality, particularly during a period of prolonged social isolation which may limit physical activity, adversely affect mental health and reduce access to usual care. One option may be to deliver healthcare interventions remotely through digital healthcare solutions. Therefore, the aim of this paper is to bring together the evidence for remote healthcare during a quarantine situation period to support people living with cardiovascular disease during COVID-19 isolation. METHODS The PubMed, CINAHL and Google Scholar were searched using telehealth OR digital health OR mHealth OR eHealth OR mobile apps AND COVID-19 OR quarantine search terms. We also searched for literature relating to cardiovascular disease AND quarantine. RESULTS The literature search identified 45 potentially relevant publications, out of which nine articles were included. Three overarching themes emerged from this review: (1) preparing the workforce and ensuring reimbursement for remote healthcare, (2) supporting mental and physical health and (3) supporting usual care. CONCLUSION To support people living with cardiovascular disease during COVID-19 isolation and to mitigate the effects of quarantine and adverse effect on mental and physical well-being, we should offer remote healthcare and provide access to their usual care.", "doc_id": "srbyxhxd"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Home monitoring for COVID-19.", "abstract": "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.", "doc_id": "mz7nuskv"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Effectiveness of quarantine measure on transmission dynamics of COVID-19 in Hong Kong", "abstract": "The rapid expansion of COVID-19 has caused a global pandemic. Although quarantine measures have been used widely, the critical steps among them to suppress the outbreak without a huge social-economic loss remain unknown. Hong Kong, unlike other regions in the world, had a massive number of travellers from Mainland China during the early expansion period, and yet the spread of virus has been relatively limited. Understanding the effect of control measures to reduce the transmission in Hong Kong can improve the control of the virus spreading. We have developed a susceptible-exposed-infectious-quarantined-recovered (SEIQR) meta-population model that can stratify the infections into imported and subsequent local infections, and therefore to obtain the control effects on transmissibility in a region with many imported cases. We fitted the model to both imported and local confirmed cases with symptom onset from 18 January to 29 February 2020 in Hong Kong with daily transportation data and the transmission dynamics from Wuhan and Mainland China. The model estimated that the reproductive number was dropped from 2.32 to 0.76 (95% CI, 0.66 to 0.86) after an infected case was estimated to be quarantined half day before the symptom onset, corresponding to the incubation time of 5.43 days (95% CI, 1.30-9.47). If the quarantine happened about one day after the onset, community spread would be likely to occur, indicated by the reproductive number larger than one. The results suggest that the early quarantine for a suspected case before the symptom onset is a key factor to suppress COVID-19.", "doc_id": "byp9heum"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Forecasting the impact of the first wave of the COVID-19 pandemic on hospital demand and deaths for the USA and European Economic Area countries", "abstract": "Summary Background: Hospitals need to plan for the surge in demand in each state or region in the United States and the European Economic Area (EEA) due to the COVID-19 pandemic. Planners need forecasts of the most likely trajectory in the coming weeks and will want to plan for the higher values in the range of those forecasts. To date, forecasts of what is most likely to occur in the weeks ahead are not available for states in the USA or for all countries in the EEA. Methods: This study used data on confirmed COVID-19 deaths by day from local and national government websites and WHO. Data on hospital capacity and utilisation and observed COVID-19 utilisation data from select locations were obtained from publicly available sources and direct contributions of data from select local governments. We develop a mixed effects non-linear regression framework to estimate the trajectory of the cumulative and daily death rate as a function of the implementation of social distancing measures, supported by additional evidence from mobile phone data. An extended mixture model was used in data rich settings to capture asymmetric daily death patterns. Health service needs were forecast using a micro-simulation model that estimates hospital admissions, ICU admissions, length of stay, and ventilator need using available data on clinical practices in COVID-19 patients. We assume that those jurisdictions that have not implemented school closures, non-essential business closures, and stay at home orders will do so within twenty-one days. Findings: Compared to licensed capacity and average annual occupancy rates, excess demand in the USA from COVID-19 at the estimated peak of the epidemic (the end of the second week of April) is predicted to be 9,079 (95% UI 253-61,937) total beds and 9,356 (3,526-29,714) ICU beds. At the peak of the epidemic, ventilator use is predicted to be 16,545 (8,083-41,991). The corresponding numbers for EEA countries are 120,080 (119,183-121,107), 32,291 (32,157-32,425) and 28,973 (28,868-29,085) at a peak of April 6. The date of peak daily deaths varies from March 30 through May 12 by state in the USA and March 27 through May 4 by country in the EEA. We estimate that through the end of July, there will be 60,308 (34,063-140,381) deaths from COVID-19 in the USA and 143,088 (101,131-253,163) deaths in the EEA. Deaths from COVID-19 are estimated to drop below 0.3 per million between May 4 and June 29 by state in the USA and between May 4 and July 13 by country in the EEA. Timing of the peak need for hospital resource requirements varies considerably across states in the USA and across regions of Europe. Interpretation: In addition to a large number of deaths from COVID-19, the epidemic will place a load on health system resources well beyond the current capacity of hospitals in the USA and EEA to manage, especially for ICU care and ventilator use. These estimates can help inform the development and implementation of strategies to mitigate this gap, including reducing non-COVID-19 demand for services and temporarily increasing system capacity. The estimated excess demand on hospital systems is predicated on the enactment of social distancing measures within three weeks in all locations that have not done so already and maintenance of these measures throughout the epidemic, emphasising the importance of implementing, enforcing, and maintaining these measures to mitigate hospital system overload and prevent deaths.", "doc_id": "c1dy5vsn"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "How to improve adherence with quarantine: Rapid review of the evidence", "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.", "doc_id": "s0zdqd6d"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "A study on control of novel corona-virus (2019-nCoV) disease process by using PID controller", "abstract": "In this paper, the SEIR dynamic model will be used to model the epidemic of coronvirus (2019-nCoV)disease. The SEIR model has been used to model infectious diseases in Malaysia.Then, the spread and control of the disease is simulated applying a PID controller. The results of this study show that the implementation of strict restrictions such as quarantine, social distancing and closure of gathering centers is effective in controlling the disease. Using the results and analyzing them, it was found that early and strict implementation of strict restrictions such as quarantine, social distance and closure of centers with a high percentage of community is very important to control this disease and prevent irreparable economic losses and depreciation of medical staff", "doc_id": "8xsuyxcg"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Modelling potential responses to severe acute respiratory syndrome in Japan: the role of initial attack size, precaution, and quarantine.", "abstract": "BACKGROUND There has been an outbreak of the severe acute respiratory syndrome (SARS) worldwide. With the use of detailed epidemiological data from other countries, this article describes the possible reason for the SARS epidemic not appearing in Japan, and simulates the impact of different control strategies that can break the transmission cycle of SARS associated coronavirus. METHOD Mathematical modelling is used for predicting the epidemiological outcome and simultaneously for evaluating the effect of interventions on SARS. The study estimates the initial attack size that would result in failed invasion. Three different interventions have been incorporated into the public health response policies; precautionary public health measures, isolation of infected people, and quarantine of exposed humans. RESULTS The maximum number of humans newly infected could be roughly estimated on the basis of the initial attack size, using simple formulas. It is seen that the introduction of only a few cases into certain communities would not lead easily to an epidemic. The possible trajectories of SARS epidemic depend on the levels of public health interventions as quarantine and precautionary public health measures greatly affected the transmissibility of the disease. It is shown that there exist threshold levels of interventions at which the SARS epidemic settles down. CONCLUSION Initial attack size is one of the determinants of whether SARS can successfully invade the community or not. Two of the most effective policy procedures to prevent new infections would be to apply stringent precautionary measures and to impose quicker and more effective quarantine of the exposed populace.", "doc_id": "5ttz48he"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Active and inactive quarantine in epidemic spreading on adaptive activity-driven networks", "abstract": "We consider an epidemic process on adaptive activity-driven temporal networks, with adaptive behaviour modelled as a change in activity and attractiveness due to infection. By using a mean-field approach, we derive an analytical estimate of the epidemic threshold for SIS and SIR epidemic models for a general adaptive strategy, which strongly depends on the correlations between activity and attractiveness in the susceptible and infected states. We focus on a strong adaptive behaviour, implementing two types of quarantine inspired by recent real case studies: an active quarantine, in which the population compensates the loss of links rewiring the ineffective connections towards non-quarantining nodes, and an inactive quarantine, in which the links with quarantined nodes are not rewired. Both strategies feature the same epidemic threshold but they strongly differ in the dynamics of active phase. We show that the active quarantine is extremely less effective in reducing the impact of the epidemic in the active phase compared to the inactive one, and that in SIR model a late adoption of measures requires inactive quarantine to reach containment.", "doc_id": "qznrjflx"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Home-based exercise note in Covid-19 quarantine situation for office workers: A commentary", "abstract": "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.", "doc_id": "sj4ohk38"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Integrated Hospital Quarantine System against COVID-19", "abstract": "", "doc_id": "pkh8puhp"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Reducing onward spread of COVID-19 from imported cases: quarantine and 'stay at home' measures for travellers and returning residents to Singapore", "abstract": "", "doc_id": "2f1gb2n6"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Is a COVID19 Quarantine Justified in Chile or USA Right Now?", "abstract": "During the current COVID-19 pandemic it is imperative to give early warnings to reduce mortality. However, non-specialist such as authorities and the general population face several problems to understand the real thread of this pandemic, and under/overestimation of its risk are a commonplace in the press and social media. Here we define an index, which we call the COVID-19 Burden Index, that relates the capacities of the healthcare system of a given country to treat severe and critical cases. Its value is 0 if there is no extra strain in the healthcare system, and it reaches 1.0 when the collapse is imminent. As of 23 March 2020, we show that Chile, the USA, UK, among other countries, must reduce the rate of infections right now, otherwise, in less than 7 days they could be in a catastrophic situation such as Italy, Spain and Iran.", "doc_id": "wnvejogu"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Spatio-temporal propagation of COVID-19 pandemics", "abstract": "The new coronavirus known as COVID-19 is spread world-wide 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 first wave of the COVID-19 virus in China and compare it to other global locations. We provide a comprehensive picture of the spatial propagation from Hubei to other provinces in China in terms of distance, population size, and human mobility and their scaling relations. Since strict quarantine has been usually applied between cities, more insight about the temporal evolution of the disease can be obtained by analyzing the epidemic within cities, especially the time evolution of the infection, death, and recovery rates which affected by policies. We study and compare the infection rate in different cities in China and provinces in Italy and find that the disease spread is characterized by a two-stages process. At early times, at order of few days, the infection rate is close to a constant probably due to the lack of means to detect infected individuals before infection symptoms are observed. Then at later times it decays approximately exponentially due to quarantines. The time evolution of the death and recovery rates also distinguish between these two stages and reflect the health system situation which could be overloaded.", "doc_id": "p8cu27ma"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "On a quarantine model of coronavirus infection and data analysis", "abstract": "Attempts to curb the spread of coronavirus by introducing strict quarantine measures apparently have different effect in different countries: while the number of new cases has reportedly decreased in China and South Korea, it still exhibit significant growth in Italy and other countries across Europe. In this brief note, we endeavour to assess the efficiency of quarantine measures by means of mathematical modelling. Instead of the classical SIR model, we introduce a new model of infection progression under the assumption that all infected individual are isolated after the incubation period in such a way that they cannot infect other people. Disease progression in this model is determined by the basic reproduction number $\\mathcal{R}_0$ (the number of newly infected individuals during the incubation period), which is different compared to that for the standard SIR model. If $\\mathcal{R}_0>1$, then the number of latently infected individuals exponentially grows. However, if $\\mathcal{R}_0<1$ (e.g.~due to quarantine measures and contact restrictions imposed by public authorities), then the number of infected decays exponentially. We then consider the available data on the disease development in different countries to show that there are three possible patterns: growth dynamics, growth-decays dynamics, and patchy dynamics (growth-decay-growth). Analysis of the data in China and Korea shows that the peak of infection (maximum of daily cases) is reached about 10 days after the restricting measures are introduced. During this period of time, the growth rate of the total number of infected was gradually decreasing. However, the growth rate remains exponential in Italy. Arguably, it suggests that the introduced quarantine is not sufficient and stricter measures are needed.", "doc_id": "t62m8uwv"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Optimal quarantine strategies for COVID-19 control models", "abstract": "Optimal control problems reflecting the finding of effective quarantine strategies are considered for two control SEIR~type models describing the spread of the COVID-19 virus in the human population. The properties of the corresponding optimal controls are established analytically by applying the Pontryagin maximum principle. The optimal solutions are obtained numerically using BOCOP 2.0.5 software. The behavior of the appropriate optimal solutions and their dependence on the basic reproductive ratio and length of quarantine are discussed in detail. Necessary conclusions are made.", "doc_id": "s2gidnce"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Only strict quarantine measures can curb the coronavirus disease (COVID-19) outbreak in Italy, 2020", "abstract": "Several Italian towns are under lockdown to contain the COVID-19 outbreak. The level of transmission reduction required for physical distancing interventions to mitigate the epidemic is a crucial question. We show that very high adherence to community quarantine (total stay-home policy) and a small household size is necessary for curbing the outbreak in a locked-down town. The larger the household size and amount of time in the public, the longer the lockdown period needed.", "doc_id": "phibo0fc"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Assessing the Efficiency of Different Control Strategies for the Coronavirus (COVID-19) Epidemic", "abstract": "The goal of this work is to analyse the effects of control policies for the coronavirus (COVID-19) epidemic in Brazil. This is done by considering an age-structured SEIR model with a quarantine class and two types of controls. The first one studies the sensitivity with regard to the parameters of the basic reproductive number R0 which is calculated by the next generation method. The second one evaluates different quarantine strategies by comparing their relative total number of deaths.", "doc_id": "4qrssc82"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Recurrent PCR positivity after hospital discharge of people with coronavirus disease 2019 (COVID-19)", "abstract": "", "doc_id": "dc4vwvx7"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Epidemics, quarantine and mental health", "abstract": "", "doc_id": "n4n2ij4n"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Achieving Safe, Effective and Compassionate Quarantine or Isolation of Older Adults with Dementia in Nursing Homes.", "abstract": "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.", "doc_id": "q03884i9"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "A method for evaluating health care workers\u2019 personal protective equipment technique", "abstract": "BACKGROUND: Given the potential for the transfer of infectious diseases among patients in isolation, health care workers (HCWs), and other patients in the hospital environment, the proper use of personal protective equipment (PPE) is paramount. The literature is limited regarding studies of HCWs\u2019 use of PPE in patient care tasks. METHODS: A pilot study was conducted to examine the feasibility of using a simulated health care environment to assess HCWs\u2019 technique when implementing standard airborne and contact isolation precautions. The participants (n = 10) were assigned patient care tasks based on their specific professional roles. The encounters were digitally recorded during donning and doffing of PPE, as well as during interactions with the simulated patient. Powdered fluorescent marker was used as a measure of contamination. RESULTS: The pilot data show various inconsistencies in the HCWs\u2019 PPE technique. Each of the 10 participants committed at least one breach of standard airborne and contact isolation precautions. CONCLUSION: An expanded research study of HCW behaviors is needed to properly examine these contamination and exposure pathways. Training programs should be developed that emphasize the common errors in HCWs\u2019 PPE technique.", "doc_id": "ryiuuyuz"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Systems modeling in support of evidence-based disaster planning for rural areas", "abstract": "Abstract The objective of this communication is to introduce a conceptual framework for a study that applies a rigorous systems approach to rural disaster preparedness and planning. System Dynamics is a well-established computer-based simulation modeling methodology for analyzing complex social systems that are difficult to change and predict. This approach has been applied for decades to a wide variety of issues of healthcare and other types of service capacity and delivery, and more recently, to some issues of disaster planning and mitigation. The study will use the System Dynamics approach to create computer simulation models as \u201cwhat-if\u201d tools for disaster preparedness planners. We have recently applied the approach to the issue of hospital surge capacity, and have reached some preliminary conclusions \u2013 for example, on the question of where in the hospital to place supplementary nursing staff during a severe infectious disease outbreak\u2014some of which we had not expected. Other hospital disaster preparedness issues well suited to System Dynamics analysis include sustaining employee competence and reducing turnover, coordination of medical care and public health resources, and hospital coordination with the wider community to address mass casualties. The approach may also be applied to preparedness issues for agencies other than hospitals, and could help to improve the interactions among all agencies represented in a community's local emergency planning committee. The simulation models will support an evidence-based approach to rural disaster planning, helping to tie empirical data to decision-making. Disaster planners will be able to simulate a wide variety of scenarios, learn responses to each and develop principles or best practices that apply to a broad spectrum of disaster scenarios. These skills and insights would improve public health practice and be of particular use in the promotion of injury and disease prevention programs and practices.", "doc_id": "ij3faz52"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "COVID-19 Outbreak and Cancer Radiotherapy Disruption in Lombardy, Northern Italy", "abstract": "", "doc_id": "y0rc2agf"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "\u201cCOVID-19 Drive Through Testing: An Effective Strategy for Conserving Personal Protective Equipment\u201d", "abstract": "", "doc_id": "id3iu30t"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "In states with prominent virus crisis, door wide open for move to telehealth", "abstract": "Amid ever\u2010changing policy developments in response to the COVID\u201019 crisis, many states have identified loosening restrictions on telehealth services as a front\u2010burner item. This has allowed mental health provider agencies, particularly in the states hardest hit so far by the virus that causes COVID\u201019, to move more quickly to transition in\u2010person outpatient services to telehealth.", "doc_id": "cr2tbe73"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Recommendations for protecting against and mitigating the COVID-19 pandemic in long-term care facilities", "abstract": "Abstract The COVID-19 outbreak has drawn heightened attention from public health scholars researching ways to limit its spread. Much of the research has been focused on minimizing transmission in hospitals and in the general community. However, a particularly vulnerable community that has received relatively little attention is elders residing in long-term care facilities (LTCFs). In this article we address this relative lack of attention, arguing that enhanced traffic control bundling (eTCB) can and should be adopted and implemented as a means of protecting LTCF residents and staff. Enhanced TCB has been widely applied in hospital settings and has proven effective at limiting droplet and fomite transmissions both within hospitals and between hospitals and the general community. By effectively adapting eTCB to LTCF conditions, particularly by incorporating compartmentalization within zones plus active surveillance, COVID-19 transmission into and throughout LTCFs can be minimized, thereby saving numerous lives among an especially vulnerable population.", "doc_id": "p3juk2vv"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "The 1995 Kikwit Ebola outbreak: lessons hospitals and physicians can apply to future viral epidemics", "abstract": "Abstract Objective This article looks at lessons learned from the 1995 Kikwit Ebola outbreak and suggests how modern hospitals should apply these lessons to the next lethal viral epidemic that occurs. Method The 1995 Kikwit Ebola outbreak in the Democratic Republic of the Congo (formally Zaire) is one of the most well studied epidemics to have occurred to date. Many of the lessons learned from identifying, containing and treating that epidemic are applicable to future viral outbreaks, natural disasters and bioterrorist attacks. This is due to Ebola's highly contagious nature and high mortality rate. Results When an outbreak occurs, it often produces fear in the community and causes the basic practice of medicine to be altered. Changes seen at Kikwit included limited physical examinations, hesitance to give intravenous medications and closure of supporting hospital facilities. The Kikwit Ebola outbreak also provided beneficial psychological insight into how patients, staff and the general community respond to a biological crisis and how this will affect physicians working in an epidemic. Conclusions General lessons from the outbreak include the importance of having simple, well-defined triage procedures; staff who are flexible and able to adapt to situations with unknowns; and the need to protect staff physically and emotionally to ensure a sustained effort to provide care.", "doc_id": "w9r97v71"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Contributions and challenges of general practitioners in China fighting against the novel coronavirus crisis", "abstract": "", "doc_id": "07jfjjo1"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Use of quarantine in the control of SARS in Singapore", "abstract": "BACKGROUND: A total of 238 cases of the severe acute respiratory syndrome (SARS) occurred in Singapore between February 25 and May 11, 2003. Control relied on empirical methods to detect early and isolate all cases and quarantine those who were exposed to prevent spread in the community. METHODS: On April 28, 2003, the Infectious Diseases Act was amended in Parliament to strengthen the legal provisions for serving the Home Quarantine Order (HQO). In mounting large-scale quarantine operations, a framework for contact tracing, serving quarantine orders, surveillance, enforcement, health education, transport, and financial support was developed and urgently put in place. RESULTS: A total of 7863 contacts of SARS cases were served with an HQO, giving a ratio of 38 contacts per case. Most of those served complied well with quarantine; 26 (0.03%) who broke quarantine were penalized. CONCLUSION: Singapore's experience underscored the importance of being prepared to respond to challenges with extraordinary measures. With emerging diseases, health authorities need to rethink the value of quarantine to reduce opportunities for spread from potential reservoirs of infection.", "doc_id": "mia3dytz"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Advocates for the homeless seeking funding for COVID\u201019", "abstract": "Now that the federal $8.3 billion appropriations bill has passed and been signed into law this month to stem the spread of the new coronavirus (COVID\u201019), advocates are hoping some of that funding reaches one of this country's most vulnerable populations: the homeless.", "doc_id": "khk9s3zw"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Are infection control measures helpful in reducing paediatric ward infections?", "abstract": "As the majority of children on paediatric wards, especially in winter, have infections all paediatricians will be involved in infection control and prevention (ICP) without realising it. ICP measures include decisions on isolation of patients, which can be difficult with small numbers of cubicles. Children, who are highly infectious, have potential severe infections and those who are more at risk of developing severe infections (e.g. immunocompromised) should be isolated. Handwashing/decontamination is the central and most essential part of ICP measures. It should be actively encouraged and regularly monitored to ensure adherence. The ward layout will influence how we manage ICP. This includes placement and number of alcohol dispensers, sinks, bathrooms, equipment storage and the number of cubicles. It is also worth reviewing ward cleaning policies to assess whether these can be streamlined, potentially freeing up beds/cubicles earlier and leading to cost improvement without putting patients and staff at risk. We encourage all our staff to be fully vaccinated (including seasonal influenza vaccines and MMR). Paediatricians need to be closely involved in antibiotic stewardship and act as role models for all aspects of infection control, particularly proper handwashing.", "doc_id": "qva3q7o9"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Self-contamination during doffing of personal protective equipment by healthcare workers to prevent Ebola transmission", "abstract": "BACKGROUND: Healthcare workers (HCWs) use personal protective equipment (PPE) in Ebola virus disease (EVD) situations. However, preventing the contamination of HCWs and the environment during PPE removal crucially requires improved strategies. This study aimed to compare the efficacy of three PPE ensembles, namely, Hospital Authority (HA) Standard Ebola PPE set (PPE1), Dupont Tyvek Model, style 1422A (PPE2), and HA isolation gown for routine patient care and performing aerosol-generating procedures (PPE3) to prevent EVD transmission by measuring the degree of contamination of HCWs and the environment. METHODS: A total of 59 participants randomly performed PPE donning and doffing. The trial consisted of PPE donning, applying fluorescent solution on the PPE surface, PPE doffing of participants, and estimation of the degree of contamination as indicated by the number of fluorescent stains on the working clothes and environment. Protocol deviations during PPE donning and doffing were monitored. RESULTS: PPE2 and PPE3 presented higher contamination risks than PPE1. Environmental contaminations such as those originating from rubbish bin covers, chairs, faucets, and sinks were detected. Procedure deviations were observed during PPE donning and doffing, with PPE1 presenting the lowest overall deviation rate (%) among the three PPE ensembles (p < 0.05). CONCLUSION: Contamination of the subjects\u2019 working clothes and surrounding environment occurred frequently during PPE doffing. Procedure deviations were observed during PPE donning and doffing. Although PPE1 presented a lower contamination risk than PPE2 and PPE3 during doffing and protocol deviations, the design of PPE1 can still be further improved. Future directions should focus on designing a high-coverage-area PPE with simple ergonomic features and on evaluating the doffing procedure to minimise the risk of recontamination. Regular training for users should be emphasised to minimise protocol deviations, and in turn, guarantee the best protection to HCWs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13756-018-0433-y) contains supplementary material, which is available to authorized users.", "doc_id": "atfa8deg"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Are We Ready? Evidence of Support Mechanisms for Canadian Health Care Workers in Multi-jurisdictional Emergency Planning", "abstract": "BACKGROUND: Federal, provincial and municipal leaders in Canada have adopted a culture of preparedness with the development and update of emergency plans in anticipation of different types of disasters. As evident during the 2003 global outbreak of Severe Acute Respiratory Syndrome (SARS), it is important to provide support for health care workers (HCWs) who are vulnerable during infectious outbreak scenarios. Here we focus on the identification and evaluation of existing support mechanisms incorporated within emergency plans across various jurisdictional levels. METHODS: Qualitative content analysis of 12 emergency plans from national, provincial and municipal levels were conducted using NVIVOTM software. The plans were scanned and coded according to 1) informational, 2) instrumental, and 3) emotional support mechanisms for HCWs and other first responders. RESULTS: Emergency plans were comprised of a predominance of informational and instrumental supports, yet few emotional or social support mechanisms. All the plans lacked gender-based analysis of how infectious disease outbreaks impact male and female HCWs differently. Acknowledgement of the need for emotional supports was evident at higher jurisdictional levels, but recommended for implementation locally. CONCLUSIONS: While support mechanisms for HCWs are included in this sample of emergency plans, content analysis revealed few emotional or social supports planned for critical personnel; particularly for those who will be required to work in extremely stressful conditions under significant personal risk. The implications of transferring responsibilities for support to local and institutional jurisdictions are discussed.", "doc_id": "6ka8bqnu"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "The active role of a blood center in outpacing the transfusion transmission of COVID-19", "abstract": "", "doc_id": "taxr9sjr"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Review of Literature for Air Medical Evacuation High-Level Containment Transport", "abstract": "Abstract Introduction Aeromedical evacuation (AE) is a challenging process, further complicated when a patient has a highly hazardous communicable disease (HHCD). We conducted a review of the literature to evaluate the processes and procedures utilized for safe AE high-level containment transport (AE-HLCT) of patients with HHCDs. Methods A literature search was performed in PubMed/MEDLINE (from 1966 through January 2019). Authors screened abstracts for inclusion criteria and full articles were reviewed if the abstract was deemed to contain information related to the aim. Results Our search criteria yielded 14 publications and were separated based upon publication dates, with the natural break point being the beginning of the 2013-2016 Ebola virus disease epidemic. Best practices and recommendations from identified articles are subdivided into pre-flight preparations, inflight operations, and post-flight procedures. Conclusions Limited peer-reviewed literature exists on AE-HLCT, including important aspects related to healthcare worker fatigue, alertness, shift scheduling, and clinical care performance. This hinders the sharing of best practices to inform evacuations and equip teams for future outbreaks. Despite the successful use of different aircraft and technologies, the unique nature of the mission opens the opportunity for greater coordination and development of consensus standards for AE-HLCT operations.", "doc_id": "dbrp4vxc"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Addressing the Gaps in Preparation for Quarantine", "abstract": "INTRODUCTION: In the event of an outbreak of a communicable respiratory illness, quarantine may become necessary. The New York Institute for All Hazard Preparedness (NYIAHP) of the State University of New York (SUNY) Downstate Medical Center, in cooperation with the New York City Department of Health and Mental Hygiene's Healthcare Emergency Preparedness Program, (NYC DOHMH-HEPP) quarantine working group, has developed a series of clinical protocols to help health care facilities respond to such an event. PROBLEM: Two full-scale exercises (FSEs) were designed and conducted a year apart in the quarantine unit at Kings County Hospital Center (KCHC) to test the efficacy and feasibility of these quarantine protocols. The goal of these exercises was to identify the gaps in preparedness for quarantine and increase hospital readiness for such an event. METHODS: Evaluators monitored for efficient management of critical physical plants, personnel and material resources. Players were expected to integrate and practice emergency response plans and protocols specific to quarantine. In developing the exercise objectives, five activities were selected for evaluation: Activation of the Unit, Staffing, Charting/Admission, Symptom Monitoring and Infection Control, and Client Management. RESULTS: The results of the initial FSE found that there were incomplete critical tasks within all five protocols: These deficiencies were detailed in an After Action Report and an Improvement Plan was presented to the KCHC Disaster Preparedness Committee a month after the initial FSE. In the second FSE a year later, all critical tasks for Activation of the unit, Staffing and Charting/Admission were achieved. Completion of critical tasks related to Symptom Monitoring and Infection Control and Client Management was improved in the second FSE, but some tasks were still not performed appropriately. CONCLUSION: In short, these exercises identified critical needs in disaster preparedness of the KCHC Quarantine Unit. The lessons learned from this logistical exercise enabled the planning group to have a better understanding of leadership needs, communication capabilities, and infection control procedures. Kings County Hospital Center performed well during these exercises. It was clear that performance in the second exercise was improved, and many problems noted in the first exercise were corrected. Staff also felt better prepared the second time. This supports the idea that frequent exercises are vital to maintain disaster readiness. R Nathawad, PM Roblin, D Pruitt, B Arquilla. Addressing the gaps in preparation for quarantine. Prehosp Disaster Med. 2013;28(2):1-7 23158909.", "doc_id": "hdbbgee2"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Management of inpatients exposed to an outbreak of severe acute respiratory syndrome (SARS)", "abstract": "Abstract This is a prospective observational study of a cohort of inpatients exposed to a severe acute respiratory syndrome (SARS) outbreak. Strict infection control policies were instituted. The 70 patients exposed to the SARS outbreak were isolated from the rest of the hospital. They were triaged, quarantined and cohorted in three open plan wards. Selective isolation was carried out immediately when symptoms and signs suspicious of SARS manifested clinically. The patients' ages ranged from 21 to 90 years and 56% had surgery before the quarantine. Sixteen patients with unexplained fever during the period of quarantine were isolated, seven of whom were eventually diagnosed with probable SARS. The crude incidence of SARS in our cohort was 10%. The SARS case fatality was 14%. No secondary transmission of the SARS virus within the cohort was observed. Strict infection control, together with appropriate triaging, cohorting and selective isolation, is an effective and practical model of intervention in cohorts exposed to a SARS outbreak. Such a management strategy eases the logistic constraints imposed by demands for large numbers of isolation facilities in the face of a massive outbreak.", "doc_id": "wf5p0ecl"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Preventing the Transmission of COVID-19 Amongst Healthcare Workers", "abstract": "", "doc_id": "5oextxkm"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Containing Emerging Epidemics: a Quantitative Comparison of Quarantine and Symptom Monitoring", "abstract": "Strategies for containing an emerging infectious disease outbreak must be non-pharmaceutical when drugs or vaccines for the pathogen do not yet exist or are unavailable. The success of these non-pharmaceutical strategies will depend not only on the effectiveness of quarantine or other isolation measures but also on the epidemiological characteristics of the infection. However, there is currently no systematic framework to assess the relationship between different containment strategies and the natural history and epidemiological dynamics of the pathogen. Here, we compare the effectiveness of quarantine and symptom monitoring, implemented via contact tracing, in controlling epidemics using an agent-based branching model. We examine the relationship between epidemic containment and the disease dynamics of symptoms and infectiousness for seven case study diseases with diverse natural histories including Ebola, Influenza A, and Severe Acute Respiratory Syndrome (SARS). We show that the comparative effectiveness of symptom monitoring and quarantine depends critically on the natural history of the infectious disease, its inherent transmissibility, and the intervention feasibility in the particular healthcare setting. The benefit of quarantine over symptom monitoring is generally maximized for fast-course diseases, but we show the conditions under which symptom monitoring alone can control certain outbreaks. This quantitative framework can guide policy-makers on how best to use non-pharmaceutical interventions to contain emerging outbreaks and prioritize research during an outbreak of a novel pathogen. Quarantine and symptom monitoring of contacts with suspected exposure to an infectious disease are key interventions for the control of emerging epidemics; however, there does not yet exist a quantitative framework for comparing the control performance of each. Here, we use a mathematical model of seven case study diseases to show how the choice of intervention is influenced by the natural history of the infectious disease, its inherent transmissibility, and the intervention feasibility in the particular healthcare setting. We use this information to identify the most important characteristics of the disease and setting that need to be characterized for an emerging pathogen in order to make an informed decision between quarantine and symptom monitoring.", "doc_id": "2j4z5rp8"} {"topic_name": "coronavirus quarantine", "topic_id": "12", "title": "Appraisal of recommended respiratory infection control practices in primary care and emergency department settings", "abstract": "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.", "doc_id": "v6pqwgsy"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Changes in population movement make COVID-19 spread differently from SARS.", "abstract": "This comment discusses the contribution of population movement to the spread of COVID-19, with a reference to the spread of SARS 17 years ago. We argue that the changing geography of migration, the diversification of jobs taken by migrants, the rapid growth of tourism and business trips, and the longer distance taken by people for family reunion are what make the spread of COVID-19 so differently from that of SARS. These changes in population movement are expected to continue. Hence, new strategies in disease prevention and control should be taken accordingly, which are also proposed in the comment.", "doc_id": "0fbmelx0"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "A cluster of tertiary transmissions of 2019 novel coronavirus (SARS-CoV-2) in the community from infectors with common cold symptoms.", "abstract": "Background/Aims As the global impact of the novel coronavirus disease 2019 (COVID-19) has been severe, many countries have intensified containment activities to eliminate virus transmission, through early detection and isolation strategies. To establish a proper quarantine strategy, it is essential to understand how easily the virus can spread in the communities. Methods In this study, we collected detailed information on the circumstances in which human-to-human transmission occurred in the tertiary transmission cases of COVID-19 in the community. Results On January 26, 2020, an imported case of COVID-19 was confirmed, and by February 10, 2020, one secondary transmission and three tertiary transmissions were identified. Secondary transmission occurred on the first day of illness of the infector, and his symptoms were suggestive of a common cold. The transmission occurred during a 90-minute long meal together in a restaurant. The people were sitting within one meter of each other, and had no direct contact. The tertiary transmission also occurred on the first-day illness of the other infector, and his only symptom was slight chills. The transmission occurred at a church during 2-hour-long worship, and two rows separated them. Conclusions Our findings suggest that mildly symptomatic patients with COVID-19 could transmit the virus from the first day of illness through daily activities in the community. Early detection and isolation of patients with COVID-19 may be challenging.", "doc_id": "try8yju1"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "[Epidemiological analysis on a family cluster of COVID-19].", "abstract": "Objective: To understand the possible transmission route of a family cluster of COVID-19 in Zhengzhou and the potential infectivity of COVID-19 in incubation period, and provide scientific evidence for the timely control of infectious source and curb the spread of the epidemic. Methods: Epidemiological investigation was conducted for a family cluster of COVID-19 (8 cases) with descriptive epidemiological method, and respiratory tract samples of the cases were collected for the nucleic acid detection of 2019-nCoV by RT-PCR. Results: Two primary cases, which occurred on 31 January and 1 February, 2020, respectively, had a common exposure history in Wuhan. The other six family members had onsets on 30 January, 31 January, 1 February (three cases) and 3 February, 2020. Conclusions: In this family cluster of COVID-19, six family members were infected through common family exposure to the 2 primary cases. Five secondary cases had onsets earlier than or on the same day as the primary cases, indicating that COVID-19 is contagious in incubation period, and the home isolation in the early phase of the epidemic might lead to the risk of family cluster of COVID-19.", "doc_id": "voofruqm"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Air pollution and COVID-19: Is the connect worth its weight?", "abstract": "Primary route of transmission of SARS-CoV-2 among humans is droplets and direct contact. Airborne transmission of this virus is not established conclusively and so is the role of airborne particulate matter. This commentary examines the existing evidence about the role of particulate matter pollutants in SARS-CoV-2 transmission. PM2.5and other small particulate matter have been shown to carry viable virus particles in the air and incriminated in spread of measles and SARS coronavirus. Empirical evidence has been provided regarding role of air pollution in accelerated transmission of SARS-CoV-2 in Italy as well as Wuhan. Lockdown-related reduction in PM2.5levels in ambient air may have contributed to reduce transmission of SARS-CoV-2. High PM2.5levels in the past might have added to SARS-CoV-2 related mortality due to air pollution relate comorbidities. Post-lockdown increase in PM2.5levels may accelerate covid-19 transmission and can add to the burden of COVID-19 morbidity and mortality.", "doc_id": "wlpoxabu"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "The Presence of SARS-CoV-2 RNA in Feces of COVID-19 Patients.", "abstract": "BACKGROUND In December 2019, Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, and has spread globally. However, the transmission route of SARS-CoV-2 has not been fully understood. In this study, we aimed to investigate the SARS-CoV-2 shedding in excreta of COVID-19 patients. METHODS Electronical medical records, including demographics, clinical characteristics, laboratory and radiological findings, of enrolled patients were extracted and analyzed. Pharyngeal swab, stool and urine specimens were collected and tested for SARS-CoV-2 RNA by RT-PCR. Viral shedding at multiple time points in specimens was recorded, and analyzed its correlation with clinical manifestations and the severity of illness. RESULTS A total of 42 laboratory-confirmed patients were enrolled, 8 (19.05%) of whom had gastrointestinal symptoms. 28 (66.67%) patients tested positive for SARS-CoV-2 RNA in stool specimens, which was not associated with the presence of gastrointestinal symptoms and the severity of illness. Among them, 18 (64.29%) patients remained positive for viral RNA in feces after pharyngeal swabs turned negative. The duration of viral shedding from feces after negative conversion in pharyngeal swabs was 7 (6-10) days, regardless of COVID-19 severity. The demographics, clinical characteristics, laboratory and radiologic findings did no differ between patients tested positive and negative for SARS-CoV-2 RNA in feces. Viral RNA was not detectable in urine specimens from 10 patients. CONCLUSIONS Our results demonstrated the presence of SARS-CoV-2 RNA in feces of COVID-19 patients, and suggested the possibility of SARS-CoV-2 transmission via the fecal-oral route. This article is protected by copyright. All rights reserved.", "doc_id": "cx3v56ri"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Relative contributions of transmission routes for COVID-19 among healthcare personnel providing patient care.", "abstract": "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 \u00b5m) 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.", "doc_id": "izxqtril"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "A Computer Simulation Study on novel Corona Virus Transmission among the People in a Queue", "abstract": "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.", "doc_id": "9x4d6skf"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Comparison of the COVID-19 infection risks by close contact and aerosol transmission", "abstract": "A comprehensive understanding of the transmission routes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of great importance for the effective control of the spread of Corona Virus Disease 2019 (COVID-19). Human-to-human transmission by close contact where large respiratory droplets play a significant role has been established as the main transmission route. At the same time the transmission by small aerosol is getting increasing attention. There is no distinct boundary between droplets and aerosol in nature so it is natural to investigate the infection risk due to aerosol. Here, we utilized a newly developed dose-response relation, combined with a box model for the exposure estimation, to quantitatively evaluate the infection risk of SARS-CoV-2 through aerosol transmission and compared with the risk due to close contact. The results indicated that the median infection risk via aerosol transmission was about 3.7x10-5 (95% confidence interval: 3.5x10-6 to 4.4x10-4) for one hour of exposure in a room with the size of 10 m (width)x10 m (length)x3 m (height) with one infected individual in it. The risk was more than three orders of magnitude lower than the risk at short distance, about 12.8% within 1 m, based on a meta-analysis. A simple exponential regression model Risk=10-0.90xD+0.10 (D<=5 m) could be utilized to characterize the magnitude of infection risk in the considered scenario based on the distance D from the infected individual. With prolonged exposure duration and large exposed population, the infection caused by aerosol transmission could be considerable, thus it is necessary to be cautious for the potential aerosol transmission risk in such situations.", "doc_id": "kt76tu24"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "A letter about the airborne transmission of sars-cov-2 based on the current evidence", "abstract": "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.", "doc_id": "a1ha0hx4"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "MATHEMATICAL MODELING FOR TRANSMISSIBILITY OF COVID-19 VIA MOTORCYCLES", "abstract": "In this paper, we present a mathematical model of trigonometric type for transmissibility and deaths as a result of COVID-19. In the model, we analyze the spread of COVID-19 by considering a new parameter, the motorcycle as a means of public transport, which has not been considered in several other models for COVID-19. We use the mathematical model to predict the spread and deaths and we suggest strategies that can be put in place to prevent the spread caused by motorcycle as a means of public transport.", "doc_id": "9zy7xqig"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Is there an airborne component to the transmission of COVID-19? : a quantitative analysis study", "abstract": "Objectives While COVID-19 is known to be spread by respiratory droplets (which travel <2m horizontally), much less is known about its transmission via aerosols, which can become airborne and be widely distributed throughout room spaces. In order to quantify the risk posed by COVID-19 infectors exhaling respiratory aerosols in enclosed spaces, we undertook a computer modelling study to simulate transmission in an office building. Methods Respiratory droplet data from four published datasets were analysed to quantify the number and volume of droplets <100m diameter produced by a typical cough and speaking event (i.e. counting from 1 to 100). This was used in a stochastic model to simulate (10,000 simulations) the number of respiratory particles, originating from a COVID-19 infector, that would be inhaled in one hour by a susceptible individual practicing socially distancing in a 5 x 5 x 2.75m office space. Several scenarios were simulated that mimicked the presence of both symptomatic and asymptomatic COVID-19 infectors. Results On average, each cough and speaking event produced similar numbers of droplets <100 m diameter (median range = 955 - 1010). Computer simulations (at ventilation rate = 2AC/h) revealed that sharing the office space with a symptomatic COVID-19 infector (4 coughs per hour) for one hour resulted in the inhalation of 187.3 (median value) respiratory droplets, whereas sharing with an asymptomatic COVID-19 positive person (10 speaking events per hour) resulted in the inhalation of 482.9 droplets. Increasing the ventilation rate resulted in only modest reductions in particle numbers inhaled. Conclusions Given that live SARS-CoV-2 virions are known to be shed in high concentrations from the nasal cavity of both symptomatic and asymptomatic COVID-19 patients, the results suggest that individuals who share enclosed spaces with an infector may be at risk of contracting COVID-19 by the aerosol route, even when practicing social distancing.", "doc_id": "a0oxgop2"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "A pilot study to investigate the fecal dissemination of SARS-CoV-2 virus genome in COVID-19 patients in Odisha, India", "abstract": "In infectious diseases, the routes of transmission play major roles in determining the rate and extent of disease spread. Though fomites and aerosol droplets are major sources of SARS-CoV-2 human to human transmission, studies have also reported possible involvement of other routes of transmission like fecal-oral. Multiple studies around the world have reported shedding of the SARS-CoV-2 viral genome in certain COVID-19 patient fecal samples. Hence, the major objective of this study was to get the experimental evidence whether in Indian COVID-19 patients fecal dissemination of the SARS-CoV-2 genome occurs or not. Information obtained from twelve number of patients from a COVID-19 hospital of Odisha has demonstrated that both symptomatic and asymptomatic Indian patients could be positive for the SARS-CoV-2 genome in their fecal component. The findings have also established a protocol to collect and extract viral RNA for SARS-CoV-2 detection in fecal samples. Together, the study supports the hypothesis of possible fecal-oral transmission of SARS-CoV-2 virus and provides a rationale to extend this study in a larger cohort of patient samples and correlate the significance of the SARS-CoV-2 virus genome detection in fecal samples with disease severity and transmission.", "doc_id": "plnukt32"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "SARS-CoV-2 possible contamination of genital area: implications for sexual and vertical transmission routes", "abstract": "", "doc_id": "i1mzr5x0"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "[Consideration and prevention for the aerosol transmission of 2019 novel coronavirus]", "abstract": "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: ).", "doc_id": "cfwtyud2"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "COVID-19 outbreak: Migration, effects on society, global environment and prevention", "abstract": "The COVID-19 pandemic is considered as the most crucial global health calamity of the century and the greatest challenge that the humankind faced since the 2nd World War. In December 2019, a new infectious respiratory disease emerged in Wuhan, Hubei province, China and was named by the World Health Organization as COVID-19 (coronavirus disease 2019). A new class of corona virus, known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been found to be responsible for occurrence of this disease. As far as the history of human civilization is concerned there are instances of severe outbreaks of diseases caused by a number of viruses. According to the report of the World Health Organization (WHO as of April 18 2020), the current outbreak of COVID-19, has affected over 2164111 people and killed more than 146,198 people in more than 200 countries throughout the world. Till now there is no report of any clinically approved antiviral drugs or vaccines that are effective against COVID-19. It has rapidly spread around the world, posing enormous health, economic, environmental and social challenges to the entire human population. The coronavirus outbreak is severely disrupting the global economy. Almost all the nations are struggling to slow down the transmission of the disease by testing & treating patients, quarantining suspected persons through contact tracing, restricting large gatherings, maintaining complete or partial lock down etc. This paper describes the impact of COVID-19 on society and global environment, and the possible ways in which the disease can be controlled has also been discussed therein.", "doc_id": "v0bt747q"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) in Dentistry. Management of Biological Risk in Dental Practice", "abstract": "The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus first identified in Wuhan, China, and the etiological agent of Coronavirus Disease-2019 (COVID-19). This infection spreads mainly through direct contact with Fl\u00fcgge micro droplets or core droplets that remain suspended as aerosol. Moreover, it has been reported that infected subjects, both with and without clinical signs of COVID-19, can transmit the virus. Since the infection typically enters through mouth, nose, and eyes, dentistry is one of the medical practices at highest risk of infection due to the frequent production of aerosol and the constant presence of saliva. The World Health Organization (WHO) has suggested that only emergency/urgent procedures should be performed during the coronavirus outbreak. Considering the virus' route of transmission, a specific protocol should be applied to reduce the risk of infection in addition to measures that prevent the spread of infection from a patient to another person or medical tools and equipment (cross-infection). This protocol should be implemented by modifying both patient management and clinical practice, introducing particular devices and organizational practices. This paper aims to discuss and suggest the most appropriate procedures in every aspect of dental practice to reduce infection risk.", "doc_id": "r5h8z259"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "A cluster of tertiary transmissions of 2019 novel coronavirus (SARS-CoV-2) in the community from infectors with common cold symptoms", "abstract": "Background/Aims: As the global impact of the novel coronavirus disease 2019 (COVID-19) has been severe, many countries have intensified containment activities to eliminate virus transmission, through early detection and isolation strategies. To establish a proper quarantine strategy, it is essential to understand how easily the virus can spread in the communities. Methods: In this study, we collected detailed information on the circumstances in which human-to-human transmission occurred in the tertiary transmission cases of COVID-19 in the community. Results: On January 26, 2020, an imported case of COVID-19 was confirmed, and by February 10, 2020, one secondary transmission and three tertiary transmissions were identified. Secondary transmission occurred on the first day of illness of the infector, and his symptoms were suggestive of a common cold. The transmission occurred during a 90-minute long meal together in a restaurant. The people were sitting within one meter of each other, and had no direct contact. The tertiary transmission also occurred on the first-day illness of the other infector, and his only symptom was slight chills. The transmission occurred at a church during 2-hour-long worship, and two rows separated them. Conclusions: Our findings suggest that mildly symptomatic patients with COVID-19 could transmit the virus from the first day of illness through daily activities in the community. Early detection and isolation of patients with COVID-19 may be challenging.", "doc_id": "1vc1h7kt"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Transmission of COVID-19 in the terminal stages of the incubation period: A familial cluster", "abstract": "We report a familial cluster of 2019 novel coronavirus disease (COVID-19) to assess its potential transmission during the incubation period. The first patient in this familial cluster was identified during the presymptomatic period, as a close contact of a confirmed patient. Five family members had close contact with this first patient during his incubation period, with four of them confirmed positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the subsequent sampling tests.", "doc_id": "p116erdu"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Epidemiological analysis on a family cluster of COVID-19/ \u4e2d\u534e\u6d41\u884c\u75c5\u5b66\u6742\u5fd7", "abstract": "Objective@#To understand the possible transmission route of a family cluster of COVID-19 in Zhengzhou and the potential infectivity of COVID-19 in incubation period, and provide scientific evidence for the timely control of infectious source and curb the spread of the epidemic.@*Methods@#Epidemiological investigation was conducted for a family cluster of COVID-19 (8 cases) with descriptive epidemiological method, and respiratory tract samples of the cases were collected for the nucleic acid detection of 2019-nCoV by RT-PCR.@*Results@#Two primary cases, which occurred on 31 January and 1 February, 2020, respectively, had a common exposure history in Wuhan. The other six family members had onsets on 30 January, 31 January, 1 February (three cases) and 3 February, 2020.@*Conclusions@#In this family cluster of COVID-19, six family members were infected through common family exposure to the 2 primary cases. Five secondary cases had onsets earlier than or on the same day as the primary cases, indicating that COVID-19 is contagious in incubation period, and the home isolation in the early phase of the epidemic might lead to the risk of family cluster of COVID-19.", "doc_id": "7gl5lptp"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Possibility of Faecal-Oral Transmission of Novel Coronavirus (SARS-CoV-2) via Consumption of Contaminated Foods of Animal Origin: A Hypothesis", "abstract": "This article has no abstract DOI:10 18502/jfqhc 7 1 2445", "doc_id": "hyo1k7ig"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "COVID-19: Transmission, prevention, and potential therapeutic opportunities", "abstract": "The novel coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global challenge. Despite intense research efforts worldwide, an effective vaccine and viable treatment options have eluded investigators. Therefore, infection prevention, early viral detection and identification of successful treatment protocols provide the best approach in controlling disease spread. In this review, current therapeutic options, preventive methods and transmission routes of COVID-19 are discussed.", "doc_id": "6jsbh5or"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Observations about sexual and other routes of SARS-CoV-2 (COVID-19) transmission and its prevention", "abstract": "", "doc_id": "v69tke5z"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Unlikely SARS-CoV-2 vertical transmission from mother to child: A case report", "abstract": "As the 2019 novel coronavirus disease (COVID-19) rapidly spread across China and to more than 70 countries, an increasing number of pregnant women were affected. The vertical transmission potential of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of great concern to the obstetrics, neonatologists, and public health agencies. Though some studies indicated the risk of vertical transmission is low, few cases have been reported with comprehensive serial tests from multiple specimens. In this case, a female preterm infant was born to a mother with confirmed COVID-19. She presented with mild respiratory distress and received general management and a short period of nasal continuous positive airway pressure support. During her stay at the hospital, a series of SARS-CoV-2 nucleic test from her throat and anal swab, serum, bronchoalveolar lavage fluid, and urine were negative. The nucleic acid test from the mother's amniotic fluid, vaginal secretions, cord blood, placenta, serum, anal swab, and breast milk were also negative. The most comprehensively tested case reported to date confirmed that the vertical transmission of COVID is unlikely, but still, more evidence is needed.", "doc_id": "6nqnvxz6"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "COVID-19 vulnerability: the potential impact of genetic susceptibility and airborne transmission", "abstract": "The recent coronavirus disease (COVID-19), caused by SARS-CoV-2, is inarguably the most challenging coronavirus outbreak relative to the previous outbreaks involving SARS-CoV and MERS-CoV. With the number of COVID-19 cases now exceeding 2 million worldwide, it is apparent that (i) transmission of SARS-CoV-2 is very high and (ii) there are large variations in disease severity, one component of which may be genetic variability in the response to the virus. Controlling current rates of infection and combating future waves require a better understanding of the routes of exposure to SARS-CoV-2 and the underlying genomic susceptibility to this disease. In this mini-review, we highlight possible genetic determinants of COVID-19 and the contribution of aerosol exposure as a potentially important transmission route of SARS-CoV-2.", "doc_id": "kj6m72jt"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "A Familial Cluster of Infection Associated With the 2019 Novel Coronavirus Indicating Possible Person-to-Person Transmission During the Incubation Period", "abstract": "An ongoing outbreak of pneumonia associated with 2019 novel coronavirus was reported in China. It is unclear whether the virus is infective exists during the incubation period, although person-to-person transmission has been reported elsewhere. We report the epidemiological features of a familial cluster of 4 patients in Shanghai, including an 88-year-old man with limited mobility who was exposed only to asymptomatic family members whose symptoms developed later. The epidemiological evidence has shown possible transmission of 2019 novel coronavirus during the incubation period.", "doc_id": "yhdhy7t0"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Airborne transmission of SARS-CoV-2: The world should face the reality", "abstract": "Hand washing and maintaining social distance are the main measures recommended by the World Health Organization (WHO) to avoid contracting COVID-19. Unfortunately, these measured do not prevent infection by inhalation of small droplets exhaled by an infected person that can travel distance of meters or tens of meters in the air and carry their viral content. Science explains the mechanisms of such transport and there is evidence that this is a significant route of infection in indoor environments. Despite this, no countries or authorities consider airborne spread of COVID-19 in their regulations to prevent infections transmission indoors. It is therefore extremely important, that the national authorities acknowledge the reality that the virus spreads through air, and recommend that adequate control measures be implemented to prevent further spread of the SARS-CoV-2 virus, in particularly removal of the virus-laden droplets from indoor air by ventilation.", "doc_id": "e3rp7gtj"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Sexual transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A new possible route of infection?", "abstract": "", "doc_id": "favozcb3"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Potential fecal transmission of SARS-CoV-2: Current evidence and implications for public health", "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 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.", "doc_id": "12sbikmx"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Transmission routes of 2019-nCoV and controls in dental practice", "abstract": "A novel \u00df-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.", "doc_id": "smhcvdn0"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Possible aerosol transmission of COVID-19 and special precautions in dentistry", "abstract": "Since its emergence in December 2019, corona virus disease 2019 (COVID-19) has impacted several countries, affecting more than 90 thousand patients and making it a global public threat. The routes of transmission are direct contact, and droplet and possible aerosol transmissions. Due to the unique nature of dentistry, most dental procedures generate significant amounts of droplets and aerosols, posing potential risks of infection transmission. Understanding the significance of aerosol transmission and its implications in dentistry can facilitate the identification and correction of negligence in daily dental practice. In addition to the standard precautions, some special precautions that should be implemented during an outbreak have been raised in this review.", "doc_id": "fhaw3b6t"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Flattening the Curve: Insights From Queueing Theory", "abstract": "The worldwide outbreak of the coronavirus was first identified in 2019 in Wuhan, China. Since then, the disease has spread worldwide. As it currently spreading in the United States, policy makers, public health officials and citizens are racing to understand the impact of this virus on the United States healthcare system. They fear that the rapid influx of patients will overwhelm the healthcare system leading to unnecessary fatalities. Most countries and states in America have introduced mitigation strategies, such as social distancing, to decrease the rate of newly infected people, i.e. flattening the curve.In this paper, we analyze the time evolution of the number of people hospitalized due to the coronavirus using the methods of queueing theory. Given that the rate of new infections varies over time as the pandemic evolves, we model the number of coronavirus patients as a dynamical system based on the theory of infinite server queues with non-stationary Poisson arrival rates. With this model we are able to quantify how flattening the curve affects the peak demand for hospital resources. This allows us to characterize how aggressively society must flatten the curve in order to avoid overwhelming the capacity of healthcare system. We also demonstrate how flattening the curve impacts the elapsed time between the peak rate of hospitalizations and the time of the peak demand for the hospital resources. Finally, we present empirical evidence from China, South Korea, Italy and the United States that supports the insights from the model.", "doc_id": "mzx1ye6t"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Risk of nosocomial transmission of coronavirus disease 2019: an experience in a general ward setting in Hong Kong", "abstract": "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.", "doc_id": "4lz45ywi"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "The presence of SARS-CoV-2 RNA in the feces of COVID-19 patients", "abstract": "In December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, and has spread globally. However, the transmission route of SARS-CoV-2 has not been fully understood. In this study, we aimed to investigate SARS-CoV-2 shedding in the excreta of COVID-19 patients. Electronical medical records, including demographics, clinical characteristics, laboratory and radiological findings of enrolled patients were extracted and analyzed. Pharyngeal swab, stool, and urine specimens were collected and tested for SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction. Viral shedding at multiple time points in specimens was recorded, and its correlation analyzed with clinical manifestations and the severity of illness. A total of 42 laboratory-confirmed patients were enrolled, 8 (19.05%) of whom had gastrointestinal symptoms. A total of 28 (66.67%) patients tested positive for SARS-CoV-2 RNA in stool specimens, and this was not associated with the presence of gastrointestinal symptoms and the severity of illness. Among them, 18 (64.29%) patients remained positive for viral RNA in the feces after the pharyngeal swabs turned negative. The duration of viral shedding from the feces after negative conversion in pharyngeal swabs was 7 (6-10) days, regardless of COVID-19 severity. The demographics, clinical characteristics, laboratory and radiologic findings did not differ between patients who tested positive and negative for SARS-CoV-2 RNA in the feces. Viral RNA was not detectable in urine specimens from 10 patients. Our results demonstrated the presence of SARS-CoV-2 RNA in the feces of COVID-19 patients and suggested the possibility of SARS-CoV-2 transmission via the fecal-oral route.", "doc_id": "2brbgvqo"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Vertical Transmission of Coronavirus Disease 19 (COVID-19) from Infected Pregnant Mothers to Neonates: A Review", "abstract": "Background: Since early December 2019, the Coronavirus Disease 19 (COVID-19) infection has been prevalent in China and eventually spread to other countries. There are a few published cases of COVID-19 occurring during pregnancy and due the possibility of mother-fetal vertical transmission, there is a concern that the fetuses may be at risk of congenital COVID-19. Methods: We reviewed the risk of vertical transmission of COVID-19 to the fetus of infected mothers by using data of published articles or official websites up to March 4, 2020. Results: A total of 31 infected pregnant mothers with COVID-19 were reported. No COVID-19 infection was detected in their neonates or placentas. Two mothers died from COVID-19-related respiratory complications after delivery. Conclusions: Currently, based on limited data, there is no evidence for intrauterine transmission of COVID-19 from infected pregnant women to their fetuses. Mothers may be at increased risk for more severe respiratory complications.", "doc_id": "zkcaeeve"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Indirect Virus Transmission in Cluster of COVID-19 Cases, Wenzhou, China, 2020", "abstract": "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.", "doc_id": "yp7bniwt"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "On a knife's edge of a COVID-19 pandemic: is containment still possible?", "abstract": "", "doc_id": "x9nanc34"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "COVID-19 transmission and blood transfusion: A case report", "abstract": "The recent outbreak of the novel coronavirus disease 2019 (COVID-19) has been labelled as a pandemic by the World Health Organization. Although person-to-person transmission of the etiologic agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been confirmed, it is not known whether COVID-19 may be transmitted by blood transfusion. Notwithstanding the urgent requirement of blood, it is critical to know whether the SARS-CoV-2 virus can be transmitted by blood transfusion because many individuals may be asymptomatic carriers and may donate blood. Several cases in which specific viral RNA could be detected in the serum from patients with COVID-19 have already been reported; these findings suggest that blood donation may be an unexplored route of transmission. However, the American Association of Blood Banks and Centers for Disease Control and Prevention have not recommended any specific SARS-CoV-2-related actions to be taken at blood collection centres at this time. In this report, we describe a case of a 21-year-old man with very severe aplastic anaemia who received apheresis platelet transfusion from an individual who was subsequently diagnosed with COVID-19. Our patient tested negative for COVID-19 and is awaiting allogeneic stem cell transplantation.", "doc_id": "444jnx7m"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "SARS-CoV-2 is transmitted via contact and via the air between ferrets", "abstract": "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.", "doc_id": "5q49qq42"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Pediatric anesthetic implications of COVID\u201019\u2014A review of current literature", "abstract": "Pediatric anesthetists have an important role to play in the management of patients suspected or confirmed to have COVID\u201019. In many institutions, the COVID\u201019 intubation teams are staffed with anesthetists as the proceduralists working throughout the hospitals also in the ICU and Emergency Departments. As practitioners who perform aerosol generating procedures involving the airway, we are at high risk of exposure to the virus SARS\u2010CoV\u20102 and need to ensure we are well prepared and trained to manage such cases. This article reviews the relevant pediatric literature surrounding COVID\u201019 and summarizes the key recommendations for anesthetists involved in the care of children during this pandemic.", "doc_id": "w42jv02t"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Transmission routes of COVID-19 in the dental practice", "abstract": "", "doc_id": "vw2d7spi"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Fecal transmission in COVID\u201019: A potential shedding route", "abstract": "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.", "doc_id": "0bz4micv"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Transmission routes of SARS-CoV-2", "abstract": "", "doc_id": "4d6rq9qj"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "The Root Causes of COVID-19 Screech for Compassion", "abstract": "", "doc_id": "uih7alib"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 via Close Contact and Respiratory Droplets Among Human Angiotensin-Converting Enzyme 2 Mice", "abstract": "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.", "doc_id": "obh0q8gg"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Intrauterine vertical transmission of SARS\u2010CoV\u20102: what we know so far", "abstract": "", "doc_id": "baoqgu8v"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Can Covid\u201019 be a sexually transmitted disease? Posterity will judge", "abstract": "", "doc_id": "eab7i4f6"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Possible indirect transmission of COVID-19 at a squash court, Slovenia, March 2020: case report", "abstract": "Since the beginning of the COVID-19 epidemic, there is an ongoing debate and research regarding the possible ways of virus transmission. We conducted an epidemiological investigation which revealed a cluster of five COVID-19 cases, linked to playing squash at a sports venue in Maribor, Slovenia. Acquired data raises possibility that the transmission occurred indirectly through contaminated objects in changing room or squash hall or via aerosolisation in squash hall.", "doc_id": "o3u52mhl"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Digestive system involvement of novel coronavirus infection: Prevention and control infection from a gastroenterology perspective", "abstract": "An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) in Wuhan, China, now known as coronavirus disease 2019 (COVID\u201019), 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\u201019 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\u2010oral 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\u201019; (b) microbiological and virological investigations; (c) the role of fecal\u2010oral transmission; and (d) prevention and control of SARS\u2010CoV\u20102 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.", "doc_id": "xj9md751"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Middle East respiratory syndrome coronavirus: epidemiology and disease control measures", "abstract": "The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in 2012 resulted in an increased concern of the spread of the infection globally. MERS-CoV infection had previously caused multiple health-care-associated outbreaks and resulted in transmission of the virus within families. Community onset MERS-CoV cases continue to occur. Dromedary camels are currently the most likely animal to be linked to human MERS-CoV cases. Serologic tests showed significant infection in adult camels compared to juvenile camels. The control of MERS-CoV infection relies on prompt identification of cases within health care facilities, with institutions applying appropriate infection control measures. In addition, determining the exact route of transmission from camels to humans would further add to the control measures of MERS-CoV infection.", "doc_id": "nat8xl41"} {"topic_name": "how does coronavirus spread", "topic_id": "13", "title": "Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits", "abstract": "Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission.", "doc_id": "eumuid3r"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Searching for Superspreaders: Identifying Epidemic Patterns Associated with Superspreading Events in Stochastic Models", "abstract": "The importance of host transmissibility in disease emergence has been demonstrated in historical and recent pandemics that involve infectious individuals, known as superspreaders, who are capable of transmitting the infection to a large number of susceptible individuals. To investigate the impact of superspreaders on epidemic dynamics, we formulate deterministic and stochastic models that incorporate differences in superspreaders versus nonsuperspreaders. In particular, continuous-time Markov chain models are used to investigate epidemic features associated with the presence of superspreaders in a population. We parameterize the models for two case studies, Middle East respiratory syndrome (MERS) and Ebola. Through mathematical analysis and numerical simulations, we find that the probability of outbreaks increases and time to outbreaks decreases as the prevalence of superspreaders increases in the population. In particular, as disease outbreaks occur more rapidly and more frequently when initiated by superspreaders, our results emphasize the need for expeditious public health interventions.", "doc_id": "1tkevj8v"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Epidemiologic, Clinical, and Laboratory Findings of the COVID-19 in the current pandemic", "abstract": "BACKGROUND: The COVID-19 caused the pandemic affected the world deeply, with more than 3,000,000 people infected and nearly 200,000 deaths. This article aimed to summarize the epidemiologic traits, clinical spectrum, CT results and laboratory findings of COVID-19 pandemic. METHODS: We scoped for relevant literatures published during 1st Dec 2019 to 23rd Apr 2020 based on four databases by using English and Chinese. The evidence was synthesized narratively. RESULTS: The COVID-19 pandemic was found to have a higher transmission rate compared to SARS and MERS, and involved 4 stages of evolution. The basic reproduction number (R0) is 3.32 (95% CI:3.24\u20133.39) and the incubation period was 5.24 days (95% CI:3.97\u20136.50, 5 studies) on average, and the average time for symptoms onset varied by countries. Common clinical spectrums identified included fever (38.1\u201339.0\u00b0C), cough and fatigue, with Acute Respiratory Distress Syndrome (ARDS) being the most common complication reported. Body temperatures above 39.0 \u00b0C, dyspnea, and anorexia were more common symptoms in severe patients. Aged over 60 years old, having co-morbidities, and developing complications were the commonest high-risk factors associated with severe conditions. Leucopenia and lymphopenia were the most common signs of infection while liver and kidney damage were rare but may cause bad outcomes for patients. The bilateral, multifocal Ground-Glass Opacification (GGO) on peripheral, and the consolidative pulmonary opacity were the most frequent CT results and the tendency of mortality rates differed by region. CONCLUSIONS: We provided a bird\u2019s-eye view of the COVID-19 during the current pandemic, which will help better understanding the key traits of the disease. The findings could be used for disease\u2019s future research, control and prevention.", "doc_id": "jxu3056n"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "[Investigation of a cluster epidemic of COVID-19 in Ningbo].", "abstract": "Objective: To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations. Methods: The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR. Results: From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+ generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission. Conclusion: It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.", "doc_id": "hsgx534y"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Descriptive study of COVID-19 outbreak among passengers and crew on Diamond Princess cruise ship, Yokohama Port, Japan, 20 January to 9 February 2020.", "abstract": "An outbreak of coronavirus disease (COVID-19) occurred on the Diamond Princess cruise ship making an international journey, which led to quarantine of the ship at Yokohama Port, Japan. A suspected COVID-19 case was defined as a passenger or crew member who developed a fever or respiratory symptoms, and a confirmed COVID-19 case had laboratory-confirmation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Between 3 and 9 February 2020, 490 individuals were tested for SARS-CoV-2 and 172 were positive (152 passengers (median age: 70 years; interquartile range (IQR): 64-75; males: 45%) and 20 crew (median age: 40 years; IQR: 35-48.5; males: 80%). Other than the Hong Kong-related index case, symptom onset for the earliest confirmed case was 22 January, 2 days after the cruise ship left port. Attack rates among passengers were similar across the decks, while beverage (3.3%, 2/61) and food service staff (5.7%, 14/245) were most affected. Attack rates tended to increase with age. A comprehensive outbreak response was implemented, including surveillance, provision of essential medical care, food and medicine delivery, isolation, infection prevention and control, sampling and disembarkation.", "doc_id": "0av6gx7r"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Significance of super spreader events in COVID-19.", "abstract": "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.", "doc_id": "na3vrf5q"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Transmission of severe acute respiratory syndrome in dynamical small-world networks", "abstract": "The outbreak of severe acute respiratory syndrome (SARS) is still threatening the world because of a possible resurgence. In the current situation that effective medical treatments such as antiviral drugs are not discovered yet, dynamical features of the epidemics should be clarified for establishing strategies for tracing, quarantine, isolation, and regulating social behavior of the public at appropriate costs. Here we propose a network model for SARS epidemics and discuss why superspreaders emerged and why SARS spread especially in hospitals, which were key factors of the recent outbreak. We suggest that superspreaders are biologically contagious patients, and they may amplify the spreads by going to potentially contagious places such as hospitals. To avoid mass transmission in hospitals, it may be a good measure to treat suspected cases without hospitalizing them. Finally, we indicate that SARS probably propagates in small-world networks associated with human contacts and that the biological nature of individuals and social group properties are factors more important than the heterogeneous rates of social contacts among individuals. This is in marked contrast with epidemics of sexually transmitted diseases or computer viruses to which scale-free network models often apply.", "doc_id": "vpl2xu2r"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Superspreading in Early Transmissions of COVID-19 in Indonesia", "abstract": "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.", "doc_id": "ogrlidrs"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Modeling COVID-19 on a network: super-spreaders, testing and containment", "abstract": "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.", "doc_id": "7kovd82v"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Power Laws in Superspreading Events: Evidence from Coronavirus Outbreaks and Implications for SIR Models", "abstract": "While they are rare, superspreading events (SSEs), wherein a few primary cases infect an extraordinarily large number of secondary cases, are recognized as a prominent determinant of aggregate infection rates (R0). Existing stochastic SIR models incorporate SSEs by fitting distributions with thin tails, or finite variance, and therefore predicting almost deterministic epidemiological outcomes in large populations. This paper documents evidence from recent coronavirus outbreaks, including SARS, MERS, and COVID-19, that SSEs follow a power law distribution with fat tails, or infinite variance. We then extend an otherwise standard SIR model with estimated power law distributions, and show that idiosyncratic uncertainties in SSEs will lead to large aggregate uncertainties in infection dynamics, even with large populations. That is, the timing and magnitude of outbreaks will be unpredictable. While such uncertainties have social costs, we also find that they on average decrease the herd immunity thresholds and the cumulative infections because per-period infection rates have decreasing marginal effects. Our findings have implications for social distancing interventions: targeting SSEs reduce not only the average rate of infection (R0) but also its uncertainty. To understand this effect, and to improve inference of the average reproduction numbers under fat tails, estimating the tail distribution of SSEs is vital.", "doc_id": "jfeu4tho"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Mobility network modeling explains higher SARS-CoV-2 infection rates among disadvantaged groups and informs reopening strategies", "abstract": "Fine-grained epidemiological modeling of the spread of SARS-CoV-2 -- capturing who is infected at which locations -- can aid the development of policy responses that account for heterogeneous risks of different locations as well as the disparities in infections among different demographic groups. Here, we develop a metapopulation SEIR disease model that uses dynamic mobility networks, derived from US cell phone data, to capture the hourly movements of millions of people from local neighborhoods (census block groups, or CBGs) to points of interest (POIs) such as restaurants, grocery stores, or religious establishments. We simulate the spread of SARS-CoV-2 from March 1-May 2, 2020 among a population of 105 million people in 10 of the largest US metropolitan statistical areas. We show that by integrating these mobility networks, which connect 60k CBGs to 565k POIs with a total of 5.4 billion hourly edges, even a relatively simple epidemiological model can accurately capture the case trajectory despite dramatic changes in population behavior due to the virus. Furthermore, by modeling detailed information about each POI, like visitor density and visit length, we can estimate the impacts of fine-grained reopening plans: we predict that a small minority of \"superspreader\" POIs account for a large majority of infections, that reopening some POI categories (like full-service restaurants) poses especially large risks, and that strategies restricting maximum occupancy at each POI are more effective than uniformly reducing mobility. Our models also predict higher infection rates among disadvantaged racial and socioeconomic groups solely from differences in mobility: disadvantaged groups have not been able to reduce mobility as sharply, and the POIs they visit (even within the same category) tend to be smaller, more crowded, and therefore more dangerous. By modeling who is infected at which locations, our model supports fine-grained analyses that can inform more effective and equitable policy responses to SARS-CoV-2.", "doc_id": "q2d2sut8"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "The Potential role of Particulate Matter in the Spreading of COVID-19 in Northern Italy: First Evidence-based Research Hypotheses", "abstract": "Background: An epidemic model based only on respiratory droplets and close contact could not fully explain the regional differences in the spread of the recent severe acute respiratory syndrome COVID-19 in Italy, which was fast and dramatic only in Lombardy and Po Valley. On March 16th 2020, we presented a Position Paper proposing a research hypothesis concerning the association between higher mortality rates due to COVID-19 observed in Northern Italy and the peaks of particulate matter concentrations, frequently exceeding the legal limit of 50 micrograms/m3 as PM10 daily average Methods: To assess environmental factors related to the spread of the COVID-19 in Italy from February 24th to March 13th (the date when the lockdown has been imposed over Italy), official daily data relevant to ambient PM10 levels were collected from all Italian Provinces between February 9th and February 29th , taking into account the average time (estimated in 17 days) elapsed between the initial infection and the recorded COVID positivity. In addition to the number of exceedances of PM10 daily limit value, we considered also population data and daily travelling information per each Province. Results. PM10 daily limit value exceedances appear to be a significant predictor (p <0.001) of infection in univariate analyses. Less polluted Provinces had a median of 0.03 infection cases over 1000 residents, while most polluted Provinces had a median of 0.26 cases over 1000 residents. Thirty-nine out of 41 Northern Italian Provinces resulted in the category with highest PM10 levels, while 62 out of 66 Southern Provinces presented low PM10 concentrations (p<0.001). In Milan, the average growth rate before the lockdown was significantly higher than Rome (0.34 vs. 0.27 per day, with a doubling time of 2.0 days vs. 2.6), suggesting a basic reproductive number R0>6.0, comparable with the highest values estimated for China.", "doc_id": "hu6iwoab"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Heterogeneity in SIR epidemics modeling: superspreaders", "abstract": "Deterministic epidemic models, such as the Susceptible-Infected-Recovered (SIR) model, are immensely useful even if they lack the nuance and complexity of social contacts at the heart of network science modeling. Here we present a simple modification of the SIR equations to include the heterogeneity of social connection networks. A typical power-law model of social interactions from network science reproduces the observation that individuals with a high number of contacts, ``hubs'' or ``superspreaders'', can become the primary conduits for transmission. Conversely, once the tail of the distribution is saturated, herd immunity sets in at a smaller overall recovered fraction than in the analogous SIR model. The new dynamical equations suggest that cutting off the tail of the social connection distribution, i.e., stopping superspreaders, is an efficient non-pharmaceutical intervention to slow the spread of a pandemic, such as COVID-19.", "doc_id": "umz2n1os"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Preliminary estimating the reproduction number of the coronavirus disease (COVID-19) outbreak in Republic of Korea and Italy by 5 March 2020", "abstract": "The novel coronavirus disease 2019 (COVID-19) outbreak and Italy has caused 6088 cases and 41 deaths in Republic of Korea and 3144 cases and 107 death in Italy by 5 March 2020. We modeled the transmission process in Republic of Korea and Italy with a stochastic model and estimated the basic reproduction number R0 as 2.6 (95% CI: 2.3-2.9) or 3.2 (95% CI: 2.9-3.5) in Republic of Korea, under the assumption that the exponential growth starting on 31 January or 5 February 2020, and 2.6 (95% CI: 2.3-2.9) or 3.3 (95% CI: 3.0-3.6) in Italy, under the assumption that the exponential growth starting on 5 February or 10 February 2020. Estimates of dispersion term (k) were 10 (95% CI: 5-56) or 22 (95% CI: 8-61) in Republic of Korea, and 13 (95% CI: 5-61) or 37 (95% CI: 13-61) in Italy, and all of which imply few super-spreading events.", "doc_id": "etl9uwt7"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Super-Spreader Businesses and Risk of COVID-19 Transmission", "abstract": "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.", "doc_id": "8ngri1x0"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Minimising lockdown periods for regional elimination of covid-19", "abstract": "Some nations have the option of pursuing a policy of complete elimination of covid-19 instead of a policy of \"flattening the curve\" so that the load the dis- ease places on medical facilities is bearable. A policy of elimination requires a rather onerous \"lockdown\". As the goal of elimination is approached, it is therefore important that there be an informed trade-off between the risk of disease re-emergence and the duration of the \"lockdown\". Here it is shown that an important factor in assessing this trade-off, is the distribution of secondary cases, not just the expected value of this distribution, R0 . It is shown that a distribution in which \"super-spreaders\" are more prominent in the epidemiology, allows for an earlier release from \"lockdown\" with reasonable safety despite some probability of asymptomatic cases. There is some evidence to support such a distribution for covid-19. Analytical calculations and simulations show that once there is only one recognised case in some subregion, release from \"lockdown\" will be reasonably safe after just one or two further incubation periods.", "doc_id": "1ir2ptuj"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Multi-chain Fudan-CCDC model for COVID-19 -- a revisit to Singapore's case", "abstract": "Background: COVID-19 has been impacting on the whole world critically and constantly since late December 2019. Rapidly increasing infections has raised intense worldwide attention. How to model the evolution of COVID-19 effectively and efficiently is of great significance for prevention and control. Methods: We propose the multi-chain Fudan-CCDC model based on the original single-chain model in [8] to describe the evolution of COVID-19 in Singapore. Multi-chains can be considered as the superposition of several single chains with different characteristics. We identify parameters of models by minimizing the penalty function. Results: The numerical simulation results exhibit the multi-chain model performs well on data fitting. Though unsteady the increments are, they could still fall within the range of 25% fluctuation from simulation results. It is predicted by multi-chain models that Singapore are experiencing a nonnegligible risk of explosive outbreak, thus stronger measures are urgently needed to contain the epidemic. Conclusion: The multi-chain Fudan-CCDC model provides an effective way to early detect the appearance of imported infectors and super spreaders and forecast a second outbreak. It can also explain the data in those countries where the single-chain model shows deviation from the data.", "doc_id": "etnf4i8v"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Susceptibility-adjusted herd immunity threshold model and potential R0 distribution fitting the observed Covid-19 data in Stockholm", "abstract": "The reproduction number, R0, is commonly used, and sometimes misused, in conjunction with the classic Kermack and McKindrick theory based on the assumption of homogeneity, in order to estimate herd immunity threshold (HIT). This provides a crude first estimate of HIT, with more elaborate modelling required to arrive at a more realistic value. Early estimates of HIT for Covid-19 were based on this simplistic homogeneous approach, yielding high HIT values that have since been revised downwards with more sophisticated network modelling taking account of R0 heterogeneity and with reference to the low HIT found from serological sampling in Stockholm County. The aim of this paper is to describe a simple model in which host susceptibility is directly linked to the heterogeneous R0 distribution, to shed further light on the mechanisms involved and to arrive at a bimodal R0 distribution consistent with the Covid-19 HIT observed in Stockholm County.", "doc_id": "hfd4eqkv"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Evaluating transmission heterogeneity and super-spreading event of COVID-19 in a metropolis of China", "abstract": "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.", "doc_id": "uicvudil"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Super-spreading events of SARS in a hospital setting: who, when, and why?", "abstract": "", "doc_id": "qhrvi9e7"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020", "abstract": "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.", "doc_id": "fjwmp2fi"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "A Pandemic in Times of Global Tourism: Superspreading and Exportation of COVID-19 Cases from a Ski Area in Austria", "abstract": "", "doc_id": "ki9om3bq"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Propagation and mitigation of epidemics in a scale-free network", "abstract": "The epidemic curve and the final extent of the COVID-19 pandemic are usually predicted from the rate of early exponential raising using the SIR model. These predictions implicitly assume a full social mixing, which is not plausible generally. Here I am showing a counterexample to the these predictions, based on random propagation of an epidemic in Barab\\'asi--Albert scale-free network models. The start of the epidemic suggests $R_0=2.6$, but unlike $\\Omega\\approx 70\\%{}$ predicted by the SIR model, they reach a final extent of only $\\Omega\\approx 4\\%{}$ without external mitigation and $\\Omega\\approx 0.5$--$1.5\\%{}$ with mitigation. Daily infection rate at the top is also 1--1.5 orders of magnitude less than in SIR models. Quarantining only the 1.5\\%{} most active superspreaders has similar effect on extent and top infection rate as blind quarantining a random 50\\%{} of the full community.", "doc_id": "byzemhvu"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan and Singapore", "abstract": "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.", "doc_id": "2t4fsfy9"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "[Investigation of a cluster epidemic of COVID-19 in Ningbo]", "abstract": "Objective: To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations. Methods: The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR. Results: From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+ generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission. Conclusion: It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.", "doc_id": "x9c2ymra"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Unlinking super-linkers: the topology of epidemic response (Covid-19)", "abstract": "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.", "doc_id": "qla3go2i"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Clinical and Transmission Characteristics of Covid-19 - A Retrospective Study of 25 Cases from a Single Thoracic Surgery Department", "abstract": "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.", "doc_id": "xwqxji63"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "A note on community-detection (Kemeny) based testing for COVID-19", "abstract": "The Kemeny constant of a graph can be used to identify and analyse bridges between communities in a graph. Testing, tracking and tracing abilities have been identified as pivotal in helping countries to safely reopen activities after the first wave of the COVID-19 virus. Tracing techniques aim at reconstructing past history of contacts, but can face practical limits in an exponential growth of either testing or overly conservative quarantining. We show how this application of graph theory can be conveniently used to efficiently intercept new virus outbreaks, when they are still in their early stage. Simulations provide promising results in early identification and blocking of possible\"super-spreader links that transmit disease between different communities.", "doc_id": "eofrf2em"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Chest tube with air leaks is a potential \"super spreader\" of COVID-19", "abstract": "", "doc_id": "z19xdrxu"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Significance of super spreader events in COVID-19", "abstract": "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.", "doc_id": "p48bw6s4"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Evaluating Transmission Heterogeneity and Super-Spreading Event of COVID-19 in a Metropolis of China", "abstract": "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.", "doc_id": "uo7ixk9r"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Super-spreading events and contribution to transmission of MERS, SARS, and SARS-CoV-2 (COVID-19)", "abstract": "", "doc_id": "zpib6e2z"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "A super-spreader of COVID-19 in Ningbo city in China", "abstract": "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.", "doc_id": "37katpp3"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "COVID-19 Super-spreaders: Definitional Quandaries and Implications", "abstract": "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.", "doc_id": "v0vjkwy9"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Mathematical Modeling of COVID-19 Transmission Dynamics with a Case Study of Wuhan", "abstract": "Abstract We propose a compartmental mathematical model for the spread of the COVID-19 disease with special focus on the transmissibility of super-spreaders individuals. We compute the basic reproduction number threshold, we study the local stability of the disease free equilibrium in terms of the basic reproduction number, and we investigate the sensitivity of the model with respect to the variation of each one of its parameters. Numerical simulations show the suitability of the proposed COVID-19 model for the outbreak that occurred in Wuhan, China.", "doc_id": "h2gwzypy"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Pausing super spreader events for COVID-19 mitigation: International Hajj pilgrimage cancellation", "abstract": "", "doc_id": "k6ijng66"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Estimating finite-population reproductive numbers in heterogeneous populations", "abstract": "Abstract The basic reproductive number, R 0 , is one of the most important epidemiological quantities. R 0 provides a threshold for elimination and determines when a disease can spread or when a disease will die out. Classically, R 0 is calculated assuming an infinite population of identical hosts. Previous work has shown that heterogeneity in the host mixing rate increases R 0 in an infinite population. However, it has been suggested that in a finite population, heterogeneity in the mixing rate may actually decrease the finite-population reproductive numbers. Here, we outline a framework for discussing different types of heterogeneity in disease parameters, and how these affect disease spread and control. We calculate \u201cfinite-population reproductive numbers\u201d with different types of heterogeneity, and show that in a finite population, heterogeneity has complicated effects on the reproductive number. We find that simple heterogeneity decreases the finite-population reproductive number, whereas heterogeneity in the intrinsic mixing rate (which affects both infectiousness and susceptibility) increases the finite-population reproductive number when R 0 is small relative to the size of the population and decreases the finite-population reproductive number when R 0 is large relative to the size of the population. Although heterogeneity has complicated effects on the finite-population reproductive numbers, its implications for control are straightforward: when R 0 is large relative to the size of the population, heterogeneity decreases the finite-population reproductive numbers, making disease control or elimination easier than predicted by R 0 .", "doc_id": "ao2w4v71"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "The prominence of asymptomatic superspreaders in transmission mean universal face masking should be part of COVID-19 de-escalation strategies", "abstract": "", "doc_id": "3zlpkidj"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Identifying and Interrupting Superspreading Events\u2014Implications for Control of Severe Acute Respiratory Syndrome Coronavirus 2", "abstract": "It appears inevitable that severe acute respiratory syndrome coronavirus 2 will continue to spread. Although we still have limited information on the epidemiology of this virus, there have been multiple reports of superspreading events (SSEs), which are associated with both explosive growth early in an outbreak and sustained transmission in later stages. Although SSEs appear to be difficult to predict and therefore difficult to prevent, core public health actions can prevent and reduce the number and impact of SSEs. To prevent and control of SSEs, speed is essential. Prevention and mitigation of SSEs depends, first and foremost, on quickly recognizing and understanding these events, particularly within healthcare settings. Better understanding transmission dynamics associated with SSEs, identifying and mitigating high-risk settings, strict adherence to healthcare infection prevention and control measures, and timely implementation of nonpharmaceutical interventions can help prevent and control severe acute respiratory syndrome coronavirus 2, as well as future infectious disease outbreaks.", "doc_id": "582h1w0h"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Superspreaders and the spread pattern of COVID-19: Response to: \u201cDo superspreaders generate new superspreaders? A hypothesis to explain the propagation pattern of COVID-19\u201d, International Journal of Infectious Diseases 96 (2020) 461\u2013463", "abstract": "", "doc_id": "g83oxgig"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Novel Percutaneous Tracheostomy for Critically Ill Patients with COVID-19", "abstract": "Abstract Background COVID-19 is a worldwide pandemic, with many patients requiring prolonged mechanical ventilation. Tracheostomy is not recommended by current guidelines as it is considered a super-spreading event due to aerosolization that unduly risks healthcare workers. Methods Patients with severe COVID-19 that were on mechanical ventilation \u2265 5 days were evaluated for percutaneous dilational tracheostomy. We developed a novel percutaneous tracheostomy technique that placed the bronchoscope alongside the endotracheal tube, not inside it. This improved visualization during the procedure and continued standard mechanical ventilation after positioning the inflated endotracheal tube cuff in the distal trachea. This technique offers a significant mitigation for the risk of virus aerosolization during the procedure. Results From March 10 to April 15, 2020, 270 patients with COVID-19 required invasive mechanical ventilation at New York University Langone Health Manhattan\u2019s campus of which 98 patients underwent percutaneous dilational tracheostomy. The mean time from intubation to the procedure was 10.6 days (SD \u00b15 days). Currently, thirty-two (33%) patients do not require mechanical ventilatory support, 19 (19%) have their tracheostomy tube downsized and 8 (8%) were decannulated. Forty (41%) patients remain on full ventilator support, while 19 (19%) are weaning from mechanical ventilation. Seven (7%) died as result of respiratory and multiorgan failure. Tracheostomy related bleeding was the most common complication (5 patients). None of health care providers have developed symptoms or tested positive for COVID-19. Conclusions Our percutaneous tracheostomy technique appears to be safe and effective for COVID-19 patients and safe for healthcare workers.", "doc_id": "qhq3slti"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Short communication: Low risk of transmission of severe acute respiratory syndrome on airplanes: the Singapore experience", "abstract": "The risk of transmission of severe acute respiratory syndrome (SARS) on airplanes is of major concern to the public and airline industry. We examined data from flights to Singapore with SARS patients on board in order to assess this risk. In\u2010flight transmission occurred only in one of the three flights with symptomatic SARS patients on board. The incidence was estimated to be 1 out of 156 passengers. The risk of in\u2010flight transmission of SARS appears to be far lower than that reported for influenza, but may be increased with superspreaders on board.", "doc_id": "58tj4csz"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Evolving Transmission Network Dynamics of COVID-19 Cluster Infections in South Korea: a descriptive study", "abstract": "Background. Extensive contact tracing and testing in South Korea allows us to investigate the transmission dynamics of the COVID-19 into diverse local communities. Objective. Understand the critical aspects of transmission dynamics in a different age, sex, and clusters with various activities. Methods. We conducted a retrospective observational study with 3,127 confirmed cases' contact tracing data from the Center for Disease and Prevention (CDC) of South Korea. We investigated network property concerning infected persons' demographics and different infection clusters. Findings. Overall, women had higher centrality scores than men after week four, when the confirmed cases rapidly increased. Older adults have higher centrality than young/middle-aged adults after week 9. In the infection clusters, young/middle-aged adults' infection clusters (such as religious gatherings and gym facilities) have higher average path lengths and diameter than older adults' nursing home infection clusters. Interpretation. Some women had higher reproduction numbers and bridged successive transmission than men when the confirmed cases rapidly increased. Similarly, some older adults (who were not residents of nursing homes) had higher reproduction numbers and bridged successive transmission than young/middle-aged adults after the peak has passed. The young/middle-aged adults' religious gatherings and group workout have caused long successive transmissions. In contrast, the older adults' nursing homes were a small world where the transmissions within a few steps can reach out to many persons.", "doc_id": "5w70yhvy"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Epidemiological characteristics of the first 100 cases of coronavirus disease 2019 (COVID-19) in Hong Kong Special Administrative Region, China, a city with a stringent containment policy", "abstract": "BACKGROUND: Hong Kong (HK) is a densely populated city near the epicentre of the coronavirus disease 2019 (COVID-19) outbreak. Stringent border control together with aggressive case finding, contact tracing, social distancing and quarantine measures were implemented to halt the importation and spread of the virus. METHODS: We performed an epidemiological study using government information covering the first 100 confirmed cases to examine the epidemic curve, incidence, clusters, reproduction number (R(t)), incubation period and time to containment. RESULTS: A total of 93 of the 100 cases were HK residents (6 infected in Mainland China, 10 on the Diamond Princess Cruise). Seven were visitors infected in Mainland China before entering HK. The majority (76%) were aged \u226545 years, and the incidence increased with age (P < 0.001). Escalation of border control measures correlated with a decrease in the proportion (62.5% to 0%) of cases imported from Mainland China, and a reduction in R(t) (1.07 to 0.75). The median incubation period was 4.2 days [95% confidence interval (CI), 4.0\u20134.5; 5th and 95th percentiles: 1.3 and 14.0). Most clusters with identifiable epidemiological links were households involving 2\u20134 people. Three medium-spreading events were identified: two from New Year gatherings (6\u201311 people), and another from environmental contamination of a worship hall (12 people). Despite intensified contact tracing, containment was delayed in 78.9% of cases (mean = 5.96 days, range = 0\u201324 days). An unusual transmission in a multi-storey building via faulty toilet plumbing was suspected with >100 residents evacuated overnight. Our analysis indicated that faulty plumbing was unlikely to be the source of this transmission. CONCLUSIONS: Timely stringent containment policies minimized the importation and transmission of COVID-19 in HK.", "doc_id": "hmi061vn"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "COVID-19: Facts, Cultural Considerations, and Risk of Stigmatization", "abstract": "Data on COVID-19 supports targeted social distancing could be an effective way to reduce morbidity and mortality, but could inadvertently increase stigma for affected populations. As health care providers we must be aware of the facts of COVID-19, cultural implications, and potential for stigmatization of populations affected by COVID-2019. It is important to consider the real economic impact related to lost workdays due to quarantine and social isolation efforts as well as travel restrictions that may negatively impact access to care and ability to pay for care. Efforts geared towards general education about the disease and the rationale for quarantine and public health information provided to the general public can reduce stigmatization. Countries who are successful at aggressive screening, early identification, patient isolation, contact tracing, quarantine, and infection control methods should also address the risk of stigmatization among populations and the negative effects which could occur. The cases of COVID-19 will continue to rise and the virus will be sustainable for future infections. Timely and appropriate public health interventions addressing cultural impact and risk for stigmatization along with proper screening, treatment, and follow up for affected individuals and close contacts can reduce the number of infections, serious illness, and deaths.", "doc_id": "pmc55dw0"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Secondary attack rate and superspreading events for SARS-CoV-2", "abstract": "", "doc_id": "r03x527x"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Preparing for the Next Wave of COVID-19: Resilience in the Face of a Spreading Pandemic", "abstract": "COVID-19 painfully demonstrates how little resilience our societies have to novel viruses. Societies, decision makers, and scientists lack (1) a comprehensive understanding of the complexity of viral outbreaks and their impact on society; (2) intervention portfolios; and (3) a global crisis and resilience policy, all of which are required to develop appropriate measures and to improve societal resilience. We highlight COVID-19 immunity as one key benchmark in preparation for the next wave of the pandemic. Specifically, using network scenarios, we demonstrate the substantial advantage of reintegrating health care workers with acquired COVID-19 immunity in epidemic hotspots, which would not only enable their safe contribution to the health care system but also drastically contain further spread.", "doc_id": "hdt7aooi"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Summary of the COVID-19 outbreak in Vietnam \u2013 Lessons and suggestions", "abstract": "", "doc_id": "0gvizlt9"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "Chest tube with air leaks is a potential \u201csuper spreader\u201d of COVID-19", "abstract": "", "doc_id": "y42o6exe"} {"topic_name": "coronavirus super spreaders", "topic_id": "14", "title": "COVID-19: preparing for superspreader potential among Umrah pilgrims to Saudi Arabia", "abstract": "", "doc_id": "n1zvt5wu"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "Identification of SARS-CoV-2 RNA in Healthcare Heating, Ventilation, and Air Conditioning Units", "abstract": "Available information on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission by small particle aerosols continues to evolve rapidly. To assess the potential role of heating, ventilation, and air conditioning (HVAC) systems in airborne viral transmission, this study sought to determine the viral presence, if any, on air handling units in a healthcare setting where Coronavirus Disease 2019 (COVID-19) patients were being treated. The presence of SARS-CoV-2 RNA was detected in approximately 25% of samples taken from nine different locations in multiple air handlers. While samples were not evaluated for viral infectivity, the presence of viral RNA in air handlers raises the possibility that viral particles can enter and travel within the air handling system of a hospital, from room return air through high efficiency MERV-15 filters and into supply air ducts. Although no known transmission events were determined to be associated with these specimens, the findings suggest the potential for HVAC systems to facilitate transmission by environmental contamination via shared air volumes with locations remote from areas where infected persons reside. More work is needed to further evaluate the risk of SARS-CoV-2 transmission via HVAC systems and to verify effectiveness of building operations mitigation strategies for the protection of building occupants. These results are important within and outside of healthcare settings and may present a matter of some urgency for building operators of facilities that are not equipped with high-efficiency filtration.", "doc_id": "cjt2y67m"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "Modelling aerosol transport and virus exposure with numerical simulations in relation to SARS-CoV-2 transmission by inhalation indoors", "abstract": "We provide research findings on the physics of aerosol dispersion relevant to the hypothesized aerosol transmission of SARS-CoV-2. We utilize physics-based modeling at different levels of complexity, and literature on coronaviruses, to investigate the possibility of airborne transmission. The previous literature, our 0D-3D simulations by various physics-based models, and theoretical calculations, indicate that the typical size range of speech and cough originated droplets (d<20microns) allows lingering in the air for O(1h) so that they could be inhaled. Consistent with the previous literature, numerical evidence on the rapid drying process of even large droplets, up to sizes O(100microns), into droplet nuclei/aerosols is provided. Based on the literature and the public media sources, we provide evidence that the infected individuals could have been exposed to aerosols/droplet nuclei by inhaling them in significant numbers e.g. O(100). By 3D computational fluid dynamics (CFD) simulations, we give examples on the transport and dilution of aerosols (d<20microns) over distances O(10m) in generic environments. We study susceptible and infected individuals in generic public places by Monte-Carlo modeling. The model accounts for the locally varying aerosol concentration levels which the susceptible accumulate via inhalation. The introduced concept, 'exposure time' to virus containing aerosols is proposed to complement the traditional 'safety distance' thinking. We show that the exposure time to inhale O(100) aerosols could range from O(1s) to O(1min) or even to O(1h) depending on the situation. The Monte Carlo analysis provides clear quantitative insight to the exposure time in different public indoor environments.", "doc_id": "0n8x3i0v"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "A Guide to COVID-19: a global pandemic caused by the novel coronavirus SARS-CoV-2", "abstract": "The emergence of the SARS-CoV-2 strain of the human coronavirus has thrown the world into the midst of a new pandemic. In the human body, the virus causes COVID-19, a disease characterized by shortness of breath, fever, and pneumonia, which can be fatal in vulnerable individuals. SARS-CoV-2 has characteristics of past human coronaviruses, with close genomic similarities to SARS-CoV, the virus that causes the disease SARS. Like these related coronaviruses, SARS-CoV-2 is transmitted through the inhalation of droplets and interaction with contaminated surfaces. Across the world, laboratories are developing candidate vaccines for the virus - with vaccine trials underway in the United States and the United Kingdom - and considering various drugs for possible treatments and prophylaxis. Here, we provide an overview of SARS-CoV-2 by analyzing its virology, epidemiology, and modes of transmission while examining the current progress of testing procedures and possible treatments through drugs and vaccines.", "doc_id": "wq7ljx2f"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "Infection Control in Dental Practice During the COVID-19 Pandemic", "abstract": "COVID-19 is the disease supported by SARS-CoV-2 infection, which causes a severe form of pneumonia. Due to the pathophysiological characteristics of the COVID-19 syndrome, the particular transmissibility of SARS-CoV-2, and the high globalization of our era, the epidemic emergency from China has spread rapidly all over the world. Human-to-human transmission seems to occur mainly through close contact with symptomatic people affected by COVID-19, and the main way of contagion is via the inhalation of respiratory droplets, for example when patients talk, sneeze or cough. The ability of the virus to survive outside living organisms, in aerosol or on fomites has also been recognized. The dental practitioners are particularly exposed to a high risk of SARS-CoV-2 infection because they cannot always respect the interpersonal distance of more than a meter and are exposed to saliva, blood, and other body fluids during surgical procedures. Moreover, many dental surgeries can generate aerosol, and the risk of airborne infection is to be considered higher. The aim of this paper is to provide practical advice for dentists based on the recent literature, which may be useful in reducing the risk of spreading COVID-19 during clinical practice.", "doc_id": "1d4gf7kr"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "Stability and Viability of SARS-CoV-2", "abstract": "", "doc_id": "wyh7t6rr"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as coronavirus disease 2019 (COVID-19) pandemic: A global health emergency", "abstract": "According to data compiled by researchers at Johns Hopkins University in Baltimore, Maryland, more than two and half million cases of coronavirus disease 2019 (COVID-19), caused by a newly discovered virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed on April 20, 2020 (Nature, 2020b). Since the emergence of this infectious disease in Asia (Wuhan, China) late last year, it has been subsequently span to every continent of the world except Antarctica (Rodr\u00edguez-Morales et al., 2020). Along with a foothold in every country, the current disease pandemic is disrupting practically every aspect of life all over the world. As the outbreak are continuing to evolve, several research activities have been conducted for better understanding the origin, functions, treatments, and preventions of this novel coronavirus. This review will be a summa of the key features of novel coronavirus (nCoV), the virus causing disease 2019 and the present epidemic situation worldwide up to April 20, 2020. It is expected that this record will play an important role to take more preventive measures for overcoming the challenges faced during this current pandemic.", "doc_id": "hpx4723v"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "SARS-CoV-2 Virulence: Interplay of Floating Virus-Laden Particles, Climate, and Humans", "abstract": "With the emergence of COVID-19, it is important to address the possible scenarios of SARS-CoV-2 virulence. Although several researchers have addressed the possible mechanisms of enveloped virus transfection, for example, influenza, here, the relationship between exhaled virus laden-particles, the climate, and transfection probability is discussed by interpreting the findings of prior studies. Importantly, the higher probability of viral transfection in cold and dry public spaces such as near cold shelves of groceries is illustrated. Thus, additional protective measures in such spaces are recommended.", "doc_id": "e138dm8k"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "The influenza virus, SARS-CoV-2, and the airways: Clarification for the otorhinolaryngologist", "abstract": "The influenza virus and SARS-CoV-2 cause trivial upper and severe lower respiratory infections (Influenza virus 290,000 to 650,000 deaths/year). These viruses come into contact with the airways either by direct projection, by secondary inhalation of airborne droplets, or by handling (fomites). The objective of this article is to clarify the mechanisms of production and penetration of droplets of secretions emitted during all expiratory phenomena likely to transport these viruses and come into contact with the respiratory mucosa. The droplets>5\u00b5m follow the laws of ballistics, those<5\u00b5m follow Brownian motion and remain suspended in the air. The aerosols of droplets are very heterogeneous whether the subject is healthy or sick. During an infectious period, not all droplets contain viral RNA. If these RNAs are detectable around patients, on surfaces, and in the ambient air at variable distances according to the studies (from 0.5m to beyond the patient's room), this is without prejudice to the infectious nature (viability) of the virus and the minimum infectious dose. There is a time lag between the patient's infectious period and that of RNA detection for both viruses. Subsequently, the inhaled particles must meet the laws of fluid dynamics (filtration) to settle in the respiratory tree. All of this partly explains the contagiousness and the clinical expression of these two viruses from the olfactory cleft to the alveoli.", "doc_id": "nr42k23h"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "A chronicle of SARS-CoV-2: Part-I - Epidemiology, diagnosis, prognosis, transmission and treatment", "abstract": "In order to benefit the public, community workers and scientific community, we hereby present a chronicle of SARS-CoV-2 that leads to the unseen precedent of social distancing and lockdown owing to coronavirus disease (COVID-19). Information on this life-threatening pandemic of COVID-19 is sparse and discrete; and the urgency is such that the dissemination of information is increasing with numerous daily publications on the topic. Therefore, we developed a comprehensive review on various aspects of SARS-CoV-2 and COVID-19. We scientifically compiled published research, news, and reports from various sources to comprehend and summarize the information and findings on Coronaviruses. The review explicitly covers the aspects like genome and pedigree of SARS-CoV-2; epidemiology, prognosis, pathogenesis, symptoms and diagnosis of COVID-19 in order to catalog the right information on transmission route, and influence of environmental factors on virus transmissions, for the robust understanding of right strategical steps for proper COVID-19 management. We have explicitly highlighted several useful information and facts like: i) No established relationship between progression of SARS-CoV-2 with temperature, humidity and/or both, ii) The underlying mechanism of SARS-CoV-2 is not fully understood, iii) Respiratory droplet size determines drop and airborne-based transmission, iv) Prognosis of COVID-19 can be done by its effects on various body organs, v) Infection can be stopped by restricting the binding of S protein and AE2, vi) Hydroxychloroquine is believed to be better than chloroquine for COVID-19, vii) Ivermectin with Vero-hSLAM cells is able to reduce infection by ~5000 time within 2 days, and viii) Nafamostat mesylate can inhibit SARS-CoV-2 S protein-initiated membrane fusion. We have also suggested future research perspectives, challenges and scope.", "doc_id": "daprgv9i"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "SARS\u2010CoV\u20102 Virulence: Interplay of Floating Virus\u2010Laden Particles, Climate, and Humans", "abstract": "With the emergence of COVID\u201019, it is important to address the possible scenarios of SARS\u2010CoV\u20102 virulence. Although several researchers have addressed the possible mechanisms of enveloped virus transfection, for example, influenza, here, the relationship between exhaled virus laden\u2010particles, the climate, and transfection probability is discussed by interpreting the findings of prior studies. Importantly, the higher probability of viral transfection in cold and dry public spaces such as near cold shelves of groceries is illustrated. Thus, additional protective measures in such spaces are recommended.", "doc_id": "92ijxah4"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "Protections against the Risk of Airborne SARS-CoV-2 Infection", "abstract": "", "doc_id": "3n0widf9"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "Overview of transnational recommendations for COVID\u201019 transmission control in dental care settings", "abstract": "On 11 March 2020, the World Health Organization (WHO) declared the coronavirus disease (COVID\u201019) caused by severe acute respiratory syndrome coronavirus (SARS\u2010CoV\u20102) as a pandemic. Until an effective treatment or a vaccine is developed, the current recommendations are to contain the disease, and control its transmission. It is now clear that the primary mode of SARS\u2010CoV\u20102 transmission is aerosol/droplet spread, and by contacting virus\u2010contaminated surfaces acting as fomites (inanimate vectors). Furthermore, recent data indicate that the live virus particles are present in saliva, and, more alarmingly, asymptomatic individuals may transmit the infection. By virtue of the nature of the practice of dentistry where intrinsically, a high volume of aerosols is produced, as well as the close proximity of dentists and patients during treatment, dentists and allied health staff are considered the highest risk health professional group for acquiring SARS\u2010CoV\u20102 during patient management. Therefore, several organizations and specialty associations have proposed guidelines and recommendations for limiting the transmission of SARS\u2010COV\u20102 from carriers to dentists and vice versa. This paper aims to provide a review of these guidelines, and concludes with a brief look at how the practice of dentistry may be impacted by COVID\u201019, in the post\u2010pandemic era.", "doc_id": "gc1wwcpo"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "Forensic DNA testing during the SARS-CoV-2 pandemic", "abstract": "The aggressive nature of the new SARS-2 corona virus now referred to as SARS-CoV-2 ; the seriousness and length of the period of infection; the fast and far-reaching transmissibility via liquid droplets that become air-borne when someone coughs, sneezes or speaks with increasing evidence to support actual airborne transmission; the presence of viral particles especially in body fluids and tissues, of viral positive individuals; and the persistence of the virus on different types of surfaces pose serious concerns for forensic practitioners, including forensic DNA analysts. Many forensic laboratories and law enforcement agencies need to address the inevitable changes that must be made in forensic DNA testing. In this article, we explore the effects of the COVID-19 pandemic on the collection, handling, storage and transport of biological samples for downstream DNA testing. This paper aims to open discussions on the urgency of balancing the need to conduct investigations in order to maintain public order with the requirements of effective biosafety protocols specifically formulated to protect human resources within the forensic science community.", "doc_id": "40bpu5nk"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "Novel coronavirus transmission to water bodies; risk of COVID-19 pneumonia to aquatic mammals", "abstract": "[Figure: see text]", "doc_id": "34m7y2l1"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "Editorial: Stay safe during this coronavirus crisis", "abstract": "", "doc_id": "6305q2f5"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "The influenza virus, SARS-CoV-2, and the airways: clarification for the otorhinolaryngologist", "abstract": "Abstract The influenza virus and SARS-CoV-2 cause trivial upper and severe lower respiratory infections (Influenza virus 290,000 to 650,000 deaths/year). These viruses come into contact with the airways either by direct projection, by secondary inhalation of airborne droplets, or by handling (fomites). The objective of this article is to clarify the mechanisms of production and penetration of droplets of secretions emitted during all expiratory phenomena likely to transport these viruses and come into contact with the respiratory mucosa. The droplets > 5 \u00b5m follow the laws of ballistics, those < 5 \u00b5m follow Brownian motion and remain suspended in the air. The aerosols of droplets are very heterogeneous whether the subject is healthy or sick. During an infectious period, not all droplets contain viral RNA. If these RNAs are detectable around patients, on surfaces, and in the ambient air at variable distances according to the studies (from 0.5 m to beyond the patient\u2019s room), this is without prejudice to the infectious nature (viability) of the virus and the minimum infectious dose. There is a time lag between the patient\u2019s infectious period and that of RNA detection for both viruses. Subsequently, the inhaled particles must meet the laws of fluid dynamics (filtration) to settle in the respiratory tree. All of this partly explains the contagiousness and the clinical expression of these two viruses from the olfactory cleft to the alveoli.", "doc_id": "9is5vmxu"} {"topic_name": "coronavirus outside body", "topic_id": "15", "title": "SARS-CoV-2 in wastewater: State of the knowledge and research needs", "abstract": "Abstract The ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a Public Health Emergency of International Concern, which was officially declared by the World Health Organization. SARS-CoV-2 is a member of the family Coronaviridae that consists of a group of enveloped viruses with single-stranded RNA genome, some of which have been known to cause common colds. Although the major transmission routes of SARS-CoV-2 are inhalation from person-to-person and aerosol/droplet transmission, currently available evidence indicates that the viral RNA is present in wastewater, suggesting the need to better understand wastewater as potential sources of epidemiological data and human health risks. Here, we review the current knowledge related to the potential of wastewater surveillance to understand the epidemiology of COVID-19, methodologies for the detection and quantification of SARS-CoV-2 in wastewater, and information relevant for human health risk assessment of SARS-CoV-2. There has been growing evidence of gastrointestinal symptoms caused by SARS-CoV-2 infections and the presence of viral RNA not only in feces of COVID-19 patients but in wastewater. One of the major challenges in SARS-CoV-2 detection/quantification in wastewater samples is the lack of an optimized and standardized protocol. Currently available data are also limited for conducting a quantitative microbial risk assessment (QMRA) for SARS-CoV-2 exposure pathways. However, modeling-based approaches have a potential role to play in reducing the impact of the ongoing COVID-19 outbreak, and QMRA parameters obtained from previous studies on relevant respiratory viruses help to inform risk assessments of SARS-CoV-2. Our understanding on the potential role of wastewater in SARS-CoV-2 transmission is largely limited by knowledge gaps in its occurrence, persistence, and removal in wastewater. There is an urgent need for further research to establish methodologies for wastewater surveillance and understand the implications of the presence of SARS-CoV-2 in wastewater.", "doc_id": "g2yy8e99"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Response to Letters to the Editor about the Safe Handling of Containers of Expressed Human Milk in all Settings During the SARS-CoV-2 (COVID-19) Pandemic.", "abstract": "", "doc_id": "yenrolv7"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Persistence of infectious SARS-CoV-2 on inert surfaces and hand-mediated transmission.", "abstract": "", "doc_id": "2vqxgfea"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Detection of Severe Acute Respiratory Syndrome Coronavirus 2 RNA on Surfaces in Quarantine Rooms.", "abstract": "We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination in 2 rooms of a quarantine hotel after 2 presymptomatic persons who stayed there were laboratory-confirmed as having coronavirus disease. We detected SARS-CoV-2 RNA on 8 (36%) of 22 surfaces, as well as on the pillow cover, sheet, and duvet cover.", "doc_id": "ee8wjp5u"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "A Surface Coating that Rapidly Inactivates SARS-CoV-2.", "abstract": "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.", "doc_id": "gxo13x70"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Investigating SARS-CoV-2 surface and air contamination in an acute healthcare setting during the peak of the COVID-19 pandemic in London.", "abstract": "BACKGROUND Evaluation of SARS-CoV-2 surface and air contamination during the COVID-19 pandemic in London. METHODS We performed this prospective cross-sectional observational study in a multi-site London hospital. Air and surface samples were collected from seven clinical areas, occupied by patients with COVID-19, and a public area of the hospital. Three or four 1.0 m3 air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected by RT-qPCR and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined. RESULTS Viral RNA was detected on 114/218 (52.3%) of surfaces and 14/31 (38.7%) air samples but no virus was cultured. The proportion of surface samples contaminated with viral RNA varied by item sampled and by clinical area. Viral RNA was detected on surfaces and in air in public areas of the hospital but was more likely to be found in areas immediately occupied by COVID-19 patients than in other areas (67/105 (63.8%) vs. 29/64 (45.3%) (odds ratio 0.5, 95% confidence interval 0.2-0.9, p=0.025, Chi squared test)). The high PCR Ct value for all samples (>30) indicated that the virus would not be culturable. CONCLUSIONS Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from environmental contamination in managing COVID-19, and the need for effective use of PPE, physical distancing, and hand/surface hygiene.", "doc_id": "2wnfl4pr"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Coronaviruses widespread on nonliving surfaces: important questions and promising answers.", "abstract": "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.", "doc_id": "9xv9t5ba"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Rapid Inactivation of SARS-CoV-2 by Silicon Nitride, Copper, and Aluminum Nitride", "abstract": "Introduction Viral disease spread by contaminated commonly touched surfaces is a global concern. Silicon nitride, an industrial ceramic that is also used as an implant in spine surgery, has known antibacterial activity. The mechanism of antibacterial action relates to the hydrolytic release of surface disinfectants. It is hypothesized that silicon nitride can also inactivate the coronavirus SARS-CoV-2. Methods SARS-CoV-2 virions were exposed to 15 wt.% aqueous suspensions of silicon nitride, aluminum nitride, and copper particles. The virus was titrated by the TCD50 method using VeroE6/TMPRSS2 cells, while viral RNA was evaluated by real-time RT-PCR. Immunostaining and Raman spectroscopy were used as additional probes to investigate the cellular responses to virions exposed to the respective materials. Results All three tested materials showed >99% viral inactivation at one and ten minutes of exposure. Degradation of viral RNA was also observed with all materials. Immunofluorescence testing showed that silicon nitride-treated virus failed to infect VeroE6/TMPRSS2 cells without damaging them. In contrast, the copper-treated virus suspension severely damaged the cells due to copper ion toxicity. Raman spectroscopy indicated differential biochemical cellular changes due to infection and metal toxicity for two of the three materials tested. Conclusions Silicon nitride successfully inactivated the SARS-CoV-2 in this study. The mechanism of action was the hydrolysis-mediated surface release of nitrogen-containing disinfectants. Both aluminum nitride and copper were also effective in the inactivation of the virus. However, while the former compound affected the cells, the latter compound had a cytopathic effect. Further studies are needed to validate these findings and investigate whether silicon nitride can be incorporated into personal protective equipment and commonly touched surfaces, as a strategy to discourage viral persistence and disease spread.", "doc_id": "2tioh80m"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Evaluation of Ultraviolet-C Light for Rapid Decontamination of Airport Security Bins in the Era of SARS-CoV-2", "abstract": "BACKGROUND: Contaminated surfaces are a potential source for spread of respiratory viruses including SARS-CoV-2 Ultraviolet-C (UV-C) light is effective against RNA and DNA viruses and could be useful for decontamination of high-touch fomites that are shared by multiple users 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 UV-C light for rapid decontamination of plastic airport security bins inoculated at 3 sites with methicillin-resistant Staphylococcus aureus (MRSA) and bacteriophages MS2, PhiX174, and Phi6, an enveloped RNA virus used as a surrogate for coronaviruses Reductions of 3 log(10) on inoculated plastic bins were considered effective for decontamination RESULTS: UV-C light administered as 10-, 20-, or 30-second cycles in proximity to a plastic bin reduced contamination on each of the test sites, including vertical and horizontal surfaces The 30-second cycle met criteria for decontamination of all 3 test sites for all the test organisms except bacteriophage MS2 which was reduced by greater than 2 log(10) PFU at each site CONCLUSIONS: UV-C light is an attractive technology for rapid decontamination of airport security bins Further work is needed to evaluate the utility of UV-C light in real-world settings and to develop methods to provide automated movement of bins through a UV-C decontamination process", "doc_id": "5oe77t20"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Modeling the Stability of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on Skin, Currency, and Clothing", "abstract": "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.", "doc_id": "ywusapij"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Luminore CopperTouch\u00e2\u0084\u00a2 surface coating effectively inactivates SARS-CoV-2, Ebola and Marburg viruses in vitro", "abstract": "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.", "doc_id": "v8rbfnhz"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Detection of SARS-CoV-2 RNA on public surfaces in a densely populated urban area of Brazil", "abstract": "Importance: The COVID-19 pandemic has resulted in more than 3.5 million cases and 245 thousand deaths worldwide as of May 6, 2020. Determining the extent of the presence of the virus on public surfaces is critical for understanding the potential risk of infection in these areas. Objective: To evaluate the presence of SARS-CoV-2 RNA on public surfaces in a densely populated urban area in Brazil. Design and Setting: A total of 101 samples were collected from different surfaces in public places in the region of Belo Horizonte with the highest number of COVID-19 cases. Samples were collected near the hospital and public transportation areas using sterile swabs, and then submitted to nucleic acid extraction and genomic detection and quantification by one-step qPCR. Results: Seventeen of the 101 samples tested positive (16.8%) for SARS-CoV-2 RNA, including samples from bus stations/terminals, public squares, and sidewalks, including those near hospitals. Conclusions and Relevance: Our data indicated the contamination of public surfaces by SARS-CoV-2, especially near hospital areas, highlighting the risk of infection for the population. Constant monitoring of the virus in urban areas is required as a strategy to fight the pandemic and prevent further infections.", "doc_id": "rxhv83o5"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Detection of air and surface contamination by SARS-CoV-2 in hospital rooms of infected patients", "abstract": "Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ2 test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 \u00b5m and 1-4 \u00b5m in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2.", "doc_id": "4frdzp4c"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Experimental and numerical study of potential infection risks from exposure to bioaerosols in one BSL-3 laboratory", "abstract": "Laboratory-acquired infections (LAIs) are defined as infections of laboratory staff by exposure to pathogenic microorganisms during an experimental procedure. For a biosafety level-3 (BSL-3) laboratory with a high potential of exposure, reducing risks and threats relevant to LAIs has become a critical concern, especially after the recent outbreak of Novel Coronavirus causing COVID-19 in Wuhan, China. This study aimed to investigate the spatial-temporal characteristics of bioaerosol dispersion and deposition of two kinds of bioaerosols (Serratia marcescens and phage ΦX174). A combination of laboratory experiment and numerical simulation was adopted to explore bioaerosol removal. Three-dimensional concentration iso-surface mapping in conjunction with flow field analysis was employed to elucidate bioaerosol migration and deposition behavior. The total deposition number and unit area deposition ratio were calculated for different surfaces. The results indicate that bioaerosol concentration remains stable for up to 400 s after release, and that almost 70% of all bioaerosol particles become deposited on the surfaces of walls and equipment. Vortex flow regions and high-concentration regions were determined, and the most severely contaminated surfaces and locations were identified. Our results could provide the scientific basis for controlling the time interval between different experiments and also provide guidelines for a laboratory disinfection routine. Furthermore, future work regarding laboratory layout optimization and high efficiency air distribution for bioaerosol removal in a BSL-3 laboratory should be emphasized.", "doc_id": "jcq2394b"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1", "abstract": "", "doc_id": "mx1kfy4o"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Detection of SARS-CoV-2 on high-touch surfaces in a clinical microbiology laboratory", "abstract": "", "doc_id": "p7sczj2e"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Persistance du SARS-CoV-2 infectieux sur les surfaces inertes et transmission par les mains./ Persistence of infectious SARS-CoV-2 on inert surfaces and hand-mediated transmission", "abstract": "", "doc_id": "vx15h52s"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Detection of Severe Acute Respiratory Syndrome Coronavirus 2 RNA on Surfaces in Quarantine Rooms", "abstract": "We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination in 2 rooms of a quarantine hotel after 2 presymptomatic persons who stayed there were laboratory-confirmed as having coronavirus disease. We detected SARS-CoV-2 RNA on 8 (36%) of 22 surfaces, as well as on the pillow cover, sheet, and duvet cover.", "doc_id": "2t2it6f5"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "SARS-CoV-2: air/aerosols and surfaces in laboratory and clinical settings", "abstract": "", "doc_id": "act83kcd"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020", "abstract": "To determine distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards in Wuhan, China, we tested air and surface samples. Contamination was greater in intensive care units than general wards. Virus was widely distributed on floors, computer mice, trash cans, and sickbed handrails and was detected in air ≈4 m from patients.", "doc_id": "mu9imoff"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Investigating SARS-CoV-2 surface and air contamination in an acute healthcare setting during the peak of the COVID-19 pandemic in London", "abstract": "BACKGROUND: Evaluation of SARS-CoV-2 surface and air contamination during the COVID-19 pandemic in London. METHODS: We performed this prospective cross-sectional observational study in a multi-site London hospital. Air and surface samples were collected from seven clinical areas, occupied by patients with COVID-19, and a public area of the hospital. Three or four 1.0 m3 air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected by RT-qPCR and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined. RESULTS: Viral RNA was detected on 114/218 (52.3%) of surfaces and 14/31 (38.7%) air samples but no virus was cultured. The proportion of surface samples contaminated with viral RNA varied by item sampled and by clinical area. Viral RNA was detected on surfaces and in air in public areas of the hospital but was more likely to be found in areas immediately occupied by COVID-19 patients than in other areas (67/105 (63.8%) vs. 29/64 (45.3%) (odds ratio 0.5, 95% confidence interval 0.2-0.9, p=0.025, Chi squared test)). The high PCR Ct value for all samples (>30) indicated that the virus would not be culturable. CONCLUSIONS: Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from environmental contamination in managing COVID-19, and the need for effective use of PPE, physical distancing, and hand/surface hygiene.", "doc_id": "ebr716xv"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Presence of SARS-CoV-2 RNA in isolation ward environment 28 days after exposure", "abstract": "Recent studies have reported that surfaces and objects in the rooms of infected patients that are frequently touched by both medical staff and patients could be contaminated with SARS-CoV-2. In December 2019, Wuhan China suffered the earliest from this COVID-19 pandemic, and we took that opportunity to investigate whether the SARS-CoV-2 RNA exists in the ward environment after a long time from exposure. We found that on the 28th day following the discharge of COVID-19 patients, SARS-CoV-2 RNA could still be detected on the surfaces of pagers and in drawers in the isolation wards. Thorough disinfection of the ward environment was subsequently performed, after which these surfaces in the isolation wards tested negative for the presence of SARS-CoV-2 RNA. The findings remind us that the contaminated environment in the wards may become potential infectious resources and that despite a long time from exposure, the thorough disinfection in the COVID-10 units after is still necessary.", "doc_id": "9bh8h2tq"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Minimization of spreading of SARS-CoV-2 via household waste produced by subjects affected by COVID-19 or in quarantine", "abstract": "Currently available evidence supports that the predominant route of human-to-human transmission of the SARS-CoV-2 is through respiratory droplets. Indirect hands contact with surfaces contaminated by infectious droplets subsequently touching the mouth, nose or eyes seems to be another route of an indirect contact transmission. Persistence of the virus on different surfaces and other materials has been reported in recent studies: SARS-CoV-2 was more stable on plastic and stainless steel than on copper and cardboard. Viable virus was detected up to 72 h after application to different surfaces, although infectivity decay was also observed. This evidence suggests the likelihood that waste generated from patients affected by COVID-19 or subjects in quarantine treated in private houses or in areas different from hospitals and medical centres could be contaminated by SARS-CoV-2. Consequently, waste streams may represent a route for viral spreading being a potential risk also for the operators directly involved in the different phases of waste management. To address this concern, a specific multidisciplinary working group was settled by the Italian National Institute of Health (ISS) during the COVID-19 emergency, in order to establish guidelines related to solid waste collection, delivering, withdrawal, transport, treatment and disposal. Temporary stop of waste sorting, instructions for the population on how to package waste, instructions for Companies and operators for the adoption of adequate personal protection equipment (PPE), the use and sanitation of proper vehicles were among the main recommendations provided to the community by publications of freely downloadable reports and infographics in layman language. Incineration, sterilization and properly managed landfills were identified as the facilities to be preferentially adopted for the treatment of this kind of waste, considering the main inactivation strategies of SARS-CoV-2 (e.g. treatment length > 9 days and temperature > 70 \u00b0C for more than 5 min).", "doc_id": "ts4hxku0"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Environmental contamination by SARS-CoV-2 of an imported case during incubation period", "abstract": "We collected environmental surface samples prior to and after disinfection of a quarantine room to evaluate the stability of SARS-CoV-2 during the incubation period of an imported case traveling to Qingdao, China. Overall, 11 of 23 (47.8%) of the first batch of environmental surface samples (within 4 h after case confirmation) were tested positive for SARS-CoV-2. Whereas only 2 of 23 (8.7%) of the second batch of environmental samples (after first disinfection) were tested positive for SARS-CoV-2. The majority of samples from the bedroom (70%) were positive for SARS-CoV-2, followed by 50% of samples from the bathroom and that of 33% from the corridor. The inner walls of toilet bowl and sewer inlet were the most contaminated sites with the highest viral loads. SARS-CoV-2 was widely distributed on object surfaces in a quarantine room of a later diagnosed COVID-19 case during the incubation period. Proper disinfection is crucial to minimize community transmission of this highly contagious virus.", "doc_id": "sh3h6ggg"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Corrigendum to \"Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents\" [J Hosp Infect 104 (2020) 246-251]", "abstract": "", "doc_id": "4xhc0lgu"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Simulated Sunlight Rapidly Inactivates SARS-CoV-2 on Surfaces", "abstract": "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\u00b0N 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.", "doc_id": "mixy6roy"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "What Does COVID-19 Mean for the Pathology-Urology Interaction?", "abstract": "", "doc_id": "d3wobkq3"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Reply to \u201cDoes hand hygiene reduce SARS-CoV-2 transmission?\u201d", "abstract": "", "doc_id": "d3b5o5d9"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Surface Alterations to Impart Antiviral Properties to Combat COVID-19 Transmission", "abstract": "A global epidemic caused by highly transmittable COVID-19 is causing severe loss of human life. In this study, two aspects of reducing transmission of COVID-19 virus, due to surface contact, are discussed: first refers to the effect of nanocarbon fullerene C(60) coating on surface, that causes lipid peroxidation on the phospholipid layer present in the outer envelope of COVID-19; the second aspect refers to creating hydrophobic surfaces by texturing them, so that the contact area between virus and surface is minimized due to the presence of entrapped air between the topographies. These can be similar to micro-/nano-multiscale textured surfaces that have anti-biofouling properties. Fullerene-coated surfaces can be seen as a possible solution to decrease the adhesion of virus on the surface, as they will be hydrophobic as well as toxic to the envelope.", "doc_id": "mczrufe0"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "High-flow nasal cannula may be no safer than non-invasive positive pressure ventilation for COVID-19 patients", "abstract": "", "doc_id": "38rov4ux"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Temporary carriage of bovine coronavirus and bovine respiratory syncytial virus by fomites and human nasal mucosa after exposure to infected calves", "abstract": "BACKGROUND: In order to prevent spread of the endemic pathogens bovine coronavirus (BCoV) and bovine respiratory syncytial virus (BRSV) between herds, knowledge of indirect transmission by personnel and fomites is fundamental. The aims of the study were to determine the duration of viral RNA carriage and the infectivity of viral particles on fomites and human nasal mucosa after exposure to BCoV and BRSV. During two animal infection experiments, swabs were collected from personnel (nasal mucosa) and their clothes, boots and equipment after contact with calves shedding either virus. Viral RNA was quantified by RT-qPCR or droplet digital RT-PCR (RT-ddPCR), and selected samples with high levels of viral RNA were tested by cell culture for infectivity. RESULTS: For BCoV, 46% (n = 80) of the swabs from human nasal mucosa collected 30 min after exposure were positive by RT-qPCR. After two, four and six hours, 15%, 5% and 0% of the swabs were positive, respectively. Infective virions were not detected in mucosal swabs (n = 2). A high viral RNA load was detected on 97% (n = 44) of the fomites 24 h after exposure, and infective virions were detected in two of three swabs. For BRSV, 35% (n = 26) of the human nasal mucosa swabs collected 30 min after exposure, were positive by RT-ddPCR, but none were positive for infective virions. Of the fomites, 89% (n = 38) were positive for BRSV RNA 24 h after exposure, but all were negative for infective viruses. CONCLUSIONS: The results indicate that human nasal mucosa can carry both BCoV and BRSV RNA after exposure to virus shedding calves, but the carriage seems short-lived and the transmission potential is likely limited. High viral loads on contaminates fomites 24 h after exposure to infected animals, and detection of infective BCoV, indicate that contaminated fomites represent a significant risk for indirect transmission between herds.", "doc_id": "hf5k04da"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Should I be worried about carrying the virus that causes COVID\u201019 home on my clothes?", "abstract": "", "doc_id": "hww01e4z"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Can N95 Respirators Be Reused after Disinfection? How Many Times?", "abstract": "[Image: see text] The coronavirus disease 2019 (COVID-19) pandemic has led to a major shortage of N95 respirators, which are essential for protecting healthcare professionals and the general public who may come into contact with the virus. Thus, it is essential to determine how we can reuse respirators and other personal protective equipment in these urgent times. We investigated multiple commonly used disinfection schemes on media with particle filtration efficiency of 95%. Heating was recently found to inactivate the virus in solution within 5 min at 70 \u00b0C and is among the most scalable, user-friendly methods for viral disinfection. We found that heat (\u226485 \u00b0C) under various humidities (\u2264100% relative humidity, RH) was the most promising, nondestructive method for the preservation of filtration properties in meltblown fabrics as well as N95-grade respirators. At 85 \u00b0C, 30% RH, we were able to perform 50 cycles of heat treatment without significant changes in the filtration efficiency. At low humidity or dry conditions, temperatures up to 100 \u00b0C were not found to alter the filtration efficiency significantly within 20 cycles of treatment. Ultraviolet (UV) irradiation was a secondary choice, which was able to withstand 10 cycles of treatment and showed small degradation by 20 cycles. However, UV can potentially impact the material strength and subsequent sealing of respirators. Finally, treatments involving liquids and vapors require caution, as steam, alcohol, and household bleach all may lead to degradation of the filtration efficiency, leaving the user vulnerable to the viral aerosols.", "doc_id": "mx7xyd76"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Detection of Novel Coronavirus on the Surface of Environmental Materials Contaminated by COVID-19 Patients in the Republic of Korea", "abstract": "This study aimed to determine the presence of SARS-CoV-2 on surfaces frequently touched by COVID-19 patients, and assess the scope of contamination and transmissibility in facilities where the outbreaks occurred. In the course of this epidemiological investigation, a total of 80 environmental specimens were collected from 6 hospitals (68 specimens) and 2 \u201cmass facilities\u201d (6 specimens from a rehabilitation center and 6 specimens from an apartment building complex). Specific reverse transcriptase-polymerase chain reaction targeting of RNA-dependent RNA polymerase, and envelope genes, were used to identify the presence of this novel coronavirus. The 68 specimens from 6 hospitals (A, B, C, D, E, and G), where prior disinfection/cleaning had been performed before environmental sampling, tested negative for SARS-CoV-2. However, 2 out of 12 specimens (16.7%) from 2 \u201cmass facilities\u201d (F and H), where prior disinfection/cleaning had not taken place, were positive for SARS-CoV-2 RNA polymerase, and envelope genes. These results suggest that prompt disinfection and cleaning of potentially contaminated surfaces is an effective infection control measure. By inactivating SARS-CoV-2 with disinfection/cleaning the infectivity and transmission of the virus is blocked. This investigation of environmental sampling may help in the understanding of risk assessment of the COVID-19 outbreak in \u201cmass facilities\u201d and provide guidance in using effective disinfectants on contaminated surfaces.", "doc_id": "7v2hdy8a"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Management of the SARS-CoV-2 (Covid 19) coronavirus epidemic in hemodialysis units", "abstract": "Summary The current outbreak of SARS-CoV-2 represents a special risk for renal patients due to their comorbidities and advanced age. The usual performance of hemodialysis treatment s in collective rooms increases the risk. The specific information at this time in this regard is very limited. This manuscript includes a proposal for action to prevent infection in the N ephrology S ervices, and in particular in H emodialysis U nits, with the objective of early identification of patients who meet the definition of a suspected case of infection by SARS-CoV-2 and propose circuits and mechanisms to carry out hemodialysis treatment s. They are recommendations in continuous review and can be modified if the epidemiological situation, the diagnostic and therapeutic options so require.", "doc_id": "ibfcfdcw"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Absence of contamination of personal protective equipment (PPE) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)", "abstract": "", "doc_id": "mkpd5wva"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Environmental surface testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during prolonged isolation of an asymptomatic carrier", "abstract": "Environmental surface testing was performed to search for evidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) environmental contamination by an asymptomatic SARS-CoV-2 carrier with persistently high viral loads under isolation. No evidence of environmental contamination was found. Further studies are needed to measure environmental contamination by SARS-CoV-2 carriers and to determine reasonable isolation periods.", "doc_id": "vejvv9r1"} {"topic_name": "how long does coronavirus survive on surfaces", "topic_id": "16", "title": "Sports balls as potential SARS-CoV-2 transmission vectors", "abstract": "Abstract Objects passed from one player to another have not been assessed for their ability to transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that the surface of sport balls, notably a football, tennis ball, golf ball, and cricket ball could not harbour inactivated virus when it was swabbed onto the surface, even for 30 seconds. However, when high concentrations of 5,000 dC/mL and 10,000 dC/mL are directly pipetted onto the balls, it could be detected after for short time periods. Sports objects can only harbour inactivated SARS-CoV-2 under specific, directly transferred conditions, but wiping with a dry tissue or moist \u2018baby wipe\u2019 or dropping and rolling the balls removes all detectable viral traces. This has helpful implications to sporting events.", "doc_id": "ccbc1k1m"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Rethinking cancer clinical trials for COVID-19 and beyond", "abstract": "The risks posed to patients with cancer by the current COVID-19 pandemic demand rapid structural changes in healthcare delivery, with many positive changes likely to continue long term. An immediate critical reassessment of trial methodology based on clinical and scientific priorities is essential to ensure the resilience of clinical cancer research and optimize patient-centered care.", "doc_id": "mvqeftu1"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "More than 80 clinical trials launch to test coronavirus treatments.", "abstract": "", "doc_id": "h10o18ss"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Pressure-controlled versus volume-controlled ventilation for acute respiratory failure due to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS).", "abstract": "BACKGROUND Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) account for one-quarter of cases of acute respiratory failure in intensive care units (ICUs). A third to half of patients will die in the ICU, in hospital or during follow-up. Mechanical ventilation of people with ALI/ARDS allows time for the lungs to heal, but ventilation is invasive and can result in lung injury. It is uncertain whether ventilator-related injury would be reduced if pressure delivered by the ventilator with each breath is controlled, or whether the volume of air delivered by each breath is limited. OBJECTIVES To compare pressure-controlled ventilation (PCV) versus volume-controlled ventilation (VCV) in adults with ALI/ARDS to determine whether PCV reduces in-hospital mortality and morbidity in intubated and ventilated adults. SEARCH METHODS In October 2014, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Isssue 9), MEDLINE (1950 to 1 October 2014), EMBASE (1980 to 1 October 2014), the Latin American Caribbean Health Sciences Literature (LILACS) (1994 to 1 October 2014) and Science Citation Index-Expanded (SCI-EXPANDED) at the Institute for Scientific Information (ISI) Web of Science (1990 to 1 October 2014), as well as regional databases, clinical trials registries, conference proceedings and reference lists. SELECTION CRITERIA Randomized controlled trials (RCTs) and quasi-RCTs (irrespective of language or publication status) of adults with a diagnosis of acute respiratory failure or acute on chronic respiratory failure and fulfilling the criteria for ALI/ARDS as defined by the American-European Consensus Conference who were admitted to an ICU for invasive mechanical ventilation, comparing pressure-controlled or pressure-controlled inverse-ratio ventilation, or an equivalent pressure-controlled mode (PCV), versus volume-controlled ventilation, or an equivalent volume-controlled mode (VCV). DATA COLLECTION AND ANALYSIS Two review authors independently screened and selected trials, assessed risk of bias and extracted data. We sought clarification from trial authors when needed. We pooled risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with their 95% confidence intervals (CIs) using a random-effects model. We assessed overall evidence quality using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. MAIN RESULTS We included three RCTs that randomly assigned a total of 1089 participants recruited from 43 ICUs in Australia, Canada, Saudi Arabia, Spain and the USA. Risk of bias of the included studies was low. Only data for mortality and barotrauma could be combined in the meta-analysis. We downgraded the quality of evidence for the three mortality outcomes on the basis of serious imprecision around the effect estimates. For mortality in hospital, the RR with PCV compared with VCV was 0.83 (95% CI 0.67 to 1.02; three trials, 1089 participants; moderate-quality evidence), and for mortality in the ICU, the RR with PCV compared with VCV was 0.84 (95% CI 0.71 to 0.99; two trials, 1062 participants; moderate-quality evidence). One study provided no evidence of clear benefit with the ventilatory mode for mortality at 28 days (RR 0.88, 95% CI 0.73 to 1.06; 983 participants; moderate-quality evidence). The difference in effect on barotrauma between PCV and VCV was uncertain as the result of imprecision and different co-interventions used in the studies (RR 1.24, 95% CI 0.87 to 1.77; two trials, 1062 participants; low-quality evidence). Data from one trial with 983 participants for the mean duration of ventilation, and from another trial with 78 participants for the mean number of extrapulmonary organ failures that developed with PCV or VCV, were skewed. None of the trials reported on infection during ventilation or quality of life after discharge. AUTHORS' CONCLUSIONS Currently available data from RCTs are insufficient to confirm or refute whether pressure-controlled or volume-controlled ventilation offers any advantage for people with acute respiratory failure due to acute lung injury or acute respiratory distress syndrome. More studies including a larger number of people given PCV and VCV may provide reliable evidence on which more firm conclusions can be based.", "doc_id": "g8h6cpzr"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "RECOVERY trial: the UK covid-19 study resetting expectations for clinical trials.", "abstract": "", "doc_id": "fpn064ne"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "A Comprehensive Analysis of Clinical Trials in the COVID-19 Pandemic Era.", "abstract": "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.", "doc_id": "bl4d808v"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Efficacy and safety of interferon \u03b2-1a in treatment of severe COVID-19: A randomized clinical trial.", "abstract": "OBJECTIVES To the best of our knowledge, there is no published study regarding use of IFN \u03b2-1a in the treatment of severe COVID-19. In this randomized clinical trial efficacy and safety of IFN \u03b2-1a has been evaluated in patients with severe COVID-19. METHODS Forty-two patients in the interferon group received IFN \u03b2-1a in addition to the national protocol medications (hydroxychloroquine plus lopinavir/ritonavir or atazanavir/ritonavir). Each 44 micrograms/ml (12 million IU/ml) of interferon \u03b2-1a was subcutaneously injected three times weekly for two consecutive weeks. The control group consisted 39 patients that received only the national protocol medications. Primary outcome of study was time to reach clinical response. Secondary outcomes were duration of hospital stay, length of ICU stay, 28-day mortality, effect of early or late administration of IFN on mortality, adverse effects and complications during the hospitalization. RESULTS Between 29th February to 3rd April 2020, 92 patients were recruited that finally 42 patients in the IFN group and 39 patients in the control group completed the study. As primary outcome, time to the clinical response was not significantly different between the IFN and the control groups (9.7 \u00b1 5.8 vs. 8.3 \u00b1 4.9 days respectively, P=0.95). On day 14, 66.7% vs. 43.6% of patients in the IFN group and the control group were discharged, respectively (OR= 2.5; 95% CI: 1.05- 6.37). The 28-day overall mortality was significantly lower in the IFN than the control group (19% vs. 43.6% respectively, p= 0.015). Early administration significantly reduced mortality (OR=13.5; 95% CI: 1.5-118). CONCLUSION Although IFN did not change time to reach the clinical response, adding it to the national protocol significantly increased discharge rate on day 14 and decreased 28-day mortality.", "doc_id": "x061q8t7"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.", "abstract": "Importance There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. Objective To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. Design, Setting, and Participants This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Interventions Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). Main Outcomes and Measures Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Results Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). Conclusions and Relevance The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. Trial Registration ClinicalTrials.gov Identifier: NCT04323527.", "doc_id": "oynbwas9"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Comprehensive overview of COVID-19 clinical trials.", "abstract": "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.", "doc_id": "fti60hts"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "COVID-19 clinical trials: see it big and keep it simple.", "abstract": "", "doc_id": "tqboenbd"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Biggest COVID-19 trial tests repurposed drugs first.", "abstract": "", "doc_id": "2h6qr25n"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Plasma from donors recovered from the new Coronavirus 2019 as therapy for critical patients with COVID-19 (COVID-19 plasma study): a multicentre study protocol.", "abstract": "Since the end of 2019, a new coronavirus strain has been reported in the Chinese province of Wuhan, indicated as 2019-nCoV or SARS-CoV-2. In February 2020, the first case of transmission on Italian soil was reported. On March 09, 2020, at the time of protocol design, the Italian Ministry of Health reported 10,149 people who had contracted the virus; of these, 8514 were positive, of which 5038 were hospitalized with symptoms (59.2%) and 877 in intensive care (10.3%), while the remaining 2599 were in home isolation; 631 were deceased (6.2%) and 1004 healed (9.9%). To date there are no studies in the literature that demonstrate its feasibility and efficacy in the context of the worldwide SARS-CoV-2 epidemic. Based upon the little existing evidence, we planned to assess the efficacy of the infusion of hyperimmune plasma in COVID-19 patients in a one-arm proof-of-concept clinical trial. The primary objective of our study is to evaluate the efficacy of the administration of plasma taken from convalescent donors of COVID-19 to critically ill patients with COVID-19 in terms of their survival. Death from any cause will be considered. The main limit of this study is its one-arm proof-of-concept design with only 43 patients enrolled. However, in the absence of previous evidence, larger and/or randomized trials did not appear to be ethically acceptable. Moreover, the results from this study, if encouraging, will allow us to plan further informed large clinical trials. Trial registration: NCT04321421 March 23, 2020.", "doc_id": "hsv18n5c"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Covid19db -- An online database of trials of medicinal products to prevent or treat COVID-19, with a specific focus on drug repurposing", "abstract": "Background: The global pandemic caused by SARS-CoV-2 virus has prompted an unprecedented international effort to seek medicines for prevention and treatment of infection. Drug repurposing has played a key part in this response. The rapid increase in trial activity has raised questions about efficiency and lack of coordination. Our objective was to develop a user-friendly, open access, online database of interventional trials of medicinal products to monitor and rapidly identify trials of medicinal products. Methods and Findings: Using the US clinicaltrials.gov (NCT) registry, the EU Clinical Trials Register (EUCTR) and the WHO International Clinical Trials Registry Platform (WHO ICTRP), we identified all COVID-19 trials of medicinal products and combined data from the 3 sources into a single data table. Trials that were out of scope and duplicates were excluded. A manual encoding was performed to ascertain key information (e.g. trial aim, type of intervention etc). The database, Covid19db, was published online at: http://www.redo-project.org/covid19db/. Descriptive statistics of the database from April 4th 2020 through to May 19th show an increase from 186 to 955 trials, or an average of 17 new trials registered per day. Over this period, the proportion of trials including a repurposing arm decreased slightly over time (from a maximum of 75% to 68% at the end of the covered period) as did the proportion of trials aiming to prevent infection (from a maximum of 16% to 12% at the end of the covered period). The most popular intervention is hydroxychloroquine (180 trials), followed by azithromycin (57 trials), chloroquine, tocilizumab and lopinavir/ritonavir (36 trials). Total planned enrolment is 468,559 participants as of 19th May 2020. Conclusions: we have developed an open access, online and regularly updated tool to monitor clinical trials of medicinal products to prevent or treat infection by SARS-CoV-2 globally. Our analysis shows a high number of 'me-too' trials, in particular for some repurposed drugs, such as hydroxychloroquine, azithromycin and tocilizumab, substantiating calls for better coordination and better use of trial resources.", "doc_id": "mwix78qb"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Key points of serious adverse event and protection of patients in ophthalmic clinical trials during novel coronavirus pneumonia outbreak/ \u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u80ba\u708e\u9632\u63a7\u671f\u95f4\u773c\u79d1\u4e34\u5e8a\u8bd5\u9a8c\u6d41\u7a0b\u7ba1\u7406\u53ca\u53d7\u8bd5\u8005\u968f\u8bbf\u9632\u62a4\u8981\u70b9", "abstract": "The prevention and control of novel coronavirus pneumonia is the most priority recently, and various measures during the prevention and control period will have varying degrees of impact on the implement of clinical trials.However, various examinations in ophthalmological clinical trials need close contact between operators and patients, which put us at risk of cross-infection.This paper indicated some suggestions based on the criteria of clinical trials under major public health emergencies, the management of clinical trials during epidemic period, including the follow-up of subjects, the treatment of epidemic serious adverse event (SAE) and the management requirements of co-sponsors, as well as the requirements and management principles for environment, subjects, examiners and inspection equipment in the process of ophthalmic clinical trials.It may be helpful to the ophthalmic clinical trial researchers and subjects during the period of novel coronavirus infection.", "doc_id": "0mn4b0fp"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19)", "abstract": "Objective In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study. Methods Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ 400 mg twice for 1 d and HCQ 200 mg twice daily for 6 days were administered. Both study group and controlled group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020. Results There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1-9 days) and 10 days (95% CI; 2-12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70). Conclusions Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.", "doc_id": "9yql0qbr"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Randomization amid a pandemic - a critical appraisal regarding convalescent plasma therapy clinical trials for COVID-19 patients", "abstract": "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", "doc_id": "eqo1lrjv"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "COVID-19: Why SOLIDARITY and DisCoVeRy trials may fail to bring informative and timely results", "abstract": "Objective: The SOLIDARITY and DisCoVeRy trials were launched to facilitate the rapid worldwide comparison of the efficacy and safety of treatments against COVID-19. This study aimed to review the trial designs of SOLIDARITY and DisCoVeRy and their feasibility to generate high-quality evidence. Method: A systematic search of the European Clinical trial registry, the U.S. National Library of Medicine ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) created by the World Health Organization (WHO) was conducted on May 10th, 2020 to identify the study details of the SOLIDARITY and DisCoVeRy trials. A supplementary search of PubMed, the websites of the WHO and French authorities, and Google search engine was conducted. A critical review was performed on the findings. Results: The DisCoVeRy trial design was detailed consistently in both the European and the US clinical rial registries. SOLIDARITY was registered on ICTRP, with country-specific information reported on country-level registry platforms. The design of DisCoVeRy trial appears to be ideal from the methodological perspective. Both trials appear difficult to implement, impractical, and disconnected from the pandemic reality. This is consistent with the apparent failure of the trials to deliver conclusions before the end of the pandemic. Conclusion: Both trials constitute an interesting initiative yet may lack the resources to support a high-quality implementation. The authors call for a pandemic task force, with various experts on the front-line of COVID-19, to inform policy-makers to make effective decisions that may not be based on traditional, methodological state-of-the-art evidence, but rather pragmatic and revisable decisions reflecting emerging evidence for the benefit of patients and society.", "doc_id": "6s2adeam"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Clinical Outcomes and Plasma Concentrations of Baloxavir Marboxil and Favipiravir in COVID-19 Patients: an Exploratory Randomized, Controlled Trial", "abstract": "Background: Effective antiviral drugs for COVID-19 are still lacking. This study aims to evaluate the clinical outcomes and plasma concentrations of baloxavir marboxil and favipiravir in COVID-19 patients. Methods: Favipiravir and baloxavir acid were evaluated for their antiviral activity against SARS-CoV-2 in vitro before the trial initiation. We conducted an exploratory trial with 3 arms involving hospitalized adult patients with COVID-19. Patients were randomized assigned in a 1:1:1 ratio into baloxavir marboxil group, favipiravir group, and control group. The primary outcome was the percentage of subjects with viral negative by Day 14 and the time from randomization to clinical improvement. Virus load reduction, blood drug concentration and clinical presentation were also observed. The trial was registered with Chinese Clinical Trial Registry (ChiCTR 2000029544). Results: Baloxavir showed antiviral activity in vitro with the half-maximal effective concentration (EC50) of 5.48 M comparable to arbidol and lopinavir, but favipiravir did not demonstrate significant antiviral activity up to 100 M. Thirty patients were enrolled. The percentage of patients who turned viral negative after 14-day treatment was 70%, 77%, and 100% in the baloxavir, favipiravir, and control group respectively, with the medians of time from randomization to clinical improvement was 14, 14 and 15 days, respectively. One reason for the lack of virological effect and clinical benefits may be due to insufficient concentrations of these drugs relative to their antiviral activities. Conclusions: Our findings do not support that adding either baloxavir or favipiravir under the trial dosages to the existing standard treatment.", "doc_id": "qujtxkxn"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Current status of clinical trial registration regarding coronavirus disease 2019", "abstract": "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.", "doc_id": "tjsa86l7"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Ongoing Clinical Trials for the Management of the COVID-19 Pandemic", "abstract": "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.", "doc_id": "ibuqz948"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "An evidence mapping and analysis of registered COVID-19 clinical trials in China", "abstract": "BACKGROUND: This article aims to summarize the key characteristics of registered trials of 2019 novel coronavirus (COVID-19), in terms of their spatial and temporal distributions, types of design and interventions, and patient characteristics among others. METHODS: A comprehensive search of the registered COVID-19 trials has been performed on platforms including ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (WHO ICTRP), Chinese Clinical Trials Registry (CHiCTR), Australian Clinical Trials Registry, Britain's National Research Register (BNRR), Current Control Trials (CCT), and Glaxo Smith Kline Register. Trials registered at the first 8 weeks of the COVID-19 outbreak are included, without language restrictions. For each study, the registration information, study design, and administrator information are collected and summarized. RESULTS: A total of 220 registered trials were evaluated as of February 27, 2020. Hospital-initiated trials were the majority and account for 80% of the sample. Among the trials, pilot studies and phase 4 trials are more common and represent 35% and 19.1% of the sample, respectively. The median sample size of the registered trials is 100, with interquartile range 60-240. Further, 45.9% of the trials mentioned information on a data monitoring committee. 54.5% of the trials did not specify the disease severity among patients they intend to recruit. Four types of interventions are most common in the experimental groups across the registered studies: antiviral drugs, Traditional Chinese Medicine (TCM), biological agents, and hormone drugs. Among them, the TCM and biological agents are frequently used in pilot study and correspond to a variety of primary endpoints. In contrast, trials with antiviral drugs have more targeted primary outcomes such as \"COVID-19 nucleic acid test\" and \"28-day mortality.\" CONCLUSIONS: We provide an evidence mapping and analysis of registered COVID-19 clinical trials in China. In particular, it is critical for ongoing and future studies to refine their research hypothesis and better identify their intervention therapies and the corresponding primary outcomes. It is also imperative for multiple public health divisions and research institutions to work together for integrative clinical data capture and sharing, with a common objective of improving future studies that evaluate COVID-19 interventions.", "doc_id": "9gw2vfkn"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "More than 80 clinical trials launch to test coronavirus treatments", "abstract": "", "doc_id": "dzvfaa8z"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "The CREST-2 experience with the evolving challenges of COVID-19: A clinical trial in a pandemic", "abstract": "The coronavirus disease 2019 pandemic has disrupted the lives of whole communities and nations. The multinational multicenter National Institute of Neurological Disorders and Stroke Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial stroke prevention trial rapidly experienced the effects of the pandemic and had to temporarily suspend new enrollments and shift patient follow-up activities from in-person clinic visits to telephone contacts. There is an ethical obligation to the patients to protect their health while taking every feasible step to ensure that the goals of the trial are successfully met. Here, we describe the effects of the pandemic on the trial and steps that are being taken to mitigate the effects of the pandemic so that trial objectives can be met.", "doc_id": "cojw51gr"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Profiles of COVID-19 clinical trials in the Chinese Clinical Trial Registry", "abstract": "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..", "doc_id": "pxzbkde0"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Clinical trials for the prevention and treatment of COVID-19: current state of play", "abstract": "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.", "doc_id": "pftu5qea"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Clinical Trials during the SARS-CoV-2 Pandemic", "abstract": "", "doc_id": "gwcvfeik"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Clinical trial analysis of 2019-nCoV therapy registered in China", "abstract": "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.", "doc_id": "g7rjtlht"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Umbilical cord blood therapy to prevent progression of COVID-19 related pneumonia: a structured summary of a study protocol for a pilot randomised controlled trial", "abstract": "OBJECTIVES: Objective: To undertake a pilot, feasibility RCT of umbilical cord blood derived cell therapy for treatment of adult patients infected with SARS-CoV-2 virus related moderate-to-severe pneumonia to prevent progression to severe ARDS. HYPOTHESIS: Expanded cord blood derived cell therapy will be feasible, well tolerated and show potential efficacy in the treatment of acute COVID-19 related moderate to severe pneumonia in adult patients because of their powerful anti-inflammatory and immunomodulatory properties. TRIAL DESIGN: Pilot, parallel design randomised controlled trial. PARTICIPANTS: The trial will recruit 24 hospitalised patients with confirmed SARS-CoV-2 infection and pneumonia from July to December 2020 at Monash Medical Centre in Melbourne, Australia. INTERVENTION AND COMPARATOR: Intervention: Intravenous injection of expanded umbilical cord blood cells at a dose of 5 million cells/kg (maximum dose - 500 million cells). Cell infusion will occur over 30-60 minutes through a peripheral intravenous cannula. Standard supportive care will continue as needed. Comparator: Standard supportive care. MAIN OUTCOMES: Safety and tolerability of cell administration within first 24 hours of administration; clinical improvement on a seven-category clinical improvement ordinal scale. RANDOMISATION: Randomisation will be done using computer generated allocation to intervention/ control groups in a 1:1 ratio (in blocks of 6) using sealed opaque envelopes. BLINDING (MASKING): This will be an unblinded study, given that it is the first study using expanded cord blood cells in COVID-19 patients. There will be no placebo infusion. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Twelve participants in each group. Total n=24. TRIAL STATUS: CBC-19 protocol v2, dated 23rd April 2020. Recruitment has not started yet. Estimated recruitment timeline is between 1st July - 31st December 2020. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12620000478910, registered 16th 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.", "doc_id": "0bk2t0h0"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Towards Optimization of Hydroxychloroquine Dosing in Intensive Care Unit COVID-19 Patients", "abstract": "Hydroxychloroquine (HCQ) appears to be a promising treatment for COVID-19. However, all ongoing clinical trials with HCQ use different dosing regimens, resulting on various concentrations PK studies are therefore needed to define the optimal dosing regimen.", "doc_id": "onqy21w5"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial", "abstract": "BACKGROUND: Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir-ritonavir, and ribavirin for treating patients with COVID-19. METHODS: This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688. FINDINGS: Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3-7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5-11]) than the control group (12 days [8-15]; hazard ratio 4\u00b737 [95% CI 1\u00b786-10\u00b724], p=0\u00b70010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir-ritonavir because of biochemical hepatitis. No patients died during the study. INTERPRETATION: Early triple antiviral therapy was safe and superior to lopinavir-ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted. FUNDING: The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.", "doc_id": "rh6luded"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial", "abstract": "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.", "doc_id": "w5bpoms2"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Characteristics of COVID-19 Clinical Trials in China Based on the Registration Data on ChiCTR and ClinicalTrials.gov", "abstract": "Objective: This study aimed to evaluate the fundamental characteristics of coronavirus disease (COVID-19) clinical trials registered in China. Methods: COVID-19 clinical trials registered in China were analyzed from databases on ChiCTR and ClinicalTrials.gov. The study designs, samples, primary end points, and intervention measures were evaluated. Results: In total, 262 intervention clinical trials were retrieved on March 10, 2020. Overall, 181 (69.1%) trials involved two groups, 200 (76.3%) trials were randomized parallel trials, 24 (9.2%) trials were double blind, and 60.3% of trials included ≤100 participants. Sixty (22.9%) trials considered symptom improvement as the primary endpoint and 43 (16.4%) trials considered the rate or time at which the subjects became virus-free as the primary endpoint. Of 262 intervention studies, chemical drugs and biological products were studied in 105 (40.1%) intervention studies, of which antiviral drugs accounted for 15.3% and malaria drugs accounted for 8.4% of the studies. Among all trials, 27.9% of the studies used traditional Chinese medicine (TCM), 10.3% used cell therapy, and 5.0% used plasma therapy. Conclusion: This study is the first snapshot of the landscape of COVID-19 clinical trials registered in China and provided the basic features of clinical trial designs for the treatment and prevention of COVID-19 to offer useful information to guide future clinical trials on COVID-19 in other countries.", "doc_id": "7izjhyyk"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "A randomized multicenter clinical trial to evaluate the efficacy of melatonin in the prophylaxis of SARS-CoV-2 infection in high-risk contacts (MeCOVID Trial): A structured summary of a study protocol for a randomised controlled trial", "abstract": "OBJECTIVES: Primary objective: to evaluate the efficacy of melatonin as a prophylactic treatment on prevention of symptomatic SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Secondary objectives: To evaluate the efficacy of melatonin as a prophylactic treatment on prevention of asymptomatic SARS-CoV-2 infection.To evaluate the efficacy of melatonin to prevent the development of severe COVID-19 in the participants enrolled in this study who develop SARS-CoV-2 infection along the trial.To evaluate the duration of COVID-19 symptoms in participants receiving melatonin before the infection.To evaluate seroconversion timing post-symptom onset. Exploratory objectives:To compare severity of COVID-19 between men and women.To evaluate the influence of sleep and diet on prevention from SARS-CoV-2 infection.To evaluate the effect of melatonin on the incidence and characteristics of lymphopenia and increase of inflammatory cytokines related to COVID-19. TRIAL DESIGN: This is a two-arm parallel randomised double-blind controlled trial to evaluate the efficacy of melatonin versus placebo in the prophylaxis of coronavirus disease 2019 among healthcare workers. PARTICIPANTS: Inclusion Criteria: Male or female participants ≥ 18 and ≤ 80 years of age.Healthcare workers from the public and private Spanish hospital network at risk of SARS-CoV 2 infection.Not having a previous COVID19 diagnosis.Understanding the purpose of the trial and not having taken any pre-exposure prophylaxis (PrEP) including HIV PrEP from March 1st 2020 until study enrolment.Having a negative SARS-CoV 2 reverse-transcription PCR (RT-PCR) result or a negative serologic rapid test (IgM/IgG) result before randomization.Premenopausal women must have a negative urinary pregnancy test in the 7 days before starting the trial treatment.Premenopausal women and males with premenopausal couples must commit to using a high efficiency anticonceptive method. EXCLUSION CRITERIA: HIV infection.Active hepatitis B infection.Renal failure (CrCl < 60 mL/min/1.73 m2) or need for hemodialysis.Osteoporosis.Myasthenia gravis.Pre-existent maculopathy.Retinitis pigmentosa.Bradycardia (less than 50 bpm).Weight less than 40 Kg.Participant with any immunosuppressive condition or hematological disease.Treatment with drugs that may prolong QT in the last month before randomization for more than 7 days including: azithromycin, chlorpromazine, cisapride, clarithromycin, domperidone, droperidol, erythromycin, halofantrine, haloperidol, lumefantrine, mefloquine, methadone, pentamidine, procainamide, quinidine, quinine, sotalol, sparfloxacin, thioridazine, amiodarone.Hereditary intolerance to galactose, Lapp lactase deficiency or glucose or galactose malabsorption.Treatment with fluvoxamine.Treatment with benzodiazepines or benzodiazepine analogues such as zolpidem, zopiclone or zaleplon.Pregnancy.Breastfeeding.History of potentially immune derived diseases such as: lupus, Crohn's disease, ulcerative colitis, vasculitis or rheumatoid arthritis.Insulin-dependent diabetes mellitus.Known history of hypersensitivity to the study drug or any of its components.Patients that should not be included in the study at the judgment of the research team. Participants will be recruited from the following eight hospitals in Madrid, Spain: Hospital Universitario La Paz, Hospital Ram\u00f3n y Cajal, Hospital Infanta Sof\u00eda, Hospital 12 de Octubre, Hospital Cl\u00ednico San Carlos, Hospital Central de la defensa G\u00f3mez Ulla,Hospital de La Princesa and Hospital Infanta Leonor. INTERVENTION AND COMPARATOR: Experimental: Melatonin (Circadin\u00ae, Exeltis Healthcare, Spain): 2 mg of melatonin orally before bedtime for 12 weeks. Comparator: Identical looking placebo (Laboratorios Liconsa, Spain) orally before bedtime for 12 weeks. MAIN OUTCOMES: Number of SARS-CoV-2 (COVID-19) symptomatic infections confirmed by polymerase chain reaction (PCR) test or serologic test or according to each centre diagnosis protocol. Primary outcome will be measured until the end of treatment for each participant (until the date of the last dose taken by each patient). RANDOMISATION: Patients who meet all inclusion and no exclusion criteria will be randomised, stratified by centres, sex and age (<50 and ≥ 50 years old). The randomisation sequence was created using SAS version 9.4 statistical software (procedure 'PROC PLAN') with a 1:1 allocation. No randomisation seed was specified. The randomisation seed was generated taking the hour of the computer where the program was executed. Randomization will be done centrally through the electronic system RedCAP\u00ae in order to conceal the sequence until interventions are assigned BLINDING (MASKING): Participants, caregivers, and those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 450 participants are planned to be enrolled in this clinical trial, 225 in the experimental arm and 225 in the placebo arm. TRIAL STATUS: Protocol version 3.0, 17th of April 2020. Recruitment ongoing. First participant was recruited on the 21st of April 2020. The final participant is anticipated to be recruited on the 31st of May 2020. As of May 18th, 2020, a total of 312 participants have been enrolled (154 at Hospital La Paz, 85 at Hospital Infanta Sof\u00eda and 73 at Hospital 12 de Octubre). TRIAL REGISTRATION: EU Clinical Trials Register: 2020-001530-35; Date of trial registration: 13th of April 2020; https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001530-35/ES 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.", "doc_id": "2s9zd99r"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Safety and efficacy assessment of allogeneic human dental pulp stem cells to treat patients with severe COVID-19: structured summary of a study protocol for a randomized controlled trial (Phase I / II)", "abstract": "OBJECTIVES: To assess the safety and therapeutic effects of allogeneic human dental pulp stem cells (DPSCs) in treating severe pneumonia caused by COVID-19. TRIAL DESIGN: This is a single centre, two arm ratio 1:1, triple blinded, randomized, placebo-controlled, parallel group, clinical trial. PARTICIPANTS: Twenty serious COVID-19 cases will be enrolled in the trial from April 6th to December 31st 2020. INCLUSION CRITERIA: hospitalised patients at Renmin Hospital of Wuhan University satisfy all criteria as below: 1)Adults aged 18-65 years;2)Voluntarily participate in this clinical trial and sign the \"informed consent form\" or have consent from a legal representative.3)Diagnosed with severe pneumonia of COVID-19: nucleic acid test SARS-CoV-2 positive; respiratory distress (respiratory rate > 30 times / min); hypoxia (resting oxygen saturation < 93% or arterial partial pressure of oxygen / oxygen concentration < 300 mmHg).4)COVID-19 featured lung lesions in chest X-ray image. EXCLUSION CRITERIA: Patients will be excluded from the study if they meet any of the following criteria. 1.Patients have received other experimental treatment for COVID-19 within the last 30 days;2.Patients have severe liver condition (e.g., Child Pugh score >=C or AST> 5 times of the upper limit);3.Patients with severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m2) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis;4.Patients who are co-infected with HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses;5.Female patients who have no sexual protection in the last 30 days prior to the screening assessment;6.Pregnant or lactating women or women using estrogen contraception;7.Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period;8.Other conditions that the researchers consider not suitable for participating in this clinical trial. INTERVENTION AND COMPARATOR: There will be two study groups: experimental and control. Both will receive all necessary routine treatment for COVID-19. The experimental group will receive an intravenous injection of dental pulp stem cells suspension (3.0x107 human DPSCs in 30ml saline solution) on day 1, 4 and 7; The control group will receive an equal amount of saline (placebo) on the same days. Clinical and laboratory observations will be performed for analysis during a period of 28 days for each case since the commencement of the study. MAIN OUTCOMES: 1. Primary outcome The primary outcome is Time To Clinical Improvement (TTCI). By definition, TTCI is the time (days) it takes to downgrade two levels from the following six ordered grades [(grade 1) discharge to (grade 6) death] in the clinical state of admission to the start of study treatments (hDPSCs or placebo). Six grades of ordered variables: GradeDescriptionGrade 1:Discharged of patient;Grade 2:Hospitalized without oxygen supplement;Grade 3:Hospitalized, oxygen supplement is required, but NIV / HFNC is not required;Grade 4:Hospitalized in intensive care unit, and NIV / HFNC treatment is required;Grade 5:Hospitalized in intensive care unit, requiring ECMO and/or IMV;Grade 6:Death. ABBREVIATIONS: NIV, non-invasive mechanical ventilation; HFNC, high-flow nasal catheter; IMV, invasive mechanical ventilation. 2. Secondary outcomes 2.1 vital signs: heart rate, blood pressure (systolic blood pressure, diastolic blood pressure). During the screening period, hospitalization every day (additional time points of D1, D4, D7 30min before injection, 2h \u00b1 30min, 24h \u00b1 30min after the injection) and follow-up period D90 \u00b1 3 days. 2.2 Laboratory examinations: during the screening period, 30 minutes before D1, D4, D7 infusion, 2h \u00b1 30min, 24h \u00b1 30min after the end of infusion, D10, D14, D28 during hospitalization or discharge day and follow-up period D90 \u00b1 3 days. 2.3 Blood routine: white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, neutrophils, lymphocytes, monocytes, eosinophils Acidic granulocyte count, basophil count, red blood cell, hemoglobin, hematocrit, average volume of red blood cells, average red blood cell Hb content, average red blood cell Hb concentration, RDW standard deviation, RDW coefficient of variation, platelet count, platelet specific platelet average Volume, platelet distribution width,% of large platelets; 2.4 Liver and kidney function tests: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, \u00ce\u00b3-glutamyl transferase, prealbumin, total protein, albumin, globulin, white / globule ratio , Total bilirubin, direct bilirubin, cholinesterase, urea, creatinine, total carbon dioxide, uric acid glucose, potassium, sodium, chlorine, calcium, corrected calcium, magnesium, phosphorus, calcium and phosphorus product, anion gap, penetration Pressure, total cholesterol, triacylglycerol, high density lipoprotein cholesterol, Low density lipoprotein cholesterol, lipoprotein a, creatine kinase, lactate dehydrogenase, estimated glomerular filtration rate. 2.5 Inflammation indicators: hypersensitive C-reactive protein, serum amyloid (SAA); 2.6 Infectious disease testing: Hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb), Hepatitis C (Anti-HCV), AIDS (HIVcombin), syphilis (Anti-TP), cytomegalovirus CMV-IgM, cytomegalovirus CMV-IgG; only during the screening period and follow-up period D90 \u00b1 3. 2.7 Immunological testing: Collect peripheral blood to detect the phenotype of T lymphocyte, B lymphocyte, natural killer cell, Macrophage and neutrophil by using flow cytometry. Collect peripheral blood to detect the gene profile of mononuclear cells by using single-cell analyses. Collect peripheral blood serum to detect various immunoglobulin changes: IgA, IgG, IgM, total IgE; Collect peripheral blood serum to explore the changes of cytokines, Th1 cytokines (IL-1 \u00df, IL-2, TNF-a, ITN-\u00ce\u00b3), Th2 cytokines (IL-4, IL-6, IL -10). 2.8 Pregnancy test: blood \u00df-HCG, female subjects before menopause are examined during the screening period and follow-up period D90 \u00b1 3. 2.9 Urine routine: color, clarity, urine sugar, bilirubin, ketone bodies, specific gravity, pH, urobilinogen, nitrite, protein, occult blood, leukocyte enzymes, red blood cells, white blood cells, epithelial cells, non-squamous epithelial cells , Transparent cast, pathological cast, crystal, fungus; 2.10 Stool Routine: color, traits, white blood cells, red blood cells, fat globules, eggs of parasites, fungi, occult blood (chemical method), occult blood (immune method), transferrin (2h \u00b1 30min after the injection and not detected after discharge). RANDOMIZATION: Block randomization method will be applied by computer to allocate the participants into experimental and control groups. The random ratio is 1:1. BLINDING (MASKING): Participants, outcomes assessors and investigators (including personnel in laboratory and imaging department who issue the sample report or image observations) will be blinded. Injections of cell suspension and saline will be coded in accordance with the patient's randomisation group. The blind strategy is kept by an investigator who does not deliver the medical care or assess primary outcome results. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Twenty participants will be randomized to the experimental and control groups (10 per group). TRIAL STATUS: Protocol version number, hDPSC-CoVID-2019-02-2020 Version 2.0, March 13, 2020. Patients screening commenced on 16th April and an estimated date of the recruitment of the final participants will be around end of July. . TRIAL REGISTRATION: Registration: World Health Organization Trial Registry: ChiCTR2000031319; March 27,2020. ClinicalTrials.gov Identifier: NCT04336254; April 7, 2020 Other Study ID Numbers: hDPSC-CoVID-2019-02-2020 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.", "doc_id": "hielbtqo"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Core Outcome Set for Clinical Trials on Coronavirus Disease 2019 (COS-COVID)", "abstract": "Since its outbreak in December 2019, a series of clinical trials on Coronavirus Disease 2019 (COVID-19) have been registered or carried out. However, the significant heterogeneity and less critical outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) handbook (version 1.0), a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine, evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019-nCoV reverse transcription-polymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital stay, composite events, score of clinical symptoms, and time to 2019-nCoV RT-PCR negativity), five outcomes for the severe type (composite events, length of hospital stay, arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2), duration of mechanical ventilation, and time to 2019-nCoV RT-PCR negativity), one outcome for critical type (all-cause mortality), and one outcome for rehabilitation period (pulmonary function). The COS-COVID is currently the most valuable and practical clinical outcome set for the evaluation of intervention effect, and is useful for evidence assessment and decision-making. With a deepening understanding of COVID-19 and application feedback, the COS-COVID should be continuously updated.", "doc_id": "3suh7nj7"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "[Analysis on clinical study protocols of traditional Chinese medicine for coronavirus disease 2019]", "abstract": "To analyze the registered clinical trial protocols of traditional Chinese medicine(TCM) for the prevention and treatment of coronavirus disease 2019(COVID-19), in order to provide information for improving the quality of research design. The website of the Chinese Clinical Trial Registry(www.chictr.org.cn) and the American Clinical Trial Registry(clinicaltrials.gov) were searched to collect protocols of TCM for COVID-19. Documents were screened following the inclusion criteria, and data were extracted in regard to registration date, study objective, type of design, sponsor, patient, sample size, intervention, and evaluation index. Descriptive analysis was conducted. A total of 49 clinical trial protocols of TCM for COVID-19 were included. Primary sponsors were mainly hospitals or universities in places like Hubei, Beijing, Zhejiang and other regions. The implementation units are mainly in Hubei, Guangdong, Zhejiang, Henan and other regional hospitals. The types of study design were mainly experimental studies(40), including 30 randomized parallel controlled trials, 7 non-randomized controlled trials, 2 single arm trials and 1 consecutively recruited trial; besides, there were also 6 observational studies, 2 health service studies and 1 preventive study. The sample size reached a total of 30 562 cases, with a maximum of 20 000 for a single study and a minimum of 30. The 49 trials subjects included healthy people(3), isolation and observation cases(1), suspected cases(10),confirmed COVID-19 patients(31) and COVID-19 recovery patients(4). Of the 31 trials planned to include confirmed COVID-19 patients, 16 protocols no definite disease classification, 3 with a clear exclusion of severe subjects, 4 with common subjects, 2 with light, common or severe subjects, 1 with light and common subjects, 1 with common or severe subjects, 3 with severe subjects, and 1 with severe or critical subjects. The experimental interventions included Chinese patent medicine(Lianhua Qingwen Capsules/Granules, Huoxiang Zhengqi Dropping Pills/Oral Liquid, Babao Dan, Gubiao Jiedu Ling, Jinhao Jiere Granules, Compound Yu-xingcao Mixture, Jinye Baidu Granules, Shufeng Jiedu Capsuless, Shuanghuanglian Oral Liquid, Tanreqing Injection, Xuebijing Injection, Reduning Injection, Xiyanping Injection), Chinese medicinal decoction and taichi. The primary evaluation outcomes mainly included antipyretic time, clinical symptom relief, novel coronavirus nucleic acid turning to negative, conversion rate of severe cases and chest CT. There was a quick response of clinical research on the prevention and treatment of COVID-19 with TCM, with the current registered protocols covers the whole process of disease prevention, treatment and rehabilitation. However, issues need to be concerned, including unclear definition of patient's condition, unclear research objectives, unclear intervention process and inappropriate outcomes, etc. In addition, researchers should consider the actual difficulties and workload of doctors in epidemic response environment, and make effort to optimize the process and improve the operability of research protocols under the principle of medical ethics.", "doc_id": "6jb9kub4"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "ChemoPROphyLaxIs with hydroxychloroquine For covId-19 infeCtious disease (PROLIFIC) to prevent covid-19 infection in frontline healthcare workers: A structured summary of a study protocol for a randomised controlled trial", "abstract": "OBJECTIVES: PRIMARY OBJECTIVE: To determine whether chemoprophylaxis with hydroxychloroquine versus placebo increases time to contracting coronavirus disease 2019 (COVID-19) in frontline healthcare workers. SECONDARY OBJECTIVES: 1) To determine whether chemoprophylaxis with daily versus weekly dosing of hydroxychloroquine increases time to contracting COVID-19 disease in frontline healthcare workers. 2) To compare the number of COVID-19 cases between each trial arm on the basis of positive tests (as per current clinical testing methods and/or serology) 3) To compare the percentage of COVID-19 positive individuals with current testing methods versus serologically-proven COVID-19 in each trial arm 4) To compare COVID-19 disease severity in each trial arm 5) To compare recovery time from COVID-19 infection in each trial arm EXPLORATORY OBJECTIVES: 1) To determine compliance (as measured by trough pharmacokinetic hydroxychloroquine levels) on COVID-19 positive tests 2) To determine if genetic factors determine susceptibility to COVID-19 disease or response to treatment 3) To determine if blood group determines susceptibility to COVID-19 disease 4) To compare serum biomarkers of COVID-19 disease in each arm TRIAL DESIGN: Double-blind, multi-centre, 2-arm (3:3:2 ratio) randomised placebo-controlled trial PARTICIPANTS: National Health Service (NHS) workers who have direct patient contact delivering care to patients with COVID-19. Participants in the trial will be recruited from a number of NHS hospitals directly caring for patients with COVID-19. INCLUSION CRITERIA: To be included in the trial the participant MUST: 1) Have given written informed consent to participate 2) Be aged 18 years to 70 years 3) Not previously have been diagnosed with COVID-19 4) Work in a high-risk secondary or tertiary healthcare setting (hospitals accepting COVID-19 patients) with direct patient-facing care EXCLUSION CRITERIA: The presence of any of the following will mean participants are ineligible: 1) Known COVID-19 positive test at baseline (if available) 2) Symptomatic for possible COVID-19 at baseline 3) Known hypersensitivity reaction to hydroxychloroquine, chloroquine or 4-aminoquinolines 4) Known retinal disease 5) Known porphyria 6) Known chronic kidney disease (CKD; eGFR<30ml/min) 7) Known epilepsy 8) Known heart failure or conduction problems 9) Known significant liver disease (Gilbert's syndrome is permitted) 10) Known glucose-6-phosphate dehydrogenase (G6PD) deficiency 11) Currently taking any of the following contraindicated medications: Digoxin, Chloroquine, Halofantrine, Amiodarone, Moxifloxacin, Cyclosporin, Mefloquine, Praziquantel, Ciprofloxacin, Clarithromycin, Prochlorperazine, Fluconazole 12) Currently taking hydroxychloroquine or having a clinical indication for taking hydroxychloroquine 13) Currently breastfeeding 14) Unable to be followed-up during the trial 15) Current or future involvement in the active treatment phase of other interventional research studies (excluding observational/non-interventional studies) before study follow-up visit 16) Not able to use or have access to a modern phone device/web-based technology 17) Any other clinical reason which may preclude entry in the opinion of the investigator INTERVENTION AND COMPARATOR: Interventions being evaluated are: A) Daily hydroxychloroquine or B) Weekly hydroxychloroquine or C) Placebo The maximum treatment period is approximately 13 weeks per participant. Hydroxychloroquine-identical matched placebo tablets will ensure that all participants are taking the same number and dosing regimen of tablets across the three trial arms. There is no variation in the dose of hydroxychloroquine by weight. The dosing regimen for the three arms of the study (A, B, C) are described in further detail below. Arm A: Active Hydroxychloroquine (- daily dosing and placebo-matched hydroxychloroquine - weekly dosing). Form: Tablets Route: Oral. Dose and Frequency: Active hydroxychloroquine: Days 1-2: Loading phase - 400mg (2 x 200mg tablets) taken twice a day for 2 days Days 3 onwards: Maintenance Phase - 200mg (1 x 200mg tablet) taken once daily, every day for 90 days (~3 months) Matched Placebo hydroxychloroquine: Days 3 onwards: Maintenance Phase - 2 tablets taken once a week on the same day each week (every 7th day) for 90 days (~3 months) Arm B: Active Hydroxychloroquine (- weekly dosing and placebo matched hydroxychloroquine - daily dosing.) Form: Tablets Route: Oral. Dose and Frequency: Active hydroxychloroquine: Days 1-2: Loading Phase - 400mg (2 x 200mg tablets) taken twice daily for 2 days Days 3 onwards: Maintenance Phase - 400mg (2 x 200mg tablets) taken once a week on the same day each week (every 7th day) for 90 days (~3 months) Matched Placebo hydroxychloroquine: Days 3 onwards: Maintenance Phase - 1 tablet taken once daily for 90 days (~3 months) Arm C: Matched placebo Hydroxychloroquine (- daily dosing and matched placebo hydroxychloroquine - weekly dosing.) Form: Table. Route: Oral. Frequency: Matched placebo hydroxychloroquine - daily dosing: Days 1-2: Loading Phase - 2 tablets taken twice daily for 2 days Days 3 onwards: Maintenance Phase - 1 tablet taken once daily for 90 days (~3 months) Matched placebo hydroxychloroquine - weekly dosing: Days 3 onwards: Maintenance Phase - 2 tablets taken once a week on the same day each week (every 7th day) for 90 days (~3 months) A schematic of the dosing schedule can be found in the full study protocol (Additional File 1). MAIN OUTCOMES: Time to diagnosis of positive COVID-19 disease (defined by record of date of symptoms onset and confirmed by laboratory test) RANDOMISATION: Participants will be randomised to either hydroxychloroquine dosed daily with weekly placebo, HCQ dosed weekly with daily placebo, or placebo dosed daily and weekly. Randomisation will be in a 3:3:2 ratio [hydroxychloroquine-(daily), hydroxychloroquine-(weekly), placebo], using stratified block randomisation. Random block sizes will be used, and stratification will be by study site. BLINDING (MASKING): Participants and trial investigators consenting participants, delivering trial assessments and procedures will be blinded to intervention. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A sufficient number of participants will be enrolled so that approximately 1000 participants in total will have data suitable for the primary statistical analysis. It is anticipated that approximately 1,200 participants will need to be enrolled in total, to allow for a 20% dropout over the period of the trial. This would result in approximately 450:450:300 participants randomised to hydroxychloroquine daily, hydroxychloroquine weekly+daily matched placebo or matched-placebo daily and weekly. TRIAL STATUS: V 1.0, 7th April 2020 EU Clinical Trials Register EudraCT Number: 2020-001331-26 Date of registration: 14th April 2020 Trial registered before first participant enrolment. Trial site is Cambridge University Hospitals NHS Foundation Trust. Recruitment started on 11th May 2020. It is anticipated that the trial will run for 12 months. The recruitment end date cannot yet be accurately predicted. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).", "doc_id": "2wb007gf"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Is there any supportive evidence for low dose radiotherapy for COVID-19 pneumonia?", "abstract": "Since early April 2020, there has been intense debate over proposed clinical use of ionizing radiation to treat life-threatening pneumonia in Coronavirus Disease 2019 (COVID-19) patients. At least twelve relevant papers appeared by 20 May 2020. The radiation dose proposed for clinical trials are a single dose (0.1-1 Gy) or two doses (a few mGy followed by 0.1-0.25 Gy involving a putative adaptive response, or 1-1.5 Gy in two fractions 2-3 days apart). The scientific rationale for such proposed so-called low dose radiotherapy (LDRT) is twofold (note that only doses below 0.1 Gy are considered as low doses in the field of radiation protection, but here we follow the term as conventionally used in the field of radiation oncology). Firstly, the potentially positive observations in human case series and biological studies in rodent models on viral or bacterial pneumonia that were conducted in the pre-antibiotic era. Secondly, the potential anti-inflammatory properties of LDRT, which have been seen when LDRT is applied locally to subacute degenerative joint diseases, mainly in Germany. However, the human and animal studies cited as supportive evidence have significant limitations, and whether LDRT produces anti-inflammatory effects in the inflamed lung or exacerbates ongoing COVID-19 damage remains unclear. Therefore, we conclude that the available scientific evidence does not justify clinical trials of LDRT for COVID-19 pneumonia, with unknown benefit and known mortality risks from radiogenic cancer and circulatory disease. Despite the significant uncertainties in these proposals, some clinical trials are ongoing and planned. This paper gives an overview of current situations surrounding LDRT for COVID-19 pneumonia.", "doc_id": "1zti6kin"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Efficient adaptive designs for clinical trials of interventions for COVID-19", "abstract": "The COVID-19 pandemic has led to an unprecedented response in terms of clinical research activity. An important part of this research has been focused on randomized controlled clinical trials to evaluate potential therapies for COVID-19. The results from this research need to be obtained as rapidly as possible. This presents a number of challenges associated with considerable uncertainty over the natural history of the disease and the number and characteristics of patients affected, and the emergence of new potential therapies. These challenges make adaptive designs for clinical trials a particularly attractive option. Such designs allow a trial to be modified on the basis of interim analysis data or stopped as soon as sufficiently strong evidence has been observed to answer the research question, without compromising the trial's scientific validity or integrity. In this paper we describe some of the adaptive design approaches that are available and discuss particular issues and challenges associated with their use in the pandemic setting. Our discussion is illustrated by details of four ongoing COVID-19 trials that have used adaptive designs.", "doc_id": "pbk4kplv"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Evaluating the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in severely ill adults with COVID-19: A structured summary of a study protocol for a randomized controlled trial", "abstract": "OBJECTIVES: The aim of this study is to evaluate the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in hospitalized adults with severe SARS-CoV-2 infection. TRIAL DESIGN: This is a prospective, single-center, phase 2, randomized, controlled trial that is blinded to participants and clinical outcome assessor. PARTICIPANTS: Eligible participants include adults (≥ 18 years) with evidence of SARS-CoV-2 infection by PCR test of nasopharyngeal or oropharyngeal swab within 14 days of randomization, evidence of infiltrates on chest radiography, peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air, and/or need for supplemental oxygen, non-invasive mechanical ventilation, or invasive mechanical ventilation, who are willing and able to provide written informed consent prior to performing study procedures or who have a legally authorized representative available to do so. Exclusion criteria include participation in another clinical trial of anti-viral agent(s)* for coronavirus disease-2019 (COVID-19), receipt of any anti-viral agent(s)* with possible activity against SARS-CoV-2 <24 hours prior to plasma infusion, mechanical ventilation (including extracorporeal membrane oxygenation [ECMO]) for ≥ 5 days, severe multi-organ failure, history of allergic reactions to transfused blood products per NHSN/CDC criteria, known IgA deficiency, and pregnancy. Included participants will be hospitalized at the time of randomization and plasma infusion. *Use of remdesivir as treatment for COVID-19 is permitted. The study will be undertaken at Columbia University Irving Medical Center in New York, USA. INTERVENTION AND COMPARATOR: The investigational treatment is anti-SARS-CoV-2 human convalescent plasma. To procure the investigational treatment, volunteers who recovered from COVID-19 will undergo testing to confirm the presence of anti-SARS-CoV-2 antibody to the spike trimer at a 1:400 dilution. Donors will also be screened for transfusion-transmitted infections (e.g. HIV, HBV, HCV, WNV, HTLV-I/II, T. cruzi, ZIKV). If donors have experienced COVID-19 symptoms within 28 days, they will be screened with a nasopharyngeal swab to confirm they are SARS-CoV-2 PCR-negative. Plasma will be collected using standard apheresis technology by the New York Blood Center. Study participants will be randomized in a 2:1 ratio to receive one unit (200 - 250 mL) of anti-SARS-CoV-2 plasma versus one unit (200 - 250 mL) of the earliest available control plasma. The control plasma cannot be tested for presence of anti-SARS-CoV-2 antibody prior to the transfusion, but will be tested for anti- SARS-CoV-2 antibody after the transfusion to allow for a retrospective per-protocol analysis. MAIN OUTCOMES: The primary endpoint is time to clinical improvement. This is defined as time from randomization to either discharge from the hospital or improvement by one point on the following seven-point ordinal scale, whichever occurs first. 1. Not hospitalized with resumption of normal activities 2. Not hospitalized, but unable to resume normal activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, requiring high-flow oxygen therapy or non-invasive mechanical ventilation 6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both 7. Death This scale, designed to assess clinical status over time, was based on that recommended by the World Health Organization for use in determining efficacy end-points in clinical trials in hospitalized patients with COVID-19. A recent clinical trial evaluating the efficacy and safety of lopinavir- ritonavir for patients hospitalized with severe COVID-19 used a similar ordinal scale, as have recent clinical trials of novel therapeutics for severe influenza, including a post-hoc analysis of a trial evaluating immune plasma. The primary safety endpoints are cumulative incidence of grade 3 and 4 adverse events and cumulative incidence of serious adverse events during the study period. RANDOMIZATION: Study participants will be randomized in a 2:1 ratio to receive anti-SARS-CoV-2 plasma versus control plasma using a web-based randomization platform. Treatment assignments will be generated using randomly permuted blocks of different sizes to minimize imbalance while also minimizing predictability. BLINDING (MASKING): The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment. The blood bank and the clinical research team will not be blinded to group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): We plan to enroll 129 participants, with 86 in the anti-SARS-CoV-2 arm, and 43 in the control arm. Among the participants, we expect ~70% or n = 72 will achieve clinical improvement. This will yield an 80% power for a one-sided Wald test at 0.15 level of significance under the proportional hazards model with a hazard ratio of 1.5. TRIAL STATUS: Protocol AAAS9924, Version 17APR2020, 4/17/2020 Start of recruitment: April 20, 2020 Recruitment is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04359810 Date of trial registration: April 24, 2020 Retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of 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.", "doc_id": "2j3kdvva"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Reducing mortality and morbidity in patients with severe COVID-19 disease by advancing ongoing trials of Mesenchymal Stromal (stem) Cell (MSC) therapy - Achieving global consensus and visibility for cellular host-directed therapies", "abstract": "As of May 17th 2020, the novel coronavirus disease 2019 (COVID-19) pandemic has caused 307,395 deaths worldwide, out of 3,917,366 cases reported to the World Health Organization. No specific treatments for reducing mortality or morbidity are yet available. Deaths from COVID-19 will continue to rise globally until effective and appropriate treatments and/or vaccines are found. In search of effective treatments, the global medical, scientific, pharma and funding communities have rapidly initiated over 500 COVID-19 clinical trials on a range of antiviral drug regimens and repurposed drugs in various combinations. A paradigm shift is underway from the current focus of drug development targeting the pathogen, to advancing cellular Host-Directed Therapies (HDTs) for tackling the aberrant host immune and inflammatory responses which underlie the pathogenesis of SARS-CoV-2 and high COVID-19 mortality rates. We focus this editorial specifically on the background to, and the rationale for, the use and evaluation of mesenchymal stromal (Stem) cells (MSCs) in treatment trials of patients with severe COVID-19 disease. Currently, the ClinicalTrials.gov and the WHO Clinical Trials Registry Platform (WHO ICTRP) report a combined 28 trials exploring the potential of MSCs or their products for treatment of COVID-19. MSCs should also be trialed for treatment of other circulating WHO priority Blueprint pathogens such as MERS-CoV which causes upto 34% mortality rates. It's about time funding agencies invested more into development MSCs per se, and also for a range of other HDTs, in combination with other therapeutic interventions. MSC therapy could turn out to be an important contribution to bringing an end to the high COVID-19 death rates and preventing long-term functional disability in those who survive disease.", "doc_id": "foty1t0j"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Azithromycin added to hydroxychloroquine for patients admitted to intensive care due to coronavirus disease 2019 (COVID-19)-protocol of randomised controlled trial AZIQUINE-ICU", "abstract": "BACKGROUND: Novel coronavirus SARS-CoV-2 is known to be susceptible in vitro to exposure to hydroxychloroquine and its effect has been found to be potentiated by azithromycin. We hypothesise that early administration of hydroxychloroquine alone or in combination with azithromycin can prevent respiratory deterioration in patients admitted to intensive care due to rapidly progressive COVID-19 infection. METHODS: Design: Prospective, multi-centre, double-blind, randomised, controlled trial (RCT). PARTICIPANTS: Adult (> 18 years) within 24 h of admission to the intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria include duration symptoms of febrile disease for ≥ 1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, and pregnancy. INTERVENTIONS: Patients will be randomised in 1:1:1 ratio to receive Hydroxychloroquine 800 mg orally in two doses followed by 400 mg daily in two doses and azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or hydroxychloroquine + placebo (HC group) or placebo + placebo (C-group) in addition to the best standard of care, which may evolve during the trial period but will not differ between groups. Primary outcome is the composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. SECONDARY OUTCOMES: The percentage of patients who were prevented from needing intubation until day 14, ICU length of stay, and mortality (in hospital) at day 28 and 90. DISCUSSION: Although both investigational drugs are often administered off label to patients with severe COVID-19, at present, there is no data from RCTs on their safety and efficacy. In vitro and observational trial suggests their potential to limit viral replication and the damage to lungs as the most common reason for ICU admission. Therefore, patients most likely to benefit from the treatment are those with severe but early disease. This trial is designed and powered to investigate whether the treatment in this cohort of patients leads to improved clinical patient-centred outcomes, such as mechanical ventilation-free survival. TRIAL REGISTRATION: Clinical trials.gov: NCT04339816 (Registered on 9 April 2020, amended on 22 June 2020); Eudra CT number: 2020-001456-18 (Registered on 29 March 2020).", "doc_id": "05vb2ib8"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "[A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19]", "abstract": "OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in the treatment of patients with moderate coronavirus disease 2019 (COVID-19). METHODS: We prospectively enrolled 30 treatment-na\u00efve patients with confirmed COVID-19 after informed consent at Shanghai Public Health Clinical Center. The patients were randomized 1\u00ef\u00bc\u009a1 to HCQ group and the control group. Patients in HCQ group were given HCQ 400 mg per day for 5 days plus conventional treatments, while those in the control group were given conventional treatment only. The primary endpoint was negative conversion rate of SARS-CoV-2 nucleic acid in respiratory pharyngeal swab on days 7 after randomization. This study has been approved by the Ethics Committee of Shanghai Public Health Clinical Center and registered online (NCT04261517). RESULTS: One patient in HCQ group developed to severe during the treatment. On day 7, nucleic acid of throat swabs was negative in 13 (86.7%) cases in the HCQ group and 14 (93.3%) cases in the control group (P>0.05). The median duration from hospitalization to virus nucleic acid negative conservation was 4 (1,9) days in HCQ group, which is comparable to that in the control group [2 (1,4) days, Z=1.27, P>0.05]. The median time for body temperature normalization in HCQ group was 1 (0,2) day after hospitalization, which was also comparable to that in the control group [1 (0,3) day]. Radiological progression was shown on CT images in 5 cases (33.3%) of the HCQ group and 7 cases (46.7%) of the control group, and all patients showed improvement in follow-up examinations. Four cases (26.7%) of the HCQ group and 3 cases (20%) of the control group had transient diarrhea and abnormal liver function (P>0.05). CONCLUSIONS: The prognosis of COVID-19 moderate patients is good. Larger sample size study are needed to investigate the effects of HCQ in the treatment of COVID-19. Subsequent research should determine better endpoint and fully consider the feasibility of experiments such as sample size.", "doc_id": "bz6zl416"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Imaging features and mechanisms of novel coronavirus pneumonia (COVID-19): Study Protocol Clinical Trial (SPIRIT Compliant)", "abstract": "INTRODUCTION: A novel coronavirus, tentatively designated as 2019 Novel Coronavirus (2019-nCoV), now called severe acute respiratory syndrome coronavirus 2, emerged in Wuhan, China, at the end of 2019 and which continues to expand. On February 11, 2020, the World Health Organization (WHO) named the disease coronavirus disease 2019 (COVID-19). On February 28, WHO increased our assessment of the risk of spread and the risk of impact of COVID-19 to very high at a global level. The COVID-19 poses significant threats to international health.Computed tomography (CT) has been an important imaging modality in assisting in the diagnosis and management of patients withCOVID-19. Some retrospective imaging studies have reported chest CT findings of COVID-19 in the past 2 months, suggesting that several CT findings may be characteristic. To our knowledge, there has been no prospective multicentre imaging study of COVID-19 to date.We proposed a hypothesis: There are some specific CT features on Chest CT of COVID-19 patients. And the mechanism of these CT features is explicable based on pathological findings. OBJECTIVE: To investigate the specific CT features of COVID-19 and the formation mechanism of these CT features. METHOD: This study is a prospective multicenter observational study. We will recruit 100 patients with COVID-19 at 55 hospitals. All patients undergo chest CT examination with the same scan protocol. The distribution and morphology of lesions on chest CT, clinical data will be recorded. A number of patients will be pathologically examined after permission is granted. The data of these three aspects will be analyzed synthetically. DISCUSSION: This study will help us to identify the chest CT features of COVID-19 and its mechanism. ETHICS AND DISSEMINATION: This retrospective study was approved by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University (No. 2020-140). Written informed consent will be obtained from all study participants prior to enrollment in the study. To protect privacy of participants, all private information were kept anonymous. The results will be published in a peer-reviewed journal and will be disseminated electronically and in print regardless of results.", "doc_id": "8sleups8"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Clinical trials during COVID-19", "abstract": "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.", "doc_id": "2a7t447d"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19", "abstract": "BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).", "doc_id": "3736nxgo"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Controlled, double-blind, randomized trial to assess the efficacy and safety of hydroxychloroquine chemoprophylaxis in SARS CoV2 infection in healthcare personnel in the hospital setting: A structured summary of a study protocol for a randomised controlled trial", "abstract": "BACKGROUND: SARS-CoV-2 infection presents a high transmission in the group of health professionals in Spain (12-15% infected). Currently there is no accepted chemoprophylaxis but hydroxychloroquine (HDQ) is known to inhibit the coronavirus in vitro. Our hypothesis is that oral administration of hydroxychloroquine to healthcare professionals can reduce the incidence and prevalence of infection as well as its severity in this group. METHODS: Design: Prospective, single center, double blind, randomised, controlled trial (RCT). PARTICIPANTS: Adult health-care professionals (18-65 years) working in areas of high exposure and high risk of transmission of SARS-COV-2 (COVID areas, Intensive Care Unit -ICUs-, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. Exclusion criteria include previous infection with SARS CoV2 (positive SARS-CoV-2 PCR or IgG serology), pregnancy or lactation, any contraindication to hydroxychloroquine or evidence of unstable or clinically significant systemic disease. INTERVENTIONS: Patients will be randomized (1:1) to receive once-daily oral Hydroxychloroquine 200mg for two months (HC group) or placebo (P group) in addition to the protective measures appropriate to the level of exposure established by the hospital. A serological evaluation will be carried out every 15 days with PCR in case of seroconversion, symptoms or risk exposure. Primary outcome is the percentage of subjects presenting infection (seroconversion and/or PCR +ve) by the SARS-Cov-2 virus during the observation period. Additionally, both the percentage of subjects in each group presenting Pneumonia with severity criteria (Curb 65 ≥2) and that of subjects requiring admission to ICU will be determined. DISCUSSION: While awaiting a vaccine, hygiene measures, social distancing and personal protective equipment are the only primary prophylaxis measures against SARS-CoV-2, but they have not been sufficient to protect our healthcare professionals. Some evidence of the in vitro efficacy of hydroxychloroquine against this virus is known, along with some clinical data that would support the study of this drug in the chemoprophylaxis of infection. However, there are still no data from controlled clinical trials in this regard. If our hypothesis is confirmed, hydroxychloroquine can help professionals fight this infection with more guarantees. PARTICIPANTS: This is a single-center study that will be carried out at the Marqu\u00e9s de Valdecilla University Hospital. 450 health professionals working at the Hospital Universitario Marqu\u00e9s de Valdecilla in areas of high exposure and high risk of transmission of SARS COV2 (COVID hospital areas, Intensive Care Unit, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. INCLUSION CRITERIA: 1) Health professionals aged between 18 and 65 years (inclusive) at the time of the first screening visit; 2) They must provide signed written informed consent and agree to comply with the study protocol; 3) Active work in high exposure areas during the last two weeks and during the following weeks. EXCLUSION CRITERIA: 1) Previous infection with SARS CoV2 (positive coronavirus PCR or positive serology with SARS Cov2 negative PCR and absence of symptoms); 2) Current treatment with hydroxychloroquine or chloroquine; 3) Hypersensitivity, allergy or any contraindication for taking hydroxychloroquine, in the technical sheet; 4) Previous or current treatment with tamoxifen or raloxifene; 5) Previous eye disease, especially maculopathy; 6) Known heart failure (Grade III to IV of the New York Heart Association classification) or prolonged QTc; 7) Any type of cancer (except basal cell) in the last 5 years; 6) Refusal to give informed consent; 8) Evidence of any other unstable or clinically significant untreated immune, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric illness; 9) Antibodies positive for the human immunodeficiency virus; 10) Significant kidney or liver disease; 11) Pregnancy or lactation. INTERVENTION AND COMPARATOR: Two groups will be analyzed with a 1: 1 randomization rate. 1)Intervention: (n = 225): One 200 mg hydroxychloroquine sulfate coated tablet once daily for two months.2)Comparator (control group) (n = 225): One hydroxychloroquine placebo tablet (identical to that of the drug) once daily for two months MAIN OUTCOMES: The primary outcome of this study will be to evaluate: number and percentage of healthcare personnel presenting symptomatic and asymptomatic infection (see \"Diagnosis of SARS CoV2 infection\" below) by the SARS-Cov2 virus during the study observation period (8 weeks) in both treatment arms;number and percentage of healthcare personnel in each group presenting with Pneumonia with severity criteria (Curb 65 ≥2) and number and percentage of healthcare personnel requiring admission to the Intensive Care Unit (ICU) in both treatment arms. DIAGNOSIS OF SARS COV2 INFECTION: Determination of IgA, IgM and IgG type antibodies against SARS-CoV-2 using the Anti-SARS-CoV-2 ELISA kit (EUROIMMUN Medizinische Labordiagnostika AG, Germany) every two weeks. In cases of seroconversion, a SARS-CoV-2 PCR will be performed to rule out / confirm an active infection (RT-PCR in One Step: RT performed with mastermix (Takara) and IDT probes, following protocol published and validated by the CDC Evaluation of COVID-19 in case of SARS-CoV-2 infection RANDOMISATION: Participants will be allocated to intervention and comparator groups according to a balanced randomization scheme (1: 1). The assignment will be made through a computer-generated numeric sequence for all participants BLINDING (MASKING): Both participants and investigators responsible for recruiting and monitoring participants will be blind to the assigned arm. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Taking into account the current high prevalence of infection in healthcare personnel in Spain (up to 15%), to detect a difference equal to or greater than 8% in the percentage estimates through a two-tailed 95% CI, with a statistical power of 80% and a dropout rate of 5%, a total of 450 participants will need to be included (250 in each arm). TRIAL STATUS: The protocol approved by the health authorities in Spain (Spanish Agency for Medicines and Health Products \"AEMPS\") and the Ethics and Research Committee of Cantabria (CEIm Cantabria) corresponds to version 1.1 of April 2, 2020. Currently, recruitment has not yet started, with the start scheduled for the second week of May 2020. TRIAL REGISTRATION: Eudra CT number: 2020-001704-42 (Registered on 29 March 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).", "doc_id": "6t33qfea"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "A snapshot of the ongoing clinical research on COVID-19", "abstract": "The pandemic of coronavirus disease 2019 (COVID-19) presents an unprecedented challenge to rapidly develop new diagnostic, preventive and therapeutic strategies. Currently, thousands of new COVID-19 patients are quickly enrolled in clinical studies. We aimed to investigate the characteristics of the COVID-19 studies registered in ClinicalTrials.gov and report the extent to which they have incorporated features that are desirable for generating high-quality evidence. On April 28, 2020, a total of 945 studies on COVID-19 have been registered in ClinicalTrials.gov; 586 studies are interventional (62.0%), the most frequent allocation scheme is the parallel group assignment (437; 74.6%), they are open-label and the most common primary purpose is the research on treatment. Too many of the ongoing interventional studies have a small expected sample size and may not generate credible evidence at completion. This might lead to a delayed recognition of effective therapies that are urgently needed, and a waste of time and resources. In the COVID-19 pandemic era, it is crucial that the adoption of new diagnostic, preventive and therapeutic strategies is based upon evidence coming from well-designed, adequately powered and carefully conducted clinical trials.", "doc_id": "qnauff3t"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Effect of hydroxychloroquine on prevention of COVID-19 virus infection among healthcare professionals: a structured summary of a study protocol for a randomised controlled trial", "abstract": "OBJECTIVES: Comparison of the effect of hydroxychloroquine with placebo to prevent infection from the COVID -19 virus among healthcare professionals TRIAL DESIGN: Single centre, 2-arm, double-blind randomised (ratio 1:1) placebo-controlled trial PARTICIPANTS: Treatment staff who are in contact with patients and have at least 3 shifts a week in Arash hospital affiliated with Tehran University of Medical Sciences, in Iran and who consent to participate in the study. Exclusion criteria include: History of COVID -19 virus infection, clinical symptoms such as fever, nausea, dyspnea and myalgia in the past two months, history of underlying diseases hypersensitivity to hydroxychloroquine and G6PD enzyme deficiency. INTERVENTION AND COMPARATOR: Intervention group: Hydroxychloroquine 200 mg tablet of Amin Pharmaceutical. CONTROL GROUP: placebo which is completely similar in form and taste to 200 mg hydroxychloroquine tablet and is manufactured by the same factory (Amin Pharmacy). The dosage is two tablets daily, once a week for one to three months (based on the duration of the Coronavirus epidemic in Tehran). MAIN OUTCOMES: Confirmed COVID-19 virus infection using Polymerase chain reaction (PCR) test is the primary outcome. The time period for measuring the primary outcome is any infection within the trial period up to one month after taking the last dose. RANDOMISATION: The randomized block allocation method was developed using Stata version 15 software by an independent researcher, using a block size of six. Allocation to the two treatment groups will be conducted by this researcher using paper labels (random 10-digit codes) in a 1:1 ratio t The labels will be attached to the drug packages in order of randomization. Drug packages will be arranged in a box according to the randomization list. BLINDING (MASKING): Participants and caregivers are blinded to group assignment and the data will be analyzed by an independent statistical expert who is unaware of the treatment allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 282 participants will be randomised with 141 participants the Hydroxychloroquineeach intervention group and 141 participants to the placebo control group TRIAL STATUS: The protocol version number is 99-1-101-47091 and the approval ID is IR.TUMS.VCR.REC.1399.001 and recruitment began April 7, 2020, and is anticipated to be complete by August 7, 2020. TRIAL REGISTRATION: The name of the trial register is Iranian registry of clinical trial (IRCT), registration number is IRCT20120826010664N6, date of trial registration is April 7, 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.", "doc_id": "fpui9i7z"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Clinical trials for inflammatory bowel disease: a global guidance during COVID-19 pandemic", "abstract": "The severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]-causing coronavirus disease [COVID]-19 pandemic poses major challenges for patients with inflammatory bowel disease to be recruited and maintained in clinical trials. However, clinical trials offer patients who have failed multiple drugs access to study medications with alternative mode of action and the potential for relief from inflammation-mediated symptoms. Therefore, the continuation of clinical trials in IBD during the COVID-19 pandemic is important both for participants and the community of IBD patients, due to the dire need of an expanded therapeutic armamentarium. As the safety of patients in clinical trials is the leading principle, we are providing ten specific rules to guide patients and principal investigators safely through the challenging time.", "doc_id": "m23mvaf7"} {"topic_name": "coronavirus clinical trials", "topic_id": "17", "title": "Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial", "abstract": "Importance: There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. Objective: To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. Design, Setting, and Participants: This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Interventions: Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). Main Outcomes and Measures: Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Results: Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). Conclusions and Relevance: The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04323527.", "doc_id": "l40d82vq"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Bacteria bound to cloth; glucoprotamin; toluidine blue O; surgical helmets versus filtering masks", "abstract": "", "doc_id": "ew41z7wh"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Supporting the Health Care Workforce During the COVID-19 Global Epidemic.", "abstract": "", "doc_id": "pieqxttn"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "The Practice of Wearing Surgical Masks during the COVID-19 Pandemic.", "abstract": "", "doc_id": "hrhervi4"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Americans are told to wear cloth masks.", "abstract": "", "doc_id": "gk2ttxjs"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Facemasks for the prevention of infection in healthcare and community settings.", "abstract": "Facemasks are recommended for diseases transmitted through droplets and respirators for respiratory aerosols, yet recommendations and terminology vary between guidelines. The concepts of droplet and airborne transmission that are entrenched in clinical practice have recently been shown to be more complex than previously thought. Several randomised clinical trials of facemasks have been conducted in community and healthcare settings, using widely varying interventions, including mixed interventions (such as masks and handwashing), and diverse outcomes. Of the nine trials of facemasks identified in community settings, in all but one, facemasks were used for respiratory protection of well people. They found that facemasks and facemasks plus hand hygiene may prevent infection in community settings, subject to early use and compliance. Two trials in healthcare workers favoured respirators for clinical respiratory illness. The use of reusable cloth masks is widespread globally, particularly in Asia, which is an important region for emerging infections, but there is no clinical research to inform their use and most policies offer no guidance on them. Health economic analyses of facemasks are scarce and the few published cost effectiveness models do not use clinical efficacy data. The lack of research on facemasks and respirators is reflected in varied and sometimes conflicting policies and guidelines. Further research should focus on examining the efficacy of facemasks against specific infectious threats such as influenza and tuberculosis, assessing the efficacy of cloth masks, investigating common practices such as reuse of masks, assessing compliance, filling in policy gaps, and obtaining cost effectiveness data using clinical efficacy estimates.", "doc_id": "n3g5a2fg"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "High-Risk Aerosol-Generating Procedures in COVID-19: Respiratory Protective Equipment Considerations.", "abstract": "The correct selection and utilization of respiratory personal protective equipment is of the utmost importance in the current COVID-19 pandemic. This is especially true for health care workers exposed to high-risk aerosol-generating procedures, including otolaryngologists, ophthalmologists, neurosurgeons, maxillofacial surgeons, and laparoscopic surgeons. This communication provides a review of approved forms of respiratory protection and compares their characteristics, including surgical masks, N95 respirator, elastomeric respirators, powered air-purifying respirators, and controlled air-purifying respirators. For standard airborne precautions, N95 respirator are appropriate for respiratory protection. However, high-risk aerosol-generating procedures may create aerosolization of high viral loads that represent increased risk to health care workers. In these situations, enhanced respiratory protection with filters certified as 99, 100, or HEPA (high-efficiency particulate air) may be appropriate.", "doc_id": "4pkzbw6k"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "A randomized clinical trial of three options for N95 respirators and medical masks in health workers.", "abstract": "RATIONALE We compared three policy options for the use of medical masks and N95 respirators in healthcare workers (HCWs). OBJECTIVES A cluster randomized clinical trial of 1,669 hospital-based HCWs in Beijing, China in the winter of 2009-2010. METHODS Participants were randomized to medical masks, N95 respirators, or targeted use of N95 respirators while doing high-risk procedures or barrier nursing. Outcomes included clinical respiratory illness (CRI) and laboratory-confirmed respiratory pathogens in symptomatic subjects. MEASUREMENTS AND MAIN RESULTS The rate of CRI was highest in the medical mask arm (98 of 572; 17%), followed by the targeted N95 arm (61 of 516; 11.8%), and the N95 arm (42 of 581; 7.2%) (P < 0.05). Bacterial respiratory tract colonization in subjects with CRI was highest in the medical mask arm (14.7%; 84 of 572), followed by the targeted N95 arm (10.1%; 52 of 516), and lowest in the N95 arm (6.2%; 36 of 581) (P = 0.02). After adjusting for confounders, only continuous use of N95 remained significant against CRI and bacterial colonization, and for just CRI compared with targeted N95 use. Targeted N95 use was not superior to medical masks. CONCLUSIONS Continuous use of N95 respirators was more efficacious against CRI than intermittent use of N95 or medical masks. Most policies for HCWs recommend use of medical masks alone or targeted N95 respirator use. Continuous use of N95s resulted in significantly lower rates of bacterial colonization, a novel finding that points to more research on the clinical significance of bacterial infection in symptomatic HCWs. This study provides further data to inform occupational policy options for HCWs. Clinical trial registered with Australian New Zealand Clinical Trials Registry http://www.anzctr.org.au (ACTRN 12609000778280).", "doc_id": "e1mnj7bf"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "A quantitative assessment of the efficacy of surgical and N95 masks to filter influenza virus in patients with acute influenza infection.", "abstract": "We assessed the in vivo efficacy of surgical and N95 (respirator) masks to filter reverse transcription-polymerase chain reaction (RT-PCR)-detectable virus when worn correctly by patients with laboratory-confirmed acute influenza. Of 26 patients with a clinical diagnosis of influenza, 19 had the diagnosis confirmed by RT-PCR, and 9 went on to complete the study. Surgical and N95 masks were equally effective in preventing the spread of PCR-detectable influenza.", "doc_id": "0vlh67jw"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Modifying reusable elastomeric respirators to utilise breathing system filters with 3D printed adapters, a safe alternative to N95 during COVID-19", "abstract": "The COVID-19 pandemic has caused a worldwide shortage of personal protective equipment including N95 and FFP3 respirators. Reusable elastomeric respirators are suitable alternatives when used with compatible filters. These filters may be difficult to source and elastomeric respirators are not recommended for surgical use as the exhaled air is not filtered. Breathing system filters are routinely used in anaesthetic circuits to filter virus and bacteria. In this study, we designed 3D printed adapters that allowed elastomeric respirators to utilise breathing system filters and made simple modifications to the respirators to filter exhaled breaths. We then evaluated the performance and safety of our modified elastomeric respirators with quantitative fit tests. We recruited 8 volunteers to perform quantitative fit tests. Fit factors, respiratory rate and end-tidal carbon dioxide were recorded before and after wearing the modified respirators for 1 hour. All 8 volunteers obtained fit factors of 200+, the maximum achievable, for all tests exercises in all fit tests. The mean (range) end-tidal carbon dioxide was 4.5 (3.9-5.5) kPa and 4.6 (range 4.1-5.3) kPa before and after 1 hour of usage. The mean (range) respiratory rate was 16.5 (11-24) min-1 and 17.4 (15-22) min-1 before and after 1 hour of usage. Four (50%) did not experience any subjective discomfort while 2 (25%) reported pressure on the face, 1 (12.5%) reported exhalation resistance and 1 (12.5%) reported transient dizziness with exertion. Breathing system filters combined with properly fitted reusable elastomeric respirators is a safe alternative to N95 during the COVID-19 pandemic.", "doc_id": "ujk48pe7"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Commercially available endoscopy facemasks to prevent aerosolizing spread of droplets during COVID-19 outbreak", "abstract": "", "doc_id": "kqbck18f"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "A Scalable Method of Applying Heat and Humidity for Decontamination of N95 Respirators During the COVID-19 Crisis", "abstract": "A lack of N95 respirators during the COVID-19 crisis has placed healthcare workers at risk. It is important for any N95 reuse strategy to determine the effects that proposed protocols would have on the physical functioning of the mask, as well as the practical aspects of implementation. Here we propose and implement a method of heating N95 respirators with moisture (85{degrees}C, 60-85% humidity). We test both mask filtration efficiency and fit to validate this process. Our tests focus on the 3M 1860 and 3M 8210 Plus N95 models. After five cycles of the heating procedure, both respirators pass quantitative fit testing (score of >100) and show no degradation of mask filtration efficiency. We also test the Chen Heng V9501 KN95 and HKYQ N95 finding no degradation of mask filtration efficiency, however even for unheated masks these scored <50 for every fit test. The heating method presented here is scalable from individual masks to over a thousand a day with a single industrial convection oven, making this method practical for local application inside health-care facilities.", "doc_id": "1l89qtfd"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Effect of gamma sterilization on filtering efficiency of various respiratory face-masks", "abstract": "Three types of respiratory masks viz N95, non-woven fabric and double layer cotton cloth are being used as an essential inhalation protective measure against COVID-19 by suppressing the entry of respiratory droplets. The filtering efficiency of these masks were tested before and after sterilisation using gamma radiation for the two flow rate conditions corresponding normal breath rate (20lpm) and during sneezing/coughing (90lpm).Sterilisation is carried out using a gamma irradiator containing Co-60 source for the two dose exposures viz. 15kGy and 25kGy. The filtering efficiency for surgical (non-woven fabric) and double layer cotton cloth mask is found to vary from 18% to 22% for the cumulative particle of size [\u2265] 0.3 micron in both un-irradiated and irradiated condition. The filtration efficiency of N95 mask is found to be reduced to 70% for the most penetrating particle size (0.3 micron) with the flow rate of 20lpm and further reduced for particles in the range of 0.1 and 0.2 micron with flow rate of 90 lpm. The reduction in efficiency after gamma sterilization is associated with reduction of electrostatic interaction of filter medium with particles laden in the air stream. Even with reduced filtering efficiency due to gamma sterilisation, the N95 masks are much superior than the surgical and cloth masks. Instead of disposing N95 mask after single use, they can be reused a few times as N70 mask during this pandemic crisis after sterilisation using gamma radiation.", "doc_id": "njei8dj8"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Informing Homemade Emergency Facemask Design: The Ability of Common Fabrics to Filter Ultrafine Particles", "abstract": "Objectives: To examine the ability of fabrics which might be used to create homemade face masks to filter out ultrafine (smaller than 1m in diameter) particles. Method: Twenty commonly available fabrics and materials were evaluated for their ability to reduce air concentrations of ultrafine particles. Further assessment was made on the filtration ability of select fabrics while damp and of fabric combinations which might be used to construct homemade masks. Results: Single fabric layers blocked a range of ultrafine particles. When fabrics were layered, significantly more ultrafine particles were filtered. Several fabric combinations were successful in removing similar amounts of ultrafine particles when compared to an N95 mask and surgical mask. Conclusions: The current coronavirus pandemic has left many communities without access to commercial facemasks. Our findings suggest that face masks made from layered common fabric can help filter ultrafine particles and provide some protection for the wearer when commercial facemasks are unavailable.", "doc_id": "51thatw6"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Characterization of a novel, low-cost, scalable vaporized hydrogen peroxide system for sterilization of N95 respirators and other COVID-19 related personal protective equipment.", "abstract": "Due to the virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for the respiratory disease termed COVID-19, there has been a significant increase in demand for surgical masks and N95 respirators in medical clinics as well as within communities operating during the COVID-19 epidemic. Thus, community members, business owners, and even medical personnel have resorted to alternative methods for sterilizing face coverings and N95 respirators for reuse. While significant work has shown that vaporized hydrogen peroxide (VHP) can be used to sterilize N95 respirators, the cost and installation time for these sterilization systems limit their accessibility. To this end, we have designed and constructed a novel, cost-effective, and scalable VHP system that can be used to sterilize N95 respirators and other face coverings for clinical and community applications. N95 respirators inoculated with P22 bacteriophage showed a greater than 6-log10 reduction in viral load when sterilized in the VHP system for one 60-minute cycle. Further, N95 respirators treated with 20 cycles in this VHP system showed comparable filtration efficiency to untreated N95 respirators in a 50 to 200 nanometer particulate challenge filtration test. While a 23% average increase in water droplet roll-off time was observed for N95 respirators treated with 5 cycles in the sterilization, no breakdown in fluid resistance was detected. These data suggest that our VHP system is effective in sterilizing N95 respirators and other polypropylene masks for reuse. Relating to the present epidemic, deployment of this system reduces the risk of COVID-19 community transmission while conserving monetary resources otherwise spent on the continuous purchase of disposable N95 respirators and other face coverings. In summary, this novel, scientifically validated sterilization system can be easily built at a low cost and implemented in a wide range of settings.", "doc_id": "dzfewoir"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Hydrogen Peroxide Vapor sterilization of N95 respirators for reuse", "abstract": "Abstract Reprocessing of used N95 respirators may ameliorate supply chain constraints during the COVID-19 pandemic and provide a higher filtration crisis alternative. The FDA Medical Countermeasures Initiative previously funded a study of HP vapor decontamination of respirators using a Clarus C system (Bioquell, Horsham, PA) which normally is used to fumigate hospital rooms. The process preserved respirator function, but it is unknown if HP vapor would be virucidal since respirators have porous fabric that may harbor virus. We evaluated the virucidal activity of HP vapor using a BQ-50 system (Bioquell, Horsham, PA) after inoculating 3M 1870 N95 respirators (3M, St. Paul, MN) with 3 aerosolized bacteriophage that are a reasonable proxy for SARS-CoV-2. Inoculation resulted in contamination of the respirator with 9.87e4 plaque forming units (PFU) of phage phi-6, 4.17e7 PFU of phage T7 and 1.35e7 PFU of phage T1. Respirators were reprocessed with BQ-50 with a long aeration phase to reduce HP vapors. Virucidal activity was measured by a standard plaquing assay prior to and after sterilization. A single HP vapor cycle resulted in complete eradication of phage from masks (limit of detection 10 PFU, lower than the infectious dose of the majority of respiratory viral pathogens). After 5 cycles, the respirators appeared similar to new with no deformity. Use of a Bioquell machine can be scaled to permit simultaneous sterilization of a large number of used but otherwise intact respirators. HP vapor reprocessing may ease shortages and provide a higher filtration crisis alternative to non-NIOSH masks.", "doc_id": "x3n6uj21"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "A Novel Questionnaire to Ergonomically Assess Respirators among Health Care Staff: Development and Validation", "abstract": "BACKGROUND: Health care workers are at a high risk of exposure to infectious diseases spread by airborne transmission. N95 respirators are the most common respirators used in the health care system and negligence in using them may cause health problems. Hence, more emphasis should be on ergonomic aspects of this mask. This study aimed to develop a tool for ergonomic evaluation of these respirators. MATERIALS AND METHODS: After reviewing previous studies and employees\u2019 problems in the use of the N95 respirators, 50 questionnaires were designed and their validity was assessed. Then, the questionnaire was completed by 290 staff members of Masih Daneshvari Hospital and its internal consistency and reproducibility were investigated using Cronbach\u2019s alpha coefficient and test-retest method, respectively. Confirmatory factor analysis was used to assess its consistency and internal consistency (construct validity). RESULTS: With the confirmation of the face and content validities, internal consistency (0.89) calculated by the Cronbach\u2019s alpha coefficient and reproducibility of the questionnaire (0.997; p<0.001) assessed by using the ICC Index, were approved. Following examining internal consistency and stability, the questionnaire convergent construct validity was also confirmed using confirmatory factor analysis. CONCLUSION: The questionnaire contained 42 items and it is beneficial to use it in the health care system to evaluate the ergonomic problems of the respirators and to have optimal choice in this respect. Also, it can be used in the promotion of the staffs\u2019 behavior in wearing these respirators when necessary.", "doc_id": "a3hogbee"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "[Rational use of respiratory protective equipment: advice for health care professionals in time of COVID-19].", "abstract": "The current COVID-19 pandemic has led to a worldwide shortage of respiratory protective equipment. In order to offer maximum protection against infection for all healthcare workers, we need to optimise our use of the available equipment. This article provides practical advice on which type of mask is indicated in what specific situation, what requirements the mask should meet and how to optimise the local workflow, including the re-use of masks after decontamination.", "doc_id": "nk95dyln"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Nasal plugs for preventing respiratory infections.", "abstract": "Nasal plugs were made from an N-95 respirator, surgical mask or a cotton ball and inserted into the nares of volunteer healthcare workers for 30 min. Initial and persistent respiratory resistance, choking sensation, and discomfort in the mouth and nose areas were recorded for the three different nasal plugs, the N-95 respirator and a surgical mask. Nasal plugs were more convenient and better tolerated than the masks. The ability of the nasal plug material to prevent infection by droplet transmission was also tested. A piece of each material was placed on a blood agar plate, the volunteer coughed onto the plate and the material was removed. Bacterial colonies only grew in the areas not previously covered by the nasal plug material. The cotton ball nasal plug is probably as effective as the N-95 respirator or surgical masks at preventing infection, and is much cheaper.", "doc_id": "z70oduir"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "FFP3, FFP2, N95, surgical masks and respirators: what should we be wearing for ophthalmic surgery in the COVID-19 pandemic?", "abstract": "", "doc_id": "8jc7971i"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Respiratory Protection Considerations for Healthcare Workers During the COVID-19 Pandemic", "abstract": "The COVID-19 pandemic has resulted in a surge of patients that exceeds available human and physical resources in many settings, triggering the implementation of crisis standards of care. High-quality respiratory protection is essential to reduce exposure among healthcare workers, yet dire shortages of personal protective equipment in the United States threaten the health and safety of this essential workforce. In the context of rapidly changing conditions and incomplete data, this article outlines 3 important strategies to improve healthcare workers' respiratory protection. At a minimum, healthcare workers delivering care to patients with confirmed or suspected COVID-19 should wear N95 respirators and full-face shields. Several mechanisms exist to boost and protect the supply of N95 respirators, including rigorous decontamination protocols, invoking the Defense Production Act, expanded use of reusable elastomeric respirators, and repurposing industrial N95 respirators. Finally, homemade facial coverings do not protect healthcare workers and should be avoided. These strategies, coupled with longer-term strategies of investments in protective equipment research, infrastructure, and data systems, provide a framework to protect healthcare workers immediately and enhance preparedness efforts for future pandemics.", "doc_id": "zbmncsw2"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Update to device-related pressure ulcers: SECURE prevention. COVID-19, face masks and skin damage", "abstract": "The 2019 novel coronavirus disease (COVID-19) pandemic has brought the effects of device-related pressure ulcers (DRPU) into sharp focus. With the increased use of personal protective equipment (PPE), including face masks, continuous positive airway pressure (CAPP) masks and other devices, the incidence of DRPUs among health professionals and patients alike has risen starkly. As such, the Journal of Wound Care (JWC) consensus document, Device-related pressure ulcers: SECURE prevention, published in February 2020, is more relevant than ever. To help support patients and frontline health professionals, JWC is republishing the consensus in a digital format, along with a new introductory article outlining the DRPU risks posed by PPE and other medical devices used by patients and health professionals during the pandemic, and how the skin damage can be avoided. The aim is to provide frontline staff with a clear, simple strategy on how to prevent the risk of personal skin damage and/or DRPU during the pandemic, as well as point them in the direction of more indepth guidance on long-term strategies for prevention, for both themselves and patients.", "doc_id": "xbjr0svq"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Reuse of N95 Masks", "abstract": "", "doc_id": "vqp5mhsk"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Recomendaciones de la Sociedad de Gastroenterolog\u00eda del Per\u00fa para evitar la propagaci\u00f3n del SARS-CoV-2 a trav\u00e9s de procedimientos de endoscop\u00eda digestiva./ [Recommendations of the Society of Gastroenterology of Peru to avoid the spread of SARS-CoV-2 through digestive endoscopy procedures]", "abstract": "The SARS-CoV-2 coronavirus produces the disease called COVID-19, currently spreading in a rapidly evolving pandemic. It can be transmitted by contact, drops and aerosols, and has been isolated from gastrointestinal secretions and faeces. During digestive endoscopy, transmission by any of these mechanisms could occur. It is recommended to limit digestive endoscopy to cases of digestive bleeding, severe dysphagia, foreign body in the digestive tract, biliary obstruction with intractable pain or cholangitis, pseudocyst or complicated encapsulated pancreatic necrosis, gastrointestinal obstruction, and cases at risk of deterioration over time. It is recommended to screen patients based on temperature, symptoms, and epidemiological factors to classify them according to their risk of infection. For procedures in low risk patients, personnel must wear a disposable gown, gloves, eye or face shield, standard surgical mask, disposable hat, disposable shoe covers. In cases of intermediate or high risk, or confirmed COVID-19, protection should be increased using disposable waterproof gown, N95 respirator or similar, and double glove. In case of shortage it may be necessary to reuse N95 respirators for up to 5 uses, following CDC recommendations for donning, removing and storing to prevent secondary contact contamination. Likewise, all protective equipment should be put on and removed according to CDC recommendations. The presence of personnel in endoscopy should be limited to the bare minimum. Said personnel must have daily temperature control and if it is above 37.3\u00baC, the corresponding evaluation must be carried out. After each procedure, the stretcher and room surfaces should be properly disinfected. High-level disinfection of endoscopes eliminates SARS-CoV-2.", "doc_id": "6d3z1c27"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Coronavirus disease 2019 (COVID-19) pandemic: International variation of personal protective equipment (PPE) and infection prevention and control (IPC) guidelines", "abstract": "", "doc_id": "g1h27n6s"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Use of Face Masks in COVID-19", "abstract": "", "doc_id": "8b9nn5vi"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Physical distancing, face masks, and eye protection for prevention of COVID-19", "abstract": "", "doc_id": "6y0vvogy"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "High-Risk Aerosol-Generating Procedures in COVID-19: Respiratory Protective Equipment Considerations", "abstract": "The correct selection and utilization of respiratory personal protective equipment is of the utmost importance in the current COVID-19 pandemic. This is especially true for health care workers exposed to high-risk aerosol-generating procedures, including otolaryngologists, ophthalmologists, neurosurgeons, maxillofacial surgeons, and laparoscopic surgeons. This communication provides a review of approved forms of respiratory protection and compares their characteristics, including surgical masks, N95 respirator, elastomeric respirators, powered air-purifying respirators, and controlled air-purifying respirators. For standard airborne precautions, N95 respirator are appropriate for respiratory protection. However, high-risk aerosol-generating procedures may create aerosolization of high viral loads that represent increased risk to health care workers. In these situations, enhanced respiratory protection with filters certified as 99, 100, or HEPA (high-efficiency particulate air) may be appropriate.", "doc_id": "ftd24d5z"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Why not use the Easybreath snorkeling mask to prevent COVID-19 transmission during endoscopy procedures when FFP2 are lacking?", "abstract": "", "doc_id": "fb5ycn64"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Medical mask with plasma sterilizing layer", "abstract": "In this brief report we propose a new design of a medical mask with a plasma layer, which provides both additional air filtration from microdrops, bacteria and viruses due to the electrostatic effect and self-disinfecting of surfaces by a pulsed barrier discharge. The key features of the mask are the mutual arrangement of the layers, the direction of air flows and the synchronization of the discharge with respiration, which ensures the safe wearing of the mask and high degree of protection against pathogenic microorganisms.", "doc_id": "lwt83ts2"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Evaluation of the rationale for concurrent use of N95 filtering facepiece respirators with loose-fitting powered air-purifying respirators during aerosol-generating medical procedures", "abstract": "The concurrent use of N95 filtering facepiece respirators with powered air-purifying respirators during aerosol-generating medical procedures in patients with severe respiratory pathogens has been promoted as offering additional protection against infectious agents. The purpose of this article is to examine the impact of this additional respiratory equipment upon protection and personal performance. The presumed additive protective effect of an N95 filtering facepiece respirator used concurrently with a powered air-purifying respirator has not been subjected to rigorous scientific investigation. The burden imposed by additional respiratory protective equipment should not be discounted, and the potentially minor contribution to protection may be offset by the negative impact on personal performance. Novel uses of protective equipment occasionally are spawned during crisis situations, but their generalized applicability to healthcare workers should ultimately be evidence-based.", "doc_id": "89qf438h"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Dispersal of Respiratory Droplets With Open vs Closed Oxygen Delivery Masks Implications for the Transmission of Severe Acute Respiratory Syndrome", "abstract": "Nosocomial transmission of droplet-borne respiratory infections such as severe acute respiratory syndrome (SARS) may be influenced by the choice of oxygen face mask. A subject inhaled saline mist and exhaled through three oxygen masks to illustrate the pattern of dispersal of pulmonary gas. In two commonly used masks, exhaled gas formed a plume emanating from the side vents, while a third mask with a valved manifold, which was modified by adding a respiratory filter, retained the droplets. Maintaining respiratory isolation during the administration of oxygen may reduce the risk of the nosocomial transmission of respiratory infections such as SARS.", "doc_id": "53e1dyuz"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "User acceptance of reusable respirators in health care", "abstract": "BACKGROUND: Inclusion of reusable respirators, such as elastomeric half-face respirators (EHFRs) and powered air-purifying respirators (PAPRs), in hospital respiratory protection inventories may represent 1 solution to the problem of N95 respirator shortages experienced during pandemics. User acceptance of these devices is 1 potential barrier to implementing such a strategy in respiratory protection programs. METHODS: To assess user attitudes toward various respirators, health care workers enrolled in respiratory protection programs in a medical system using EHFRs, N95s, and PAPRs and completed an online questionnaire that addressed attitudes, beliefs, and respirator preferences under different risk scenarios. Responses were compared between user groups. RESULTS: Of 1,152 participants, 53% currently used N95s, 24% used EHFRs, and 23% used PAPRs. N95 users rated their respirators more favorably compared with EHFR and PAPR users (P < .001) regarding comfort and communication, however, EHFR users rated their respirators much more highly regarding sense of protection (P < .001). For all user groups, reusable respirators were significantly more likely (odds ratios 2.3-7.7) to be preferred over N95 filtering facepiece respirators in higher risk scenarios compared to \u201cusual circumstance\u201d scenarios. CONCLUSIONS: Despite somewhat less favorable ratings on comfort and communication, experienced EHFR and PAPR users still prefer reusable respirators over N95s in certain higher risk scenarios. This suggests that reusable respirators are an acceptable alternative to N95 respirators in health care and offer 1 viable solution to prevent pandemic-generated respirator shortages.", "doc_id": "edspdu5x"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Novel Coronavirus 2019 (2019-nCoV) Infection: Part I - Preparedness and Management in the Pediatric Intensive Care Unit in Resource-limited Settings", "abstract": "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.", "doc_id": "l405c850"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Evaluation of the user seal check on gross leakage detection of 3 different designs of N95 filtering facepiece respirators", "abstract": "BACKGROUND: The use of N95 respirators prevents spread of respiratory infectious agents, but leakage hampers its protection. Manufacturers recommend a user seal check to identify on-site gross leakage. However, no empirical evidence is provided. Therefore, this study aims to examine validity of a user seal check on gross leakage detection in commonly used types of N95 respirators. METHODS: A convenience sample of 638 nursing students was recruited. On the wearing of 3 different designs of N95 respirators, namely 3M-1860s, 3M-1862, and Kimberly-Clark 46827, the standardized user seal check procedure was carried out to identify gross leakage. Repeated testing of leakage was followed by the use of a quantitative fit testing (QNFT) device in performing normal breathing and deep breathing exercises. Sensitivity, specificity, predictive values, and likelihood ratios were calculated accordingly. RESULTS: As indicated by QNFT, prevalence of actual gross leakage was 31.0%-39.2% with the 3M respirators and 65.4%-65.8% with the Kimberly-Clark respirator. Sensitivity and specificity of the user seal check for identifying actual gross leakage were approximately 27.7% and 75.5% for 3M-1860s, 22.1% and 80.5% for 3M-1862, and 26.9% and 80.2% for Kimberly-Clark 46827, respectively. Likelihood ratios were close to 1 (range, 0.89-1.51) for all types of respirators. CONCLUSIONS: The results did not support user seal checks in detecting any actual gross leakage in the donning of N95 respirators. However, such a check might alert health care workers that donning a tight-fitting respirator should be performed carefully.", "doc_id": "mc0xa5om"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Novel Coronavirus International Public Health Emergency: Guidance on Radiation Oncology Facility Operation", "abstract": "", "doc_id": "no0k0es6"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Calculating an institutional personal protective equipment (PPE) burn rate to project future usage patterns during the 2020 COVID-19 pandemic", "abstract": "", "doc_id": "rtwgxzhq"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Respirators and surgical facemasks for COVID-19: implications for MRI", "abstract": "\u2022 Respirators used for COVID-19 protection have not been tested for MR safety. \u2022 Three of four respirators tested contained ferromagnetic components. \u2022 These respirators are \u2018MR unsafe\u2019. \u2022 Respirators used for COVID-19 protection should be reviewed locally for MR safety. \u2022 Surgical masks offer a WHO approved safe alternative for MR staff.", "doc_id": "ieyk26zk"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Skin Reactions of N95 masks and Medial Masks among Health Care Personnel: A self\u2010report questionnaire survey in China", "abstract": "", "doc_id": "x2klzrdz"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "AORN Guidance Statement: Human and Avian Influenza and Severe Acute Respiratory Syndrome", "abstract": "", "doc_id": "3fu9kiha"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Sensitivity and specificity of the user-seal-check in determining the fit of N95 respirators", "abstract": "Summary N95 respirators are recommended by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) to prevent the inhalation of droplets which may transmit respiratory pathogens. The reliability of N95 respirators in preventing transmission depends on their fit to the wearer. Quantitative fit testing (QNFT) is the gold standard used to determine this fit objectively. The manufacturers of the respirators also recommend performing a self-reported user-seal-check to detect for leakage. This study aims to investigate the capability of the user-seal-check in determining the fit of N95 respirators by investigating the sensitivity and specificity of the user-seal-check compared with QNFT. A prospective and cross-sectional research design was used. A total of 204 local Chinese undergraduate nursing students were recruited to test two commonly used respirator models (3M 1860S and 3M 1862). The results of the user-seal-check were compared with the results of the gold standard QNFT using the Condensation Nucleus Counter Fit Tester System. The sensitivity and specificity of the user-seal-check results obtained with the respirators were calculated. The results indicated low sensitivity, accuracy and predictive value of the user-seal-check in determining the fit of the N95 respirators. The user-seal-check was not found to be reliable as a substitute for QNFT. The results also suggested that the user-seal-check may be unreliable for detecting gross leakage. We recommend that QNFT is used to determine the fit of N95 respirators.", "doc_id": "q7598a7n"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Helmet Modification to PPE with 3D Printing During the COVID-19 Pandemic at Duke University Medical Center: A Novel Technique", "abstract": "Abstract Care for patients during COVID-19 poses challenges that require the protection of staff with recommendations that health care workers wear at minimum, an N95 mask or equivalent while performing an aerosol-generating procedure with a face shield. The United States faces shortages of personal protective equipment, and surgeons who use loupes and headlights have difficulty using these in conjunction with face shields. Most arthroplasty surgeons use surgical helmet systems, but in the current pandemic, many hospitals have delayed elective arthroplasty surgeries and the helmet systems are going unused. As a result, the authors have begun retrofitting these arthroplasty helmets to serve as personal protective equipment (PPE). The purpose of this paper is to outline the conception, design, donning technique, and safety testing of these arthroplasty helmets being re-purposed as PPE.", "doc_id": "t60ewsen"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Association between 2019-nCoV transmission and N95 respirator use", "abstract": "", "doc_id": "0kji9k18"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "SARS-CoV-2/COVID-19: Empfehlungen zu Diagnostik und Therapie", "abstract": "COVID-19, a new viral disease affecting primarily the respiratory system and the lung, has caused a pandemic with serious challenges to health systems around the world. In about 20% of patients, severe symptoms occur after a mean incubation period of 5 \u2013 6 days; 5% of patients need intensive care therapy. Morbidity is about 1 \u2013 2%. Protecting health care workers is of paramount importance in order to prevent hospital acquired infections. Therefore, during all procedures associated with aerosol production, a personal safety equipment consisting of a FFP2/FFP3 (N95) respiratory mask, gloves, safety glasses and a waterproof overall should be used. Therapy is based on established recommendations issued for patients with acute lung injury (ARDS). Lung protective ventilation, prone position, restrictive fluid management and an adequate management of organ failures are the mainstays of therapy. In case of fulminant lung failure, veno-venous extracorporeal membrane oxygenation may be used as a rescue in experienced centres. New, experimental therapies evolve with ever increasing frequency; currently, however, there is no evidence based recommendation possible. If off-label and compassionate use of these drugs is considered, an individual benefit-risk assessment is necessary, since serious side effects have been reported.", "doc_id": "7r44j3q9"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "CORONA-steps for tracheotomy in COVID-19 patients: A staff-safe method for airway management", "abstract": "\u2022 The recent outbreak of SARS\u2010CoV\u20102 has assumed worldwide proportion. \u2022 Tracheostomy in intubated COVID-19 patients requires adjunctive safeguards. \u2022 A step-by-step approach named CORONA is proposed in order to recall essential recommendations during the surgical procedure. \u2022 The CORONA-method would allow a secure space in which health workers can guarantee their activity, safely.", "doc_id": "nu0fuuxp"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Simple Respiratory Protection\u2014Evaluation of the Filtration Performance of Cloth Masks and Common Fabric Materials Against 20\u20131000 nm Size Particles", "abstract": "A shortage of disposable filtering facepiece respirators can be expected during a pandemic respiratory infection such as influenza A. Some individuals may want to use common fabric materials for respiratory protection because of shortage or affordability reasons. To address the filtration performance of common fabric materials against nano-size particles including viruses, five major categories of fabric materials including sweatshirts, T-shirts, towels, scarves, and cloth masks were tested for polydisperse and monodisperse aerosols (20\u20131000 nm) at two different face velocities (5.5 and 16.5 cm s(\u22121)) and compared with the penetration levels for N95 respirator filter media. The results showed that cloth masks and other fabric materials tested in the study had 40\u201390% instantaneous penetration levels against polydisperse NaCl aerosols employed in the National Institute for Occupational Safety and Health particulate respirator test protocol at 5.5 cm s(\u22121). Similarly, varying levels of penetrations (9\u201398%) were obtained for different size monodisperse NaCl aerosol particles in the 20\u20131000 nm range. The penetration levels of these fabric materials against both polydisperse and monodisperse aerosols were much higher than the penetrations for the control N95 respirator filter media. At 16.5 cm s(\u22121) face velocity, monodisperse aerosol penetrations slightly increased, while polydisperse aerosol penetrations showed no significant effect except one fabric mask with an increase. Results obtained in the study show that common fabric materials may provide marginal protection against nanoparticles including those in the size ranges of virus-containing particles in exhaled breath.", "doc_id": "2f7wqamp"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "The preventive effect of hydrocolloid dressing to prevent facial pressure and facial marks during use of medical protective equipment in Covid-19 pandemic", "abstract": "", "doc_id": "243tedn2"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "A Quantitative Assessment of the Total Inward Leakage of NaCl Aerosol Representing Submicron-Size Bioaerosol Through N95 Filtering Facepiece Respirators and Surgical Masks", "abstract": "Respiratory protection provided by a particulate respirator is a function of particle penetration through filter media and through faceseal leakage. Faceseal leakage largely contributes to the penetration of particles through a respirator and compromises protection. When faceseal leaks arise, filter penetration is assumed to be negligible. The contribution of filter penetration and faceseal leakage to total inward leakage (TIL) of submicron-size bioaerosols is not well studied. To address this issue, TIL values for two N95 filtering facepiece respirator (FFR) models and two surgical mask (SM) models sealed to a manikin were measured at 8 L and 40 L breathing minute volumes with different artificial leak sizes. TIL values for different size (20\u2013800 nm, electrical mobility diameter) NaCl particles representing submicron-size bioaerosols were measured using a scanning mobility particle sizer. Efficiency of filtering devices was assessed by measuring the penetration against NaCl aerosol similar to the method used for NIOSH particulate filter certification. Results showed that the most penetrating particle size (MPPS) was ~45 nm for both N95 FFR models and one of the two SM models, and ~350 nm for the other SM model at sealed condition with no leaks as well as with different leak sizes. TIL values increased with increasing leak sizes and breathing minute volumes. Relatively, higher efficiency N95 and SM models showed lower TIL values. Filter efficiency of FFRs and SMs influenced the TIL at different flow rates and leak sizes. Overall, the data indicate that good fitting higher-efficiency FFRs may offer higher protection against submicron-size bioaerosols.", "doc_id": "ed6wdbcb"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Protecting health care workers from SARS and other respiratory pathogens: A review of the infection control literature", "abstract": "BACKGROUND: Severe Acute Respiratory Syndrome (SARS) was responsible for outbreaks in Canada, China, Hong Kong, Vietnam, and Singapore. SARS focused attention on the adequacy of and compliance with infection control practices in preventing airborne and droplet-spread transmission of infectious agents. METHODS: This paper presents a review of the current scientific knowledge with respect to the efficacy of personal protective equipment in preventing the transmission of respiratory infections. The effectiveness of infection control polices and procedures used in clinical practice is examined. RESULTS: Literature searches were conducted in several databases for articles published in the last 15 years that related to infection control practices, occupational health and safety issues, environmental factors, and other issues of importance in protecting workers against respiratory infections in health care settings. CONCLUSION: Failure to implement appropriate barrier precautions is responsible for most nosocomial transmissions. However, the possibility of a gradation of infectious particles generated by aerosolizing procedures suggests that traditional droplet transmission prevention measures may be inadequate in some settings. Further research is needed in this area.", "doc_id": "0t28p4g6"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Gastrointestinal endoscopy during COVID-19 pandemic: an updated review of guidelines and statements from international and national societies", "abstract": "", "doc_id": "6ge2ihcs"} {"topic_name": "masks prevent coronavirus", "topic_id": "18", "title": "Physiologic and other effects and compliance with long-term respirator use among medical intensive care unit nurses", "abstract": "BACKGROUND: Long-term use of respiratory protection may be necessary, but compliance may be low, and physiologic effects have not been well evaluated. METHODS: Ten nurses participated; physiologic effects, subjective symptoms, and compliance with wearing an N95 alone or with a surgical mask overlay were assessed. Longitudinal analysis based on multivariate linear regression models assessed changes in outcome variables (CO(2), O(2), heart rate, perceived comfort items, compliance measures, and others). Analyses compared changes over time, and compared wearing only an N95 to wearing an N95 with a surgical mask overlay. RESULTS: Most nurses (90%, n = 9) tolerated wearing respiratory protection for two 12-hour shifts. CO(2) levels increased significantly compared with baseline measures, especially when comparing an N95 with a surgical mask to only an N95, but changes were not clinically relevant. Perceived exertion; perceived shortness of air; and complaints of headache, lightheadedness, and difficulty communicating also increased over time. Almost one-quarter (22%) of respirator removals were due to reported discomfort. N95 adjustments increased over time, but other compliance measures did not vary by time. Compliance increased on day 2, except for adjustments, touching under the N95, and eye touches. CONCLUSION: Long-term use of respiratory protection did not result in any clinically relevant physiologic burden for health care personnel, although many subjective symptoms were reported. N95 compliance was fairly high.", "doc_id": "ybjnep46"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Development of Nano-Antimicrobial Biomaterials for Biomedical Applications", "abstract": "Around the globe, there is a great concern about controlling growth of pathogenic microorganisms for the prevention of infectious diseases. Moreover, the greater incidences of cross contamination and overuse of drugs has contributed towards the development of drug resistant microbial strains making conditions even worse. Hospital acquired infections pose one of the leading complications associated with implantation of any biomaterial after surgery and critical care. In this regard, developing non-conventional antimicrobial agents which would prevent the aforementioned causes is under the quest. The rapid development in nanoscience and nanotechnology has shown promising potential for developing novel biocidal agents that would integrate with a biomaterial to prevent bacterial colonization and biofilm formation. Metals with inherent antimicrobial properties such as silver, copper, zinc at nano scale constitute a special class of antimicrobials which have broad spectrum antimicrobial nature and pose minimum toxicity to humans. Hence, novel biomaterials that inhibit microbial growth would be of great significance to eliminate medical device/instruments associated infections. This chapter comprises the state-of-art advancements in the development of nano-antimicrobial biomaterials for biomedical applications. Several strategies have been targeted to satisfy few important concern such as enhanced long term antimicrobial activity and stability, minimize leaching of antimicrobial material and promote reuse. The proposed strategies to develop new hybrid antimicrobial biomaterials would offer a potent antibacterial solution in healthcare sector such as wound healing applications, tissue scaffolds, medical implants, surgical devices and instruments.", "doc_id": "ek53y2kp"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols", "abstract": "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\u2019s 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.", "doc_id": "c1n994j6"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Epidemiologic background of hand hygiene and evaluation of the most important agents for scrubs and rubs.", "abstract": "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.", "doc_id": "btzrfs6g"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Outbreaks where food workers have been implicated in the spread of foodborne disease. Part 10. Alcohol-based antiseptics for hand disinfection and a comparison of their effectiveness with soaps.", "abstract": "Alcohol compounds are increasingly used as a substitute for hand washing in health care environments and some public places because these compounds are easy to use and do not require water or hand drying materials. However, the effectiveness of these compounds depends on how much soil (bioburden) is present on the hands. Workers in health care environments and other public places must wash their hands before using antiseptics and/or wearing gloves. However, alcohol-based antiseptics, also called rubs and sanitizers, can be very effective for rapidly destroying some pathogens by the action of the aqueous alcohol solution without the need for water or drying with towels. Alcohol-based compounds seem to be the most effective treatment against gram-negative bacteria on lightly soiled hands, but antimicrobial soaps are as good or better when hands are more heavily contaminated. Instant sanitizers have no residual effect, unlike some antimicrobial soaps that retain antimicrobial activity after the hygienic action has been completed, e.g., after hand washing. Many alcohol-based hand rubs have antimicrobial agents added to them, but each formulation must be evaluated against the target pathogens in the environment of concern before being considered for use. Wipes also are widely used for quick cleanups of hands, other body parts, and surfaces. These wipes often contain alcohol and/or antimicrobial compounds and are used for personal hygiene where water is limited. However, antiseptics and wipes are not panaceas for every situation and are less effective in the presence of more than a light soil load and against most enteric viruses.", "doc_id": "1lx84td6"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Hand sanitisers amid CoViD-19: A critical review of alcohol-based products on the market and formulation approaches to respond to increasing demand", "abstract": "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.", "doc_id": "rv2akbj8"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Hand Sanitizers: A Review on Formulation Aspects, Adverse Effects, and Regulations", "abstract": "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.", "doc_id": "i0ll585x"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 by WHO-Recommended Hand Rub Formulations and Alcohols", "abstract": "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.", "doc_id": "1v8wwn0d"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Hand disinfection in the combat against Covid-19", "abstract": "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.", "doc_id": "0macgbcn"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Evaluation of World Health Organization-Recommended Hand Hygiene Formulations", "abstract": "As a result of the coronavirus disease pandemic, commercial hand hygiene products have become scarce and World Health Organization (WHO) alcohol-based hand rub formulations containing ethanol or isopropanol are being produced for hospitals worldwide. Neither WHO formulation meets European Norm 12791, the basis for approval as a surgical hand preparation, nor satisfies European Norm 1500, the basis for approval as a hygienic hand rub. We evaluated the efficacy of modified formulations with alcohol concentrations in mass instead of volume percentage and glycerol concentrations of 0.5% instead of 1.45%. Both modified formulations met standard requirements for a 3-minute surgical hand preparation, the usual duration of surgical hand treatment in most hospitals in Europe. Contrary to the originally proposed WHO hand rub formulations, both modified formulations are appropriate for surgical hand preparation after 3 minutes when alcohol concentrations of 80% wt/wt ethanol or 75% wt/wt isopropanol along with reduced glycerol concentration (0.5%) are used.", "doc_id": "gllg9j1p"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Hidden threat lurking behind the alcohol sanitizers in COVID-19 outbreak", "abstract": "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.", "doc_id": "z6cda4o2"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "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", "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.", "doc_id": "9iyyqqmm"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Hand Sanitizers: A Review of Ingredients, Mechanisms of Action, Modes of Delivery, and Efficacy Against Coronaviruses", "abstract": "BACKGROUND: The emergence of the novel virus, SARS-CoV-2, has posed unprecedented challenges to public health around the world. 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.", "doc_id": "y777xosr"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Comparison of national and subnational guidelines for hand hygiene", "abstract": "Summary Hand hygiene promotion is considered as the cornerstone for healthcare-associated infection prevention. Over the past years, hand hygiene guidelines have been developed by different agencies at international, national and subnational levels. A comparison of these documents could help in understanding recommendations in different parts of the world and the methods used for their development. Guidelines were identified through search engines, electronic libraries, and personal contacts, and their content was analysed using an adapted version of a tool from the European DG XII-funded HARMONY project. Twenty-two guidelines were retrieved and 21 were evaluated. Documents varied in scope, approach, content and terminology. Some were primarily advisory directives, whereas others focused on the technical issues of why, when, and how to perform hand hygiene. The extent to which evidence was collected and assessed varied considerably and details were provided only in very few. Grading systems and definitions to indicate the strength of evidence and recommendations also differed. The intended outcome was to improve hand hygiene practices in healthcare, thus leading to a reduction of healthcare-associated infections and/or antimicrobial resistance. Although overall agreement on indications and procedures was noted, the range and depth of recommendations on best practices and implementation varied. Essential aspects such as compliance measurement and audits to assess guideline effectiveness were neglected in most documents. In conclusion, there is a need for a more consistent approach leading to recommendations based on a thorough evaluation of evidence and applicable worldwide. Aspects related to implementation and impact monitoring deserve greater attention.", "doc_id": "mdr360g4"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Predictors of hand hygiene practice among Saudi nursing students: A cross-sectional self-reported study", "abstract": "Summary Hand hygiene is an important component of infection control, which is critical to ensuring patients\u2019 safety in hospitals. Nursing students are regarded as healthcare workers in training and can also be vehicles of cross-contamination within the hospital. Thus, this study aimed to identify the predictors of hand hygiene practice among Saudi nursing students. A descriptive, cross-sectional, self-reported study was conducted among 198 Saudi nursing students. Knowledge, attitude, and practice of hand hygiene were assessed using the WHO Hand Hygiene Knowledge Questionnaire for Health-Care Workers and its adopted scales. A regression analysis was performed to identify the predictors of hand hygiene practice. The respondents demonstrated moderate knowledge of hand hygiene (mean 13.20\u00b12.80). The majority displayed a moderate attitude toward hand hygiene (52.1%), while only a few reported a poor attitude (13.1%). Approximately 68.7%, 29.8%, and 1.5% of the respondents reported moderate, good, and poor practice of hand hygiene, respectively. Having a good attitude toward hand hygiene, being male, being aware that hand hygiene is an effective intervention in preventing healthcare-associated infections (HAIs), attendance at hand hygiene trainings and seminars, and being in the lower academic level of nursing education were identified as predictors of better hand hygiene practice. The importance of ensuring a positive attitude toward hand hygiene and improving awareness of hand hygiene is emphasized, as are educational interventions. Educational interventions should be implemented to reinforce knowledge and instill a positive attitude toward hand hygiene.", "doc_id": "wr49giux"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Handwashing and risk of respiratory infections: a quantitative systematic review", "abstract": "Objective To determine the effect of handwashing on the risk of respiratory infection. Methods We searched PubMed, CAB Abstracts, Embase, Web of Science, and the Cochrane library for articles published before June 2004 in all languages. We had searched reference lists of all primary and review articles. Studies were included in the review if they reported the impact of an intervention to promote hand cleansing on respiratory infections. Studies relating to hospital\u2010acquired infections, long\u2010term care facilities, immuno\u2010compromised and elderly people were excluded. We independently evaluated all studies, and inclusion decisions were reached by consensus. From a primary list of 410 articles, eight interventional studies met the eligibility criteria. Results All eight eligible studies reported that handwashing lowered risks of respiratory infection, with risk reductions ranging from 6% to 44% [pooled value 24% (95% CI 6\u201340%)]. Pooling the results of only the seven homogenous studies gave a relative risk of 1.19 (95% CI 1.12%\u20131.26%), implying that hand cleansing can cut the risk of respiratory infection by 16% (95% CI 11\u201321%). Conclusions Handwashing is associated with lowered respiratory infection. However, studies were of poor quality, none related to developing countries, and only one to severe disease. Rigorous trials of the impact of handwashing on acute respiratory tract infection morbidity and mortality are urgently needed, especially in developing countries.", "doc_id": "n9wox9lg"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Zinc pyrithione in alcohol-based products for skin antisepsis: Persistence of antimicrobial effects", "abstract": "Alcohol-based products for skin antisepsis have a long history of safety and efficacy in the United States and abroad. However, alcohol alone lacks the required antimicrobial persistence to provide for the sustained periods of skin antisepsis desired in the clinical environment. Therefore, alcohol-based products must have a preservative agent such as iodine/iodophor compounds, chlorhexidine gluconate, or zinc pyrithione, to extend its antimicrobial effects. Iodine, iodophors, and chlorhexidine gluconate are well-characterized antimicrobials and preservatives. The thrust of our effort was to examine the characteristics of the lesser-known zinc pyrithione and to evaluate its utility as a preservative in the formulation of alcohol-based products for skin antisepsis. This work includes a literature review of current zinc pyrithione applications in drugs and cosmetics, a safety and toxicity evaluation, consideration of the proposed mechanisms of antimicrobial action, in vitro and in vivo efficacy data, and a discussion of the mechanisms that confer the desired antimicrobial persistence. In addition, alcohol-based, zinc pyrithione-preserved, commercially available products of skin antisepsis are compared with other commercially available antimicrobials used for skin antisepsis and with additional alcohol-based products with different preservatives. The authors' conclusion is that zinc pyrithione is not only a safe and effective antimicrobial but that its use in certain alcohol-based formulations results in antimicrobial efficacy exceeding that of iodine and chlorhexidine gluconate.", "doc_id": "sxsrz60h"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Introduction to Food Irradiation and Medical Sterilization", "abstract": "This chapter is comprehensive overview of sterilization and disinfectant processes used for food-borne disease control and medical sterilization. Pathogens such as bacteria, viruses, and endospores are described along with other infectious agents. The processes for controlling these infectious agents in food are summarized. These processes include not only irradiation by the two most important processes, electron beam and gamma ray, but by other processes such as ultraviolet, microwave, and infrared radiation. Medical sterilization and disinfectant processes are reviewed. Besides irradiative processes, thermal processes such as steam autoclave and dry heat are reviewed. Many liquid and gaseous chemical disinfectants are covered. The commercially important ethylene oxide sterilization process is discussed. Dealing with bioterrorism agents is briefly discussed. Throughout this chapter, the mechanisms, the irradiation, sterilization, and chemical disinfectant processes used to destroy the pathogens are discussed often in chemical detail.", "doc_id": "25qqr3vt"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Methanol Poisoning Emerging as the Result of COVID-19 Outbreak; Radiologic Perspective", "abstract": "", "doc_id": "hoibwxms"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "A unique water optional health care personnel handwash provides antimicrobial persistence and residual effects while decreasing the need for additional products", "abstract": "BACKGROUND: The Centers for Disease Control and Prevention (CDC) has published guidelines for hand hygiene practices, recommending a handwash regimen that alternates between waterless alcohol products and antimicrobial or nonantimicrobial soap and water. The advent of an alcohol-based product that can be used with or without water (ie, water optional) to decontaminate the hands while providing immediacy of kill and antimicrobial persistence could reduce the confusion associated with handwash guidelines. Such a product has been developed, is alcohol-based (61%), and zinc pyrithione (ZPT) preserved (61% alcohol-ZPT) and has proven to be fully compliant with the Food and Drug Administration (FDA) and CDC guidelines. METHODS: FDA-required testing of the 61% alcohol-ZPT product for the health care personnel handwash indication was performed as outlined in the Tentative Final Monograph (TFM) for Health-Care Antiseptic Drug Products, employing waterless and water-aided product applications. It was next assessed for antimicrobial persistence and residual effects by comparing it, in separate waterless and water-aided applications, with commonly available handwashes containing various antimicrobials in a 5-day study employing 49 subjects, in which samples were collected immediately and at 4 hours and 8 hours postapplication. The skin conditioning properties of this formulation were investigated via appropriate methods. RESULTS: The 61% alcohol-ZPT product easily produced >3.0 log(10) reduction in the indicator strain (Serratia marcescens) following the first wash, exceeding the 2.0 log(10) FDA requirement. This level of performance was maintained through the tenth wash, surpassing the 3.0 log(10) FDA requirement for the handwash indication. For the assessment of persistence and residual effect in the waterless mode, the water-optional, 61% alcohol-ZPT product consistently produced log(10) reductions of nearly 3.5 or greater at every point over the entire study period. In the water-aided configuration, similar results were obtained as log(10) reductions of 2.5 were observed. The formulation is nonirritating, actually contributing to hand skin condition. CONCLUSIONS: The 61% alcohol-ZPT product exceeds all FDA criteria for the health care personnel handwash indication and is a significant advancement in the concept of skin antisepsis. It represents a single product suitable for use in all hand hygiene settings, demonstrating improved antimicrobial persistence and residual effects. The 61% alcohol-ZPT formulation contributes positively to overall hand conditioning, and a previously reported study has documented it to be virucidal for several DNA and RNA viruses.", "doc_id": "gt2g1but"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Disinfection and Sterilization in Health Care Facilities An Overview and Current Issues", "abstract": "When properly used, disinfection and sterilization can ensure the safe use of invasive and noninvasive medical devices. The method of disinfection and sterilization depends on the intended use of the medical device: critical items (contact sterile tissue) must be sterilized before use; semicritical items (contact mucous membranes or nonintact skin) must be high-level disinfected; and noncritical items (contact intact skin) should receive low-level disinfection. Cleaning should always precede high-level disinfection and sterilization. Current disinfection and sterilization guidelines must be strictly followed.", "doc_id": "xphxlaat"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Personal Protective Equipment Recommendations Based on COVID-19 Route of Transmission", "abstract": "", "doc_id": "rncrk9zd"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Hidden threat lurking behind the alcohol sanitizers in COVID\u201019 outbreak", "abstract": "The ongoing COVID\u201019 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.", "doc_id": "hx8c0mxj"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Are your hands clean enough for point-of-care electrolyte analysis?", "abstract": "Summary Aim To investigate clinically significant analytical interference in point-of-care electrolyte analysis caused by contamination of blood specimens with hand disinfectant. Methods Six different hand hygiene products were added separately to heparinised blood samples in varying amounts as contaminant. The contaminated samples were analysed by three different blood gas and electrolyte analysers for assessing interference on measured whole blood sodium and potassium concentrations. Results There were significant analytical interferences caused by hand hygiene product contamination that varied depending on the combination of disinfectant and analyser. Small amounts of Microshield Antibacterial Hand Gel contamination caused large increases in measured sodium concentration. Such effect was much greater compared with the other five products tested, and started to occur at much lower levels of contamination. There was a trend towards lower sodium results in blood samples contaminated with Hexol Antiseptic Lotion (Hexol), the hand hygiene product that we used initially. Apart from AiE Hand Sanitizer, all the other hand disinfectants, especially Hexol, significantly elevated the measured potassium concentration, particularly when a direct ion-selective electrode method was used for measurement. Conclusion Hand disinfectant products can significantly interfere with blood electrolyte analysis. Proper precautions must be taken against contamination since the resultant errors can adversely affect the clinical management of patients.", "doc_id": "02azobp3"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Religion and culture: Potential undercurrents influencing hand hygiene promotion in health care", "abstract": "BACKGROUND: Health care\u2013associated infections affect hundreds of millions of patients worldwide each year. The World Health Organization's (WHO) First Global Patient Safety Challenge, \u201cClean Care is Safer Care,\u201d is tackling this major patient safety problem, with the promotion of hand hygiene in health care as the project's cornerstone. WHO Guidelines on Hand Hygiene in Healthcare have been prepared by a large group of international experts and are currently in a pilot-test phase to assess feasibility and acceptability in different health care settings worldwide. METHODS: An extensive literature search was conducted and experts and religious authorities were consulted to investigate religiocultural factors that may potentially influence hand hygiene promotion, offer possible solutions, and suggest areas for future research. RESULTS: Religious faith and culture can strongly influence hand hygiene behavior in health care workers and potentially affect compliance with best practices. Interesting data were retrieved on specific indications for hand cleansing according to the 7 main religions worldwide, interpretation of hand gestures, the concept of \u201cvisibly dirty\u201d hands, and the use of alcohol-based hand rubs and prohibition of alcohol use by some religions. CONCLUSIONS: The impact of religious faith and cultural specificities must be taken into consideration when implementing a multimodal strategy to promote hand hygiene on a global scale.", "doc_id": "c69vfs8q"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Surfactants as Antimicrobials: A Brief Overview of Microbial Interfacial Chemistry and Surfactant Antimicrobial Activity", "abstract": "In this brief overview of a large and complex subject, as presented at the 2018 Surfactants in Solution conference, the need for, and impact of, hard surface antimicrobial products is demonstrated. The composition of the interfaces of three common classes of pathological microbes, bacteria, viruses, and fungi, is discussed so that surfactant and cleaning product development scientists better understand their interfacial characteristics. Studies of antimicrobial efficacy from the four major classes of surfactants (cationic, anionic, amphoteric, and nonionic) are shown. The need for preservatives in surfactants is elucidated. The regulatory aspects of antimicrobials in cleaning products to make antimicrobial claims are stressed.", "doc_id": "s0o0egw8"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Low-cost production of handrubs and face shields in developing countries fighting the COVID19 pandemic", "abstract": "", "doc_id": "qtqjoty3"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Development and virucidal activity of a novel alcohol-based hand disinfectant supplemented with urea and citric acid", "abstract": "BACKGROUND: Hand disinfectants are important for the prevention of virus transmission in the health care system and environment. The development of broad antiviral spectrum hand disinfectants with activity against enveloped and non-enveloped viruses is limited due to a small number of permissible active ingredients able to inactivate viruses. METHODS: A new hand disinfectant was developed based upon 69.39 % w/w ethanol and 3.69 % w/w 2-propanol. Different amounts of citric acid and urea were added in order to create a virucidal claim against poliovirus (PV), adenovirus type 5 (AdV) and polyomavirus SV40 (SV40) as non-enveloped test viruses in the presence of fetal calf serum (FCS) as soil load. The exposure time was fixed to 60 s. RESULTS: With the addition of 2.0 % citric acid and 2.0 % urea an activity against the three test viruses was achieved demonstrating a four log(10) reduction of viral titers. Furthermore, this formulation was able to inactivate PV, AdV, SV40 and murine norovirus (MNV) in quantitative suspension assays according to German and European Guidelines within 60 s creating a virucidal claim. For inactivation of vaccinia virus and bovine viral diarrhea virus 15 s exposure time were needed to demonstrate a 4 log(10) reduction resulting in a claim against enveloped viruses. Additionally, it is the first hand disinfectant passing a carrier test with AdV and MNV. CONCLUSIONS: In conclusion, this new formulation with a low alcohol content, citric acid and urea is capable of inactivating all enveloped and non-enveloped viruses as indicated in current guidelines and thereby contributing as valuable addition to the hand disinfection portfolio.", "doc_id": "eyigl0wz"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Back to basics: hand hygiene and isolation", "abstract": "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.", "doc_id": "q4nzhbvt"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Bactericidal and Virucidal Activity of Povidone-Iodine and Chlorhexidine Gluconate Cleansers in an In Vivo Hand Hygiene Clinical Simulation Study", "abstract": "INTRODUCTION: Standard in vitro and in vivo tests help demonstrate efficacy of hand hygiene products; however, there is no standard in vivo test method for viruses. We investigated the bactericidal and virucidal efficacy of povidone-iodine (PVP-I) 7.5% scalp and skin cleanser, chlorhexidine gluconate (CHG) 4% hand cleanser and the reference hand wash (soft soap) in 15 healthy volunteers following European Standard EN1499 (hygienic hand wash test method for bacteria), which was adapted for virucidal testing. METHODS: Separate test series were performed for bactericidal (Escherichia coli) and virucidal [murine norovirus (MNV)] testing. After pre-washing and artificial contamination of hands with test organisms, volunteers underwent testing with 3 and 5 mL of each product for contact times of 15, 30 and 60 s according to a Latin-square randomization. The number of test organisms released from fingertips into sampling fluids was assessed before and after hand washing and mean log(10) reduction factor (RF) was calculated. RFs (test-reference) were compared using a Wilcoxon\u2013Wilcox multiple comparisons test per EN1499; efficacy was concluded if p \u2264 0.01. RESULTS: PVP-I 7.5% and CHG 4% cleansers both passed EN1499 requirements against E. coli, with statistically significantly greater (p \u2264 0.01) mean log(10) RFs compared with reference soft soap across all tests (PVP-I: 4.09\u20135.27; CHG: 4.12\u20135.22; soap: 2.75\u20133.11). The experimental design using EN1499 was applicable to testing with MNV as discriminatory and reproducible results were generated. Mean log(10) RFs of MNV were statistically significantly greater for PVP-I (1.57\u20132.57) compared with soft soap (1.24\u20131.62), while mean log(10) RFs with CHG (0.90\u20131.34) were lower than for soft soap across all tests. CONCLUSION: PVP-I 7.5% cleanser showed superior efficacy against MNV compared to soft soap and CHG 4% cleanser, while both PVP-I and CHG were superior to soft soap against E. coli. The experimental set-up may be applicable to future testing for antiviral hand washes. FUNDING: Mundipharma Manufacturing Pte Ltd. PLAIN LANGUAGE SUMMARY: Plain language summary available for this article.", "doc_id": "gyaxcvf7"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Infectious Disease Management and Control with Povidone Iodine", "abstract": "With reports of vancomycin-resistant enterococci recently emerging in hospital settings, renewed focus is turning to the importance of multifaceted infection prevention efforts. Careful compliance with established hygiene practices by healthcare workers together with effective antiseptic options is essential for the protection of patients from infectious agents. For over 60 years, povidone iodine (PVP-I) formulations have been shown to limit the impact and spread of infectious diseases with potent antiviral, antibacterial and antifungal effects. In addition to a lack of reported resistance, the benefits of PVP-I include an excellent safety profile and a broad spectrum of effect due to its multimodal action. Studies have shown that hand washing with PVP-I-based antiseptics is effective for the decontamination of skin, while PVP-I mouthwashes and gargles significantly reduce viral load in the oral cavity and the oropharynx. The importance of PVP-I has been emphasised by its inclusion in the World Health Organization\u2019s list of essential medicines, and high potency for virucidal activity has been observed against viruses of significant global concern, including hepatitis A and influenza, as well as the Middle-East Respiratory Syndrome and Sudden Acute Respiratory Syndrome coronaviruses. Together with its diverse applications in antimicrobial control, broad accessibility across the globe, and outstanding safety and tolerability profile, PVP-I offers an affordable, potent, and widely available antiseptic option. Funding Mundipharma Singapore Holding Pte Limited.", "doc_id": "nt2bbbdn"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Effects of hand disinfection with alcohol hand rub, ozonized water, or soap and water: time for reconsideration?", "abstract": "The effect of alcohol hand rub was tested in eradicating Escherichia coli, and compared with hand wash using ozonized tap water or soap and water. Alcohol eradicated all bacteria in 10 out of 35 participants, but with an average (SD) of 2330 (4227) cfu/mL left after disinfection, whereas ozonized water removed all bacteria in 10 out of 55 participants, with an average of only 538 (801) cfu/mL left (P = 0.045). Soap washing was the most effective with total removal of bacteria in six out of 20 participants, with an average of 98 (139) cfu/mL (P = 0.048 and 0.018 versus ozonized water and alcohol, respectively).", "doc_id": "jd764wk4"} {"topic_name": "what alcohol sanitizer kills coronavirus", "topic_id": "19", "title": "Rate of Compliance with Hand Hygiene by Dental Healthcare Personnel (DHCP) within a Dentistry Healthcare First Aid Facility", "abstract": "OBJECTIVES: To evaluate the compliance with the opportunities of hand hygiene by dentistry school healthcare professionals, as well as the higher choice products. METHODS: Through direct observation, the oral healthcare team-professors, oral and maxillofacial surgery residents, graduation students-for daily care were monitored: before performing the first treatment of the shift, after snacks and meals, and after going to the bathroom (initial opportunities) as well as between patients\u2019 care, and after ending the shift (following opportunities). RESULTS: The professors\u2019 category profited 78.4% of all opportunities while residents and graduation students did not reach 50.0% of compliance. Statistically significant data (P\u2264.05) were seen between categories: professors and residents, professors and graduation students, and between genders within the residents\u2019 category. When opportunities were profited, the preferred choice for hand hygiene was water and soap (82.2%), followed by 70% alcohol (10.2%), and both (7.6%). CONCLUSIONS: Although gloves were worn in all procedures, we concluded that the hygiene compliance by these professionals was under the expectation.", "doc_id": "qfck720q"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Role of the Renin-Angiotensin System in ARDS", "abstract": "The renin-angiotensin system (RAS) is a powerful biological system that plays an important role in regulation of systemic blood pressure through the maintenance of fluid and salt homeostasis. It is a multifactorial system since it includes different components (Fig. 1): The first, renin, was discovered in 1898 [1], whereas the discovery of the last component, angiotensin-converting enzyme 2 (ACE 2), is relatively recent, from 2000 [2, 3]. Three kinds of RAS are known: A) circulating, B) local, and C) intracellular.", "doc_id": "i5n3i2cy"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "EMA: continue use of ACE inhibitors, sartans during COVID-19 pandemic", "abstract": "", "doc_id": "96bq87q1"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Inhibitors of the renin-angiotensin system: The potential role in the pathogenesis of COVID-19.", "abstract": "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.", "doc_id": "5a2zi2xp"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Angiotensin-converting enzyme 2: cardioprotective player in the renin-angiotensin system?", "abstract": "", "doc_id": "dgxiwxa0"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "[Role of age, comorbidity and renin- angiotensin-aldosterone system in COVID-19. Effects of ACE inhibitors and angiotensin receptor blockers].", "abstract": "The review addressed the relationship of coronavirus disease 2019 (COVID-19) with functioning of the renin-angiotensin-aldosterone axis and the causes for unfavorable prognosis depending on patients' age and comorbidities. The authors discussed in detail potential effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists on the risk of infection and the course of COVID-2019 as well as the effect of SARS-COV2 virus on the cardiovascular system.", "doc_id": "04h53wjz"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "COVID-19 and cardiovascular diseases: viewpoint for older patients.", "abstract": "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.", "doc_id": "7rf532b9"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Relationship between ACE-inhibitors, ARBs and SARS-CoV-2 infection: where are we?", "abstract": "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.", "doc_id": "43th3c20"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "[2019 Novel coronavirus, renin-angiotension system imbalance and coronavirus disease 2019].", "abstract": "2019 Novel coronavirus (2019-nCoV) destroys angiotensin converting enzyme 2 (ACE2) and breaks the balance of renin-angiotension system (RAS) by interacting with ACE2. The imbalance of RAS takes part in the development of organ injury of different systems through pro-inflammation, oxidative stress, cell proliferation and so on. 2019-nCoV not only attacks the lung, but also influences many other systems. It is speculated that RAS imbalance plays an important role in the development of multi-organ dysfunction caused by 2019-nCoV, and the usage of angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) may become a new treatment of 2019-nCoV-related organ injury. Further studies are need to confirm the relationship between coronavirus infection, multi-organ injury and RAS imbalance.", "doc_id": "gzh15hib"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "The Effect of Coronavirus Disease 2019 on Cardiovascular Diseases.", "abstract": "Coronavirus disease 2019 (COVID-19) is a global pandemic affecting the world, seen in more than 1,300,000 patients. COVID-19 acts through the angiotensin-converting enzyme 2 (ACE2) receptor. Cardiovascular comorbidities are more common with COVID-19, and nearly 10% of cases develop myocarditis (22% of critical patients). Further research is needed to continue or discontinue ACE inhibitors and angiotensin receptor blockers, which are essential in hypertension and heart failure in COVID-19. Intensive research is promising for the treatment and prevention of COVID-19.", "doc_id": "a30ryzkj"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Comparative impacts of angiotensin converting enzyme inhibitors versus angiotensin II receptor blockers on the risk of COVID-19 mortality.", "abstract": "N/A.", "doc_id": "7a06u9uq"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Angiotensin converting enzyme 2 (ACE2) and COVID-19: using antihypertensive medications, pharmacogenetic considerations.", "abstract": "COVID-19 utilizes the angiotensin-converting enzyme-2 (ACE2) pathway as a means of infection. Early data on COVID-19 suggest heterogeneity in the severity of symptoms during transmission and infection ranging from no symptoms to death. The source of this heterogeneity is likely multifaceted and may have a genetic component. Demographic and clinical comorbidities associated with the severity of infection suggest that possible variants known to influence the renin-angiotensin-aldosterone system pathway (particularly those that influence ACE2) may contribute to the heterogenous infection response. ACE2 and angiotensin(1-7) (the product of ACE2) seem to have a protective effect on the pulmonary and cardiac systems. Hypertension medication modulation, may alter ACE2 and angiotensin(1-7), particularly in variants that have been shown to influence renin-angiotensin-aldosterone system function, which could be clinically useful in patients with COVID-19.", "doc_id": "ilufqcsq"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Blocking angiotensin earlier with RAS blockers, statins, and heparin in high-risk COVID-19 patients: Is the remedy here?", "abstract": "", "doc_id": "84jr6lwd"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Therapy with agents acting on the renin-angiotensin system and risk of SARS-CoV-2 infection.", "abstract": "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.", "doc_id": "0yumc7em"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "A hypothesis for pathobiology and treatment of COVID-19: the centrality of ACE1/ACE2 imbalance.", "abstract": "Angiotensin converting enzyme-2 (ACE2) is the receptor for the coronavirus SARS-CoV-2, which causes COVID-19. We propose the following hypothesis: Imbalance in the action of ACE1- and ACE2-derived peptides, thereby enhancing Angiotensin-II (ANG II) signaling, a primary driver of COVID-19 pathobiology. ACE1/ACE2 imbalance occurs due to the binding of SARS-CoV-2 to ACE2, reducing ACE2-mediated conversion of ANG II to ANG peptides that counteract pathophysiological effects of ACE1-generated ANGII. This hypothesis suggests several approaches to treat COVID-19 by restoring ACE1/ACE2 balance: 1) ANG II receptor blockers (ARBs); 2) ACE1 inhibitors (ACEIs); 3) Agonists of receptors activated by ACE2-derived peptides [e.g., ANG (1-7), which activates MAS1]; 4) Recombinant human ACE2 or ACE2 peptides as decoys for the virus. Reducing ACE1/ACE2 imbalance is predicted to blunt COVID-19-associated morbidity and mortality, especially in vulnerable patients. Importantly, approved ARBs and ACEIs can be rapidly repurposed to test their efficacy in treating COVID-19.", "doc_id": "f7pf3jfs"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "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.", "abstract": "", "doc_id": "2lxn4ceu"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "The renin-angiotensin system - a therapeutic target in COVID-19?", "abstract": "COVID-19, caused by infection with SARS-CoV-2, is a disease characterised by cough, fever and fatigue, which progresses to life-threatening lung injury in approximately 5% of patients. The SARS-CoV-2 virus enters the cell via ACE2. ACE2 is a component of the renin-angiotensin system (RAS) which has an important counterregulatory effect on the classical ACE-dependent pathway. Several antihypertensives increase ACE2 expression or activity, leading to concern that this may facilitate SARS-CoV-2 entry and worsen COVID-19 disease. However, ACE2 is protective against lung injury while ANG II (which is catabolised by ACE2) is associated with lung injury both in mice and humans. We propose that medications which inhibit the RAS ACE-dependent pathway may be beneficial in treating COVID-19 and should be explored in animal models and clinical trials. Here we give an overview of the RAS pathway with respect to COVID-19 and argue that strategies which manipulate this pathway might reduce the destructive lung manifestations of COVID-19 and improve patient outcomes.", "doc_id": "6qp00p3j"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "ACE inhibitors, AT1 receptor blockers and COVID-19: clinical epidemiology evidences for a continuation of treatments. The ACER-COVID study", "abstract": "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.", "doc_id": "6baw4hmt"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Mortality and use of angiotensin converting enzyme inhibitors in Covid 19 disease - a systematic review.", "abstract": "Background. Interest exits concerning the use of angiotensin converting enzyme inhibitors (ACEi) in patients with Covid-19 disease. Objectives. To perform a systematic review on mortality associated to the use of ACEi in patients with Covid 19 disease. Methods. Search in Medline (PubMed) and in ISI Web of Knowledge; use of other sources. Results. A total of 19 articles were evaluated. Four studies were selected and used to produce the meta-analyses. These four studies involved a total number of 1.423 patients treated with ACEi and 11.868 not treated with ACEi. Significant heterogeneity was seen concerning mortality associated to the use of ACEi in the context of Covid-19 disease. One report showed significantly decreased mortality associated to ACEi use, but this finding was not confirmed by the three other studies. No significant difference in mortality was seen in the meta-analysis (ACEi users versus non-users; random effects; odds ratio, 0.93; 95% confidence interval [CI], 0.44 to 1.94; P=0.84). When compared to mortality in patients treated with angiotensin receptor blockers, mortality of patients treated with ACEi was not significantly different, although a trend was noted to exist (odds ratio, 0.74; 95% confidence interval [CI], 0.41 to 1.34; P=0.32). The population studied in the report showing decreased mortality associated to ACEi use had a mean age under 50 years, whereas two other reports had a mean or median patient age over 60 years. Conclusions. The data now presented argue in favor of carrying out clinical trials studying ACEi in Covid-19 patients, to explore the hypothesis that ACEi use has a protective effect in populations with a mean age under 50 years, but not necessarily in those with a mean age over 60 years.", "doc_id": "8hsqnwyj"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Kidney and Lung ACE2 expression after an ACE inhibitor or an Ang II receptor blocker: implications for COVID-19", "abstract": "Background There have been concerns that ACE inhibitors and Ang II receptor blockers may cause an increase in ACE2, the main receptor for SARs-CoV-2. Methods Kidneys from two genetic models of kidney ACE ablation and mice treated with captopril or telmisartan were used to examine ACE2 in isolated kidney and lung membranes. Results In a global ACE KO mice, ACE2 protein abundance in kidney membranes was reduced to 42 % of wild type, p < 0.05. In ACE 8/8 mice that over-expresses cardiac ACE protein but also has no kidney ACE expression, ACE2 protein in kidney membranes was also decreased (38 % of the WT, p<0.01). In kidney membranes from mice that received captopril or telmisartan for 2 weeks there was a reduction in ACE2 protein (37% in captopril treated p<0.01) and 76% in telmisartan treated p <0.05). In lung membranes the expression of ACE2 was very low and not detected by western blotting but no significant differences in terms of ACE2 activity could be detected in mice treated with captopril (118% of control) or telmisartan (93% of control). Conclusions Genetic kidney ACE protein deficiency, suppressed enzymatic activity by Captopril or blockade of the AT1 receptor with telmisartan are all associated with a decrease in ACE2 in kidney membranes. ACE2 protein in kidney or lungs is decreased or unaffected by RAS blockers indicating that these medications can not pose a risk for SARS-CoV-2 infection related to amplification of ACE2 at these two target sites for viral entry.", "doc_id": "7f7trre3"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Renin-angiotensin-aldosterone system inhibitors and COVID-19 infection or hospitalization: a cohort study", "abstract": "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 [\u2265]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 [\u2265]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.", "doc_id": "01xdd8zf"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Treatment of patients with COVID-19 and concomitant cardiovascular diseases: Do not Forget about the Principles of Evidence-based Medicine/ \u041b\u0435\u0447\u0435\u043d\u0438\u0435 \u0431\u043e\u043b\u044c\u043d\u044b\u0445 \u0441 COVID-19 \u0438 \u0441\u043e\u043f\u0443\u0442\u0441\u0442\u0432\u0443\u044e\u0449\u0438\u043c\u0438 \u0441\u0435\u0440\u0434\u0435\u0447\u043d\u043e-\u0441\u043e\u0441\u0443\u0434\u0438\u0441\u0442\u044b\u043c\u0438 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u044f\u043c\u0438: \u043d\u0435 \u0437\u0430\u0431\u044b\u0432\u0430\u0442\u044c \u043e \u043f\u0440\u0438\u043d\u0446\u0438\u043f\u0430\u0445 \u0434\u043e\u043a\u0430\u0437\u0430\u0442\u0435\u043b\u044c\u043d\u043e\u0439 \u043c\u0435\u0434\u0438\u0446\u0438\u043d\u044b", "abstract": "The recent discussion about the dangers of using angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA) in patients with COVID-19 is analyzed in the article. There is controversy over the hypothesis that these drugs can be factors contributing to an unfavorable outcome of a viral disease, as well as the absence of any clinical evidence for this hypothesis. The opinion that withdrawal of ACE inhibitors and ARA in patients with COVID-19 may increase the risk of adverse outcomes is presented.", "doc_id": "i7scw9mu"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "[Renin-angiotensin-aldosterone blockers and Covic-19 infection : friends or enemies ?]", "abstract": "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.", "doc_id": "eccv9401"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Angiotensin-converting enzyme 2 in severe acute respiratory syndrome coronavirus and SARS-CoV-2: A double-edged sword?", "abstract": "Human angiotensin-converting enzyme 2 (ACE2) facilitates cellular entry of severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 as their common receptor. During infection, ACE2-expressing tissues become direct targets, resulting in serious pathological changes and progressive multiple organ failure or even death in severe cases. However, as an essential component of renin-angiotensin system (RAS), ACE2 confers protective effects in physiological circumstance, including maintaining cardiovascular homeostasis, fluid, and electrolyte balance. The absence of protective role of ACE2 leads to dysregulated RAS and thus acute changes under multiple pathological scenarios including SARS. This potentially shared mechanism may also be the molecular explanation for pathogenesis driven by SARS-CoV-2. We reasonably speculate several potential directions of clinical management including host-directed therapies aiming to restore dysregulated RAS caused by ACE2 deficiency. Enriched knowledge of ACE2 learned from SARS and COVID-19 outbreaks can provide, despite their inherent tragedy, informative clues for emerging pandemic preparedness.", "doc_id": "0pknmeip"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19", "abstract": "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.", "doc_id": "fskfnmig"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Inhibitors of the renin-angiotensin system: The potential role in the pathogenesis of COVID-19", "abstract": "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.", "doc_id": "g4d4bdw0"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "[Role of age, comorbidity and renin- angiotensin-aldosterone system in COVID-19. Effects of ACE inhibitors and angiotensin receptor blockers]", "abstract": "The review addressed the relationship of coronavirus disease 2019 (COVID-19) with functioning of the renin-angiotensin-aldosterone axis and the causes for unfavorable prognosis depending on patients' age and comorbidities. The authors discussed in detail potential effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists on the risk of infection and the course of COVID-2019 as well as the effect of SARS-COV2 virus on the cardiovascular system.", "doc_id": "8nn7lja8"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "The role of angiotensin-converting enzyme 2 in coronaviruses/influenza viruses and cardiovascular disease", "abstract": "Angiotensin-converting enzyme 2 (ACE2) has emerged as a key regulator of the renin-angiotensin system in cardiovascular (CV) disease and plays a pivotal role in infections by coronaviruses and influenza viruses. The present review is primarily focused on the findings to indicate the role of ACE2 in the relationship of coronaviruses and influenza viruses to CV disease. It is postulated that the risk of coronavirus or influenza virus infection is high, at least partly due to high ACE2 expression in populations with a high CV risk. Coronavirus and influenza virus vaccine usage in high CV risk populations could be a potential strategy to prevent both CV disease and coronavirus/influenza virus infections.", "doc_id": "74la14km"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Long-Term ACE Inhibitor/ARB Use Is Associated with Severe Renal Dysfunction and Acute Kidney Injury in Patients with severe COVID-19: Results from a Referral Center Cohort in the North East of France", "abstract": "BACKGROUND: In patients with severe COVID-19, data are scarce and conflicting regarding whether chronic use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) influences disease outcomes. In patients with severe COVID-19, we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and the severity of the inflammatory reaction as evaluated by biomarkers kinetics, and their association with disease outcomes. METHODS: We performed a retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19. Independent predictors were assessed through receiver operating characteristic analysis, time-series analysis, logistic regression analysis, and multilevel modeling for repeated measures. RESULTS: On the 149 patients included in the study 30% (44/149) were treated with ACEI/ARB. ACEI/ARB use was independently associated with the following biochemical variations: phosphorus >40 mg/L (odds ratio [OR], 3.35, 95% CI, 1.83-6.14), creatinine >10.1 mg/L (OR, 3.22, 2.28-4.54), and urea nitrogen (UN) >0.52 g/L (OR, 2.65, 1.89-3.73). ACEI/ARB use was independently associated with acute kidney injury, AKI stage ≥1 (OR, 3.28, 2.17-4.94). The daily dose of ACEI/ARB was independently associated with altered kidney markers with an increased risk of +25 to +31% per each 10 mg increment of lisinopril-dose equivalent. In multivariable multilevel modeling, UN >0.52 g/L was independently associated with the risk of acute respiratory failure (OR, 3.54, 1.05-11.96). CONCLUSIONS: Patients chronically treated with ACEI/ARB who have severe COVID-19 are at increased risk of acute kidney injury. In these patients, the increase in UN associated with ACEI/ARB use could predict the development of acute respiratory failure.", "doc_id": "7om3bpby"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Renin-Angiotensin System Blockers and the COVID-19 Pandemic: At Present There Is No Evidence to Abandon Renin-Angiotensin System Blockers", "abstract": "During the spread of the severe acute respiratory syndrome coronavirus-2, some reports of data still emerging and in need of full analysis indicate that certain groups of patients are at risk of COVID-19. This includes patients with hypertension, heart disease, diabetes mellitus, and clearly the elderly. Many of those patients are treated with renin-angiotensin system blockers. Because the ACE2 (angiotensin-converting enzyme 2) protein is the receptor that facilitates coronavirus entry into cells, the notion has been popularized that treatment with renin-angiotensin system blockers might increase the risk of developing a severe and fatal severe acute respiratory syndrome coronavirus-2 infection. The present article discusses this concept. ACE2 in its full-length form is a membrane-bound enzyme, whereas its shorter (soluble) form circulates in blood at very low levels. As a mono-carboxypeptidase, ACE2 contributes to the degradation of several substrates including angiotensins I and II. ACE (angiotensin-converting enzyme) inhibitors do not inhibit ACE2 because ACE and ACE2 are different enzymes. Although angiotensin II type 1 receptor blockers have been shown to upregulate ACE2 in experimental animals, the evidence is not always consistent and differs among the diverse angiotensin II type 1 receptor blockers and differing organs. Moreover, there are no data to support the notion that ACE inhibitor or angiotensin II type 1 receptor blocker administration facilitates coronavirus entry by increasing ACE2 expression in either animals or humans. Indeed, animal data support elevated ACE2 expression as conferring potential protective pulmonary and cardiovascular effects. In summary, based on the currently available evidence, treatment with renin-angiotensin system blockers should not be discontinued because of concerns with coronavirus infection.", "doc_id": "axvti3jw"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Response by Cohen et al to Letter Regarding Article, \"Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19\"", "abstract": "", "doc_id": "abosc200"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Physiological and pathological regulation of ACE2, the SARS-CoV-2 receptor", "abstract": "The renin-angiotensin system (RAS) is crucial for the physiology and pathology of all the organs. Angiotensin-converting enzyme 2 (ACE2) maintains the homeostasis of RAS as a negative regulator. Recently, ACE2 was identified as the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus that is causing the pandemic of Coronavirus disease 2019 (COVID-19). Since SARS-CoV-2 must bind with ACE2 before entering the host cells in humans, the distribution and expression of ACE2 may be critical for the target organ of the SARS-CoV-2 infection. Moreover, accumulating evidence has demonstrated the implication of ACE2 in the pathological progression in tissue injury and several chronic diseases, ACE2 may also be essential in the progression and clinical outcomes of COVID-19. Therefore, we summarized the expression and activity of ACE2 in various physiological and pathological conditions, and discussed its potential implication in the susceptibility of SARS-CoV-2 infection and the progression and prognosis of COVID-19 patients in the current review.", "doc_id": "1ju6dzxq"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Angiotensin receptor blockers and COVID-19", "abstract": "Angiotensin Receptor Blockers (ARBs) exhibit major pleiotropic protecting effects beyond their antihypertensive properties, including reduction of inflammation. ARBs directly protect the lung from the severe acute respiratory syndrome as a result of viral infections, including those from coronavirus. The protective effect of ACE2 is enhanced by ARB administration. For these reasons ARB therapy must be continued for patients affected by hypertension, diabetes and renal disease, comorbidities of the current COVID-19 pandemic. Controlled clinical studies should be conducted to determine whether ARBs may be included as additional therapy for COVID-19 patients.", "doc_id": "67j4gamu"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "SARS-CoV2: should inhibitors of the renin-angiotensin system be withdrawn in patients with COVID-19?", "abstract": "", "doc_id": "c981zfz6"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Coronavirus disease 2019 (COVID-19) and the renin-angiotensin system: A closer look at angiotensin-converting enzyme 2 (ACE2)", "abstract": "Since the first cases of atypical pneumonia linked to the Huanan Seafood Wholesale Market in Wuhan, China, were described in late December 2019, the global landscape has changed radically. In March 2020, the World Health Organization declared COVID-19 a global pandemic, and at the time of writing this review, just over three million individuals have been infected with more than 200,000 deaths globally. Numerous countries are in 'lockdown', social distancing is the new norm, even the most advanced healthcare systems are under pressure, and a global economic recession seems inevitable. A novel coronavirus (SARS-CoV-2) was identified as the aetiological agent. From experience with previous coronavirus epidemics, namely the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in 2004 and 2012 respectively, it was postulated that the angiotensin-converting enzyme-2 (ACE2) receptor is a possible port of cell entry. ACE2 is part of the renin-angiotensin system and is also associated with lung and cardiovascular disorders and inflammation. Recent studies have confirmed that ACE2 is the port of entry for SARS-CoV-2. Male sex, advanced age and a number of associated comorbidities have been identified as risk factors for infection with COVID-19. Many high-risk COVID-19 patients with comorbidities are on ACE inhibitors and angiotensin receptor blockers, and this has sparked debate about whether to continue these treatment regimes. Attention has also shifted to ACE2 being a target for future therapies or vaccines against COVID-19. In this review, we discuss COVID-19 and its complex relationship with ACE2.", "doc_id": "27t64idh"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "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", "abstract": "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 \u00b1 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.", "doc_id": "aj1yup6a"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study", "abstract": "BACKGROUND: Concerns have been raised about the possibility that inhibitors of the renin-angiotensin-aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19. METHODS: In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigaci\u00f3n Farmacoepidemiol\u00f3gica en Atenci\u00f3n Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437. FINDINGS: We collected data for 1139 cases and 11\u00e2\u0080\u0088390 population controls. Among cases, 444 (39\u00b70%) were female and the mean age was 69\u00b71 years (SD 15\u00b74), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1\u00b798, 95% CI 1\u00b762-2\u00b741) and risk factors (1\u00b746, 1\u00b723-1\u00b773) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0\u00b794 (95% CI 0\u00b777-1\u00b715). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0\u00b780, 0\u00b764-1\u00b700) or angiotensin-receptor blockers (1\u00b710, 0\u00b788-1\u00b737). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0\u00b753, 95% CI 0\u00b734-0\u00b780). The adjusted ORs were similar across severity degrees of COVID-19. INTERPRETATION: RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19. FUNDING: Instituto de Salud Carlos III.", "doc_id": "d8n4rpod"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and coronavirus", "abstract": "", "doc_id": "afx0j2wy"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Ramipril in High Risk Patients with COVID-19", "abstract": "BACKGROUND: The coronavirus disease 2019 (COVID-19) is caused by SARS-CoV2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting enzyme 2 (ACE-2). This interaction has been proposed as a potential risk factor in patients treated with RAAS-inhibitors. OBJECTIVES: To analyze if RAAS-inhibitors modify the risk for COVID-19. METHODS: RASTAVI (NCT03201185) is an ongoing randomized clinical trial randomly allocating Ramipril or control after successful transcatheter aortic valve replacement at 14 centers is Spain. We performed a non-pre-specified interim analysis to evaluate its impact on COVID-19 risk in this vulnerable population. RESULTS: As in April 1st 2020, 102 patients (50 Ramipril and 52 controls) were included in the trial. Mean age was 82.3\u00b16.1 years, 56.9% males. Median time of Ramipril treatment was 6 months [IQR:2.9-11.4]. Eleven patients (10.8%) have been diagnosed with COVID-19 (6 in control group and 5 receiving Ramipril, HR=1.150 [95%CI: 0.351-3.768]). The risk of COVID-19 was increased in older patients (p=0.019), those with atrial fibrillation (p=0.066), lower hematocrit (p=0.084), and more comorbidities according to Society of thoracic surgeons score (p=0.065). Admission and oxygen supply was required in 4.9% (2 patients in the Ramipril and 3 in control), and 4 of them died (two in each randomized group). A higher body mass index was the only factor increasing the mortality rate (p=0.039). CONCLUSIONS: In a high risk population of old patients with cardiovascular disease, randomization to Ramipril had no impact in the incidence or severity of COVID-19. This analysis supports the maintenance of RAAS-inhibitor treatment during COVID-19 crisis.", "doc_id": "67psg92z"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--The BRACE CORONA Trial", "abstract": "Angiotensin-converting enzyme-2 (ACE2) expression may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs). Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19. The impact of discontinuing ACEI and ARBs in patients with COVID-19 remains uncertain. DESIGN: BRACE CORONA is a pragmatic, multicenter, randomized, phase IV, clinical trial that aims to enroll around 500 participants at 34 sites in Brazil. Participants will be identified from an ongoing national registry of suspected and confirmed cases of COVID-19. Eligible patients using renin-angiotensin system blockers (ACEI/ARBs) with a confirmed diagnosis of COVID-19 will be randomized to a strategy of continued ACEI/ARB treatment versus temporary discontinuation for 30 days. The primary outcome is the median days alive and out of the hospital at 30 days. Secondary outcomes include progression of COVID-19 disease, all-cause mortality, death from cardiovascular causes, myocardial infarction, stroke, transient ischemic attack, new or worsening heart failure, myocarditis, pericarditis, arrhythmias, thromboembolic events, hypertensive crisis, respiratory failure, hemodynamic decompensation, sepsis, renal failure, and troponin, B-type natriuretic peptide (BNP), N-terminal-proBNP, and D-dimer levels. SUMMARY: BRACE CORONA will evaluate whether the strategy of continued ACEI/ARB therapy compared with temporary discontinuation of these drugs impacts clinical outcomes among patients with COVID-19.", "doc_id": "d0stuu6j"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Patients With Coronavirus Disease 2019: Friend or Foe?", "abstract": "When the coronavirus disease 2019 (COVID-19) wreaked an unprecedented havoc of an escalating number of deaths and hospitalization in the United States, clinicians were faced with a myriad of unanswered questions, one of the them being the implication of the renin-angiotensin-aldosterone system in patients with COVID-19. Animal data and human studies have shown that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) increase the expression of ACE2. ACE2 is an enzyme found in the heart, kidney, gastrointestinal tract, and lung and is a coreceptor for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV2), the virus responsible for COVID-19. Therefore, one can speculate that discontinuing ACE inhibitor or ARB therapy may lead to decreased ACE2 expression, thereby attenuating the infectivity of SARS-CoV-2, and mitigating the disease progression of COVID-19. However, several studies have also shown that ACE2 exhibits reno- and cardioprotection and preserves lung function in acute respiratory distress syndrome, which would favor ACE inhibitor or ARB therapy. This article is to examine and summarize the 2 opposing viewpoints and provide guideline recommendations to support the use or discontinuation of ACE inhibitors and ARBs in patients with COVID-19.", "doc_id": "19h27op5"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Angiotension-converting enzyme inhibitors and angiotensin-receptor blockers are not associated with increased risk of SARS-CoV-2 infection", "abstract": "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.", "doc_id": "amgkcxaw"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Overview of Covid-19 regarding the cardiovascular situation in the light of current reports", "abstract": "Nowadays coronavirus disease 2019 (Covid-19) is increasing mortality all over the world mercilessly. We are learning almost every day about its new symptoms and that it mutates quickly. This disease ties us up and leaves us desperate. Death from this disease has increased in patients who had with pre-existing medical conditions, especially cardiovascular ones, by eliminating the angiotensin-converting enzyme (ACE)-2 receptor in the lungs. Also, ACE1 and angiotensin receptor blockers (ARB) may stimulate ACE2 expression and worse the prognosis. Intravenous infusions of ACEIs and ARBs in experimental animals increase the numbers of ACE2 receptors. So, it may be one of the reasons that COVID-19 infects the cells of patients treating hypertension. However, most of the congress of cardiology do not recommend discontinue of these anti-hypertensive drugs. Therefore, this brief report evaluates Covid-19 in the view of cardiovascular diseases taking into account current reports and suggests some possible solutions to keep the virus under control.", "doc_id": "f3pdbv1g"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Renin-Angiotensin-System (RAS) und COVID-19 \u00ad Zur Verordnung von RAS-Blockern./ [Renin-Angiotensin-System (RAS) and COVID-19 - On The Prescription of RAS Blockers]", "abstract": "Twenty years ago, an enzyme homologous to the previously known angiotensin-converting enzyme (ACE) was identified, and subsequently named ACE2. In the renin-angiotensin system (RAS), ACE2 has counter-regulatory functions against the classical effector peptide angiotensin II, for example in blood pressure regulation and cardiovascular remodeling. However, ACE2 provides an initially unexpected interesting link between virology and cardiovascular medicine. That is, ACE2 represents the binding receptor for the cellular uptake of SARS-CoV and SARS-CoV-2 viruses. Thus, ACE2 is relevant for COVID-19. In this context, it was suspected that therapy with RAS blockers might promote transmission and complications of COVID-19 by upregulation of ACE2 expression. The aim of this short review is, to describe the link between the RAS, particularly ACE2, and COVID-19. Based on our analysis and evaluation of the available findings, we justify our conclusion: important drugs such as ACE inhibitors and angiotensin receptor blockers should continue to be prescribed according to guidelines to stable patients in the context of the COVID-19 pandemic.", "doc_id": "c3mclbgp"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Drugs acting on renin angiotensin system and use in ill patients with COVID-19", "abstract": "Some concerns about the prescription of drugs acting on the renin-angiotensin system (angiotensin-converting enzyme 1 (ACE1) inhibitors, ACEi; angiotensin II type 1 receptor blockers, ARB) have emerged due to SARS COV2 and COVID-19 pandemic. These very legitimate questions are directly the consequence of the recent recognition of the fundamental role of ACE2 (angiotensin-converting enzyme 2) in COVID-19 infection. Indeed, SARS COV2 utilizes ACE2 as a membrane receptor to enter target cells. Consequently, the putative impact of drugs modulating the renin-angiotensin system on the risk of developing severe or fatal severe acute respiratory syndrome in case of COVID-19 infection emerged. As a membrane-bound enzyme (carboxypeptidase), ACE2 inactivates angiotensin II and therefore physiologically counters its effects. Due to a different structure compared with ACE1, ACE2 is insensitive to ACEIs. In vitro, both ARBs and ACEi appear able to upregulate ACE2 tissue expression and activity but these results were not confirmed in Humans. The exact impact of both ARBs and ACEis on COVID-19 infection is definitively known and preliminary results are even in favor of a protective role confers by these drugs. Due to the crucial role of ACE2, some groups support the hypothesis that a modulation of ACE2 expression could represent a valuable therapeutic target could confer protective properties against inflammatory tissue damage in COVID-19 infection. So, studies are currently ongoing to test the impact of elevated ACE2 membrane expression, administration of ARB and infusion of soluble ACE2. In summary, based on the currently available evidences and as recommended by several medical societies, ACEi or ARB should not be systematically discontinued because to date no safety signal was raised with the use of these drugs.", "doc_id": "4rmbfgo2"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Comparative impacts of angiotensin converting enzyme inhibitors versus angiotensin II receptor blockers on the risk of COVID-19 mortality", "abstract": "N/A.", "doc_id": "4ctk5vme"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Outbreak of SARS-CoV2: Pathogenesis of infection and cardiovascular involvement", "abstract": "Since the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has emerged from China, the infection (novel corona virus disease-2019, COVID-19) has affected many countries and led to many deaths worldwide. Like SARS-CoV, angiotencin converting enzyme (ACE)2 as a functional receptor for SARS-CoV2 is essential for the virus to make an entry into the cell. ACE2 is a part of Renin-Angiotensin-Aldosterone System, which is expressed in several organs that opposes the angiotensin (Ang) II functions by converting Ang II to Ang (1-7), the one with vasodilation effects. The death rate of COVID-19 is estimated to be approximately 3.4%; however, some comorbid conditions like underlying cardiovascular disease, hypertension, and diabetes increase the risk of mortality. In addition, cardiovascular involvement as a complication of SARS-CoV2 could be direct through either ACE2 receptors that are expressed tremendously in the heart, or by the surge of different cytokines or by acute respiratory distress syndrome-induced hypoxia. Traditional risk factors could aggravate the process of COVID-19 infection that urges the triage of these high-risk patients for SARS-CoV2. Currently, there is no effective, proven treatment or vaccination for COVID-19, but many investigators are struggling to find a treatment strategy as soon as possible. Some potential medications like chloroquine by itself or in combination with azithromycin and some protease inhibitors used for the treatment of COVID-19 have cardiovascular adverse effects, which should be kept in mind while the patients taking these medications are being closely monitored.", "doc_id": "7gasxvwd"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "SARS-CoV-2 receptor ACE2-dependent implications on the cardiovascular system: From basic science to clinical implications", "abstract": "The current COVID-19 pandemic started several months ago and is still exponentially growing in most parts of the world - this is the most recent and alarming update. COVID-19 requires the collaboration of nearly 200 countries to curb the spread of SARS-CoV-2 while gaining time to explore and improve treatment options especially for cardiovascular disease (CVD) and immunocompromised patients, who appear to be at high-risk to die from cardiopulmonary failure. Currently unanswered questions are why elderly people, particularly those with pre-existing comorbidities seem to exhibit higher mortality rates after SARS-CoV-2 infection and whether intensive care becomes indispensable for these patients to prevent multi-organ failure and sudden death. To face these challenges, we here summarize the molecular insights into viral infection mechanisms and implications for cardiovascular disease. Since the infection starts in the upper respiratory system, first flu-like symptoms develop that spread throughout the body. The wide range of affected organs is presumably based on the common expression of the major SARS-CoV-2 entry-receptor angiotensin-converting enzyme 2 (ACE2). Physiologically, ACE2 degrades angiotensin II, the master regulator of the renin-angiotensin-aldosterone system (RAAS), thereby converting it into vasodilatory molecules, which have well-documented cardio-protective effects. Thus, RAAS inhibitors, which may increase the expression levels of ACE2, are commonly used for the treatment of hypertension and CVD. This, and the fact that SARS-CoV-2 hijacks ACE2 for cell-entry, have spurred controversial discussions on the role of ACE2 in COVID-19 patients. In this review, we highlight the state-of-the-art knowledge on SARS-CoV-2-dependent mechanisms and the potential interaction with ACE2 expression and cell surface localization. We aim to provide a list of potential treatment options and a better understanding of why CVD is a high risk factor for COVID-19 susceptibility and further discuss the acute as well as long-term cardiac consequences.", "doc_id": "7j4gbmf7"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Good or bad: Application of RAAS inhibitors in COVID-19 patients with cardiovascular comorbidities", "abstract": "The coronavirus disease 2019 (COVID-19) pandemic is caused by a newly emerged coronavirus (CoV) called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). COVID-19 patients with cardiovascular disease (CVD) comorbidities have significantly increased morbidity and mortality. The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor type 1 blockers (ARBs) improve CVD outcomes; however, there is concern that they may worsen the prognosis of CVD patients that become infected with SARS-CoV-2 because the virus uses the ACE2 receptor to bind to and subsequently infect host cells. Thus, some health care providers and media sources have questioned the continued use of ACE inhibitors and ARBs. In this brief review, we discuss the effect of ACE inhibitor-induced bradykinin on the cardiovascular system, on the renin-angiotensin-aldosterone system (RAAS) regulation in COVID-19 patients, and analyze recent clinical studies regarding patients treated with RAAS inhibitors. We propose that the application of RAAS inhibitors for COVID-19 patients with CVDs may be beneficial rather than harmful.", "doc_id": "795u01zb"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors", "abstract": "AIMS: The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease. Recent reports suggest an association with use of renin-angiotensin-aldosterone system (RAAS) inhibitors. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses. Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors. METHODS AND RESULTS: We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort). Results were validated in 1123 men and 575 women (validation cohort).The median age was 69 years for men and 75 years for women. The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively). In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2. In the validation cohort, ACE inhibitor (estimate = -0.17, P = 0.002) and ARB use (estimate = -0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations. CONCLUSION: In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.", "doc_id": "8d6xxjgu"} {"topic_name": "coronavirus and ACE inhibitors", "topic_id": "20", "title": "Antihypertensive drugs and risk of COVID-19? - Authors' reply", "abstract": "", "doc_id": "fv2efcf2"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Early dinner or \"dinner like a pauper\": Evidence, the habitual time of the largest meal of the day - dinner - is predisposing to severe COVID-19 outcome - death.", "abstract": "COVID-19 and metabolic syndrome are devastating pandemics. Effective control of metabolic parameters and their dysfunction may help prevent or minimize the acute and devastating effects of SARS-CoV-2 by reducing the local inflammatory response and blocking the entry of the virus into cells. With such consideration in mind, we gathered data from dietary surveys conducted in nine European countries to explore the relationship between actual clock hour of the large dinner meal and also interval in minutes between it and sunset in the respective countries and death rate above the median rate of per one million people as an index of mortality due to COVID-19 infection. Clock time of the dinner meal varied between 16:00 and 21:00 h across the European counties sampled, and the correlation between dinner mealtime and death rate was strongly correlated, R = 0.7991 (two-tailed p = 0.0098), with R 2 explaining 63% of the variation within the data. This strong linear positive correlation indicates that the later the clock time of the dinner meal, the higher is the death rate (and vice versa). The relationship between meal timing in reference to sunset, utilized as a gross surrogate marker of the activity/rest synchronizer of circadian rhythms, and death rate was negative and even slightly stronger, R = -0.8025 (two-tailed p = 0.0092), with R 2 explaining 64% of the variation within the data. This strong linear negative correlation indicates that the shorter the interval between the dinner meal and sunset, i.e., the closer the time of the largest meal of the day to bedtime, the greater is the death rate (and vice versa). Our preliminary approach to nighttime eating, in terms of the day's largest caloric intake, as a risk factor for the predisposing conditions of obesity, metabolic syndrome, type 2 diabetes, and other commonly associated comorbidities of being overweight, and death from COVID-19 infection reveals strong correlation with the time of the dinner meal, both in terms of its actual clock and circadian time.", "doc_id": "ale31a10"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Excess Mortality Estimation During the COVID-19 Pandemic: Preliminary Data from Portugal.", "abstract": "INTRODUCTION Portugal is experiencing the effects of the COVID-19 pandemic since March 2020. All-causes mortality in Portugal increased during March and April 2020 compared to previous years, but this increase is not explained by COVID-19 reported deaths. The aim of this study was to analyze and consider other criteria for estimating excessive all-cause mortality during the early COVID-19 pandemic period. MATERIAL AND METHODS Public data was used to estimate excess mortality by age and region between March 1 and April 22, proposing baselines adjusted for the lockdown period. RESULTS Despite the inherent uncertainty, it is safe to assume an observed excess mortality of 2400 to 4000 deaths. Excess mortality was associated with older age groups (over age 65). DISCUSSION The data suggests a ternary explanation for early excess mortality: COVID-19, non-identified COVID-19 and decrease in access to healthcare. The estimates have implications in terms of communication of non-pharmaceutical actions, for research, and to healthcare professionals. CONCLUSION The excess mortality occurred between March 1 and April 22 was 3 to 5 fold higher than what can be explained by the official COVID-19 deaths.", "doc_id": "1v5o4as8"} {"topic_name": "coronavirus mortality", "topic_id": "21", "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.", "abstract": "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\u00b786 (95% CI 10\u00b742-13\u00b730; I2=94\u00b71%) in female individuals and 7\u00b788 (7\u00b703-8\u00b774; I2=99\u00b71%) 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\u00b789; 95% CI 6\u00b740-9\u00b737; I2=98\u00b71%) and women (18\u00b772; 13\u00b773-23\u00b771; I2=91\u00b75%). 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.", "doc_id": "h9gfyeb8"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "SARS-CoV-2 in Italy: Population Density correlates with Morbidity and Mortality.", "abstract": "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.", "doc_id": "3t8636xa"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Rate of Intensive Care Unit admission and outcomes among patients with coronavirus: A systematic review and Meta-analysis.", "abstract": "BACKGROUND The rate of ICU admission among patients with coronavirus varied from 3% to 100% and the mortality was as high as 86% of admitted patients. The objective of the systematic review was to investigate the rate of ICU admission, mortality, morbidity, and complications among patients with coronavirus. METHODS A comprehensive strategy was conducted in PubMed/Medline; Science direct and LILACS from December 2002 to May 2020 without language restriction. The Heterogeneity among the included studies was checked with forest plot, \u03c72 test, I2 test, and the p-values. All observational studies reporting rate of ICU admission, the prevalence of mortality and its determinants among ICU admitted patients with coronavirus were included and the rest were excluded. RESULT A total of 646 articles were identified from different databases and 50 articles were selected for evaluation. Thirty-seven Articles with 24983 participants were included. The rate of ICU admission was 32% (95% CI: 26 to 38, 37 studies and 32, 741 participants). The Meta-Analysis revealed that the pooled prevalence of mortality in patients with coronavirus disease in ICU was 39% (95% CI: 34 to 43, 37 studies and 24, 983 participants). CONCLUSION The Meta-Analysis revealed that approximately one-third of patients admitted to ICU with severe Coronavirus disease and more than thirty percent of patients admitted to ICU with a severe form of COVID-19 for better care died which warns the health care stakeholders to give attention to intensive care patients. REGISTRATION This Systematic review and Meta-Analysis was registered in Prospero international prospective register of systemic reviews (CRD42020177095) on April 9/2020.", "doc_id": "0dp28rsd"} {"topic_name": "coronavirus mortality", "topic_id": "21", "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.", "abstract": "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\u00b75% 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\u00b79 years (95% UI 86\u00b77-87\u00b72), and for men in Singapore, at 81\u00b73 years (78\u00b78-83\u00b77) 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.", "doc_id": "eet3v4cs"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Mortality rate and gender differences in COVID-19 patients dying in Italy: A comparison with other countries.", "abstract": "", "doc_id": "0c21csjz"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "COVID-19 mortality rates in the European Union, Switzerland, and the UK: effect of timeliness, lockdown rigidity, and population density.", "abstract": "BACKGROUND To date the European experience with COVID-19 mortality has been different to the observed in China and Asia. We aimed to forecast mortality trends in the 27 countries of the European Union (EU), plus Switzerland and the United Kingdom (UK), where lockdown dates and confinement interventions have been heterogeneous, and to explore its determinants. METHODS We have adapted our predictive model of COVID-19-related mortality, which rested on the observed mortality within the first weeks of the outbreak and the date of the respective lockdown in each country. It was applied in a training set of three countries (Italy, Germany and Spain), and then applied to the EU plus the UK and Switzerland. In addition, we explored the effects of timeliness and rigidity of the lockdown (on a five-step scale) and population density in our forecasts. We report r2, and percent variation of expected versus observed deaths, all following TRIPOD guidance. RESULTS We identified a homogeneous distribution of deaths, and found a median of 24 days after lockdown adoption to reach the maximum daily deaths. Strikingly, cumulative deaths up to April 25th, 2020 observed in Europe separated countries in three waves, according to the time lockdown measures were adopted following the onset of the outbreak: after a week, within a week, or even prior to the outbreak (r2=0.876). In contrast, no correlation neither with lockdown rigidity nor population density were observed. CONCLUSIONS The European experience confirms that early, effective interventions of 86 lockdown are fundamental to minimizing the COVID-19 death toll.", "doc_id": "3xdzh2wj"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Mortality Rates of Patients with Proximal Femoral Fracture in a Worldwide Pandemic: Preliminary Results of the Spanish HIP-COVID Observational Study.", "abstract": "BACKGROUND The outbreak of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), in December 2019 in Wuhan, People's Republic of China, has developed into an unprecedented pandemic with enormous pressure on health-care providers around the world. A higher mortality rate has been described in older infected individuals. Patients with hip fracture are a particularly vulnerable population during this pandemic because older age is associated with a higher mortality rate. Our aim was to describe the early mortality rate and demographic variables in a hip fracture sample population in Spain during the coronavirus pandemic. METHODS This is a multicenter, observational, retrospective, descriptive study. We collected data from 13 major hospitals in Spain from the beginning of the national state of alarm (declared on March 14, 2020, by the Spanish government) until the end of our study period on April 4, 2020. All patients who were \u226565 years of age, presented to the Emergency Department of the participating hospitals during this period with a diagnosis of proximal femoral fracture, and had a minimum follow-up of 10 days were included in the cohort. In addition to mortality, demographic and other potential prognostic variables were also collected. RESULTS In this study, 136 patients with a hip fracture were included. Of these patients, 124 underwent a surgical procedure and 12 were managed nonoperatively. The total mortality rate was 9.6%. Sixty-two patients were tested for COVID-19, with 23 patients being positive. The mortality rate for these 23 patients was 30.4% (7 of 23 patients) at a mean follow-up of 14 days. The mortality rate was 10.3% (4 of 39) for patients who had been tested and had a negative result and 2.7% (2 of 74) for patients who had not been tested. Of the 12 patients who were managed nonoperatively, 8 (67%) died, whereas, of the 124 patients who were surgically treated, 5 (4%) died. Results differed among centers. CONCLUSIONS There is a higher mortality rate in patients with a hip fracture and an associated positive test for COVID-19. LEVEL OF EVIDENCE Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.", "doc_id": "9x937eus"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Assumptions for disparities in case-fatality rates of coronavirus disease (COVID-19) across the globe.", "abstract": "In a short span, Coronavirus disease (COVID-19) has become the world pandemic by rapidly spreading almost to all the countries around the globe, irrespective of the continent, population size, economic status and healthcare system. Despite the number of cases increasing exponentially in most of the countries, there exist certain disparities in terms of case-fatality rates. As of April 24, 2020, the case-fatality rate of COVID-19 is about 7.0%, with 193,671 deaths and 2,761,121 confirmed cases around the world. Although the United States of America (USA), Spain, Italy, France, and Germany are the top-most affected counties in terms of confirmed cases; France, Italy and Spain are leading the list in terms of case-fatality rates. Therefore, through this mini-review, authors sought to brief on possible assumptions (five D's) that might contribute to the varying case-fatality rates among different countries across the globe.", "doc_id": "4yihgo8u"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Covid-19: Cancer mortality could rise at least 20% because of pandemic, study finds.", "abstract": "", "doc_id": "4ni2xvyk"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "COVID-19 death rates by age and sex and the resulting mortality vulnerability of countries and regions in the world", "abstract": "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.", "doc_id": "cysj93kv"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "A statistical forecast of LOW mortality and morbidity due to COVID-19, in ARGENTINA and other Southern Hemisphere countries.", "abstract": "A set of open source programs in Python is devised to fit a parametric integrated Gaussian equation to cumulative deaths due to COVID-19 in Southern Hemisphere countries. The programs were successfully tested using data from advanced outbreak trajectories (Italy and Spain). The procedure was applied to data reported by Argentina. The projected total death toll will be 182 (277-182) with a peak of deaths (6(+/-2)) the 14 of April. The outbreak begins the 9th of March and end completely the 20th of May. However, already on 1st of May, 2 s (95.45%) of the deaths have occurred. The death toll arises from a number of infected individuals between 36412 and 2275. Then, they were to use to process data from several Southern Hemisphere countries: Argentina, Brazil, Mexico, Peru, Colombia, Ecuador, Cuba, Chile, Panama, Australia, Bolivia, Honduras, New Zealand, Paraguay, Guatemala, Venezuela, Uruguay, El Salvador, Jamaica, Haiti, Costa Rica and Nicaragua. The trend is to show low number of total deaths compared with other disease outbreaks. A total projected number of deaths between 15148 and 9939 deaths for a total population of ca. 664 M inhabitants. The projected death toll is much lower (5-10 times) than those forecasted by the Imperial College Group (ICG) even considering the best scenario of total suppression of virus transmission. Using actual mortality rates it is possible to back calculate which number of infected individuals would produce such mortality. The calculated number of infected individuals (worst case scenario) is below 2.5 million. This is significantly lower than that calculated by ICG (> 45 millions). In most countries the outbreak will end in May or early June. The dynamics of the outbreaks seems to do not saturate the health services (hospital beds) but only Peru, Ecuador and Panama should have not enough ICU beds for grave COVID-19 patients", "doc_id": "0yaqhphd"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Estimating the Size of High-risk Populations for COVID-19 Mortality across 442 US Cities", "abstract": "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.", "doc_id": "9n9irx70"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "The lower COVID-19 related mortality and incidence rates in Eastern European countries are associated with delayed start of community circulation", "abstract": "Background: The purpose of this analysis was to assess the variations in COVID-19 related mortality and incidence rates in relation to the time differences in the commencement of virus circulation and containment measures in different countries of the European Region. Methods: The data for the current analysis (N=50 countries) were retrieved from the John Hopkins University dataset on the 7th of May 2020, with countries as study units. A piecewise regression analysis was conducted with mortality and cumulative incidence rates introduced as dependent variables and time interval (days from the 22nd of January to the date when 100 first cases were reported) as the main predictor. The country average life expectancy at birth was statistically adjusted for in the regression model. Results: Mortality and incidence were strongly and inversely intercorrelated with days from January 22, respectively -0.83 (p<.0001) and -0.73 (p<.0001). Adjusting for average life expectancy, between days 33 to 50 from the 22th of the January, the average mortality rate decreased by 30.4/million per day (95% CI: 23.2, 37.1, p<0.0001). During interval 51 to 73 days, the change in mortality was no longer statistically significant but still showed a decreasing trend. A similar relationship with time interval was found in incidence. Life expectancy was not associated with mortality rate. Conclusion: Countries in Europe which observed the earliest COVID-19 circulation, suffered the worst consequences in terms of health outcomes, specifically mortality. The drastic social isolation measures, undertaken especially in Eastern European countries, where community circulation started after March 11th, may have been timely. This may explain their significantly lower COVID-related mortality compared with the Western European countries.", "doc_id": "h3ktg8xs"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "COVID-19: Spatial Analysis of Hospital Case-Fatality Rate in France", "abstract": "When the population risk factors and reporting systems are similar, the assessment of the case-fatality (or lethality) rate (ratio of cases to deaths) represents a perfect tool for analyzing, understanding and improving the overall efficiency of the health system. The objective of this article is to estimate the influence of the hospital care system on lethality in metropolitan France during the inception of the COVID-19 epidemic, by analyzing the spatial variability of the hospital case-fatality rate between French districts. The results show that the higher case-fatality rates observed in certain districts are mostly related to the level of morbidity in the district, therefore to the overwhelming of the healthcare systems during the acute phases of the epidemic. However, the magnitude of this increase of case-fatality rate represents less than 10 per cent of the average case-fatality rate and cannot explain the magnitude of the variations in case-fatality rate reported by country by international organizations or information sites. These differences can only be explained by the systems for reporting cases and deaths, which, indeed, vary greatly from country to country, and not attributed to the care or treatment of patients, even during hospital stress due to epidemic peaks.", "doc_id": "6coxz3l8"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Estimating Lower Bounds for COVID-19 Mortality from Northern Italian Towns", "abstract": "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.", "doc_id": "0ie6tkgm"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "BCG vaccination and socioeconomic variables vs Covid-19 global features: clearing up a controversial issue", "abstract": "Background: The Covid-19 pandemic is characterized by extreme variability in the outcome distribution and mortality rates across different countries. Some recent studies suggested an inverse correlation with BCG vaccination at population level, while others denied this hypothesis. In order to address this controversial issue, we performed a strict epidemiological study collecting data available on a global scale, considering additional variables such as cultural-political factors and adherence to other vaccination coverages. Methods: Data on 121 countries, accounting for about 99% of Covid-19 cases and deaths globally, were from John's Hopkins Coronavirus Resource Center, World Bank, International Monetary Fund, United Nations, Human Freedom Report, and BCG Atlas. Statistical models used were Ordinary Least Squares, Tobit and Fractional Probit, implemented on Stata/MP16 software. Results: Based on our results, countries where BCG vaccination is or has been mandated in the last decades have seen a drastic reduction in Covid-19 diffusion (-80% on average) and mortality (-50% on average), even controlling for relative wealth of countries and their governmental health expenditure. A significant contribution to this reduction (respectively -50% and -13% on average) was also associated to the outbreak onset during summer, suggesting a possible influence of seasonality. Other variables turned out to be associated, though to a lesser extent. Conclusions: Relying on a very large dataset and a wide array of control variables, our study confirms a strong and robust association between Covid-19 diffusion and mortality with BCG vaccination and a set socio-economic factors, opening new perspectives for clinical speculations and public health policies.", "doc_id": "fpmd9nzf"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "COVID-19 Pandemic: Marked Global Disparities in Fatalities According to Geographic Location and Universal Health Care", "abstract": "Since its outbreak, COVID-19 pandemic has been the biggest global concern with exponentially increasing number of cases and associated deaths across all habitable continents Various countries around the world with their diverse health care systems, have responded to the pandemic in very distinctive ways In this paper, we: compared COVID-19 mortality rates across global geographic regions;and assessed differences in COVID-19-related case fatality rate (CFR) based on presence or absence of Universal Health Coverage (UHC) We found that as of May 6, 2020, Europe had experienced the highest CFR globally of 9 6%, followed by 5 9% in North America Although the pandemic originated in Asia, the continent ranked second to the last in terms of CFR (3 5%) Countries with UHC had lower number of cases of 37 6%, but the CFR of countries with UHC was twice that of countries without UHC (10 5% versus 4 9%) In conclusion, UHC does not appear to protect against mortality in a pandemic environment such as with COVID-19", "doc_id": "ef4wyw2f"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "The COVID-19 mortality effects of underlying health conditions in India: a modelling study", "abstract": "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", "doc_id": "ekaqbruo"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Estimating the real-time case fatality rate of COVID-19 using Poisson mixtures model", "abstract": "Importance: The case fatality rate (CFR) estimation during the early stage of a disease outbreak is important, but the current estimation methods are heavily biased. Objective: We proposed using a Poisson mixtures model that utilized requires data of deaths, recoveries, and total confirmed cases recorded in each day since the outbreak of a population. Design: We collected data of deaths, recoveries, and total confirmed cases of COVID-19 in Hubei Province, China, and other parts of China up to 10th April 2020. Main Outcome(s) and Measure(s): The CFR of COVID-19 was estimated by minimizing the chi-square goodness-of-fit statistic. Results: Our proposed CRF estimates for Hubei Province became stable on 5th February in the range of 4.5% to 7.0% at which the simple CFR estimators overestimated the actual CFR by more than five folds, and that for the other parts of China (1.5% to 1.6%) were all very close to the actual CFR on the first day of CFR estimation (25th January) at which the simple CFRs were in the range between 15% and 35%. Conclusions and Relevance: Our CFR estimates for Hubei Province and other parts of China were superior to the simple CFR estimators.", "doc_id": "g1l3gi3l"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Patterns of COVID-19 related excess mortality in the municipalities of Northern Italy", "abstract": "The Coronavirus Disease 2019 (COVID-19) spatial distribution in Italy is inhomogeneous, because of its ways of spreading from the initial hotspots. The impact of COVID-19 on mortality has been described at the regional level, while less is known about mortality in demographic subgroups within municipalities. We aimed to describe the excess mortality (EM) due to COVID-19 in the three most affected Italian regions, by estimating EM in subgroups defined by gender and age classes within each municipality from February 23 to March 31, 2020. EM varied widely among municipalities even within the same region; it was similar between genders for the [\u2265]75 age group, while in the other age groups it was higher in males. Thus, nearby municipalities may show a different mortality burden despite being under common regional health policies, possibly as a result of policies adopted both at the regional and at the municipality level.", "doc_id": "9fw30fcx"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "COVID-19 FATALITY RISK: WHY IS AUSTRALIA LOWER THAN SOUTH KOREA?", "abstract": "Background: As the Covid-19 virus epidemic spreads, it is important to establish reliable estimates of fatality hazard rates. Australia and South Korea are ideal candidates for detailed consideration. Both have completed the first wave of the epidemic, they have extensive Covid-19 testing and tracking programs so that confirmed case load data are reliable, and neither country has had any significant case load stress in their hospital systems. Methods: For each country, mortality hazard models were estimated using a parameterized distributed lag model where the number of daily deaths was dependent on the number of confirmed cases in each of the preceding six weeks. Age cohort CFRs were also examined. Findings: We observed major difference in the mortality rates when comparing South Korea to Australia in both the simple age adjusted fatality rates and in the disease hazard curve. On a like-for-like basis, the CFR for South Korea appears to be close to double the Australian rate (aggregate; 2.4% vs 1.4%). Interpretation: Neither differences in the time pattern of the peaking of the case load of confirmed cases, nor differences in the size of age cohorts of confirmed cases explain the difference in mortality observed. We discuss possible explanations that point the way for further investigation. Funding: nil.", "doc_id": "e8zi99u3"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Evaluating the determinants of COVID-19 mortality: A cross-country study", "abstract": "As the COVID-19 pandemic has spread to the entire world, a race to understand the virus and to find an effective and safe vaccine or treatment has triggered interest in the factors contributing to mortality. For instance, some studies have suggested that the BCG vaccine could protect from COVID-19 and nicotine patches could be therapeutic against the virus. This study makes use of data for about 140 countries to evaluate the determinants of COVID-19 mortality. It finds that a country's share of spending on health care (as a measure of a country's effectiveness in tracking, recording, and reporting COVID-19 deaths) is positively associated with COVID-19 deaths. It also finds that the share of people above 65 years of age, obesity, and urbanization are all positively associated with COVID-19 mortality. There is no evidence that BCG vaccination, smoking prevalence, and PM25 pollution have any link to COVID-19 mortality. These estimation results are robust to alternative specifications and after controlling for confounding factors and excluding outliers. Policymakers should allocate resources towards the protection of the elderly and those suffering from underlying conditions such as obesity. They should also exercise caution about administering nicotine patches or the BCG vaccine to fight COVID-19 without the backing of concrete scientific evidence.", "doc_id": "87kzkbea"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Associations of Global Country Profiles and Modifiable Risk Factors with COVID-19 Cases and Deaths", "abstract": "Modifiable risk factors affect SARS-CoV-2 infection and mortality raising the possibility that lifestyle modification could play a role. This has not been studied at a global level. We analysed publicly available data from countries reporting COVID-19 cases and deaths. Associations of modifiable risk factors with total cases and excess deaths were determined with and without adjustment for confounders. 4,670,832 cases and 311,384 deaths were reported by 181 countries by 18th May 2020. Wealthier countries had the greatest caseload. Obesity was the primary modifiable risk factor for infection and greater age, male sex, physical inactivity and low salt consumption were associated with excess deaths. Obesity was less influential on mortality than physical inactivity. Globally, obesity confers vulnerability to SARS-CoV-2 infection and physical inactivity likely explains the greater mortality in the obese. High salt consumption may induce reductions in tissue ACE2 expression and subsequently reduce mortality rates.", "doc_id": "94c8bfd6"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Covid-19 and Population Age Structure", "abstract": "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.", "doc_id": "arfz6224"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Why Do COVID-19 Fatality Rates Differ Across Countries? An Explorative Cross-country Study Based on Select Indicators", "abstract": "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\u2019 access to the public healthcare system are worse in many countries irrespective of whether they are developed or developing countries.", "doc_id": "98n6ycwe"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Scaling COVID-19 against inequalities: should the policy response consistently match the mortality challenge?", "abstract": "Background The mortality impact of COVID-19 has thus far been described in terms of crude death counts. We aimed to calibrate the scale of the modelled mortality impact of COVID-19 using age-standardised mortality rates and life expectancy contribution against other, socially-determined, causes of death in order to inform governments and the public. Methods We compared mortality attributable to suicide, drug poisoning and socioeconomic inequality with estimates of mortality from an infectious disease model of COVID-19. We calculated age-standardised mortality rates and life expectancy contributions for the UK and its constituent nations. Results Mortality from a fully unmitigated COVID-19 pandemic is estimated to be responsible for a negative life expectancy contribution of -5.96 years for the UK. This is reduced to -0.33 years in the fully mitigated scenario. The equivalent annual life expectancy contributions of suicide, drug poisoning and socioeconomic inequality-related deaths are -0.25, -0.20 and -3.51 years respectively. The negative impact of fully unmitigated COVID-19 on life expectancy is therefore equivalent to 24 years of suicide deaths, 30 years of drug poisoning deaths, and 1.7 years of inequality-related deaths for the UK. Conclusion Fully mitigating COVID-19 is estimated to prevent a loss of 5.63 years of life expectancy for the UK. Over 10 years there is a greater negative life expectancy contribution from inequality than around six unmitigated COVID-19 pandemics. To achieve long-term population health improvements it is therefore important to take this opportunity to introduce post-pandemic economic policies to build back better.", "doc_id": "8eevfmj2"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "A County-Level Susceptibility Index and Coronavirus Disease 2019 Mortality in the United States: A Socioecological Study", "abstract": "As of June 2020, the United States (US) has experienced the highest number of deaths related to coronavirus disease 2019 (Covid-19) in the world, but significant geographic heterogeneity exists at the county-level. Therefore, we sought to classify counties in the United States across multiple domains utilizing a socioecological framework and examine the association between these county-level groups and Covid-19 mortality. We harmonized and linked county-level sociodemographic, health, and environmental metrics associated with increased susceptibility for Covid-19 mortality. Latent class analysis defined a county-level susceptibility index (CSI) based on these metrics (n=2701 counties). Next, we used linear regression models to estimate the associations of the CSI and Covid-19 deaths per capita and initial mortality doubling time (as of 6/2/20), adjusted for days since first Covid-19 case. We identified 4 groups classified by the CSI with distinct sociodemographic, health, and environmental profiles and widespread geographic dispersion. Covid-19 deaths per capita were significantly higher in the group consisting of rural, vulnerable counties (55.8 [95% CI 50.3-61.2] deaths per 100,000) compared with the group with diverse, urban counties (32.2 [27.3-37.0]) at similar points in the outbreak (76 days since first case). Our findings can inform equitable resource allocation for Covid-19 to allow targeted public health preparedness and response in vulnerable counties.", "doc_id": "0fkupng6"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Municipality- level predictors of COVID-19 mortality in Mexico: a cautionary tale", "abstract": "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.", "doc_id": "9o81djzl"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Risk factors associated with mortality of COVID-19 in 2692 counties of the United States", "abstract": "Background: The number of cumulative confirmed cases of COVID-19 in the United States has risen sharply since March. A county health ranking and roadmaps program has been established to identify factors associated with disparity in mobility and mortality of COVID-19 in all counties in the United States. Objective: To find out the risk factors associated with mortality of COVID-19 with various levels of prevalence. Design: A negative binomial design was applied to the county-level mortality counts of COVID-19 on April 15, 2020 in the United States. In this design, the infected counties were categorized into three levels of infections using clustering analysis based on time-variant cumulative confirmed cases from March 1 to April 15, 2020. Setting: United States Participants: COVID-19 patients in various counties of the United States from March 1 to April 15, 2020. Measurements: The county-level cumulative confirmed cases and mortality of COVID-19. Results. 2692 infected counties were assigned into three classes where the mild, moderate, and severe prevalence of infections were identified, respectively. Several risk factors are significantly associated with the mortality of COVID-19, where Hispanic (0.024, P=0.002), female (0.253, P=0.027), elder (0.218, P=0.017) and Native Hawaiian or other Pacific islander (2.032, P=0.027) individuals are more vulnerable to the mortality of COVID-19. More locations open to exercise (0.030, P=0.004), higher levels of air pollution (0.184, P=0.044), and segregation between non-White and White increased the mortality rate. Limitation: The study relied on mortality data on April 15, 2020. Conclusion. The mortality of COVID-19 depends on sex, ethnicity, and outdoor environment. The increasing awareness of these significant factors may lead to the reduction in the mortality rate of COVID-19.", "doc_id": "5esd2eti"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Correlation Analysis Between Disease Severity and Inflammation-related Parameters in Patients with COVID-19 Pneumonia", "abstract": "Aim: The new coronavirus pneumonia (COVID-19) outbreaking at the end of 2019 is highly contagious. Crude mortality rate reached 49% in critical patients. Inflammation matters on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early. Methods: In this cross-sectional study, 100 patients were included and divided to mild, severe or critical groups. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. Results\uff1aSignificantly, disease severity were associated with age (R=-0.564, P<0.001), interleukin-2 receptor (IL2R) (R=-0.534, P<0.001), interleukin-6 (IL-6) (R=-0.535, P<0.001), interleukin-8 (IL-8) (R=-0.308, P<0.001), interleukin-10 (IL-10) (R=-0.422, P<0.001), tumor necrosis factor \u03b1 (TNF\u03b1) (R=-0.322, P<0.001), C-reactive protein (CRP) (R=-0.604, P<0.001), ferroprotein (R=-0.508, P<0.001), procalcitonin (R=-0.650, P<0.001), white cell counts (WBC) (R=-0.54, P<0.001), lymphocyte counts (LC) (R=-0.56, P<0.001), neutrophil count (NC) (R=-0.585, P<0.001) and eosinophil counts (EC) (R=-0.299, P=0.01). Conclusion\uff1aWith following parameters such as age >67.5 years, IL2R >793.5U/mL, CRP >30.7ng/mL, ferroprotein >2252\u03bcg/L, WBC>9.5*10^9/L or NC >7.305*10^9/L, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. Inflammation is closely related to severity of COVID-19, and IL-6, TNF\u03b1 and IL-8 might be promising therapeutic targets.", "doc_id": "370fqkat"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Ethnicity and risk of death in patients hospitalised for COVID-19 infection: an observational cohort study in an urban catchment area", "abstract": "Objectives. To determine if specific ethnic groups are at higher risk of mortality from COVID19 infection. Design. Retrospective cohort study Setting. University Hospitals Birmingham NHS Foundation Trust (UHB) in Birmingham, UK Participants. Patients with confirmed SARS CoV 2 infection requiring admission to UHB between 10th March 2020 and 17th April 2020 Exposure. Ethnicity Main outcome measures. Standardised Admission Ratio (SAR) and Standardised Mortality Ratio (SMR) for each ethnicity was calculated using observed sex specific age distributions of COVID19 admissions/deaths and 2011 census data for Birmingham/Solihull. Hazard Ratio (aHR) for mortality was estimated for each ethnic group with white population as reference group, using Cox proportional hazards model adjusting for age, sex, social deprivation and co-morbidities, and propensity score matching. Results. 2217 patients admitted to UHB with a proven diagnosis of COVID19 were included. 58.2% were male, 69.5% White and the majority (80.2%) had co morbidities. 18.5% were of South Asian ethnicity, and these patients were more likely to be younger (median age 61 years vs.77 years), have no co morbidities (27.8% vs. 16.6%) but a higher prevalence of diabetes mellitus (48.0% vs 28.2%) than White patients. SAR and SMR suggested more admissions and deaths in South Asian patients than would be predicted. South Asian patients were also more likely to present with severe disease despite no delay in presentation since symptom onset. South Asian ethnicity was associated with an increased risk of death; both by Cox regression (Hazard Ratio 1.66 (95%CI 1.32 to 2.10)) after adjusting for age, sex, deprivation and comorbidities and by propensity score matching, (Hazard ratio 1.68 (1.33 to 2.13), using the same factors but categorising ethnicity into South Asian or not. Conclusions. Current evidence suggests those of South Asian ethnicity may be at risk of worse COVID19 outcomes, further studies need to establish the underlying mechanistic pathways.", "doc_id": "fr6kvil3"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Epidemiological Determinants of Acute Respiratory Syndrome Coronavirus-2 Disease Pandemic and The Role of the Bacille-Calmette-Guerin Vaccine in Reducing Morbidity and Mortality", "abstract": "This study analyzed the determinants of morbidity, mortality, and case fatality rate (CFR) of the ongoing pandemic of severe acute respiratory syndrome coronavirus-2 disease 2019 (COVID-19) Data for 210 countries and territories available in public domains were analyzed in relation to mandatory vaccination with Bacille-Calmette-Guerin (BCG), population density, median age of the country population, health care expenditure per capita, life expectancy at birth, healthy life expectancy, literacy rate, per capita gross domestic production adjusted to purchasing power (PPP), burden of tuberculosis (TB), acquired immunodeficiency disease caused by human immunodeficiency virus (HI V-AIDS), malaria, cardiovascular disease (CVD), neoplasm, diabetes, deaths due to energy-protein (food) deficiency (EPD), and per capita government spending on safe water and sanitation Mandatory BCG vaccination showed a highly significant (p<0 0001) negative correlation with COVID-19 morbidity (r = -0 62) and mortality (r = -0 58) rates, but no significant correlation with CFR The median age of the nation showed a significant (p<0 0001) positive correlation with COVID-19 morbidity (r= 0 40) and mortality (r = 0 34) rates, but no significant correlation with CFR The pandemic resulted in higher morbidity (r= 0 47, p<0 0001) and mortality (r= 0 25, p = 0 01) rates in countries with a higher PPP than in those with a lower PPP COVID-19 CFR and morbidity and mortality rates showed no significant correlation with population density, the burden of malaria or diabetes, or the level of spending on safe water and sanitation Only the burden of TB showed a positive correlation with CFR (r = 0 17, p = 0 05) However, COVID-19 morbidity showed a significant (p =0 05) negative correlation with the burden of TB, HI V-AIDS, CVD, and EPD Mortality and morbidity in COVID-19 patients showed a positive correlation with per capita health expenditure, life expectancy, the burden of neoplasia, and PPP", "doc_id": "4bnje5un"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Early dinner or \"dinner like a pauper\": Evidence, the habitual time of the largest meal of the day - dinner - is predisposing to severe COVID-19 outcome - death", "abstract": "COVID-19 and metabolic syndrome are devastating pandemics. Effective control of metabolic parameters and their dysfunction may help prevent or minimize the acute and devastating effects of SARS-CoV-2 by reducing the local inflammatory response and blocking the entry of the virus into cells. With such consideration in mind, we gathered data from dietary surveys conducted in nine European countries to explore the relationship between actual clock hour of the large dinner meal and also interval in minutes between it and sunset in the respective countries and death rate above the median rate of per one million people as an index of mortality due to COVID-19 infection. Clock time of the dinner meal varied between 16:00 and 21:00 h across the European counties sampled, and the correlation between dinner mealtime and death rate was strongly correlated, R = 0.7991 (two-tailed p = 0.0098), with R 2 explaining 63% of the variation within the data. This strong linear positive correlation indicates that the later the clock time of the dinner meal, the higher is the death rate (and vice versa). The relationship between meal timing in reference to sunset, utilized as a gross surrogate marker of the activity/rest synchronizer of circadian rhythms, and death rate was negative and even slightly stronger, R = -0.8025 (two-tailed p = 0.0092), with R 2 explaining 64% of the variation within the data. This strong linear negative correlation indicates that the shorter the interval between the dinner meal and sunset, i.e., the closer the time of the largest meal of the day to bedtime, the greater is the death rate (and vice versa). Our preliminary approach to nighttime eating, in terms of the day's largest caloric intake, as a risk factor for the predisposing conditions of obesity, metabolic syndrome, type 2 diabetes, and other commonly associated comorbidities of being overweight, and death from COVID-19 infection reveals strong correlation with the time of the dinner meal, both in terms of its actual clock and circadian time.", "doc_id": "ccvjg1g4"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "COVID: How to explain differences in lethality between different populations?", "abstract": "", "doc_id": "8hwzl8sy"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Clinical outcomes of 402 patients with COVID-2019 from a single center in Wuhan, China", "abstract": "The outbreak of SARS-CoV-2 has become a pandemic with significant mortality. Published studies described clinical characteristics of the disease contain small cohorts from individual centers or larger series consisting of mixed series from multiple different hospitals. We report here analyses of mortality and disease severity among 402 patients from a single hospital. The cohort includes 297 patients with confirmed and 105 with clinical diagnosis. The latter group consists of cases with inconclusive nucleic acid test but meeting the criteria for clinical diagnosis. Data are compared between sexes and among different age groups. The overall case fatality is 5.2%. However, age at 70 years or older is associated with a significantly higher mortality (17.8%) and higher rate of severe and critical illness (57.5%). Case fatality is 8% in patients 50 years of age or older, and 1.2% in those younger than 50 years. In addition, case fatality is 7.6% in male patients, as opposed to 2.9% in females, demonstrating a clear sex difference.", "doc_id": "adj3nw03"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Demographic science aids in understanding the spread and fatality rates of COVID-19", "abstract": "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.", "doc_id": "2sm0lnnn"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Letalidad del COVID-19: ausencia de patr\u00f3n epidemiol\u00f3gico./ [Case fatality rate of COVID-19: absence of epidemiological pattern]", "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.", "doc_id": "4qumxlq6"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Acute Physiology and Chronic Health Evaluation II Score as a Predictor of Hospital Mortality in Patients of Coronavirus Disease 2019", "abstract": "OBJECTIVES: Coronavirus disease 2019 has emerged as a major global health threat with a great number of deaths in China. We aimed to assess the association between Acute Physiology and Chronic Health Evaluation II score and hospital mortality in patients with coronavirus disease 2019, and to compare the predictive ability of Acute Physiology and Chronic Health Evaluation II score, with Sequential Organ Failure Assessment score and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65) score. DESIGN: Retrospective observational cohort. SETTING: Tongji Hospital in Wuhan, China. SUBJECTS: Confirmed patients with coronavirus disease 2019 hospitalized in the ICU of Tongji hospital from January 10, 2020, to February 10, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 178 potentially eligible patients with symptoms of coronavirus disease 2019, 23 patients (12.92%) were diagnosed as suspected cases, and one patient (0.56%) suffered from cardiac arrest immediately after admission. Ultimately, 154 patients were enrolled in the analysis and 52 patients (33.77%) died. Mean Acute Physiology and Chronic Health Evaluation II score (23.23 \u00b1 6.05) was much higher in deaths compared with the mean Acute Physiology and Chronic Health Evaluation II score of 10.87 \u00b1 4.40 in survivors (p < 0.001). Acute Physiology and Chronic Health Evaluation II score was independently associated with hospital mortality (adjusted hazard ratio, 1.07; 95% CI, 1.01-1.13). In predicting hospital mortality, Acute Physiology and Chronic Health Evaluation II score demonstrated better discriminative ability (area under the curve, 0.966; 95% CI, 0.942-0.990) than Sequential Organ Failure Assessment score (area under the curve, 0.867; 95% CI, 0.808-0.926) and CURB65 score (area under the curve, 0.844; 95% CI, 0.784-0.905). Based on the cut-off value of 17, Acute Physiology and Chronic Health Evaluation II score could predict the death of patients with coronavirus disease 2019 with a sensitivity of 96.15% and a specificity of 86.27%. Kaplan-Meier analysis showed that the survivor probability of patients with coronavirus disease 2019 with Acute Physiology and Chronic Health Evaluation II score less than 17 was notably higher than that of patients with Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 (p < 0.001). CONCLUSIONS: Acute Physiology and Chronic Health Evaluation II score was an effective clinical tool to predict hospital mortality in patients with coronavirus disease 2019 compared with Sequential Organ Failure Assessment score and CURB65 score. Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 serves as an early warning indicator of death and may provide guidance to make further clinical decisions.", "doc_id": "bgqi9h55"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Factors associated with increased all-cause mortality during the COVID-19 pandemic in Italy", "abstract": "BACKGROUND: The number of excess deaths in February-March 2020 in Italy, in comparison to the previous years, was considerably higher than recorded COVID19-related deaths. The present study is aimed at exploring the associations of excess mortality with some indices related to the epidemic and its management. METHODS: Data on all-cause mortality from February 20th to March 31st, in years from 2015 to 2020, and demographic, socioeconomic and healthcare organization data of each Italian region were obtained from Italian Institute of Statistics. Non-COVID19-Imputed Excess Mortality (NCIEM) was calculated as the difference between excess 2020 mortality and reported COVID19 mortality. The association of NCIEM with the rate of COVID-19 cases, COVID-19 mortality, and other potential moderators was assessed using linear regression models. RESULTS: The nationwide number of excess deaths, COVID-19 deaths was 26,701 and 13,710, respectively, with a difference of 12,991. NCIEM in different Regions showed a direct correlation with COVID-19 mortality (r2 = 0.61, p < 0.001) and total cases (r2 = 0.30, p = 0.012), and an inverse correlation with cases/total tests ratio (r2 = 0.49, p = 0.001). Direct correlations were also found with the proportion of institutionalized elderly, whereas inverse correlations were observed with prevalence of diabetes, cardiovascular mortality, and density of general practitioners. CONCLUSIONS: The impact of the COVID19 epidemic on all-cause mortality is considerably greater than that indicated by official counts of victims. Limited testing capacity and causes of death other than COVID19 could contribute to the increase in overall mortality rates.", "doc_id": "4d3t6kas"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "The Correlation of Comorbidities on the Mortality in Patients with COVID-19: an Observational Study Based on the Korean National Health Insurance Big Data", "abstract": "BACKGROUND: Mortality of coronavirus disease 2019 (COVID-19) is a major concern for quarantine departments in all countries. This is because the mortality of infectious diseases determines the basic policy stance of measures to prevent infectious diseases. Early screening of high-risk groups and taking action are the basics of disease management. This study examined the correlation of comorbidities on the mortality of patients with COVID-19. METHODS: We constructed epidemiologic characteristics and medical history database based on the Korean National Health Insurance Service Big Data and linked COVID-19 registry data of Korea Centers for Disease Control & Prevention (KCDC) for this emergent observational cohort study. A total of 9,148 patients with confirmed COVID-19 were included. Mortalities by sex, age, district, income level and all range of comorbidities classified by International Classification of Diseases-10 based 298 categories were estimated. RESULTS: There were 3,556 male confirmed cases, 67 deaths, and crude death rate (CDR) of 1.88%. There were 5,592 females, 63 deaths, and CDR of 1.13%. The most confirmed cases were 1,352 patients between the ages of 20 to 24, followed by 25 to 29. As a result of multivariate logistic regression analysis that adjusted epidemiologic factors to view the risk of death, the odds ratio of death would be hemorrhagic conditions and other diseases of blood and blood-forming organs 3.88-fold (95% confidence interval [CI], 1.52-9.88), heart failure 3.17-fold (95% CI, 1.88-5.34), renal failure 3.07-fold (95% CI, 1.43-6.61), prostate malignant neoplasm 2.88-fold (95% CI, 1.01-8.22), acute myocardial infarction 2.38-fold (95% CI, 1.03-5.49), diabetes was 1.82-fold (95% CI, 1.25-2.67), and other ischemic heart disease 1.71-fold (95% CI, 1.09-2.66). CONCLUSION: We hope that this study could provide information on high risk groups for preemptive interventions. In the future, if a vaccine for COVID-19 is developed, it is expected that this study will be the basic data for recommending immunization by selecting those with chronic disease that had high risk of death, as recommended target diseases for vaccination.", "doc_id": "asijbdjl"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020", "abstract": "Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence interval (CI): 0.89-6.7) and 1.3% (95% CI: 0.38-3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3-2.7) and 0.6% (95% CI: 0.2-1.3), respectively.", "doc_id": "1g1slgh8"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Case Fatality Rate of Cancer Patients with COVID-19 in a New York Hospital System", "abstract": "Patients with cancer are presumed to be at increased risk from COVID-19 infection-related fatality due to underlying malignancy, treatment-related immunosuppression, or increased comorbidities. A total of 218 COVID-19-positive patients from March 18, 2020, to April 8, 2020, with a malignant diagnosis were identified. A total of 61 (28%) patients with cancer died from COVID-19 with a case fatality rate (CFR) of 37% (20/54) for hematologic malignancies and 25% (41/164) for solid malignancies. Six of 11 (55%) patients with lung cancer died from COVID-19 disease. Increased mortality was significantly associated with older age, multiple comorbidities, need for ICU support, and elevated levels of D-dimer, lactate dehydrogenase, and lactate in multivariate analysis. Age-adjusted CFRs in patients with cancer compared with noncancer patients at our institution and New York City reported a significant increase in case fatality for patients with cancer. These data suggest the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population. SIGNIFICANCE: COVID-19 in patients with cancer is associated with a significantly increased risk of case fatality, suggesting the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population.This article is highlighted in the In This Issue feature, p. 890.", "doc_id": "fttgch3e"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Analyzing COVID-19 pandemic for unequal distribution of tests, identified cases, deaths, and fatality rates in the top 18 countries", "abstract": "BACKGROUND AND AIMS: COVID-19 pandemic has affected various countries differently due to variance in demographics, income level, health infrastructure, government response, control and enforcement, and cultural traits of different populations. This study aims to identify significant factors behind the unequal distribution of identified cases and deaths in different countries. Our study's objective is comparative analysis and identification of relations between the spread of COVID-19 pandemic, population characteristics, and government response. METHODS: The top 18 countries worst hit by COVID-19 cases were identified. The data metrics, such as the number of cases, deaths, fatality rates, tests, average life expectancy, and population, were collected and consolidated. RESULTS: Countries with significant percentage of the older population are vulnerable to a high number of deaths due to COVID-19. Developed countries have higher per capita testing, whereas testing is less intensive in developing/underdeveloped countries. There is a consensus among health experts that COVID-19 has higher fatality rates for people above 60, however, with further age, this increases exponentially. Countries with higher life expectancy are also high-income countries, and the best course of action would be to provide specialized support to self-isolate for people of ages 75 and above. CONCLUSION: The behaviour of disease occurring at a large scale and interaction with different populations is studied to understand and differentiate the factors and measures that successfully inhibited the pandemic. The study benchmarks different countries based on their performance and efforts against the pandemic and provides some useful insights on the efficiency of their governance and potential to improve & ramp up their programs. The economic status and existing healthcare infrastructure as they are the key factors in determining the country's ability to contain and minimize the losses from this pandemic.", "doc_id": "c5ps1g8t"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "SARS-CoV-2 in Italy: Population Density correlates with Morbidity and Mortality", "abstract": "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.", "doc_id": "2e90esx8"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Rate of Intensive Care Unit admission and outcomes among patients with coronavirus: A systematic review and Meta-analysis", "abstract": "BACKGROUND: The rate of ICU admission among patients with coronavirus varied from 3% to 100% and the mortality was as high as 86% of admitted patients. The objective of the systematic review was to investigate the rate of ICU admission, mortality, morbidity, and complications among patients with coronavirus. METHODS: A comprehensive strategy was conducted in PubMed/Medline; Science direct and LILACS from December 2002 to May 2020 without language restriction. The Heterogeneity among the included studies was checked with forest plot, χ2 test, I2 test, and the p-values. All observational studies reporting rate of ICU admission, the prevalence of mortality and its determinants among ICU admitted patients with coronavirus were included and the rest were excluded. RESULT: A total of 646 articles were identified from different databases and 50 articles were selected for evaluation. Thirty-seven Articles with 24983 participants were included. The rate of ICU admission was 32% (95% CI: 26 to 38, 37 studies and 32, 741 participants). The Meta-Analysis revealed that the pooled prevalence of mortality in patients with coronavirus disease in ICU was 39% (95% CI: 34 to 43, 37 studies and 24, 983 participants). CONCLUSION: The Meta-Analysis revealed that approximately one-third of patients admitted to ICU with severe Coronavirus disease and more than thirty percent of patients admitted to ICU with a severe form of COVID-19 for better care died which warns the health care stakeholders to give attention to intensive care patients. REGISTRATION: This Systematic review and Meta-Analysis was registered in Prospero international prospective register of systemic reviews (CRD42020177095) on April 9/2020.", "doc_id": "2gn0csbd"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Prevalence and mortality in \u00df-thalassaemias due to outbreak of novel coronavirus disease (COVID-19): the nationwide Iranian experience", "abstract": "", "doc_id": "cptr5a72"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "Mortality rate and gender differences in COVID-19 patients dying in Italy: A comparison with other countries", "abstract": "", "doc_id": "77vmsck0"} {"topic_name": "coronavirus mortality", "topic_id": "21", "title": "COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis", "abstract": "The aim of this study was to analyze the clinical data, discharge rate, and fatality rate of COVID-19 patients for clinical help. The clinical data of COVID-19 patients from December 2019 to February 2020 were retrieved from four databases. We statistically analyzed the clinical symptoms and laboratory results of COVID-19 patients and explained the discharge rate and fatality rate with a single-arm meta-analysis. The available data of 1994 patients in 10 literatures were included in our study. The main clinical symptoms of COVID-19 patients were fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), and dyspnea (21.9%). Minor symptoms include headache or dizziness (12.1%), diarrhea (4.8%), nausea and vomiting (3.9%). The results of the laboratory showed that the lymphocytopenia (64.5%), increase of C-reactive protein (44.3%), increase of lactic dehydrogenase (28.3%), and leukocytopenia (29.4%) were more common. The results of single-arm meta-analysis showed that the male took a larger percentage in the gender distribution of COVID-19 patients 60% (95% CI [0.54, 0.65]), the discharge rate of COVID-19 patients was 52% (95% CI [0.34,0.70]), and the fatality rate was 5% (95% CI [0.01,0.11]).", "doc_id": "2ffygeif"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Coronavirus Disease 2019: Where are we and Where are we Going? Intersections Between Coronavirus Disease 2019 and the Heart", "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has become a pandemic affecting every country in the world. In the province of Bergamo, Italy, more than 2,200 cases of COVID-19 have been reported, which include more than 300 deaths. Most hospitalisations have been at the Papa Giovanni XXIII Hospital. This has imposed a significant burden on our hospital in terms of healthcare personnel, dedicated spaces (including intensive care areas) and time spent by clinicians, who are committed to assisting COVID-19 patients. In this short expert opinion, the authors will focus on new insights related to COVID-19 and the cardiovascular system, and try to investigate the grey areas and uncertainties in this field.", "doc_id": "j8c2lk7y"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "[Cardiac biomarkers and COVID-19 - Phenotypes and Interpretation].", "abstract": "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.", "doc_id": "1nczw70h"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Usefulness of echocardiography to detect cardiac involvement in COVID-19 patients.", "abstract": "Coronavirus disease 2019 (COVID-19) outbreak is a current global healthcare burden, leading to the life-threatening severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, evidence showed that, even if the prevalence of COVID-19 damage consists in pulmonary lesions and symptoms, it could also affect other organs, such as heart, liver, and spleen. Particularly, some infected patients refer to the emergency department for cardiovascular symptoms, and around 10% of COVID-19 victims had finally developed heart injury. Therefore, the use of echocardiography, according to the safety local protocols and ensuring the use of personal protective equipment, could be useful firstly to discriminate between primary cardiac disease or COVID-19-related myocardial damage, and then for assessing and monitoring COVID-19 cardiovascular complications: acute myocarditis and arrhythmias, acute heart failure, sepsis-induced myocardial impairment, and right ventricular failure derived from treatment with high-pressure mechanical ventilation. The present review aims to enlighten the applications of transthoracic echocardiography for the diagnostic and therapeutic management of myocardial damage in COVID-19 patients.", "doc_id": "nhsn4cru"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Coronavirus Disease 2019 (COVID-19) Pandemic Implications in Pediatric and Adult Congenital Heart Disease.", "abstract": "The corona virus disease -2019 (COVID-19) is a recently described infectious disease caused by the severe acute respiratory syndrome corona virus 2 with significant cardiovascular implications. Given the increased risk for severe COVID-19 observed in adults with underlying cardiac involvement, there is concern that patients with pediatric and congenital heart disease (CHD) may likewise be at increased risk for severe infection. The cardiac manifestations of COVID-19 include myocarditis, arrhythmia and myocardial infarction. Importantly, the pandemic has stretched health care systems and many care team members are at risk for contracting and possibly transmitting the disease which may further impact the care of patients with cardiovascular disease. In this review, we describe the effects of COVID-19 in the pediatric and young adult population and review the cardiovascular involvement in COVID-19 focusing on implications for patients with congenital heart disease in particular.", "doc_id": "5f9ofdsc"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "SARS-CoV-2 and myocardial injury: Few answers, many questions.", "abstract": "Patients with COVID-19 and acute cardiac injury as measured by an elevated high-sensitivity troponin I or troponin T upon admission or during hospitalization have a mortality rate of over 50% in initial reports. The mechanism of SARS-CoV-2 and associated myocardial injury, whether SARS-CoV-2 patients with myocardial injury are a distinct population, and possible treatment options for myocardial injury associated with SARS-CoV-2 are unknown.", "doc_id": "pdvia3aq"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Approach to Acute Cardiovascular Complications in COVID-19 Infection.", "abstract": "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.", "doc_id": "mol4s3iz"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiac Troponin for the Diagnosis and Risk-Stratification of Myocardial Injury in COVID-19: JACC Review Topic of the Week.", "abstract": "Increases in cardiac troponin (cTn) indicative of myocardial injury are common in patients with COVID-19 and associated with adverse outcomes such as arrhythmias and death. These increases are more likely to occur in those with chronic cardiovascular conditions and in those with severe COVID-19 presentations. The increased inflammatory, prothrombotic, and procoagulant responses following SARS-CoV-2 infection increase the risk for acute nonischemic myocardial injury and acute myocardial infarction, particularly type 2 myocardial infarction because of respiratory failure with hypoxia and hemodynamic instability in critically ill patients. Myocarditis, stress cardiomyopathy, acute heart failure, and direct injury from SARS-CoV-2 are important etiologies, but primary non-cardiac conditions such as pulmonary embolism, critical illness, and sepsis probably cause more of the myocardial injury. The structured use of serial cTn has the potential to facilitate risk stratification, help make decisions about when to use imaging, and inform stage categorization and disease phenotyping among hospitalized COVID-19 patients.", "doc_id": "jbjn89jc"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiac manifestations in COVID-19 patients-A systematic review.", "abstract": "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.", "doc_id": "8otl3781"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Obesity accompanying COVID-19: the role of epicardial fat.", "abstract": "With interest we read the study by Simonnet A et al. (1) in which important novel evidence is addressed that obesity is highly frequent among critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) infection. Although clinically very relevant, it remains difficult to elucidate the mechanisms by which SARS-Cov-2 severity is increased in the context of obesity. As reported by Katz JN et al. (2), 28% of hospitalised patients with coronavirus disease 2019 (COVID-19) presented cardiac complications including myocarditis, arrhythmias, heart failure (HF) and sudden death. Considering that myocardial response in COVID-19 is closely associated with in-hospital mortality, local biological effects on myocardial tissue from epicardial adipose tissue (EAT) is warrant further discussion.", "doc_id": "itmd9b0k"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Takotsubo Syndrome Associated with COVID-19", "abstract": "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", "doc_id": "oa55l5cr"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiac Structural and Functional Characteristics in Patients with Coronavirus Disease 2019: A Serial Echocardiographic Study", "abstract": "BACKGROUND: Increasing attention has been paid to cardiac involvement in patients with coronavirus disease 2019 (COVID-19). Yet, scarce information is available regarding the morphological and functional features of cardiac impairments in these patients. METHODS: We conducted a prospective and serial echocardiographic study to investigate the structural and functional cardiac changes among COVID-19 patients admitted to the intensive care unit (ICU). From January 21 to April 8, 2020, a total of 51 ICU patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were monitored by serial transthoracic echocardiography examinations. Outcomes were followed up until April 8, 2020. RESULTS: Of 51 ICU patients, 33 (64.7%) had cardiovascular comorbidities. Elevations of levels of cardiac biomarkers including high-sensitivity cardiac troponin-I (hs-cTnI) and brain natriuretic peptide were observed in 62.7% and 86.3% of patients, respectively. Forty-two (82.3%) had at least one left-heart and/or right-heart echocardiographic abnormality. The overall median left ventricular ejection fraction (LVEF) was 65.0% (IQR 58.0-69.0%), with most (44,86.3%) having preserved LVEF. Sixteen patients (31.4%) had increased pulmonary artery systolic pressure, and 14 (27.5%) had right-ventricle (RV) enlargement. During the study period, 12 (23.5%) patients died. LVEF was comparable between survivors and non-survivors, while non-survivors had more often pulmonary hypertension (58.3% vs. 23.1%; P=0.028) and RV enlargement (58.3% vs. 17.9%, P=0.011). Kaplan-Meier analysis demonstrated similar survival curves between patients with vs. without echocardiographic left-heart abnormalities (P=0.450 by log-rank test), while right-heart abnormalities had adverse impact on mortality (P=0.012 by log-rank test). CONCLUSIONS: Typical cardiac abnormality in ICU patients with COVID-19 was right-heart dysfunction with preserved LVEF. Echocardiographic right-heart dysfunction was associated with disease severity and increased mortality in patients affected by COVID-19.", "doc_id": "846vqdz7"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiovascular complications of severe acute respiratory syndrome.", "abstract": "BACKGROUND AND AIMS Severe acute respiratory syndrome (SARS) is a virulent viral infection that affects a number of organs and systems. This study examined if SARS may result in cardiovascular complications. METHODS AND RESULTS 121 patients (37.5 (SD13.2) years, 36% male) diagnosed to have SARS were assessed continuously for blood pressure, pulse, and temperature during their stay in hospital. Hypotension occurred in 61 (50.4%) patients in hospital, and was found in 28.1%, 21.5%, and 14.8% of patients during the first, second, and third week, respectively. Only one patient who had transient echocardiographic evidence of impaired left ventricular systolic function required temporary inotropic support. Tachycardia was present in 87 (71.9%) patients, and was found in 62.8%, 45.4%, and 35.5% of patients from the first to third week. It occurred independent of hypotension, and could not be explained by the presence of fever. Tachycardia was also present in 38.8% of patients at follow up. Bradycardia only occurred in 18 (14.9%) patients as a transient event. Reversible cardiomegaly was reported in 13 (10.7%) patients, but without clinical evidence of heart failure. Transient atrial fibrillation was present in one patient. Corticosteroid therapy was weakly associated with tachycardia during the second (chi(2) = 3.99, p = 0.046) and third week (chi(2) = 6.53, p = 0.01), although it could not explain tachycardia during follow up. CONCLUSIONS In patients with SARS, cardiovascular complications including hypotension and tachycardia were common but usually self limiting. Bradycardia and cardiomegaly were less common, while cardiac arrhythmia was rare. However, only tachycardia persisted even when corticosteroid therapy was withdrawn.", "doc_id": "oi424aa6"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiovascular Implications of the COVID-19 Pandemic: A Global Perspective", "abstract": "The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased use of health care services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.", "doc_id": "8h36iwxi"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "A Marker of Systemic Inflammation or Direct Cardiac Injury: Should Cardiac Troponin Levels be Monitored in COVID-19 Patients?", "abstract": "", "doc_id": "nkptn7h4"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Myocardial localization of coronavirus in COVID-19 cardiogenic shock", "abstract": "We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a 69-year-old patient with flu-like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock. The patient was successfully treated with venous-arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation. Cardiac function fully recovered in 5 days and ECMO was removed. Endomyocardial biopsy demonstrated low-grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung.", "doc_id": "463a5cor"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Patterns of heart injury in COVID-19 and relation to outcome", "abstract": "", "doc_id": "cexc3ohr"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Acute myocardial injury in patients hospitalized with COVID-19 infection: A review", "abstract": "The Coronavirus Disease 2019 (COVID-19) is now a global pandemic with millions affected and millions more at risk for contracting the infection. The COVID-19 virus, SARS-CoV-2, affects multiple organ systems, especially the lungs and heart. Elevation of cardiac biomarkers, particularly high-sensitivity troponin and/or creatine kinase MB, is common in patients with COVID-19 infection. In our review of clinical analyses, we found that in 26 studies including 11,685 patients, the weighted pooled prevalence of acute myocardial injury was 20% (ranged from 5% to 38% depending on the criteria used). The plausible mechanisms of myocardial injury include, 1) hyperinflammation and cytokine storm mediated through pathologic T-cells and monocytes leading to myocarditis, 2) respiratory failure and hypoxemia resulting in damage to cardiac myocytes, 3) down regulation of ACE2 expression and subsequent protective signaling pathways in cardiac myocytes, 4) hypercoagulability and development of coronary microvascular thrombosis, 5) diffuse endothelial injury and 'endotheliitis' in several organs including the heart, and, 6) inflammation and/or stress causing coronary plaque rupture or supply-demand mismatch leading to myocardial ischemia/infarction. Cardiac biomarkers can be used to aid in diagnosis as well as risk stratification. In patients with elevated hs-troponin, clinical context is important and myocarditis as well as stress induced cardiomyopathy should be considered in the differential, along with type I and type II myocardial infarction. Irrespective of etiology, patients with acute myocardial injury should be prioritized for treatment. Clinical decisions including interventions should be individualized and carefully tailored after thorough review of risks/benefits. Given the complex interplay of SARS-CoV-2 with the cardiovascular system, further investigation into potential mechanisms is needed to guide effective therapies. Randomized trials are urgently needed to investigate treatment modalities to reduce the incidence and mortality associated with COVID-19 related acute myocardial injury.", "doc_id": "iik3mpmw"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "What should a cardiologist know about coronavirus disease 2019?", "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS\u00adCoV\u00ad2) is the cause of coronavirus disease 2019 (COVID\u00ad19). The most common symptoms of COVID\u00ad19 are: fever (81.8%-100%), cough (46.3%-86.2%), myalgia and fatigue (11%-50%), expectoration (4.4%-72%), and dyspnea (18.6%-59%). The most common laboratory abnormalities in COVID\u00ad19 include decreased lymphocyte count (35%-82.1%), thrombocytopenia (17%-36.2%), elevated serum C\u00adreactive protein (60.7%-93%), lactate dehydrogenase (41%-76%), and D\u00addimer concentrations (36%-46.4%). Among comorbidities in patients with COVID\u00ad19, cardiovascular disease is most commonly found. In addition, patients with concomitant cardiovascular diseases have worse prognosis and more often require admission to the intensive care unit (ICU), compared with patients without such comorbidities. It is estimated that about 20% of patients with COVID\u00ad19 develop cardiac injury. Cardiac injury is more prevalent among patients with COVID\u00ad19 who require ICU care. In a group of critically ill patients, 27.5% had an elevated N\u00adterminal pro-B\u00adtype natriuretic peptide concentration, and increased cardiac troponin level was found in 10% of patients. One of the life\u00adthreatening cardiac manifestations is coronavirus fulminant myocarditis, which may also occur without accompanying symptoms of pulmonary involvement. Early recognition and treatment is crucial in these cases. So far, data on the incidence of arrhythmias in patients with COVID\u00ad19 are limited. Coronavirus disease 2019 impacts patients with cardiovascular comorbidities and affects daily practice of cardiologists. Thus, it is important to know typical COVID\u00ad19 symptoms, possible clinical manifestations, complications, and recommended treatment.", "doc_id": "72vjnndw"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Single-cell RNA analysis on ACE2 expression provides insights into SARS-CoV-2 potential entry into the bloodstream and heart injury", "abstract": "Coronavirus disease-2019 (COVID-19) is a global pandemic with high infectivity and pathogenicity, accounting for tens of thousands of deaths worldwide. Recent studies have found that the pathogen of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shares the same cell receptor angiotensin converting enzyme II (ACE2) as SARS-CoV. The pathological investigation of COVID-19 deaths showed that the lungs had characteristics of pulmonary fibrosis. However, how SARS-CoV-2 spreads from the lungs to other organs has not yet been determined. Here, we performed an unbiased evaluation of cell-type-specific expression of ACE2 in healthy and fibrotic lungs, as well as in normal and failed adult human hearts, using published single-cell RNA-seq data. We found that ACE2 expression in fibrotic lungs mainly locates in arterial vascular cells, which might provide a route for bloodstream spreading of SARS-CoV-2. Failed human hearts have a higher percentage of ACE2-expressing cardiomyocytes, and SARS-CoV-2 might attack cardiomyocytes through the bloodstream in patients with heart failure. Moreover, ACE2 was highly expressed in cells infected by respiratory syncytial virus or Middle East respiratory syndrome coronavirus and in mice treated by lipopolysaccharide. Our findings indicate that patients with pulmonary fibrosis, heart failure, and virus infection have a higher risk and are more susceptible to SARS-CoV-2 infection. The SARS-CoV-2 might attack other organs by getting into the bloodstream. This study provides new insights into SARS-CoV-2 blood entry and heart injury and might propose a therapeutic strategy to prevent patients from developing severe complications.", "doc_id": "3t1tvlye"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiac and arrhythmic complications in patients with COVID-19", "abstract": "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.", "doc_id": "rmio55bx"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiac function in relation to myocardial injury in hospitalised patients with COVID-19", "abstract": "BACKGROUND: Previous studies have reported on myocardial injury in patients with coronavirus infectious disease 19 (COVID-19) defined as elevated cardiac biomarkers. Whether elevated biomarkers truly represent myocardial dysfunction is not known. The aim of this study was to explore the incidence of ventricular dysfunction and assess its relationship with biomarker analyses. METHODS: This cross-sectional study ran from April 1 to May 12, 2020, and consisted of all consecutively admitted patients to the Radboud university medical centre nursing ward for COVID-19. Laboratory assessment included high-sensitivity Troponin T and N\u00adterminal pro-B-type natriuretic peptide (NT-proBNP). Echocardiographic evaluation focused on left and right ventricular systolic function and global longitudinal strain (GLS). RESULTS: In total, 51 patients were included, with a median age of 63 years (range 51-68 years) of whom 80% was male. Troponin T was elevated (>14\u00e2\u0080\u00afng/l) in 47%, and a clinically relevant Troponin T elevation (10\u00e2\u0080\u00af\u00d7 URL) was found in three patients (6%). NT-proBNP was elevated (>300\u00e2\u0080\u00afpg/ml) in 24 patients (47%), and in four (8%) the NT-proBNP concentration was >1,000\u00e2\u0080\u00afpg/ml. Left ventricular dysfunction (ejection fraction <52% and/or GLS >-18%) was observed in 27%, while right ventricular dysfunction (TAPSE <17\u00e2\u0080\u00afmm and/or RV S'\u00e2\u0080\u00af< 10\u00e2\u0080\u00afcm/s) was seen in 10%. There was no association between elevated Troponin T or NT-proBNP and left or right ventricular dysfunction. Patients with confirmed pulmonary embolism had normal right ventricular function. CONCLUSIONS: In hospitalised patients, it seems that COVID-19 predominantly affects the respiratory system, while cardiac dysfunction occurs less often. Based on a single echocardiographic evaluation, we found no relation between elevated Troponin T or NT-proBNP, and ventricular dysfunction. Echocardiography has limited value in screening for ventricular dysfunction.", "doc_id": "mmarbtt5"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "COVID-19 and Cardiac Arrhythmias", "abstract": "BACKGROUND: Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. SARS-CoV-2 infection may cause injury to cardiac myocytes and increase arrhythmia risk. OBJECTIVE: To evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality. METHODS: We reviewed the characteristics of all COVID-19 patients admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias and in-patient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, kidney disease and ICU status as potential risk factors for each arrhythmia. RESULTS: Among 700 patients (mean age 50\u00b118 years, 45% men, 71% African American, and 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred among patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (OR 4.68 [95% CI 1.66 - 13.18]) and NSVT (OR 8.92 [95% CI 1.73 - 46.06]) after multivariable adjustment. Also, age and incident AF (OR 1.05 [95% CI 1.02 - 1.09]); and prevalent heart failure and bradyarrhythmias (OR 9.75 [95% CI 1.95 - 48.65]) were independently associated. Only cardiac arrests were associated with acute, in-hospital mortality. CONCLUSION: Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.", "doc_id": "0yq5ror7"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "The Heart in COVID19: Primary Target or Secondary Bystander?", "abstract": "In the throes of the current COVID-19 pandemic, interest has burgeoned in the cardiovascular complications of this virulent viral infection. As troponin, a biomarker of cardiac injury, often rises in hospitalized patients, its interpretation and actionability require careful consideration. Fulminant myocarditis due to direct viral infection can certainly occur, but patients with increased oxygen demands due to tachycardia and fever, and reduced oxygen delivery due to hypotension and hypoxemia can cause myocardial injury indirectly. Cytokines released during the acute infection can elicit activation of cells within pre-existing atherosclerotic lesions, augmenting thrombotic risk and risk of ischemic syndromes. Moreover, microvascular activation by cytokines can cause not only myocardial injury but harm other organ systems commonly involved in COVID-19 infections including the kidneys. Dealing with the immense challenge of COVID-19 disease, confronted with severely ill patients in dire straits with virtually no rigorous evidence base to guide our therapy, we must call upon our clinical skills and judgment. These touchstones can help guide us in selecting patients who might benefit from the advanced imaging and invasive procedures that present enormous logistical challenges in the current context. Lacking a robust evidence base, pathophysiologic reasoning can help guide our choices of therapy for individual clinical scenarios. We must exercise caution and extreme humility, as often plausible interventions fail when tested rigorously. But act today we must, and understanding the multiplicity of mechanisms of myocardial injury in COVID-19 infection will help us meet our mission unsupported by the comfort of strong data.", "doc_id": "1zfr32pc"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiovascular disease and COVID-19", "abstract": "BACKGROUND AND AIMS: Many patients with coronavirus disease 2019 (COVID-19) have underlying cardiovascular (CV) disease or develop acute cardiac injury during the course of the illness. Adequate understanding of the interplay between COVID-19 and CV disease is required for optimum management of these patients. METHODS: A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic. RESULTS: Respiratory illness is the dominant clinical manifestation of COVID-19; CV involvement occurs much less commonly. Acute cardiac injury, defined as significant elevation of cardiac troponins, is the most commonly reported cardiac abnormality in COVID-19. It occurs in approximately 8-12% of all patients. Direct myocardial injury due to viral involvement of cardiomyocytes and the effect of systemic inflammation appear to be the most common mechanisms responsible for cardiac injury. The information about other CV manifestations in COVID-19 is very limited at present. Nonetheless, it has been consistently shown that the presence of pre-existing CV disease and/or development of acute cardiac injury are associated with significantly worse outcome in these patients. CONCLUSIONS: Most of the current reports on COVID-19 have only briefly described CV manifestations in these patients. Given the enormous burden posed by this illness and the significant adverse prognostic impact of cardiac involvement, further research is required to understand the incidence, mechanisms, clinical presentation and outcomes of various CV manifestations in COVID-19 patients.", "doc_id": "659lz92w"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Effect of coronavirus infection on the human heart: A scoping review", "abstract": "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.", "doc_id": "ousuytwz"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Coronavirus Disease 2019 (COVID-19) Pandemic Implications in Pediatric and Adult Congenital Heart Disease", "abstract": "The corona virus disease -2019 (COVID-19) is a recently described infectious disease caused by the severe acute respiratory syndrome corona virus 2 with significant cardiovascular implications. Given the increased risk for severe COVID-19 observed in adults with underlying cardiac involvement, there is concern that patients with pediatric and congenital heart disease (CHD) may likewise be at increased risk for severe infection. The cardiac manifestations of COVID-19 include myocarditis, arrhythmia and myocardial infarction. Importantly, the pandemic has stretched health care systems and many care team members are at risk for contracting and possibly transmitting the disease which may further impact the care of patients with cardiovascular disease. In this review, we describe the effects of COVID-19 in the pediatric and young adult population and review the cardiovascular involvement in COVID-19 focusing on implications for patients with congenital heart disease in particular.", "doc_id": "dcf82t8n"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Emerging cardiological issues during the COVID-19 pandemic", "abstract": "", "doc_id": "15th475n"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiac Tamponade Secondary to COVID-19", "abstract": "A 67-year-old female presented with upper respiratory symptoms and was diagnosed with COVID-19. She was found to have a large hemorrhagic pericardial effusion with echocardiographic signs of tamponade and mild left ventricular impairment. Clinical course was complicated by development of Takotsubo cardiomyopathy. She was treated with pericardiocentesis, colchicine, corticosteroids and hydroxychloroquine with improvement in symptoms.", "doc_id": "6zr1v5x6"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "COVID-19 for the Cardiologist: A Current Review of the Virology, Clinical Epidemiology, Cardiac and Other Clinical Manifestations and Potential Therapeutic Strategies", "abstract": "The coronavirus disease-2019 (COVID-19), a contagious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), has reached pandemic status. As it spreads across the world, it has overwhelmed healthcare systems, strangled the global economy and led to a devastating loss of life. Widespread efforts from regulators, clinicians and scientists are driving a rapid expansion of knowledge of the SARS-CoV2 virus and the COVID-19 disease. We review the most current data with a focus on our basic understanding of the mechanism(s) of disease and translation to the clinical syndrome and potential therapeutics. We discuss the basic virology, epidemiology, clinical manifestation, multi-organ consequences, and outcomes. With a focus on cardiovascular complications, we propose several mechanisms of injury. The virology and potential mechanism of injury form the basis for a discussion of potential disease-modifying therapies.", "doc_id": "dde20n52"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Approach to Acute Cardiovascular Complications in COVID-19 Infection", "abstract": "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.", "doc_id": "gs45hgch"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "First case of COVID-19 complicated with fulminant myocarditis: a case report and insights", "abstract": "BACKGROUND: Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. CASE PRESENTATION: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization. CONCLUSION: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.", "doc_id": "4dnuilqg"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiac considerations in patients with COVID-19", "abstract": "", "doc_id": "emj1wdac"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Coronavirus fulminant myocarditis saved with glucocorticoid and human immunoglobulin ;European Heart Journal ;Oxford Academic", "abstract": "A 37-year-old male patient was admitted to hospital on 14 January 2020, with chest pain and dyspnoea for 3 days, accompanied by diarrhoea His blood pressure decreased to 80/50 mmHg X-ray chest film showed significant enlargement of the heart (Panel A: cardiothoracic ratio 0 70) Chest computed tomography (CT) examination indicated pulmonary infection, enlarged heart, and pleural effusion (Panels B and C) The electrocardiogram suspected ST-segment elevation acute myocardial infarction (III, AVF ST-segment elevation, Panels D and E), an emergency CT coronary angiography revealed no coronary stenosis Markers of myocardial injury were significantly elevated Troponin T was more than 10 000 ng/L Creatine kinase isoenzyme CKMB 112 9 ng/L Natriuretic peptide BNP was up to 21 025 ng/L Echocardiography revealed an enlarged heart and a marked decrease in ventricular systolic function [left ventricle (end diastolic) dimension (LV) 58 mm, left atrium dimension (LA) 39 mm, right ventricle dimension (RV) 25 mm, right atrium dimension (RA) 48 mm, left ventricular ejection fraction (LVEF) 27%, trace 2 mm pericardial effusion] Sputum was examined for 13 viral nucleic acids related to respiratory tract Only the coronavirus nucleic acid test was positive All of the other 12 nucleic acid tests were negative, including influenza A virus, adenovirus, bocavirus, rhinovirus, influenza A(H1N1) 2009, parainfluenza, chlamydia, partial pulmonary virus, influenza B virus, mycoplasma pneumoniae, influenza A virus H3N2, and respiratory syncytial virus The diagnosis of this patient is coronavirus fulminant myocarditis with cardiogenic shock and pulmonary infection", "doc_id": "dd0ku5ra"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Analysis of heart injury laboratory parameters in 273 COVID-19 patients in one hospital in Wuhan, China", "abstract": "An outbreak of severe acute respiratory syndrome novel coronavirus (SARS-CoV-2) epidemic spreads rapidly worldwide. SARS-CoV-2 infection caused mildly to seriously and fatally respiratory, enteric, cardiovascular, and neurological diseases. In this study, we detected and analyzed the main laboratory indicators related to heart injury, creatine kinase isoenzyme-MB (CK-MB), myohemoglobin (MYO), cardiac troponin I (ultra-TnI), and N-terminal pro-brain natriuretic peptide (NT-proBNP), in 273 patients with COVID-19 and investigated the correlation between heart injury and severity of the disease. It was found that higher concentration in venous blood of CK-MB, MYO, ultra-TnI, and NT-proBNP were associated with the severity and case fatality rate of COVID-19. Careful monitoring of the myocardiac enzyme profiles is of great importance in reducing the complications and mortality in patients with COVID-19.", "doc_id": "3sqp13p9"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis", "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.", "doc_id": "8txb9563"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "A care pathway for the cardiovascular complications of COVID-19: Insights from an institutional response", "abstract": "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.", "doc_id": "38ltcpcw"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiovascular manifestations in severe and critical patients with COVID-19", "abstract": "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 \u00b1 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.", "doc_id": "ltz62pk3"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Advances in the relationship between coronavirus infection and cardiovascular diseases", "abstract": "The outbreak of coronavirus disease 2019 (COVID-19) has once again aroused people's concern about coronavirus. Seven human coronaviruses (HCoVs) have been discovered so far, including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU115, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 2. Existing studies show that the cardiovascular disease increased the incidence and severity of coronavirus infection. At the same time, myocardial injury caused by coronavirus infection is one of the main factors contributing to poor prognosis. In this review, the recent clinical findings about the relationship between coronaviruses and cardiovascular diseases and the underlying pathophysiological mechanisms are discussed. This review aimed to provide assistance for the prevention and treatment of COVID-19.", "doc_id": "a13e4fwp"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "COVID-19 and Acute Heart Failure: Screening the Critically Ill - A Position Statement of the Cardiac Society of Australia and New Zealand (CSANZ)", "abstract": "Up to one-third of COVID-19 patients admitted to intensive care develop an acute cardiomyopathy, which may represent myocarditis or stress cardiomyopathy. Further, while mortality in older patients with COVID-19 appears related to multi-organ failure complicating acute respiratory distress syndrome (ARDS), the cause of death in younger patients may be related to acute heart failure. Cardiac involvement needs to be considered early on in critically ill COVID-19 patients, and even after the acute respiratory phase is passing. This Statement presents a screening algorithm to better identify COVID-19 patients at risk for severe heart failure and circulatory collapse, while balancing the need to protect health care workers and preserve personal protective equipment (PPE). The significance of serum troponin levels and the role of telemetry and targeted transthoracic echocardiography (TTE) in patient investigation and management are addressed, as are fundamental considerations in the management of acute heart failure in COVID-19 patients.", "doc_id": "ihciswq4"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "2019-Novel Coronavirus-Related Acute Cardiac Injury Cannot Be Ignored", "abstract": "PURPOSE OF THE REVIEW: Coronavirus disease 2019 (COVID-19), a new infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has reached a pandemic status. Although SARSCoV-2 causes primarily respiratory problems, concurrent cardiac injury cannot be ignored since it may be an independent predictor for adverse outcomes. To resolve these issues, we aim to summarize the prevalence and its underlying mechanisms of acute cardiac injury in the setting of SARS-CoV-2 infection. RECENT FINDINGS: The main clinical manifestation of SARS-CoV-2 infection is pneumonia, cardiovascular complications have also been identified in the earliest reported cases from Wuhan, the epicenter of the outbreak. Given the SARS-CoV-2 likely uses the angiotensin-converting enzyme-2 (ACE2) receptors as its host receptor, ACE2-related signaling pathways may play a key role in mediating myocardial injury. SARS-CoV-2 infection related acute cardiac injury cannot be ignored, and its underlying mechanisms remain speculated. We would suggest that health professionals investigate cardiac function as part of the routine care.", "doc_id": "o988xoxn"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart", "abstract": "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.", "doc_id": "0376d6vf"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Prognostic significance of cardiac injury in COVID-19 patients with and without coronary artery disease", "abstract": "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 \u00b1 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.", "doc_id": "dxfyfhnd"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "HEART BRAKE-An unusual cardiac manifestation of Coronavirus disease 2019 (COVID-19)", "abstract": "A 49-year-old male presented with worsening high-grade fevers, dry cough and shortness of breath, tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and was noted to have bradycardia with intermittent high-degree AV block. However, cardiac biomarkers and echocardiography were normal, making this an unusual and interesting manifestation showing myocardial involvement of this novel coronavirus.", "doc_id": "02mmdgjk"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiovascular Collapse in COVID-19 Infection: The Role of Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO)", "abstract": "COVID-19 has been associated with cardiovascular complications including acute cardiac injury, heart failure and cardiogenic shock. The role of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in the event of COVID-19-associated cardiovascular collapse has not yet been established. We reviewed existing literature surrounding the role of VA-ECMO in the treatment of coronavirus-related cardiovascular collapse. COVID-19 is associated with higher incidence of cardiovascular complications compared to previous coronavirus outbreaks (SARS-CoV, MERS-CoV). We found only one case report from China where COVID-19-associated fulminant myocarditis and cardiogenic shock (CS) was successfully rescued using VA-ECMO as a bridge to recovery (BTR). We identified potential clinical scenarios (cardiac injury, myocardial infarction with and without obstructive coronary artery disease, viral myocarditis, and decompensated heart failure) leading to CS and risk factors for poor/uncertain benefit (age, sepsis, mixed/predominantly vasodilatory shock, prothrombotic state and/or coagulopathy, severe acute respiratory distress syndrome, multi-organ failure or high-risk prognostic scores) specific to using VA-ECMO as BTR in COVID-19 infection. Additional considerations and proposed recommendations specific to the COVID-19 pandemic were formulated with guidance from published data and expert consensus. A small subset of patients with cardiovascular complications from COVID-19 infection may progress to refractory CS. Accepting that resource scarcity may be the overwhelming concern for healthcare systems during this pandemic, VA-ECMO can be considered in highly selected cases of refractory CS and echocardiographic evidence of biventricular failure. The decision to initiate this therapy should take into consideration availability of resources, perceived benefit as well as risks of transmitting disease.", "doc_id": "nqrtk06s"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities", "abstract": "This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients. Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern. One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia. Multifocal acute injury of cardiac myocytes was frequently observed. Lymphocytic myocarditis was reported in 1 case. In addition to major pulmonary pathology, the 3 Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis. Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 g heart), dilated cardiomyopathy (1070 g heart), and hypertrophic cardiomyopathy (670 g heart). All 3 subjects were obese (BMIs of 33.8, 51.65, and 35.2 Kg/m2). Overall, the autopsy findings support the concept that the pathogenesis of severe COVID-19 disease involves direct viral-induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy.", "doc_id": "n1rlloc5"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "The clinical characteristics of myocardial injury in severe and very severe patients with 2019 novel coronavirus disease", "abstract": "", "doc_id": "21z135sq"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiac Troponin for the Diagnosis and Risk-Stratification of Myocardial Injury in COVID-19: JACC Review Topic of the Week", "abstract": "Increases in cardiac troponin (cTn) indicative of myocardial injury are common in patients with COVID-19 and associated with adverse outcomes such as arrhythmias and death. These increases are more likely to occur in those with chronic cardiovascular conditions and in those with severe COVID-19 presentations. The increased inflammatory, prothrombotic, and procoagulant responses following SARS-CoV-2 infection increase the risk for acute nonischemic myocardial injury and acute myocardial infarction, particularly type 2 myocardial infarction because of respiratory failure with hypoxia and hemodynamic instability in critically ill patients. Myocarditis, stress cardiomyopathy, acute heart failure, and direct injury from SARS-CoV-2 are important etiologies, but primary non-cardiac conditions such as pulmonary embolism, critical illness, and sepsis probably cause more of the myocardial injury. The structured use of serial cTn has the potential to facilitate risk stratification, help make decisions about when to use imaging, and inform stage categorization and disease phenotyping among hospitalized COVID-19 patients.", "doc_id": "agk7v67l"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Does SARS-CoV-2 cause viral myocarditis in COVID-19 patients?", "abstract": "", "doc_id": "b3vey2m8"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiac manifestations in COVID-19 patients-A systematic review", "abstract": "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.", "doc_id": "qbby61wj"} {"topic_name": "coronavirus heart impacts", "topic_id": "22", "title": "Cardiovascular system and COVID-19: perspectives from a developing country", "abstract": "A novel coronavirus, SARS-CoV-2, thought to have originated from bats causes COVID-19 infection which was first reported from Wuhan, China in December 2019. This virus has a high infectivity rate and has impacted a significant chunk of the population worldwide. The spectrum of disease ranges from mild to severe with respiratory system being the most commonly affected. Cardiovascular system often gets involved in later stages of the disease with acute cardiac injury, heart failure and arrhythmias being the common complications. In addition, the presence of cardiovascular co-morbidities such as hypertension, coronary artery disease in these patients are often associated with poor prognosis. It is still not clear regarding the exact mechanism explaining cardiovascular system involvement in COVID-19. Multiple theories have been put forward however, more robust studies are required to fully elucidate the \"heart and virus\" link. The disease has already made its presence felt on the global stage and its impact in the developing countries is going to be profound. These nations not only have a poorly developed healthcare system but there is also a huge burden of cardiovascular diseases. As a result, COVID-19 would adversely impact the already overburdened healthcare network leading to impaired cardiovascular care delivery especially for acute coronary syndrome and heart failure patients.", "doc_id": "iqbc09sz"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Unusually Rapid Development of Pulmonary Hypertension and Right Ventricular Failure after COVID-19 Pneumonia", "abstract": "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 \u2013 in the absence of emboli on multiple CT angiograms \u2013 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.", "doc_id": "7xqmuoye"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "The COVID-19 pandemic prevents patients with pulmonary hypertension from seeking medical help.", "abstract": "", "doc_id": "ru9aeq27"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Severity of COVID-19: The importance of being hypertensive.", "abstract": "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).", "doc_id": "xm9k6fn2"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Could anti-hypertensive drug therapy affect the clinical prognosis of hypertensive patients with COVID-19 infection? Data from centers of southern Italy.", "abstract": "Background Coronavirus-19 (COVID-19) is the cause of a pandemic disease, with severe acute respiratory syndrome by binding target epithelial lung cells through angiotensin converting enzyme 2 (ACE2) in humans. Thus, hypertensive patients with COVID-19 could have worse prognosis. Indeed, angiotensin converting enzyme (ACEi) inhibitors and/or angiotensin receptor blockers (ARBs) may interfere with ACE2 expression/activity. Thus, hypertensive patients undergoing ACEi and/or ARBs drug therapy may be at a higher risk of contracting a serious COVID-19 infection and should be monitored. Moreover, in the present study we investigated the effects of ACEi vs. ARBs vs. calcium channel blockers on clinical outcomes as mechanical ventilation, Intensive Care Unit (ICU) admissions, heart injury and death in 62 hypertensive patients hospitalized for COVID-19 infection. Methods and Results The multicenter study was prospectively conducted at Department of Infectious Diseases of Sant'Anna Hospital of Caserta, and of University of Campania \"Luigi Vanvitelli\" of Naples, at Department of Advanced Surgical and Medical Sciences of University of Campania \"Luigi Vanvitelli\", Naples, and at General Medical Assistance Unit \"FIMG\", Naples, Italy. Lowest values of left ventricle ejection fraction predicted deaths (1.142; [1.008-1.294], p <0.05), while highest values of interleukin 6 (IL6) predicted the admission to ICU (1.617; [1.094-2.389]), mechanical ventilation (1.149; [1.082-1.219]), heart injuries (1.367; [1.054-1.772]) and deaths (4.742; [1.788-8.524]). ConclusionsAnti-hypertensive drugs didn't affect the prognosis in COVID-19 patients. Consequently, tailored anti-inflammatory and immune therapies in addition to chronic antihypertensive therapy, could prevent a worse prognosis, as well as improve the clinical outcomes in hypertensive patients with COVID-19 infection.", "doc_id": "rbi4kg69"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Prevalence of Self-Reported Hypertension and Antihypertensive Medication Use by County and Rural-Urban Classification - United States, 2017.", "abstract": "In 2017, approximately one in three U.S. adults reported having been told by a health care professional that they had high blood pressure (hypertension) (1). Although hypertension prevalence is well documented at national and state levels, less is known about rural-urban variation and county-level prevalence. To examine prevalence of self-reported hypertension and antihypertensive medication use by rural-urban classification and county, CDC analyzed data reported by 442,641 adults aged \u226518 years who participated in the 2017 Behavioral Risk Factor Surveillance System (BRFSS). In rural (noncore) areas, 40.0% (unadjusted prevalence) of adults reported having hypertension, whereas in the most urban (large central metro) areas, 29.4% reported having hypertension. Age-standardized hypertension prevalence was significantly higher in the most rural areas, compared with the most urban areas within nearly all categories of age, sex, and other demographic characteristics. Model-based hypertension prevalence across counties ranged from 18.0% to 55.0% and was highest in Southeastern* and Appalachian\u2020 counties. Model-based county-level prevalence of antihypertensive medication use among adults with hypertension ranged from 54.3% to 84.7%. Medication use also was higher in rural areas compared with use in most urban areas, with prevalence highest in Southeastern and Appalachian counties as well as counties in the Dakotas and Nebraska. CDC is working with states to enhance hypertension awareness and management through a strategy of team-based care that involves physicians, nurses, pharmacists, dietitians, and community health workers. The increased use of telemedicine to support this strategy might improve access to care among underserved populations.", "doc_id": "d63miqjd"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "A Significance of High Prevalence of Diabetes and Hypertension in Severe COVID-19 Patients", "abstract": "", "doc_id": "gmraihg6"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Care of patients with pulmonary arterial hypertension during the coronavirus (COVID-19) pandemic", "abstract": "The COVID-19 pandemic presents many unique challenges when caring for patients with pulmonary hypertension The COVID-19 pandemic has altered routine standard of care practice and the acute management particularly for those patients with pulmonary arterial hypertension, where pulmonary arterial hypertension-specific treatments are used It is important to balance the ongoing care and evaluation of pulmonary arterial hypertension patients with \"exposure risk\" to COVID-19 for patients coming to clinic or the hospital If there is a morbidity and mortality benefit from starting pulmonary arterial hypertension therapies, for example in a patient with high-likelihood of pulmonary arterial hypertension, then it remains important to complete the thorough evaluation However, the COVID-19 outbreak may also represent a unique time when pulmonary hypertension experts have to weigh the risks and benefits of the diagnostic work-up including potential exposure to COVID-19 versus initiating targeted pulmonary arterial hypertension therapy in a select high-risk, high likelihood World Symposium Pulmonary Hypertension Group 1 pulmonary arterial hypertension patients This document will highlight some of the issues facing providers, patients, and the pulmonary arterial hypertension community in real-time as the COVID-19 pandemic is evolving and is intended to share expected common clinical scenarios and best clinical practices to help the community at-large", "doc_id": "hj6dobhd"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Management of hospitalized patients with pulmonary arterial hypertension and COVID-19 infection", "abstract": "", "doc_id": "j8b64a1a"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Coronavirus SARS-Cov-2 and arterial hypertension - facts and myths.", "abstract": "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.", "doc_id": "r7vx32o2"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Hypertension in patients with coronavirus disease 2019 (COVID-19): a pooled analysis", "abstract": "INTRODUCTION: As the outbreak of coronavirus disease 2019 (COVID\u00ad19) 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 COVID\u00ad19. 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 COVID\u00ad19 or in COVID-19 survivors and nonsurvivors. The obtained data were pooled into a meta\u00adanalysis to calculate odds ratios (ORs) with 95% CIs. RESULTS: Hypertension was associated with a nearly 2.5\u00adfold increased risk of severe COVID\u00ad19 (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 meta\u00adregression analysis, a correlation was observed between an increase in the mean age of patients with severe COVID\u00ad19 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 2.5\u00adfold higher risk of severe or fatal COVID\u00ad19, especially in older individuals.", "doc_id": "g484ymy9"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic?", "abstract": "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.", "doc_id": "gwefujal"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "A Proposed Plan for Prenatal Care to Minimize Risks of COVID-19 to Patients and Providers: Focus on Hypertensive Disorders of Pregnancy", "abstract": "Hypertensive disorders are the most common medical complications of pregnancy and a major cause of maternal and perinatal morbidity and death. The detection of elevated blood pressure during pregnancy is one of the cardinal aspects of optimal antenatal care. With the outbreak of novel coronavirus disease 2019 (COVID-19) and the risk for person-to-person spread of the virus, there is a desire to minimize unnecessary visits to health care facilities. Women should be classified as low risk or high risk for hypertensive disorders of pregnancy and adjustments can be accordingly made in the frequency of maternal and fetal surveillance. During this pandemic, all pregnant women should be encouraged to obtain a sphygmomanometer. Patients monitored for hypertension as an outpatient should receive written instructions on the important signs and symptoms of disease progression and provided contact information to report the development of any concern for change in status. As the clinical management of gestational hypertension and preeclampsia is the same, assessment of urinary protein is unnecessary in the management once a diagnosis of a hypertensive disorder of pregnancy is made. Pregnant women with suspected hypertensive disorders of pregnancy and signs and symptoms associated with the severe end of the disease spectrum (e.g., headaches, visual symptoms, epigastric pain, and pulmonary edema) should have an evaluation including complete blood count, serum creatinine level, and liver transaminases (aspartate aminotransferase and alanine aminotransferase). Further, if there is any evidence of disease progression or if acute severe hypertension develops, prompt hospitalization is suggested. Current guidelines from the American College of Obstetricians and Gynecologists (ACOG) and The Society for Maternal-Fetal Medicine (SMFM) for management of preeclampsia with severe features suggest delivery after 34 0/7 weeks of gestation. With the outbreak of COVID-19, however, adjustments to this algorithm should be considered including delivery by 30 0/7 weeks of gestation in the setting of preeclampsia with severe features. KEY POINTS: \u00b7 Outbreak of novel coronavirus disease 2019 (COVID-19) warrants fewer office visits.. \u00b7 Women should be classified for hypertension risk in pregnancy.. \u00b7 Earlier delivery suggested with COVID-19 and hypertensive disorder..", "doc_id": "mnxmb5pz"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study", "abstract": "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.", "doc_id": "gjahdnay"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression", "abstract": "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 \u00e2\u00a9\u00be 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.", "doc_id": "z9u229yg"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Clinical characteristics of coronavirus disease 2019 (COVID-19) patients with hypertension on renin-angiotensin system inhibitors", "abstract": "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 \u00d7 109/L vs 1.26 \u00d7 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.", "doc_id": "faz8uw2d"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Hypertension and COVID-19", "abstract": "", "doc_id": "bzz8ydcs"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "The importance of hypertension as a risk factor for severe illness and mortality in COVID-19", "abstract": "", "doc_id": "tmrcgdal"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "COVID-19 and arterial hypertension: Hypothesis or evidence?", "abstract": "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.", "doc_id": "9nbj3ckb"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Antihypertensive treatment with ACEI/ARB of patients with COVID-19 complicated by hypertension", "abstract": "", "doc_id": "w0e0jhda"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Could anti-hypertensive drug therapy affect the clinical prognosis of hypertensive patients with COVID-19 infection? Data from centers of southern Italy", "abstract": "Background Coronavirus-19 (COVID-19) is the cause of a pandemic disease, with severe acute respiratory syndrome by binding target epithelial lung cells through angiotensin converting enzyme 2 (ACE2) in humans. Thus, hypertensive patients with COVID-19 could have worse prognosis. Indeed, angiotensin converting enzyme (ACEi) inhibitors and/or angiotensin receptor blockers (ARBs) may interfere with ACE2 expression/activity. Thus, hypertensive patients undergoing ACEi and/or ARBs drug therapy may be at a higher risk of contracting a serious COVID-19 infection and should be monitored. Moreover, in the present study we investigated the effects of ACEi vs. ARBs vs. calcium channel blockers on clinical outcomes as mechanical ventilation, Intensive Care Unit (ICU) admissions, heart injury and death in 62 hypertensive patients hospitalized for COVID-19 infection. Methods and Results The multicenter study was prospectively conducted at Department of Infectious Diseases of Sant'Anna Hospital of Caserta, and of University of Campania \"Luigi Vanvitelli\" of Naples, at Department of Advanced Surgical and Medical Sciences of University of Campania \"Luigi Vanvitelli\", Naples, and at General Medical Assistance Unit \"FIMG\", Naples, Italy. Lowest values of left ventricle ejection fraction predicted deaths (1.142; [1.008-1.294], p <0.05), while highest values of interleukin 6 (IL6) predicted the admission to ICU (1.617; [1.094-2.389]), mechanical ventilation (1.149; [1.082-1.219]), heart injuries (1.367; [1.054-1.772]) and deaths (4.742; [1.788-8.524]). ConclusionsAnti-hypertensive drugs didn't affect the prognosis in COVID-19 patients. Consequently, tailored anti-inflammatory and immune therapies in addition to chronic antihypertensive therapy, could prevent a worse prognosis, as well as improve the clinical outcomes in hypertensive patients with COVID-19 infection.", "doc_id": "75apu1m4"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers", "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.", "doc_id": "1y78dfsl"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Decreased Mortality of COVID-19 With Renin-Angiotensin-Aldosterone System Inhibitors Therapy in Patients With Hypertension: A Meta-Analysis", "abstract": "", "doc_id": "32p4oa4w"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Could renin\u2013angiotensin\u2013aldosterone system inhibitors be used for hypertensive patients with coronavirus disease 2019?", "abstract": "", "doc_id": "4thw6knl"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Antagonizing the renin\u2013angiotensin\u2013aldosterone system in the era of COVID-19", "abstract": "", "doc_id": "ei598viq"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility", "abstract": "Patients with hypertension, diabetes, coronary heart disease, cerebrovascular illness, chronic obstructive pulmonary disease, and kidney dysfunction have worse clinical outcomes when infected with SARS-CoV-2, for unknown reasons. The purpose of this review is to summarize the evidence for the existence of elevated plasmin(ogen) in COVID-19 patients with these comorbid conditions. Plasmin, and other proteases, may cleave a newly inserted furin site in the S protein of SARS-CoV-2, extracellularly, which increases its infectivity and virulence. Hyperfibrinolysis associated with plasmin leads to elevated D-dimer in severe patients. The plasmin(ogen) system may prove a promising therapeutic target for combating COVID-19.", "doc_id": "tzxrztr7"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "The interplay of Hypertension, ACE-2 and SARS-CoV-2: Emerging data as the \u201cAriadne\u2019s thread\u201d for the \u201clabyrinth\u201d of COVID-19", "abstract": "", "doc_id": "lqmixm7s"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "COVID-19 in a young man with hypertension: A case study of missed opportunities in intensive progression", "abstract": "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.", "doc_id": "wyxdodxd"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "The association of hypertension with the severity and mortality of COVID-19 patients: evidence based on adjusted effect estimates", "abstract": "", "doc_id": "i7ng9gzw"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "A new normal for hypertension medicine with coronavirus disease-2019 (COVID-19): proposal from the president of the Japanese Society of Hypertension", "abstract": "", "doc_id": "hg34wsj0"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Clinical characteristics associated with COVID-19 severity in California", "abstract": "Given the rapidly progressing coronavirus disease 2019 (COVID-19) pandemic, this report on a US cohort of 54 COVID-19 patients from Stanford Hospital and data regarding risk factors for severe disease obtained at initial clinical presentation is highly important and immediately clinically relevant. We identified low presenting oxygen saturation as predictive of severe disease outcomes, such as diagnosis of pneumonia, acute respiratory distress syndrome, and admission to the intensive care unit, and also replicated data from China suggesting an association between hypertension and disease severity. Clinicians will benefit by tools to rapidly risk stratify patients at presentation by likelihood of progression to severe disease.", "doc_id": "3d8up3zo"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "No adequate evidence indicating hypertension as an independent risk factor for COVID-19 severity", "abstract": "", "doc_id": "5efzormt"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Hypertension and coronavirus disease 2019: what do we really know?", "abstract": "", "doc_id": "9m5fl3m3"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "COVID\u201019 and arterial hypertension: Hypothesis or evidence?", "abstract": "Investigations reported that hypertension, diabetes, and cardiovascular diseases were the most prevalent comorbidities among the patients with coronavirus disease 2019 (COVID\u201019). Hypertension appeared consistently as the most prevalent risk factors in COVID\u201019 patients. Some investigations speculated about the association between renin\u2010angiotensin\u2010aldosterone system (RAAS) and susceptibility to COVID\u201019, 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\u201019. There are only a few follow\u2010up 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\u201019 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\u201019 and the role of hypertension on outcome in these patients.", "doc_id": "hzb2fkj5"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "COVID-19 patients with hypertension have more severity condition, and ACEI/ARB treatment have no infulence on the clinical severity and outcome", "abstract": "", "doc_id": "ljs80v45"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Effect of hypertension on outcomes of adult inpatients with COVID-19 in Wuhan, China: a propensity score\u2013matching analysis", "abstract": "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\u2013matching (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\u2019 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\u20136.440]; P < 0.001). Increased D-dimer levels and higher ratio of neutrophils to lymphocytes (N/L) were also found to increase these patients\u2019 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.", "doc_id": "xj50b7zo"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "Hypertension and diabetes mellitus in patients with COVID 19: a viewpoint on mortality", "abstract": "", "doc_id": "vkxrbav7"} {"topic_name": "coronavirus hypertension", "topic_id": "23", "title": "RAAS blockers in hypertension posing a higher risk towards the COVID\u201019", "abstract": "", "doc_id": "o5031cxp"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Coronavirus infection in patients with diabetes.", "abstract": "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.", "doc_id": "ifmwfm43"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Severity of COVID-19 and diabetes mellitus: there is still a lot to be learned.", "abstract": "", "doc_id": "f4aiot6d"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Personal Experience With COVID-19 and Diabetes in the South of France: Technology Facilitates the Management of Diabetes in Disruptive Times.", "abstract": "We report our experience with COVID-19 epidemic in patients with type 1 diabetes using diabetes technology in the South of France. Use of insulin pumps and continuous glucose monitoring appeared as an effective way to prevent the risk of acute metabolic complications related to the changes of daily life associated with requested confinement . Care by telemedicine was facilitated in these patients who used diabetes technology while structured education delivered during training and support from home care services were helpful to master the disruptive conditions.", "doc_id": "kzoumf3k"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "[The Management of Blood Glucose Should be Emphasized in the Treatment of COVID-19].", "abstract": "Based on the higher mortality and the higher proportion of critically ill adults in coronavirus disease 2019 (COVID-19) patients with diabetes, good inpatient glycemic control is particularly important in the comprehensive treatment of COVID-19. Individualized blood glucose target goals and treatment strategies should be made according to specific circumstances of COVID-19 inpatients with diabetes. For mild patients, a strict glycemic control target (fasting plasma glucose (FPG) 4.4-6.1 mmol/L, 2-hour postprandial plasma glucose (2 h PG) 6.1-7.8 mmol/L) are recommended; a target for the glycemic control of common type patients (FPG 6.1-7.8 mmol/L, 2 h PG 7.8-10.0 mmol/L) and subcutaneous insulin deliver therapy are recommended; a target nonfasting blood glucose range of 10.0 mmol or less per liter for severe-type COVID-19 patients, a relatively Less stringent blood glucose control target (FPG 7.8-10.0 mmol/L, 2 h PG 7.8-13.9 mmol/L) for critically ill patients and intravenous insulin infusion therapy are recommended. Due to the rapid changes in the condition of some patients, the risk of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar status (HHS) maybe occur during the treatment. Blood glucose monitoring, dynamic evaluation and timely adjustment of strategies should be strengthened to ensure patient safety and promote early recovery of patients.", "doc_id": "1oudnxmt"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Diabetes Epidemiology in the COVID-19 Pandemic.", "abstract": "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.", "doc_id": "ina400b0"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "CLINICAL CHARACTERISTICS OF 28 PATIENTS WITH DIABETES AND COVID-19 IN WUHAN, CHINA.", "abstract": "Objective: Previous studies on coronavirus disease 2019 (COVID-19) were based on information from the general population. We aimed to further clarify the clinical characteristics of diabetes with COVID-19. Methods: Twenty-eight patients with diabetes and COVID-19 were enrolled from January 29, 2020, to February 10, 2020, with a final follow-up on February 22, 2020. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were analyzed. Results: The average age of the 28 patients was 68.6 \u00b1 9.0 years. Most (75%) patients were male. Only 39.3% of the patients had a clear exposure of COVID-19. Fever (92.9%), dry cough (82.1%), and fatigue (64.3%) were the most common symptoms, followed by dyspnea (57.1%), anorexia (57.1%), diarrhea (42.9%), expectoration (25.0%), and nausea (21.4%). Fourteen patients were admitted to the intensive care unit (ICU). The hemoglobin A1c level was similar between ICU and non-ICU patients. ICU patients had a higher respiratory rate, higher levels of random blood glucose, aspartate transaminase, bilirubin, creatine, N-terminal prohormone of brain natriuretic peptide, troponin I, D-dimers, procalcitonin, C-reactive protein, ferritin, interleukin (IL)-2R, IL-6, and IL-8 than non-ICU patients. Eleven of 14 ICU patients received noninvasive ventilation and 7 patients received invasive mechanical ventilation. Twelve patients died in the ICU group and no patients died in the nonICU group. Conclusion: ICU cases showed higher rates of organ failure and mortality than non-ICU cases. The poor outcomes of patients with diabetes and COVID-19 indicated that more supervision is required in these patients. (Endocr Pract. 2020;26:xxx-xxx).", "doc_id": "flqtiz52"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Usefulness and safety of remote continuous glucose monitoring for a severe COVID-19 patient with diabetes.", "abstract": "Diabetes is associated with mortality and severity of COVID-19. Protecting against infection in healthcare workers at high risk of COVID-19 are critical. This report investigates the usefulness and safety of remote continuous glucose monitoring in a patient with diabetes and severe interstitial pneumonia caused by the coronavirus disease. The Dexcom G4 Platinum continuous glucose monitoring system\u00ae was used to monitor blood glucose levels from outside the patient's isolation room. Continuous insulin infusion rates and boluses were determined based on the patient's blood glucose levels. Real-time continuous glucose monitoring made it possible to track blood glucose trends and prevent dramatic variations in blood glucose, although the rate of insulin infusion changed dynamic. Furthermore, the need for healthcare workers to enter the isolation room was minimized because the Dexcom G4 Platinum continuous glucose monitoring system can evaluate from a distance of up to 6.0 meters.", "doc_id": "hnp0gn6o"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Cellular exocytosis gene (EXOC6/6B): a potential molecular link for the susceptibility and mortality of COVID-19 in diabetic patients", "abstract": "Diabetes is one of the most critical comorbidities linked to an increased risk of severe complications in the current coronavirus disease 2019 (COVID-19) pandemic. A better molecular understanding of COVID-19 in people with type diabetes mellitus (T2D) is mandatory, especially in countries with a high rate of T2D, such as the United Arab Emirates (UAE). Identification of the cellular and molecular mechanisms that make T2D patients prone to aggressive course of the disease can help in the discovery of novel biomarkers and therapeutic targets to improve our response to the disease pandemic. Herein, we employed a system genetics approach to explore potential genomic, transcriptomic alterations in genes specific to lung and pancreas tissues, affected by SARS-CoV-2 infection, and study their association with susceptibility to T2D in Emirati patients. Our results identified the Exocyst complex component, 6 (EXOC6/6B) gene (a component for docks insulin granules to the plasma membrane) with documented INDEL in 3 of 4 whole genome sequenced Emirati diabetic patients. Publically available transcriptomic data showed that lung infected with SARS-CoV-2 showed significantly lower expression of EXOC6/6B compared to healthy lungs. In conclusion, our data suggest that EXOC6/6B might be an important molecular link between dysfunctional pancreatic islets and ciliated lung epithelium that makes diabetic patients more susceptible to severe SARS-COV-2 complication.", "doc_id": "gfx7zi53"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "COVID 19: Diabetes and Obesity API-ICP Recommendations.", "abstract": "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.", "doc_id": "25v7qies"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "COVID-19 infection in Italian people with diabetes: Lessons learned for our future (an experience to be used)", "abstract": "", "doc_id": "3x1b9epe"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Prevalence and impact of diabetes among people infected with SARS-CoV-2", "abstract": "", "doc_id": "ec2u0qwr"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Estimation of effects of nationwide lockdown for containing coronavirus infection on worsening of glycosylated haemoglobin and increase in diabetes-related complications: A simulation model using multivariate regression analysis", "abstract": "INTRODUCTION: and aims: To prevent the spread of coronavirus disease (COVID19) total lockdown is in place in India from March 24, 2020 for 21 days. In this study, we aim to assess the impact of the duration of the lockdown on glycaemic control and diabetes-related complications. MATERIALS AND METHODS: A systematic search was conducted using Cochrane library. A simulation model was created using glycemic data from previous disasters (taken as similar in impact to current lockdown) taking baseline HBA1c and diabetes-related complications data from India-specific database. A multivariate regression analysis was conducted to analyse the relationship between the duration of lockdown and glycaemic targets & diabetes-related complications. RESULTS: The predictive model was extremely robust (R2 = 0.99) and predicted outcomes for period of lockdown up to 90 days. The predicted increment in HBA1c from baseline at the end of 30 days and 45 days lockdown was projected as 2.26% & 3.68% respectively. Similarly, the annual predicted percentage increase in complication rates at the end of 30-day lockdown was 2.8% for non-proliferative diabetic retinopathy, 2.9% for proliferative diabetic retinopathy, 1.5% for retinal photocoagulation, 9.3% for microalbuminuria, 14.2% for proteinuria, 2.9% for peripheral neuropathy, 10.5% for lower extremity amputation, 0.9% for myocardial infarction, 0.5% for stroke and 0.5% for infections. CONCLUSION: The duration of lockdown is directly proportional to the worsening of glycaemic control and diabetes-related complications. Such increase in diabetes-related complications will put additional load on overburdened healthcare system, and also increase COVID19 infections in patients with such uncontrolled glycemia.", "doc_id": "b2tsladw"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Letter to the Editor: CoVid-19 and type 1 diabetes: Every cloud has a silver lining. Searching the reason of a lower aggressiveness of the CoronaVirus disease in type 1 diabetes", "abstract": "", "doc_id": "gi5eiikc"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Association of diabetes mellitus with disease severity and prognosis in COVID-19: A retrospective cohort study", "abstract": "AIMS: 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.", "doc_id": "8ydwzl4z"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Issues of Cardiovascular Risk Management in People With Diabetes in the COVID-19 Era", "abstract": "People with diabetes compared with people without exhibit worse prognosis if affected by coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly when compromising metabolic control and concomitant cardiovascular disorders are present. This Perspective seeks to explore newly occurring cardio-renal-pulmonary organ damage induced or aggravated by the disease process of COVID-19 and its implications for the cardiovascular risk management of people with diabetes, especially taking into account potential interactions with mechanisms of cellular intrusion of SARS-CoV-2. Severe infection with SARS-CoV-2 can precipitate myocardial infarction, myocarditis, heart failure, and arrhythmias as well as an acute respiratory distress syndrome and renal failure. They may evolve along with multiorgan failure directly due to SARS-CoV-2-infected endothelial cells and resulting endotheliitis. This complex pathology may bear challenges for the use of most diabetes medications in terms of emerging contraindications that need close monitoring of all people with diabetes diagnosed with SARS-CoV-2 infection. Whenever possible, continuous glucose monitoring should be implemented to ensure stable metabolic compensation. Patients in the intensive care unit requiring therapy for glycemic control should be handled solely by intravenous insulin using exact dosing with a perfusion device. Although not only ACE inhibitors and angiotensin 2 receptor blockers but also SGLT2 inhibitors, GLP-1 receptor agonists, pioglitazone, and probably insulin seem to increase the number of ACE2 receptors on the cells utilized by SARS-CoV-2 for penetration, no evidence presently exists that shows this might be harmful in terms of acquiring or worsening COVID-19. In conclusion, COVID-19 and related cardio-renal-pulmonary damage can profoundly affect cardiovascular risk management of people with diabetes.", "doc_id": "34qqxkby"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Diabetes patients with COVID-19 need better blood glucose management in Wuhan, China", "abstract": "", "doc_id": "0plv0uc7"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "COVID-19: Perspectives from people with diabetes", "abstract": "", "doc_id": "dvio0yjg"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Diabetes management during Ramadan amid Covid-19 pandemic", "abstract": "Management of fasting patients with diabetes during Ramadan has always posed a great challenge on clinicians. This year, Ramadan has coincided with the Covid-19 pandemic which per se can complicate diabetes care. Although patients with diabetes should be generally discouraged from fasting, those who insist to fact during the current Covid-19 pandemic should undergo strict risk assessment and receive thorough education. In patients with type 2 diabetes, administered antidiabetics and their dose should be modified to minimize the risk of hypoglycemia and dehydration. In type 1 diabetic patients, insulin dose and it timing should be precisely calculated based on regular and rigorous blood glucose monitoring. Nonetheless, it would be prudent to generally discourage patients with diabetes form fasting this Ramadan to avoid the risk of life-threatening complications such severe dehydration and ensuing kidney damage.", "doc_id": "9wemrd22"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Diabetes and COVID-19 : Disease-Management-People", "abstract": "The current pandemic of SARS-CoV\u00ad2 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.", "doc_id": "7ptxz652"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "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?", "abstract": "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.", "doc_id": "hycd9zua"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "The clinical characteristics and outcomes of patients with diabetes and secondary hyperglycaemia with coronavirus disease 2019: A single-centre, retrospective, observational study in Wuhan", "abstract": "AIM: To explore whether coronavirus disease 2019 (COVID-19) patients with diabetes and secondary hyperglycaemia have different clinical characteristics and prognoses than those without significantly abnormal glucose metabolism. MATERIALS AND METHODS: We retrospectively analysed 166 COVID-19 patients at Tongji Hospital (Wuhan) from 8 February to 21 March 2020. Clinical characteristics and outcomes (as of 4 April 2020) were compared among control (group 1), secondary hyperglycaemia (group 2: no diabetes history, fasting plasma glucose levels of ≥7.0 mmol/L once and HbA1c values <6.5%) and patients with diabetes (group 3). RESULTS: Compared with group 1, groups 2 and 3 had higher rates of leukocytosis, neutrophilia, lymphocytopenia, eosinopenia and levels of hypersensitive C-reactive protein, ferritin and d-dimer (P < .05 for all). Group 2 patients had higher levels of lactate dehydrogenase, prevalence of liver dysfunction and increased interleukin-8 (IL-8) than those in group 1, and a higher prevalence of increased IL-8 was found in group 2 than in group 3 (P < .05 for all). The proportions of critical patients in groups 2 and 3 were significantly higher compared with group 1 (38.1%, 32.8% vs. 9.5%, P < .05 for both). Groups 2 and 3 had significantly longer hospital stays than group 1, which was nearly 1 week longer. The composite outcomes risks were 5.47 (1.56-19.82) and 2.61 (0.86-7.88) times greater in groups 2 and 3 than in group 1. CONCLUSIONS: Hyperglycaemia in both diabetes and secondary hyperglycaemia patients with COVID-19 may indicate poor prognoses. There were differences between patients with secondary hyperglycaemia and those with diabetes. We recommend that clinicians pay more attention to the blood glucose status of COVID-19 patients, even those not diagnosed with diabetes before admission.", "doc_id": "269kzfd7"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "COVID-19 and diabetes: What does the clinician need to know?", "abstract": "COVID-19 and diabetes are currently two global pandemics. Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19. This review aims to summarize currently available data about prevalence, possible pathophysiological mechanisms and management of patients with diabetes and COVID-19.", "doc_id": "ff04vt1d"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review", "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 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.", "doc_id": "dlv0kyb2"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "COVID-19: Impact of and on Diabetes", "abstract": "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.", "doc_id": "3mm3xe1g"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "COVID-19 and diabetes management: What should be considered?", "abstract": "", "doc_id": "iim21pta"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Clinical characteristics and outcomes of patients with severe covid-19 with diabetes", "abstract": "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) PaO2/FiO2≤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.", "doc_id": "lf88bwh2"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Covid-19 and diabetes mellitus: unveiling the interaction of two pandemics", "abstract": "A novel RNA betacoronavirus causing coronavirus disease 2019 (Covid-19) has now been declared pandemic disease by WHO. Guo et al published the first report of biochemical features in patients with diabetes and the further risk that this disease can determine to the progression of Covid-19. Among different cytokines found significantly higher in patients with diabetes compared to those without, Interleukin-6 (IL-6), which is already increased in conditions of chronic inflammation, may play a more deleterious role in Covid-19 infection. Targeting the overexpression of Il-6 effects with a monoclonal antibody against IL-6 receptor or using Janus Kinase inhibitors may be particularly helpful for treatment of Covid-19 pneumonia in diabetes.", "doc_id": "hjsy9rmc"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Recommendations for management of diabetic foot ulcers during COVID-19 outbreak", "abstract": "COVID-19 pandemia began in Wuhan, China, in December 2019. A total of 1 878 489 people were infected and 119 044 people were lost because of the disease and its complications by 15 April. Severe morbidity and mortality complications are mostly seen in elderly and patients having comorbidities. Diabetic foot ulcers (DFUs) are one of severe complications of diabetes mellitus and it may require urgent surgical interventions. In this paper, we aimed to create a management algorithm to prevent the unexpected complications that may occur in the patients and health care workers during the evaluation of COVID-19 in DFU patients who require urgent surgical intervention. We advise the use of thorax computerised tomography for preoperative screening in all DFU patients with severe signs of infection and especially those requiring urgent surgery for both the detection of the possible undiagnosed COVID-19 in the patient for the need for close follow-up and protection of the surgical and anaesthesiology team.", "doc_id": "ap3asmql"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Coronavirus Infections and Type 2 Diabetes-Shared Pathways with Therapeutic Implications", "abstract": "Individuals with diabetes are at increased risk for bacterial, mycotic, parasitic, and viral infections. The severe acute respiratory syndrome (SARS)-CoV-2 (also referred to as COVID-19) coronavirus pandemic highlights the importance of understanding shared disease pathophysiology potentially informing therapeutic choices in individuals with type 2 diabetes (T2D). Two coronavirus receptor proteins, angiotensin-converting enzyme 2 (ACE2) and dipeptidyl peptidase-4 (DPP4) are also established transducers of metabolic signals and pathways regulating inflammation, renal and cardiovascular physiology, and glucose homeostasis. Moreover, glucose-lowering agents such as the DPP4 inhibitors, widely used in subjects with T2D, are known to modify the biological activities of multiple immunomodulatory substrates. Here, we review the basic and clinical science spanning the intersections of diabetes, coronavirus infections, ACE2, and DPP4 biology, highlighting clinical relevance and evolving areas of uncertainty underlying the pathophysiology and treatment of T2D in the context of coronavirus infection.", "doc_id": "j1zztfzj"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study", "abstract": "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 \u00b1 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.", "doc_id": "hlnjp7v6"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "The Relationship between Diabetes Mellitus and COVID-19 Prognosis: A Retrospective Cohort Study in Wuhan, China", "abstract": "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\u00e2\u0080\u00af=\u00e2\u0080\u00af0.014), c-reactive protein (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.008), procalcitonin (p < 0.01), and D-dimer (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.033), and lower levels of lymphocytes (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.032) and albumin (p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.035). Furthermore, diabetic patients had a significant higher incidence of bilateral pneumonia (86.9%, p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.020). In terms of complications and clinical outcomes, the incidence of respiratory failure (36.9% vs. 24.2%, p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.022), acute cardiac injury (47.4% vs. 21.2%, p < 0.01) and death (20.2% vs. 8.0%, p\u00e2\u0080\u00af=\u00e2\u0080\u00af0.001) 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\u00e2\u0080\u00af=\u00e2\u0080\u00af0.031) 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.", "doc_id": "f4qljghz"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Letter to the Editor: Mechanisms of increased morbidity and mortality of SARS-CoV-2 infection in individuals with diabetes: what this means for an effective management strategy", "abstract": "", "doc_id": "96xcbmtb"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Letter to the editor in response to article: \"Clinical considerations for patients with diabetes in times of COVID-19 epidemic (Gupta et al.)", "abstract": "", "doc_id": "kjxietjx"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Challenges of diabetes care management in developing countries with a high incidence of COVID-19: A brief report", "abstract": "BACKGROUND AND AIMS: Diabetes mellitus (DM) is one of the most critical risk factors for complications and death in COVID-19 patients. The present study aims to highlight challenges in the management of diabetic patients during the COVID-19 outbreak in developing countries. METHODS: We reviewed the literature to obtain information about diabetic care during the Covid-19 crisis. We also seek opinions of clinicians working in undeveloped countries. RESULTS: Current challenges faced by clinicians in the management of diabetic patients in developing countries are as follows: lack of preventive measures, inadequate number of visits, loss of the traditional method of communication with the patient, shortage of medications, impaired routine diabetic care, and absence of telehealth services. CONCLUSIONS: Developing countries are faced with many challenges in diabetes management due to a lack of resources.", "doc_id": "3h8g5xbm"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Newly diagnosed diabetes is associated with a higher risk of mortality than known diabetes in hospitalized patients with COVID-19", "abstract": "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 ≥7 mmol/L and/or HbA1c ≥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.", "doc_id": "k9p82pt5"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Impact of diabetes mellitus on clinical outcomes in patients affected by Covid-19", "abstract": "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?", "doc_id": "5759p02f"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Diabetes and covid-19: a global health challenge", "abstract": "", "doc_id": "azaxwi6q"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Coping with diabetes during the COVID - 19 lockdown in India: Results of an online pilot survey", "abstract": "AIM: The management of diabetes has become a challenge due to the COVID 19 lockdown. An online-based pilot survey was conducted to study how people with diabetes were coping with their Diabetes during the COVID - 19 lockdown. METHOD: The questions were designed in an online survey, Survey Monkey, to conduct this cross-sectional study. The link was generated and sent to 100 registered patients of the MV Hospital for Diabetes Royapuram who had not contacted the hospital after the lockdown announcement. The survey was done between April 1 and April 15, 2020.Oral consent was obtained through telephone before the link was sent by Whatsapp to them.The questionnaire consisted of questions on home blood glucose monitoring, regularity in doing their physical activity and dietary compliance and anxiety about the viral infection. RESULTS: 92% of the participants had Type 2 diabetes. Only 28% of the participants were checking their blood glucose levels regularly. 80% of the participants mentioned that they were following regular exercise and diet control during the lockdown period. 40% of the participants were anxious about the Covid infection. CONCLUSION: SMBG needs to be practiced on regular basis, especially among the patients with diabetes on insulin therapy. Most of the people surveyed were coping well with their Diabetes. Patients have reported that they were able to maintain proper dietary compliance and be more physically active at home during this lockdown. These findings need to be ascertained in larger sample of patients.", "doc_id": "1lfm24wz"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "COVID-19 in diabetic patients: Related risks and specifics of management", "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 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.", "doc_id": "lfdeowsl"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Practical recommendations for the management of diabetes in patients with COVID-19", "abstract": "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.", "doc_id": "grz8hhal"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Letter to the Editor in Response to article: \"Clinical considerations for patients with diabetes in times of COVID-19 epidemic (Gupta et al.)\"", "abstract": "", "doc_id": "im8fd0yd"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Infecci\u00f3n por coronavirus en pacientes con diabetes", "abstract": "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", "doc_id": "5ps6pw6c"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Characteristics and outcomes of COVID-19 positive patients with diabetes managed as outpatients", "abstract": "We analyzed disease outcomes for patients with diabetes and laboratory-confirmed COVID-19 who were managed outpatient and followed by the Emory COVID-19 Virtual Outpatient Management Clinic (ECVOMC). The rate of hospitalization for patients with diabetes was double the overall rate of hospitalization for patients in the ECVOMC.", "doc_id": "2eterq28"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Influence of diabetes mellitus on the severity and fatality of SARS-CoV-2 (COVID-19) infection", "abstract": "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.", "doc_id": "i8uwia3a"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "The Silver Lining to COVID-19: Avoiding Diabetic Ketoacidosis Admissions with Telehealth", "abstract": "Background: The Stay at Home order in Colorado and The Stay Safe at Home order in California during COVID-19 pandemic have forced a majority of the endocrinologists/diabetologists to adapt to providing diabetes care remotely through telehealth. This may provide increased access to diabetes health care in certain settings. However, health care disparities continue to challenge availability of diabetes technologies for underprivileged communities. We report our experience with two patients providing diabetes care effectively and preventing hospital admissions by using telehealth. Methods: Two adult patients with type 1 diabetes (T1D): one new onset and the other one with established T1D are presented where telehealth facilitated by Clarity Software and the \"Share\" feature with the use of Dexcom G6 continuous glucose monitoring (CGM) for management of diabetic ketosis and hyperglycemia. Results: Both patients were managed effectively virtually despite higher risk of diabetic ketoacidosis (DKA). Shared glucose data through CGM facilitated frequent insulin dose adjustments, increased fluid and carbohydrate intake, and prevented hospital admissions in both cases. In the case of new onset patient with T1D, most of the education was done remotely by certified diabetes care and education specialists. Conclusion: Acute diabetes complication like DKA increases morbidity and mortality in addition to adding cost to the health care system. The current pandemic of COVID-19 has allowed newer ways (with the help of newer technologies) to manage high-risk patients with T1D and DKA through telehealth and may result in lasting benefits to people with T1D.", "doc_id": "47k83vz1"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Dissecting the Interaction between Coronavirus Disease 2019 and Diabetes Mellitus", "abstract": "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.", "doc_id": "09qp0sts"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Management of diabetic persons with foot ulceration during COVID-19 health care emergency: Effectiveness of a new triage pathway", "abstract": "AIM: To define the outcomes of persons with diabetes and foot ulcers (DFUs) managed through a specific triage pathway during the COVID-19 crisis. METHODS: Patients who had an active DFU during the COVID-19 emergency were included. All participants were managed using a specific triage system driven both by ulcer'severity and concomitant co-diseases. Subjects with severely complicated DFUs were urgently referred to hospital regardless of the concomitant comorbidities. Subjects with complicated DFUs received outpatient evaluation (within 48-72 h) and were admitted to hospital if required (revascularization, surgical intervention, intravenous antibiotic therapy); after the first outpatient visit or hospitalization, patients were followed according to the number of comorbidities (in the case of 3 or more comorbidities patients were followed up by telemedicine). Patients with uncomplicated DFUs were managed by telemedicine after outpatient evaluation. Healing, major amputation, death and rate of COVID-19 infection were evaluated. The minimum follow-up was 1 month. RESULTS: The study group included 151 patients. The mean age was 69.9 \u00b1 14.2 years, 58.9% were male and 91.4% had type 2 diabetes; 58.7% had severely complicated, 21% complicated and 20.3% uncomplicated DFUs. Among those, 78.8% presented with 3 or more comorbidities. One hundred and six patients had regular clinical follow-ups, while 45 were managed through telemedicine. Forty-one (27.1%) patients healed, 3 (1.9%) had major amputations and 3 (1.9%) died. One patient (0.6%) reported COVID-19 positivity due to infection acquired at home. CONCLUSION: The triage pathway adopted during the COVID-19 pandemic showed adequate management of DFUs and no cases of hospital virus exposure.", "doc_id": "9z7guc3a"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Diabetic ketoacidosis precipitated by Covid-19 in a patient with newly diagnosed diabetes mellitus", "abstract": "", "doc_id": "9t7ds2tt"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Saving the Diabetic Foot During the COVID-19 Pandemic: A Tale of Two Cities", "abstract": "Of all the late complications of diabetes, those involving the foot have traditionally required more face-to-face patient visits to clinics to treat wounds by debridement, offloading, and many other treatment modalities. The advent of the coronavirus disease 2019 (COVID-19) pandemic has resulted not only in the closing of most outpatient clinics for face-to-face consultations but also in the inability to perform most laboratory and imaging investigations. This has resulted in a paradigm shift in the delivery of care for those with diabetic foot ulcers. The approaches to this challenge in two centers with an interest in diabetic foot disease, including virtual consultations using physician-to-patient and physician-to-home nurse telemedicine as well as home podiatry visits, are described in this review and are illustrated by several case vignettes. The outcomes from these two centers suggest that we may be witnessing new possibilities in models of care for the diabetic foot.", "doc_id": "8o0h3vm5"} {"topic_name": "coronavirus diabetes", "topic_id": "24", "title": "Diabetes or endocrinopathy admitted in the COVID-19 ward", "abstract": "The Covid-19 pandemic confronted us with unknown clinical pictures, also in diabetology and endocrinology. Sharing clinical experiences is therefore of enormous importance. Actually, information about the care given in the Covid-19 ward (in contrast to that provided in the Emergency Room/ICU) is still sparse. The last weeks we built experience and gathered knowledge while giving hospital care to patients who had a pre-existent endocrine disease (and diabetes; most patients suffered from a type two diabetes). In our contribution we presented our insights obtained from this intensive period obtained in the Covid-19 ward.", "doc_id": "aljeiu8d"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Prognostic value of Cardiac Biomarkers in COVID-19 Infection: A Meta-analysis", "abstract": "Background Multiple Biomarkers have recently been shown to be elevated in COVID-19, a respiratory infection with multi-organ dysfunction; however, information regarding the prognostic value of cardiac biomarkers as it relates to disease severity and cardiac injury are inconsistent. Research Question The goal of this meta-analysis was to summarize the evidence regarding the prognostic relevance of cardiac biomarkers from data available in published reports. Study Design and Methods PubMed was searched from inception through April 2020 for studies comparing median values of cardiac biomarkers in critically ill versus non-critically ill COVID-19 patients, or patients who died versus those who survived. The weighted mean differences (WMD) and 95% confidence interval (CI) between the groups were calculated for each study and combined using a random effects meta-analysis model. The odds ratio (OR) for mortality based on cardiac injury was combined from studies reporting it. Results Troponin levels were significantly higher in COVID-19 patients who died or were critically ill versus those who were alive or not critically ill (WMD 0.58, 95% CI 0.42-0.71, p<0.001). Cardiac injury was independently associated with significantly increased odds of mortality (OR 6.641, 95% CI 1.26 - 35.1, p=0.03). No difference in BNP was seen between the two groups. A significant difference in levels of D-dimer was seen in those who died or were critically ill. CK levels were only significantly higher in those who died versus those who were alive (WMD 0.47 95% CI 0.09-0.84, p=0.014). Interpretation Cardiac biomarkers add prognostic value to the determination of the severity of COVID-19 and can predict mortality.", "doc_id": "7c96e00e"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "A comprehensive appraisal of laboratory biochemistry tests as major predictors of COVID-19 severity.", "abstract": "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 \u226418 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.", "doc_id": "dakuwflh"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Prediction of the severity of Corona Virus Disease 2019 and its adverse clinical outcomes.", "abstract": "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.", "doc_id": "dmbc8kb4"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "[Value of neutrophil-to-lymphocyte ratio in the classification diagnosis of coronavirus disease 2019].", "abstract": "OBJECTIVE To investigate the clinical significance of neutrophil-to-lymphocyte ratio (NLR) in classification of patients with coronavirus disease 2019 (COVID-19). METHODS A retrospective analysis was performed on 72 patients with COVID-19 admitted to the critical ward of Cancer Center of Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in Wuhan from February to March in 2020. The patients were divided into two groups: moderate type (non-severe group) and severe/critical type (severe group). The results of white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), interleukin-6 (IL-6) and D-dimer were collected at the 2nd day after admission from the two groups, and the NLR was calculated. The diagnostic value of WBC, NEU, LYM, IL-6, D-dimer and NLR on COVID-19 classification was evaluated by the receiver operating characteristic (ROC) curve. RESULTS A total of 72 COVID-19 patients were enrolled, among whom 52 were moderate, 17 were severe, and 3 were critical. The most common clinical manifestations of patients were fever (70.8%), cough (36.1%), chest tightness and breathlessness (37.5%), diarrhea (15.3%), fatigue (15.3%), vomiting and nausea (11.1%), occasionally accompanied by acute dyspnea (2.8%), and only one patient had no clinical symptom (1.4%). The levels of WBC, NEU, IL-6, D-dimer and NLR in the severe group were significantly higher than those in the non-severe group [WBC (\u00d7109/L): 7.81\u00b13.65 vs. 5.34\u00b11.69, NEU (\u00d7109/L): 5.83\u00b13.13 vs. 3.24\u00b11.53, IL-6 (ng/L): 133.63 (71.09, 249.61) vs. 28.05 (6.41, 101.24), D-dimer (mg/L): 0.86 (0.31, 2.56) vs. 0.33 (0.20, 0.71), NLR: 6.14\u00b14.75 vs. 2.66\u00b11.93, all P < 0.05], and the level of LYM was significantly lower than that in the non-severe group (\u00d7109/L: 1.09\u00b10.56 vs. 1.49\u00b10.74, P < 0.05). The results of ROC curve analysis showed that the areas under ROC curve (AUC) of WBC, NEU, LYM, IL-6, D-dimer and NLR for COVID-19 classification were 0.790 [95% confidence interval (95%CI) was 0.684-0.897), 0.869 (95%CI was 0.789-0.949), 0.719 (95%CI was 0.592-0.847), 0.790 (95%CI was 0.682-0.898), 0.676 (95%CI was 0.526-0.827), and 0.888 (95%CI was 0.814-0.963) respectively. The AUC of NLR was the highest, which was of high diagnostic value; when the optimum cut-off value of NLR was 3.00, the sensitivity was 100%, and the specificity was 73.1%. CONCLUSIONS NLR can be used as a biomarker to predict classification of COVID-19 patients independently, which can provide a theoretical basis for the classification management of COVID-19 patients.", "doc_id": "jnyd2uk2"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "[Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia].", "abstract": "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-\u03b1), 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.", "doc_id": "0deyspy2"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "The Association Between Biomarkers and Clinical Outcomes in Novel Coronavirus (COVID-19) Pneumonia in a U.S. Cohort", "abstract": "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", "doc_id": "93a34bnd"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "The role of comorbidities and clinical predictors of severe disease in COVID-19: a systematic review and meta-analysis", "abstract": "Background COVID_19 is unpredictable due to non-specific symptoms and clinical course diversity in different individuals. We analyzed studies regarding the factors associated with severe status of the disease to identify unique findings in severely affected patients. Methods We systematically searched the electronic databases, including PubMed, Scopus, EMBASE, Web of \u200eScience, and Google Scholar from inception to 12th of March 2020. Cochranes Q and I-square statistics were used to assess the existence of heterogeneity between the included \u200estudies. We used the random-effects model to pool \u200ethe odds ratios (ORs) at 95% confidence \u200eintervals (CIs).\u200e Results Seventeen articles out of 3009 citations were included. These contained 3189 patients, of whom 732 were severely affected (severe group) and 3189 were in non-severe group. Using the random-effects model, our meta-analyses showed that the odds of comorbidities, including COPD, DM, HTN, CVD, CKD, and symptoms, including dyspnea, dizziness, anorexia, and cough, were significantly higher among the severe group compared with the non-\u200esevere group. There were no significant changes in odds of CVA, liver disease, immunodeficiency/immunosuppression, fever, fatigue, myalgia, headache, diarrhea, sore throat, nasal congestion, sputum, nausea, vomiting, chest pain between the two groups. Conclusions Early recognition and intervention can be critical in management, and might stop progression to severe disease. Predictive symptoms and comorbidities can be used as a predictor in patients who are at risk of severe disease.", "doc_id": "4su6v83t"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "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", "abstract": "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.", "doc_id": "0hxwkzvy"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Plasma levels of soluble ACE2 are associated with sex, Metabolic Syndrome, and its biomarkers in a large cohort, pointing to a possible mechanism for increased severity in COVID-19", "abstract": "We examined the associations between plasma concentrations of soluble ACE2 and biomarkers of Metabolic Syndrome in a large (N=2,051) sample of individuals who participated in a commercial wellness program and who underwent deep molecular phenotyping. sACE2 levels were significantly higher in men, compared to women, and in individuals with Metabolic Syndrome, compared to controls. sACE2 levels showed reliable associations with all individuals components of Metabolic Syndrome, including obesity, hypertension, insulin resistance, hyperlipidemia, and as well as markers of liver damage. This profile of associations was statistically significantly stronger in men, compared to women, and suggests that preexisting cardiometabolic conditions might confer increased severity of symptoms in some COVID-19 patients through increased expression of ACE2 in the liver.", "doc_id": "07ryzlt0"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients", "abstract": "Objective Evidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers. Methods Based on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severe versus mild disease, Intensive Care Unit (ICU) versus general ward admission, and expired versus survivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease. Results Cohorts with elevated levels of white blood cells (WBCs) (OR=1.75), neutrophil count (OR=2.62), D-dimer (OR=3.97), prolonged prothrombin time (PT) (OR=1.82), fibrinogen (OR=3.14), erythrocyte sedimentation rate (OR=1.60), procalcitonin (OR=4.76), IL-6 (OR=2.10), and IL-10 (OR=4.93) had higher odds of progression to severe phenotype. Decision tree model (sensitivity=100%, specificity=81%) showed the high performance of neutrophil count at a cut-off value of more than 3.74 x109/L for identifying patients at high risk of severe COVID-19. Likewise, ICU admission was associated with higher levels of WBCs (OR=5.21), neutrophils (OR=6.25), D-dimer (OR=4.19), and prolonged PT (OR=2.18). Patients with high IL-6 (OR=13.87), CRP (OR=7.09), D-dimer (OR=6.36), and neutrophils (OR=6.25) had the highest likelihood of mortality. Conclusions Several hematological and immunological markers, in particular neutrophilic count, could be helpful to be included within the routine panel for COVID-19 infection evaluation to ensure risk stratification and effective management.", "doc_id": "8nz2lcsa"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "A descriptive study of the impact of diseases control and prevention on the epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai, lessons learned for metropolis epidemics prevention", "abstract": "Objective: To describe and evaluate the impact of diseases control and prevention on epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai. Design: A retrospective descriptive study Setting: China Participants: Epidemiology information was collected from publicly accessible database. 265 patients admitted to Shanghai Public Health Center with confirmed COVID-19 were enrolled for clinical features analysis. Main outcome measure: Prevention and control measures taken by Shanghai government, epidemiological, demographic, clinical, laboratory and radiology data were collected. Weibull distribution, Chi-square test, Fisher's exact test, t test or Mann-Whitney U test were used in statistical analysis. Results: COVID-19 transmission rate within Shanghai had reduced over 99% than previous speculated, and the exponential growth has been stopped so far. Epidemic was characterized by the first stage mainly composed of imported cases and the second stage where >50% of cases were local. The incubation period was 6.4 (95% CI 5.3 to 7.6) days and the mean onset-admission interval was 5.5 days (95% CI, 5.1 to 5.9). Median time for COVID-19 progressed to severe diseases were 8.5 days (IQR: 4.8-11.0 days). By February 11th, proportion of patients being mild, moderate, severe and critically ill were 1.9%(5/265), 89.8%(238/265), 3.8%(10/265), 4.5%(12/265), respectively; 47 people in our cohort were discharged, and 1 patient died. Conclusion: Strict controlling of the transmission rate at the early stage of an epidemic in metropolis can quickly prohibit the spread of the diseases. Controlling local clusters is the key to prevent outbreaks from imported cases. Most COVID-19 severe cases progressed within 14 days of disease onset. Multiple systemic laboratory abnormalities had been observed before significant respiratory dysfunction. Keyword: COVID-19, SARS-CoV-2, epidemics dynamics, diseases control, clinical features", "doc_id": "dbzrd23n"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "A link between inflammatory biomarkers and lung ultrasound observations in patients with SARS-CoV-2 infection", "abstract": "ABSTRACT: Lung ultrasound (LUS) has shown to correlate well with the findings obtained by chest computed tomography (CT) in acute-phase COVID-19. Although there is a significant correlation between blood biomarkers and CT radiological findings, a potential correlation between biochemical parameters and LUS images is still unknown. Our purpose was to evaluate a potential association between lung lesions visualised by LUS and blood biomarkers as well as the ability to predict mortality from two different lung ultrasound scoring systems (LUSS). We performed a retrospective observational study on 45 patients aged >70 years with SARS-CoV-2 infection who required hospitalisation. LUS was carried out at admission and on day 7, when the clinical course was favourable or earlier in case of worsening. Disease severity was scored by means of LUSS in 8 (LUSS8) and in 12 (LUSS12) quadrants. LUS and blood draw for inflammatory marker analysis were performed at the same time. The correlation between biochemical parameters and either LUSS score was significant for ferritin levels. It was 0.486 (p=0.001) for LUSS8 and 0.458 (p=0.002) for LUSS12. Using a threshold score of 15 with LUSS12 predicted mortality in 86.7% of cases (ORcrude 31, CI 95% 4.79-200.51). Applying a threshold of 10 with LUSS8 predicted mortality in 88.9% (ORcrude 69.75, CI 95% 6.90-705.20). There is a correlation between ferritin levels and LUSS. The prognostic capacity of LUSS12 does not surpass that of LUSS8.", "doc_id": "gw767i37"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Characteristics of lymphocyte subsets and their predicting values for the severity of COVID-19 patients", "abstract": "Severe COVID-19 patients showed worse clinical outcomes compared to mild and moderate patients. However, effective indicators are still lacking to predict the severity of the disease. In the present study, we retrospectively analyzed the clinical and laboratory data of 16 COVID-19 patients and found that the absolute counts of three T-cells (CD3+, CD4+, and CD8+) were significantly lower in the moderate and severe patients than those in mild patients and were significantly lower in severe patients than in moderate patients on admission. With the recovery of the COVID-19, serum levels of inflammatory biomarkers (CRP, PCT, and IL6) of moderate and severe patients gradually decreased. In contrast, the counts of lymphocytes and their subsets including CD3+, CD4+, and CD8+ T cells gradually increased in severe patients, and eventually showed comparable levels with moderate patients. ROC analysis showed that the counts of CD3+, CD4+, and CD8+ T-cells with AUC > 0.9 have potential values for predicting the severity of COVID-19 patients. In conclusion, the reduction of CD3+, CD4+, and CD8+ T-cells is related to the severity of COVID-19 and dynamic detection of these T-lymphocyte subsets may help predict the outcome of the patients.", "doc_id": "99j84ovg"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "From Community Acquired Pneumonia to COVID-19: A Deep Learning Based Method for Quantitative Analysis of COVID-19 on thick-section CT Scans", "abstract": "Background: Thick-section CT scanners are more affordable for the developing countries. Considering the widely spread COVID-19, it is of great benefit to develop an automated and accurate system for quantification of COVID-19 associated lung abnormalities using thick-section chest CT images. Purpose: To develop a fully automated AI system to quantitatively assess the disease severity and disease progression using thick-section chest CT images. Materials and Methods: In this retrospective study, a deep learning based system was developed to automatically segment and quantify the COVID-19 infected lung regions on thick-section chest CT images. 531 thick-section CT scans from 204 patients diagnosed with COVID-19 were collected from one appointed COVID-19 hospital from 23 January 2020 to 12 February 2020. The lung abnormalities were first segmented by a deep learning model. To assess the disease severity (non-severe or severe) and the progression, two imaging bio-markers were automatically computed, i.e., the portion of infection (POI) and the average infection HU (iHU). The performance of lung abnormality segmentation was examined using Dice coefficient, while the assessment of disease severity and the disease progression were evaluated using the area under the receiver operating characteristic curve (AUC) and the Cohen's kappa statistic, respectively. Results: Dice coefficient between the segmentation of the AI system and the manual delineations of two experienced radiologists for the COVID-19 infected lung abnormalities were 0.74 {+/-} 0.28 and 0.76 {+/-} 0.29, respectively, which were close to the inter-observer agreement, i.e., 0.79 {+/-} 0.25. The computed two imaging bio-markers can distinguish between the severe and non-severe stages with an AUC of 0.9680 (p-value < 0.001). Very good agreement ({kappa} = 0.8220) between the AI system and the radiologists were achieved on evaluating the changes of infection volumes. Conclusions: A deep learning based AI system built on the thick-section CT imaging can accurately quantify the COVID-19 associated lung abnormalities, assess the disease severity and its progressions.", "doc_id": "h899xkfy"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Systemic hypoferraemia and severity of hypoxaemic respiratory failure in COVID-19", "abstract": "Coronavirus disease 2019 (COVID-19) mortality is associated with hypoxaemia, multiorgan failure, and thromboinflammation. However severity of disease varies considerably and understanding physiological changes that may link to poor outcomes is important. Although increased serum ferritin has been observed in COVID-19 patients consistent with inflammation, other iron parameters have not been examined to our knowledge. Because iron is required for immunity and oxygen utilisation, and dysregulated iron homeostasis has been observed in COPD, we investigated serum iron concentrations in 30 patients with COVID-19 requiring ICU admission. All patients had low serum iron but patients with severe hypoxemic respiratory failure had more profound hypoferraemia. The area under the curve for receiver operating characteristic curves for serum iron to identify severe hypoxemia was 0.95; the optimal Youden Index for distinguishing between severe and non-severe hypoxemia was a serum iron concentration of 2.9 micromol/L. By linear regression, serum iron was associated with lymphocyte count and PaO2/FiO2. In conclusion, profound hypoferraemia identifies COVID-19 patients with severe hypoxaemia. Serum iron is a simple biomarker that could be usefully employed to stratify patients and monitor disease. Severe hypoferraemia may plausibly impair critical iron-dependent processes such as lymphocyte responses and hypoxia sensing, contributing to pathology, and is potentially treatable.", "doc_id": "0ux8nwn7"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Validation of reported risk factors for disease classification and prognosis in COVID-19: a descriptive and retrospective study", "abstract": "Risk indicators viral load (ORF1ab Ct), lymphocyte percentage (LYM%), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and lactic acid (LA) in COVID-19 patients have been proposed in recent studies. However, the predictive effects of those indicators on disease classification and prognosis remains largely unknown. We dynamically measured those reported indicators in 132 cases of COVID-19 patients including the moderate-cured (moderated and cured), severe-cured (severe and cured) and critically ill (died). Our data showed that CRP, PCT, IL-6, LYM%, lactic acid and viral load could predict prognosis and guide classification of COVID-19 patients in different degrees. CRP, IL-6 and LYM% were more effective than other three factors in predicting prognosis. For disease classification, CRP and LYM% were sensitive in identifying the types between critically ill and severe (or moderate). Notably, among the investigated factors, LYM% was the only one that could distinguish between the severe and moderate types. Collectively, we concluded that LYM% was the most sensitive and reliable predictor for disease typing and prognosis. During the COVID-19 pandemic, the precise classification and prognosis prediction are critical for saving the insufficient medical resources, stratified treatment and improving the survival rate of critically ill patients. We recommend that LYM% be used independently or in combination with other indicators in the management of COVID-19.", "doc_id": "j90jc0rj"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Time-series plasma cell-free DNA analysis reveals disease severity of COVID-19 patients", "abstract": "Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. Detection of individuals at high risk for critical condition is crucial for control of the disease. Herein, for the first time, we profiled and analyzed plasma cell-free DNA (cfDNA) of mild and severe COVID-19 patients. We found that in comparison between mild and severe COVID-19 patients, Interleukin-37 signaling was one of the most relevant pathways; top significantly altered genes included POTEH, FAM27C, SPATA48, which were mostly expressed in prostate and testis; adrenal glands, small intestines and liver were tissues presenting most differentially expressed genes. Our data thus revealed potential tissue involvement, provided insights into mechanism on COVID-19 progression, and highlighted utility of cfDNA as a noninvasive biomarker for disease severity inspections.", "doc_id": "h184u2x2"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Elevated interleukin-6, interleukin-10 and neutrophil : lymphocyte ratio as identifiers of severe coronavirus disease 2019", "abstract": "", "doc_id": "ae1i0pzv"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "The value of clinical parameters in predicting the severity of COVID-19", "abstract": "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.", "doc_id": "a049fnva"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis", "abstract": "BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease with lack of established laboratory markers available to evaluate illness severity. In this study, we investigate whether platelet count could differentiate between COVID-19 patients with or without severe disease. Additionally, we evaluate if thrombocytopenia is associated with severe COVID-19. METHODS: An electronic search in Medline, Scopus and Web of Science was performed to identify studies reporting data on platelet count in COVID-19 patients. A meta-analysis was performed, with calculation of weighted mean difference (WMD) of platelet number in COVID-19 patients with or without severe disease and odds ratio (OR) of thrombocytopenia for severe form of COVID-19. RESULTS: Nine studies with 1779 COVID-19 patients, 399 (22.4%) with severe disease, were included in the meta-analysis. The pooled analysis revealed that platelet count was significantly lower in patients with more severe COVID-19 (WMD -31 \u00d7 109/L; 95% CI, from -35 to -29 \u00d7 109/L). A subgroup analysis comparing patients by survival, found an even lower platelet count was observed with mortality (WMD, -48 \u00d7 109/L; 95% CI, -57 to -39 \u00d7 109/L. In the four studies (n = 1427) which reported data on rate of thrombocytopenia, a low platelet count was associated with over fivefold enhanced risk of severe COVID-19 (OR, 5.1; 95% CI, 1.8-14.6). CONCLUSIONS: Low platelet count is associated with increased risk of severe disease and mortality in patients with COVID-19, and thus should serve as clinical indicator of worsening illness during hospitalization.", "doc_id": "ibx322nj"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Neutrophil to CD4+ lymphocyte ratio as a potential biomarker in predicting virus negative conversion time in COVID-19", "abstract": "BACKGROUND: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. Our study aimed to evaluate the robustness of neutrophil to CD4+ lymphocyte ratio (NCD4LR) in predicting the negative conversion time (NCT) of SARS-CoV-2 in COVID-19 patients. METHODS: Univariate and multivariate analysis were conducted to evaluate the independency of NCD4LR in predicting NCT. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) were used to assess the diagnostic accuracy. RESULTS: Compared with low NCD4LR patients, patients with high NCD4LR had an older age; higher incidence of fever, fatigue, chest distress/breath shortness, severer disease assessment on admission; higher levels of inflammatory indicators; low levels of lymphocyte subsets, and a longer NCT. Multivariate analysis also identified NCD4LR as an independent risk factor for delayed NCT. ROC analysis showed that NCD4LR had a better performance than neutrophil to lymphocyte ratio in predicting the virus negative conversion within 2 weeks (AUC = 0.772), 3 weeks (AUC = 0.710), 4 weeks (AUC = 0.728), or 5 weeks (AUC = 0.815). CONCLUSION: This study suggests that NCD4LR is a potential and useful biomarker for predicting the virus negative conversion time in COVID-19 patients. Furthermore, due to the NCDLR value is easily calculated, it can be widely used as a clinical biomarker for disease progression and clinical outcomes in COVID-19 patients.", "doc_id": "dvpl8dfx"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Prediction of severe illness due to COVID-19 based on an analysis of initial Fibrinogen to Albumin Ratio and Platelet count", "abstract": "Concomitant coagulation disorder can occur in severe patients withCOVID-19, but in-depth studies are limited. This study aimed to describe the parameters of coagulation function of patients with COVID-19 and reveal the risk factors of developing severe disease. This study retrospectively analyzed 113patients with SARS-CoV-2 infection in Taizhou Public Health Center. Clinical characteristics and indexes of coagulation function were collected. A multivariate Cox analysis was performed to identify potential biomarkers for predicting disease progression. Based on the results of multivariate Cox analysis, a Nomogram was built and the predictive accuracy was evaluated through the calibration curve, decision curve, clinical impact curve, and Kaplan-Meier analysis. Sensitivity, specificity, predictive values were calculated to assess the clinical value. The data showed that Fibrinogen, FAR, and D-dimer were higher in the severe patients, while PLTcount, Alb were much lower. Multivariate Cox analysis revealed that FAR and PLT count were independent risk factors for disease progression. The optimal cutoff values for FAR and PLT count were 0.0883 and 135*109/L, respectively. The C-index [0.712 (95% CI = 0.610-0.814)], decision curve, clinical impact curve showed that Nomogram could be used to predict the disease progression. In addition, the Kaplan-Meier analysis revealed that potential risk decreased in patients with FAR<0.0883 and PLT count>135*109/L.The model showed a good negative predictive value [(0.9474 (95%CI = 0.845-0.986)].This study revealed that FAR and PLT count were independent risk factors for severe illness and the severity of COVID-19 might be excluded when FAR<0.0883 and PLT count>135*109/L.", "doc_id": "fef87ie5"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID-19 in Chongqing", "abstract": "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) PaO2 /FiO2 ≤ 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] ≥ 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.", "doc_id": "i7ztzbn2"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Plasma albumin levels predict risk for nonsurvivors in critically ill patients with COVID-19", "abstract": "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.", "doc_id": "kbp47abd"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Clinical analysis of risk factors for severe patients with novel coronavirus pneumonia/ \u4e2d\u534e\u4f20\u67d3\u75c5\u6742\u5fd7", "abstract": "Objective To analyze the clinical features of patients with coronavirus disease 2019 (COVID-19) in Shanghai and to investigate the risk factors for disease progression to severe cases. Methods The clinical data of 292 adult patients with COVID-19 hospitalized in Shanghai Public Health Clinical Center from January 20, 2020 to February 10, 2020 were retrospectively analyzed, including 21 severe patients and 271 mild patients. The demographic characteristics, epidemiological history, history of underlying diseases and laboratory examinations were compared between the two groups. Measurement data were compared using t test or Mann-Whitney U test. The count data were compared using hi-square test. The binary logistic regression equation was used to analyze the risk factors for the progression of patients to severe cases. Results Among the 292 patients, 21 were severe cases with the rate of 7.2% (21/292). One patient died, and the mortality rate was 4.8% in severe patients. The severe patients aged (65.0\u00b115.7) years old, 19 (90.5%) were male, 11 (52.4%) had underlying diseases, 7 (33.3%) had close relatives diagnosed with COVID-19. The mild patients aged (48.7\u00b115.7) years old, 135 (49.8%) were male, 74 (27.3%) had underlying diseases, 36 (13.3%) had close relatives diagnosed with COVID-19. The differences between two groups were all significant statistically ( t =-4.730, \u03c7 2 =12.930, 5.938 and 4.744, respectively, all P <0.05). Compared with the mild patients, the levels of absolute numbers of neutrophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine, serum cystatin C, C reactive protein (CRP), procalcitonin , D -dimer, pro-B-type natriuretic peptide (proBNP), serum myoglobin, creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum troponin I (cTnI) in severe patients were all significantly higher ( U =2 091.5, 1 928.0, 1 215.5, 729.0, 1 580.5, 1 375.5, 917.5, 789.5, 1 209.0, 1 434.0, 638.0, 964.5, 1 258.0 and 1 747.5, respectively, all P <0.05), while the levels of lymphocyte count, albumin, transferrin, CD3 + T lymphocyte count, CD8 + T lymphocyte count and CD4 + T lymphocyte count in severe patients were all significantly lower ( U =1 263.5, t =4.716, U =1 214.0, 962.0, 1 167.5 and 988.0, respectively, all P <0.05). Further logistic regression analysis showed that the albumin (odds ratio ( OR )=0.806, 95% CI 0.675-0.961), CRP ( OR =1.016, 95% CI 1.000-1.032), serum myoglobin ( OR =1.010, 95% CI 1.004-1.016), CD3 + T lymphocyte count ( OR =0.996, 95% CI 0.991-1.000) and CD8 + T lymphocyte count ( OR =1.006, 95% CI 1.001-1.010) at admission were independent risk factors for the progression of COVID-19 patients to severe illness (all P <0.05). Conclusions Severe cases of patients with COVID-19 in Shanghai are predominantly elderly men with underlying diseases. Albumin, CRP, serum myoglobin, CD3 + T lymphocyte count and CD8 + T lymphocyte count could be used as early warning indicators for severe cases, which deserve more clinical attention.", "doc_id": "izqxpk6q"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Identification and validation of a novel clinical signature to predict the prognosis in confirmed COVID-19 patients", "abstract": "BACKGROUND: This study aims to identify a prognostic biomarker to predict the disease prognosis and reduce the mortality rate of COVID-19, which has caused a worldwide pandemic. METHODS: COVID-19 patients were randomly divided into training and test groups. Univariate and multivariate Cox regression analyses were performed to identify the disease prognosis signature, which was selected to establish a risk model in the training group. Furthermore, the disease prognosis signature of COVID-19 was validated in the test group. RESULTS: The signature of COVID-19 was combined with five indicators, namely neutrophil count, lymphocyte count, procalcitonin, older age, and C-reactive protein. The signature stratified patients into high- and low-risk groups with significantly relevant disease prognosis (log-rank test, P<0.001) in the training group. The survival analysis indicated that the high-risk group displayed substantially lower survival probability than the low-risk group (log-rank test P<0.001). The area under ROC curve (AUC) showed that the signature of COVID-19 displayed the highest predictive accuracy regarding disease prognosis, which was 0.955 in the training group and 0.945 in the test group. The ROC analysis of both groups demonstrated that the predictive ability of the signature surpassed the use of each of the five indicators alone. CONCLUSION: The signature of COVID-19 presents a novel predictor and prognostic biomarker for closely monitoring patients and providing timely treatment for those who are severely or critically ill.", "doc_id": "0tte9rf6"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "The clinical study on the relationship between serum albumin concentration and lymphocyte levels in patients with 2019-novel coronavirus pneumonia/ \u4e2d\u534e\u6025\u8bca\u533b\u5b66\u6742\u5fd7", "abstract": "Objective@#To explore the relationship between different serum albumin and lymphocyte levels in patients with 2019-novel coronavirus (2019-nCoV) pneumonia (COVID-19).@*Methods@#A retrospective study was performed to identify the characteristics of the clinical data of 205 COVID-19 patients who were hospitalized in the Happy Street of Hanchuan People's Hospital, Xiaogan, Hubei Province from January 24 to February 12, 2020, including their general information, serum albumin (ALB) levels, lymphocyte counts (LYM), percentage of lymphocytes (LYM%) and other laboratory parameter levels. Low ALB group and normal ALB group were demarcated by the concentration of 35g/L, further to identify the differences of LYM and LYM% levels and the incidence of LYM and LYM% decline at different ALB levels between groups,as well as the correlation between ALB and LYM, LYM% levels in hypoalbuminemia conditions .@*Results@#17.5% of COVID-19 patients were associated with hypoalbuminemia. The levels of LYM and LYM% in the low ALB group were significantly lower than those in the normal ALB group (P <0.001). The incidence of LYM and LYM% decline in the low ALB group was significantly higher than those in the normal ALB group (P <0.001). The levels of LYM and LYM% in the low ALB group were significantly positively correlated with serum ALB concentrations (P <0.05).@*Conclusions@#The decrease of lymphocyte levels in COVID-19 patients may be correlated to hypoalbuminemia. COVID-19 patients complicated by hypoalbuminemia should be actively intervened to maintain serum albumin in the normal range.", "doc_id": "5yvburwy"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "IL-6 may be a good biomarker for earlier detection of COVID-19 progression", "abstract": "", "doc_id": "bl4eqsga"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Infection with SARS-CoV-2 causes abnormal laboratory results of multiple organs in patients", "abstract": "AIM: To evaluate the clinical value of abnormal laboratory results of multiple organs in patients with coronavirus disease 2019 (COVID-2019) and to help clinicians perform correct treatment. RESULTS: Elevated neutrophil-to-LYM ratio (NLR), D-dimer(D-D), interleukin (IL)-6, IL-10, IL-2, interferon-Y, and age were significantly associated with the severity of illness. However, significant and sustained decreases were observed in the LYM subset (p<0.05). D-D, T cell counts, and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of mild cases. Second, D-D increased from 0.5 to 8, and the risk ratio increased from 2.75 to 55, eventually leading to disseminated intravascular coagulation. Moreover, the acute renal function damage occurred earlier than abnormal heart and liver functions (p<0.05). CONCLUSIONS: The degrees of lymphopenia and proinflammatory cytokine storm were higher in severe COVID-19 patients than in mild cases. The degree was associated with the disease severity. Advanced age, NLR, D-D, and cytokine levels may serve as useful prognostic factors for the early identification of severe COVID-19 cases. METHODS: Peripheral blood samples were collected from 93 confirmed COVID-19 patients. The samples were examined for lymphocyte (LYM) subsets by flow cytometry and cytokine profiles by specific immunoassays. The receiver operating characteristic curve was applied to determine the best diagnostic thresholds for laboratory results, and principal component analysis was used to screen the major risk factors. The prognostic values were assessed using the Kaplan-Meier curve and univariate and multivariate COX regression models.", "doc_id": "hjowelkb"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Prediction of the severity of Corona Virus Disease 2019 and its adverse clinical outcomes", "abstract": "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.", "doc_id": "2bjn0fmr"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19", "abstract": "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-\u00ce\u00b3-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-\u00ce\u00b3-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.", "doc_id": "dm5cf4hw"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "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", "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 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.", "doc_id": "hf9q39m7"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "The role of biomarkers in diagnosis of COVID-19 - A systematic review", "abstract": "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.", "doc_id": "aph6yf7n"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "The profile of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus pneumonia", "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.", "doc_id": "97q9e8u7"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Tumor biomarkers predict clinical outcome of COVID-19 patients", "abstract": "", "doc_id": "86jwep6f"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early", "abstract": "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.", "doc_id": "6uxo7q4m"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "AI-Driven CT-based quantification, staging and short-term outcome prediction of COVID-19 pneumonia", "abstract": "Chest computed tomography (CT) is widely used for the management of Coronavirus disease 2019 (COVID-19) pneumonia because of its availability and rapidity. The standard of reference for confirming COVID-19 relies on microbiological tests but these tests might not be available in an emergency setting and their results are not immediately available, contrary to CT. In addition to its role for early diagnosis, CT has a prognostic role by allowing visually evaluating the extent of COVID-19 lung abnormalities. The objective of this study is to address prediction of short-term outcomes, especially need for mechanical ventilation. In this multi-centric study, we propose an end-to-end artificial intelligence solution for automatic quantification and prognosis assessment by combining automatic CT delineation of lung disease meeting performance of experts and data-driven identification of biomarkers for its prognosis. AI-driven combination of variables with CT-based biomarkers offers perspectives for optimal patient management given the shortage of intensive care beds and ventilators.", "doc_id": "hyk93ons"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Presepsin as a predictive biomarker of severity in COVID-19: A case series", "abstract": "", "doc_id": "gygw29fj"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Correlation between Heart fatty acid binding protein and severe COVID-19: A case-control study", "abstract": "BACKGROUND: Heart-fatty acid binding protein (HFABP) has been recognized as a highly heart-specific marker. However, it is currently unknown that its HFABP is also closely related to the severity of COVID-19. METHODS: We retrospectively screened 46 patients who met our inclusion criteria within 4 weeks. They were tested for HFABP after the diagnosis of COVID-19, and monitored for HFABP during their hospital stay. We tracked the patients during their hospital stay to determine if they had severe COVID-19 or mild-to-severe transition features. We calculated the chi-square test values found for HFABP to predict the correlation between HFABP levels and the severity of the COVID-19. RESULTS: Of these 46 cases, 16 cases with confirmed COVID-19 were tested for HFABP> 7 ng / mL upon admission; among them, 14 cases were diagnosed with severe COVID-19 within the hospitalization. The Odds ratio of the measured HFABP elevation was 6.81(95% confidence interval [CI] 5.23-8.40), and 3 patients with severe COVID-19 progressed in 5 patients with mild HFABP> 7 ng/mL. CONCLUSION: These data indicate that the elevation of HFABP is closely related to the severity of COVID-19 in the patients, and the elevated HFABP may cause rapid development of patients with mild COVID-19 into severe COVID-19. But serum HFABP negative maybe make patients with mild COVID-19 safer, the current data show no effect on the all-cause mortality. TRIAL REGISTRATION: Our study has been registered with the Chinese Clinical Trial Registry, the registration number: ChiCTR2000029829.", "doc_id": "alf7dvqq"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Serum Amyloid A is a biomarker of severe Coronavirus Disease and poor prognosis", "abstract": "BACKGROUND: To explore the significance of SAA in evaluating the severity and prognosis of COVID-19. METHODS: A total of 132 patients with confirmed COVID-19 who were admitted to a designated COVID-19 hospital in Wuhan, China from January 18, 2020 to February 26, 2020 were collected. The dynamic changes of blood SAA, CRP, PCT, WBC, Lymphocyte (L), PLT, CT imaging, and disease progression were studied. All patients completed at least twice laboratory data collection and clinical condition assessment at three time points indicated for this study; The length of hospital stay was longer than 14 days prior to February 26, 2020. RESULTS: COVID-19 patients had significantly increased SAA and CRP levels, while L count decreased, and PCT, WBC, and PLT were in the normal range. As disease progressed from mild to critically severe, SAA and CRP gradually increased, while L decreased, and PLT, WBC, and PCT had no significant changes; ROC curve analysis suggests that SAA/L, CRP, SAA, and L count are valuable in evaluating the severity of COVID-19 and distinguishing critically ill patients from mild ones; Patients with SAA consistently trending down during the course of disease have better prognosis, compared with the patients with SAA continuously rising; The initial SAA level is positively correlated with the dynamic changes of the serial CT scans. Patient with higher initial SAA level are more likely to have poor CT imaging. CONCLUSIONS: SAA and L are sensitive indicators in evaluating the severity and prognosis of COVID-19. Monitoring dynamic changes of SAA, combined with CT imaging could be valuable in diagnosis and treatment of COVID-19.", "doc_id": "k26sm2pr"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Biochemical biomarkers alterations in Coronavirus Disease 2019 (COVID-19)", "abstract": "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.", "doc_id": "9qn6dlwl"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Prognostic value of C-reactive protein in patients with COVID-19", "abstract": "BACKGROUND: Elevated serum C-reactive protein (CRP) level was observed in most patients with COVID-19. METHODS: Data of COVID-19 patients with clinical outcome in a designated hospital in Wuhan, China, were retrospectively collected and analyzed from Jan 30 to Feb 20, 2020. The prognostic value of admission CRP was evaluated in patients with COVID-19. RESULTS: Out of 298 patients enrolled, 84 died and 214 recovered. Most non-survivors tended to be males, old aged, or with chronic diseases. Compared to survivors, non-survivors showed significantly elevated white blood cell and neutrophil count, neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII, defined by platelet count multiply by NLR), CRP, procalcitonin, and D-dimer, and decreased red blood cell, lymphocyte, and platelet count. Age, neutrophil count, platelet count, and CRP were identified as independent predictors of adverse outcome. The area under the receiver operating characteristic (ROC) curve (AUC) of CRP (0.896) was significantly higher than that of age (0.833), neutrophil count (0.820), and platelet count (0.678) in outcome prediction (all p<0.05). With a cut-off value of 41.4, CRP exhibited sensitivity 90.5%, specificity 77.6%, positive predictive value 61.3%, and negative predictive value 95.4%. Subgroup analysis revealed that CRP remained robust accuracy in adverse outcome prediction in patients with different disease severity (AUC 0.832, z=10.23, p<0.001; AUC 0.989, z=44.04, p<0.001). CRP was also an independent discriminator of severe/critical illness on admission (AUC 0.783, z=10.69, p<0.001). CONCLUSIONS: In patients with COVID-19, admission CRP correlated with disease severity and tended to be a good predictor of adverse outcome.", "doc_id": "bisocp5y"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "A novel simple scoring model for predicting severity of patients with SARS-CoV-2 infection", "abstract": "An outbreak of pneumonia caused by a novel coronavirus (COVID-19) began in Wuhan, China in December 2019 and quickly spread throughout the country and world. An efficient and convenient method based on clinical characteristics was needed to evaluate the potential deterioration in patients. We aimed to develop a simple and practical risk scoring system to predict the severity of COVID-19 patients on admission. We retrospectively investigated the clinical information of confirmed COVID-19 patients from 10 February 2020 to 29 February 2020 in Wuhan Union Hospital. Predictors of severity were identified by univariate and multivariate logistic regression analysis. A total of 147 patients with confirmed SARS-CoV-2 infection were grouped into non-severe (94 patients) and severe (53 patients) groups. We found that an increased level of white blood cells (WBC), neutrophils, D-dimer, fibrinogen (FIB), IL-6, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), α-hydroxybutyrate dehydrogenase (HBDH), serum amyloid A (SAA) and a decreased level of lymphocytes were important risk factors associated with severity. Furthermore, three variables were used to formulate a clinical risk scoring system named COVID-19 index = 3 \u00d7 D-dimer (\u00b5g/L) + 2 \u00d7 lgESR (mm/hr) - 4 \u00d7 lymphocyte (\u00d7109 /L) + 8. The area under the receiver operating characteristic (ROC) curve was 0.843 (95% CI, 0.771-0.914). We propose an effective scoring system to predict the severity of COVID-19 patients. This simple prediction model may provide healthcare workers with a practical method and could positively impact decision-making with regard to deteriorating patients.", "doc_id": "4a5qqs4l"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Dynamic changes of D-dimer and neutrophil-lymphocyte count ratio as prognostic biomarkers in COVID-19", "abstract": "BACKGROUND: Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use. METHODS: In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR. RESULTS: Three hundred forty-nine participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors (P < 0.001). There was a more significant upward trend of D-Dimer and NLR during hospitalization in the deceased patients, initial D-Dimer and NLR were lower than the peak tests (MD) -25.23, 95% CI: - 31.81- -18.64, P < 0.001; (MD) -43.73, 95% CI:-59.28- -31.17, P < 0.001. The test showed a stronger correlation between hospitalization days, PCT and peak D-Dimer than initial D-Dimer. The areas under the ROC curves of peak D-Dimer and peak NLR tests were higher than the initial tests (0.94(95%CI: 0.90-0.98) vs. 0.80 (95% CI: 0.73-0.87); 0.93 (95%CI:0.90-0.96) vs. 0.86 (95%CI:0.82-0.91). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR was 0.73 mg/L, 3.78 mg/L,7.13 and 14.31 respectively. 35 (10.03%) patients were intubated. In the intubated patients, initial and peak D-Dimer and NLR were much higher than non-intubated patients (P < 0.001). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR in prognosticate of intubation was 0.73 mg/L, 12.75 mg/L,7.28 and 27.55. The multivariable Cox regression analysis showed that age (HR 1.04, 95% CI 1.00-1.07, P = 0.01), the peak D-Dimer (HR 1.03, 95% CI 1.01-1.04, P < 0.001) were prognostic factors for COVID-19 patients' death. CONCLUSIONS: To dynamically observe the ratio of D-Dimer and NLR was more valuable during the prognosis of COVID-19. The rising trend in D-Dimer and NLR, or the test results higher than the critical values may indicate a risk of death for participants with COVID-19.", "doc_id": "fvak9c65"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients", "abstract": "AIM: To accumulate evidence that indicated the key role played by virus-triggered inflammation in the 2019-novel coronavirus disease (COVID-19) which emerged in Wuhan City and rapidly spread throughout China. METHODS: Age, neutrophil(NEU)-to-lymphocyte (LYM) ratio (NLR), lymphocyte-to-monocyte (MON) ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) of 93 patients with laboratory confirmed COVID-19 were investigated and compared. The receiver operating characteristic curve was applied to determine the thresholds for five bio-markers, and their prognostic values were assessed via the Kaplan-Meier curve and multivariate COX regression models. RESULTS: The median age was 46.4 years old, and 37cases were females. A total of 27.8% of patients had been to Wuhan, and 73.1% had contacted with people from Wuhan. Fever (83.8%) and cough (70.9%) were the two most common symptoms. Elevated NLR and age were significantly associated with illness severity. The binary logistic analysis identified elevated NLR (hazard risk [HR] 2.46, 95% confidence interval [CI] 1.98-4.57) and age (HR 2.52, 95% CI 1.65-4.83) as independent factors for poor clinical outcome of COVID-19. NLR exhibited the largest area under the curve at 0.841, with the highest specificity (63.6%) and sensitivity (88%). CONCLUSIONS: Elevated age and NLR can be considered independent biomarkers for indicating poor clinical outcomes.", "doc_id": "82x01x0x"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Erythrocyte sedimentation rate is associated with severe coronavirus disease 2019 (COVID-19): a pooled analysis", "abstract": "", "doc_id": "8dw6f4gu"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Predictors of progression from moderate to severe coronavirus disease 2019: a retrospective cohort", "abstract": "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.", "doc_id": "52ewsgwk"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Laboratory Biomarkers Predicting COVID-19 Severity in the Emergency Room", "abstract": "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.", "doc_id": "8kswnd8a"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Soluble Urokinase Plasminogen Activator Receptor: A Biomarker for Predicting Complications and Critical Care Admission of COVID-19 Patients", "abstract": "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.", "doc_id": "3sy3jc5c"} {"topic_name": "coronavirus biomarkers", "topic_id": "25", "title": "Liver injury is associated with severe coronavirus disease 2019 (COVID-19) infection: A systematic review and meta-analysis of retrospective studies", "abstract": "The coronavirus disease 2019 (COVID-19) outbreak is a major threat to human beings. Lung injury has been reported as the major outcome of COVID-19 infection. However, liver damage has also been considered to occur in severe cases. The current meta-analysis of retrospective studies was carried out to summarize available findings on the association between liver injury and severity of COVID-19 infection. Online databases including PubMed, Scopus, Web of Science, and Cochrane Library were searched to detect relevant publications up to 1 April 2020, using relevant keywords. To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies. Furthermore, publication bias test and sensitivity analysis were also applied. In total, 20 retrospective studies with 3428 COVID-19 infected patients (severe cases, n = 1455; mild cases, n = 1973), were included in this meta-analysis. Higher serum levels of aspartate aminotransferase (weighted mean difference, 8.84 U/L; 95% confidence interval [CI] 5.97 to 11.71; P < 0.001), alanine aminotransferase (weighted mean difference, 7.35 U/L; 95% CI, 4.77 to 9.93; P < 0.001), total bilirubin (weighted mean difference, 2.30 mmol/L; 95% CI, 1.24 to 3.36; P < 0.001), and lower serum levels of albumin (weighted mean difference, -4.24 g/L; 95% CI, -6.20 to -2.28; P < 0.001) were associated with a significant increase in the severity of COVID-19 infection. The incidence of liver injury, as assessed by serum analysis (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin levels), seems to be higher in patients with severe COVID-19 infection.", "doc_id": "3vtc2tvv"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Case of COVID-19 presenting with gastrointestinal symptoms.", "abstract": "Patients with coronavirus disease 2019 (COVID-19) predominantly present with the pulmonary symptoms such as fever, cough, and shortness of breath. We present a case of an 83 years old patient with COVID-19 who presented with only gastrointestinal symptoms without respiratory complaints. Our case raises the concern regarding our current lack of understanding of extrapulmonary manifestations of COVID-19. Given genetic homology between 2019 severe acute respiratory syndrome coronavirus (SARS-CoV) 2 and SARS-CoV, our case underscores the urgent need for further studies to understand the role of the gastrointestinal system in 2019 SARS-CoV-2 transmission and COVID-19 pathogenesis.", "doc_id": "3ae7ekwd"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Real-time tracking of self-reported symptoms to predict potential COVID-19.", "abstract": "A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.", "doc_id": "atn333j9"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "[Analysis of gastrointestinal symptoms in 80 patients with coronavirus disease 2019].", "abstract": "OBJECTIVE To investigate the clinical characteristics of gastrointestinal symptoms in patients with coronavirus disease 2019 (COVID-19) during the whole disease process, and provide reference for etiological diagnosis and treatment. METHODS The clinical data of patients with COVID-19 admitted in the Infectious Diseases Branch of the First Affiliated Hospital of University of Science and Technology of China from January 22nd, 2020 to March 8th, 2020 were analyzed retrospectively. According to whether there were gastrointestinal symptoms (poor appetite, nausea/vomiting and diarrhea), all patients were divided into gastrointestinal symptom group and asymptomatic group. The characteristics of gastrointestinal symptoms, such as poor appetite, nausea, vomiting and diarrhea were counted and analyzed, and the correlation between gastrointestinal symptoms and gender, age, basic diseases, disease severity, laboratory examination and drug treatment were analyzed. RESULTS A total of 80 COVID-19 patients were involved, 43 cases (53.8%) presented with poor appetite, 17 cases (21.3%) had nausea and vomiting, and 33 cases (41.3%) had diarrhea. Among them, 5 cases, 1 case and 4 cases respectively preformed poor appetite, nausea/vomiting and diarrhea before admission, while the others experienced gastrointestinal symptoms within 48 hours after admission. Duration of poor appetite, nausea/vomiting and diarrhea (days) of all patients were 5.3\u00b12.1, 2.2\u00b11.0 and 1.4\u00b10.9, respectively. The patients with poor appetite were older than those without symptoms (years old: 48.2\u00b117.6 vs. 39.3\u00b115.1), albumin (Alb) level and the lymphocytes ratio were lower than those in asymptomatic group [Alb (g/L): 39.8 (35.7, 45.1) vs. 46.1 (42.6, 49.4), lymphocytes ratio: 0.19 (0.09, 0.28) vs. 0.28 (0.17, 0.35)], while the neutrophil ratio, the levels of C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) were higher than those in asymptomatic group [the neutrophil ratio: 0.74 (0.61, 0.85) vs. 0.64 (0.52, 0.76), CRP (mg/L): 21.4 (3.9, 52.9) vs. 5.6 (2.4, 14.0), D-dimer (mg/L): 0.2 (0.2, 0.5) vs. 0.2 (0.1, 0.3), LDH (\u03bcmol\u00d7s-1\u00d7L-1): 4.49 (3.59, 5.19) vs. 3.12 (2.77, 4.90)]; at the same time, more traditional Chinese medicine was used in the patients with gastrointestinal symptoms [65.1% (28/43) vs. 40.5% (15/37), all P < 0.05]. In addition, 14 cases of 18 patients with cardiovascular diseases presented with poor appetite, 7 patients had nausea and vomiting symptoms. All of the 3 patients with chronic kidney disease presented with poor appetite, nausea and vomiting, and 2 of them had diarrhea. CONCLUSIONS The gastrointestinal symptoms in patients with COVID-19 are common. Whether it is caused by the virus or related drugs, diet and mental conditions, clinicians should analyze the causes of these symptoms timely, and then provide a better treatment for patients with COVID-19.", "doc_id": "deka17f9"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "CT Scans Obtained for Nonpulmonary Indications: Associated Respiratory Findings of COVID-19.", "abstract": "Background Atypical manifestations of COVID-19 are being encountered as the pandemic unfolds, leading to non-chest CT scans that may uncover unsuspected pulmonary disease. Purpose To investigate patients with primary non-respiratory symptoms who underwent abdomen/pelvis or cervical spine/neck CT with unsuspected findings highly suspicious for pulmonary COVID-19. Materials and Methods This retrospective study from March 10, 2020 to April 6, 2020 involved three institutions, two in a region considered a hotspot (area of high prevalence) for COVID-19. Patients without known COVID-19 were included who presented to the emergency room (ER) with primary non-respiratory [gastrointestinal (GI) or neurological] symptoms, had lung parenchymal findings suspicious for COVID-19 on a non-chest CT but no concurrent chest CT and had COVID-19 testing in the ER. Group 1 patients had RT PCR obtained pre-CT read (COVID-19 suspected on presentation); Group 2 had RT PCR obtained post-CT read (COVID-19 not suspected). Presentation and imaging findings were compared and outcomes were evaluated. Descriptive statistics and Fisher exact tests were used for analysis. Results Group 1 comprised 62 patients [31 men, 31 women, mean age 67(SD \u00b117) years] and group 2 comprised 57 patients [28 men, 29 women, mean age 63(SD \u00b1 16) years). Cough and fever were more common in group 1 (37/62, 60%, 29/62, 47%) than group 2 (9/57, 16%, 12/57, 21%) respectively, with no significant difference in the remaining symptoms. There were 101 abdomen/pelvis and 18 cervical spine/neck CTs. In Group 1, non-chest CT findings provided the initial evidence of COVID-19 related pneumonia in 32/62 (52%); for Group 2, it was 44/57 (77%). Overall, the most common CT findings were ground glass opacity (114/119, 96%) and consolidation (47/119,40%). 29/119 (24%) patients required major interventions (vasopressor medication or intubation) and 27/119 (23%) died. Patients who underwent cervical spine/neck CT had worse outcomes than those with abdominal/pelvic CT (p =0.01). Conclusion In a substantial percentage of patients with primary non-respiratory symptoms who underwent non-chest CT, the CT provided the first evidence of COVID-19 related pneumonia.", "doc_id": "2v7yh3wf"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry.", "abstract": "OBJECTIVE The coronavirus disease 2019 (COVID-19) has spread worldwide since December 2019. Neurological symptoms have been reported as part of the clinical spectrum of the disease. We aim to determine whether neurological manifestations are common in hospitalized COVID-19 patients and to describe their main characteristics. METHODS We systematically review all patients diagnosed with COVID-19 admitted to hospital in a Spanish population during March 2020. Demographic characteristics, systemic and neurological clinical manifestations, and complementary tests were analyzed. RESULTS Of 841 patients hospitalized with COVID-19 (mean age 66.4 years, 56.2% men) 57.4% developed some form of neurological symptom. Nonspecific symptoms such as myalgias (17.2%), headache (14.1%), and dizziness (6.1%) were present mostly in the early stages of infection. Anosmia (4.9%) and dysgeusia (6.2%) tended to occur early (60% as the first clinical manifestation) and were more frequent in less severe cases. Disorders of consciousness occurred commonly (19.6%), mostly in older patients and in severe and advanced COVID-19 stages. Myopathy (3.1%), dysautonomia (2.5%), cerebrovascular diseases (1.7%), seizures (0.7%), movement disorders (0.7%), encephalitis (n=1), Guillain-Barr\u00e9 syndrome (n=1), and optic neuritis (n=1) were also reported, but less frequent. Neurological complications were the main cause of death in 4.1% of all deceased study subjects. CONCLUSIONS Neurological manifestations are common in hospitalized COVID-19 patients. In our series, more than half of patients presented some form of neurological symptom. Clinicians need to maintain close neurological surveillance for prompt recognition of these complications. The investigation of the mechanisms and emerging consequences of SARS-CoV-2 neurological involvement require further studies.", "doc_id": "7wvejgtf"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Sniffing out the evidence; It's now time for public health bodies recognize the link between COVID-19 and smell and taste disturbance.", "abstract": "Since the outbreak of the pandemic, anecdotal observations have been accumulating rapidly that sudden anosmia and dysgeusia are peculiar symptoms associated with the COVID-19 infection. Prof C. Hopkins, as President of British Rhinological Society, published a letter describing \"the loss of sense of smell as a marker of COVID-19 infection\" and proposed that adults presenting with anosmia but no other symptoms should self-isolate for seven days. The Hopkins team published the first case report and case series as well as other evidence that isolated sudden onset anosmia (ISOA), should be considered highly suspicious for SARS-CoV-2(1). Subsequently, a larger series of 2428 patients presenting with new onset anosmia during the COVID-19 pandemic has been reported, of whom 16% report loss of sense of smell as an isolated symptom. Only 51% reported the recognized symptoms of cough or fever. A major limitation of this series however, was a lack of access to testing to confirm the COVID-19 status of the patients(2); in the 80 who had been tested 74% were positive. In the same way, the American Academy of Otolaryngology-head and neck surgery (AA0-HNS) proposed \"that anosmia could be added to the list of screening tools for possible COVID-19 infection. More, they warrant serious consideration for self-isolation and testing those patients\".", "doc_id": "6yl3oh6n"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Gastrointestinal Symptoms and outcomes in hospitalized COVID-19 patients.", "abstract": "INTRODUCTION Gastrointestinal (GI) symptoms are increasingly being recognized in coronavirus disease 2019 (COVID-19). It is unclear if the presence of GI symptoms is associated with poor outcomes in COVID-19. We aim to assess if GI symptoms could be used for prognostication in hospitalized patients with COVID-19. METHODS We retrospectively analyzed patients admitted to a tertiary medical center in Brooklyn, NY, from March 18, 2020, to March 31, 2020, with COVID-19. The patients' medical charts were reviewed for the presence of GI symptoms at admission, including nausea, vomiting, diarrhea, and abdominal pain. COVID-19 patients with GI symptoms (cases) were compared with COVID-19 patients without GI symptoms (control). RESULTS A total of 150 hospitalized COVID-19 patients were included, of which 31 (20.6%) patients had at least one or more of the GI symptoms (cases). They were compared with the 119 COVID-19 patients without GI symptoms (controls). The average age among cases was 57.6 years (SD 17.2) and, control was 63.3 years (SD 14.6). No statistically significant difference was noted in comorbidities and laboratory findings. The primary outcome was mortality, which did not differ between cases and controls (41.9% vs. 37.8%, p=0.68). No statistically significant differences were noted in secondary outcomes, including the length of stay (LOS, 7.8 days vs. 7.9 days, p=0.87) and need for mechanical ventilation (29% vs. 26.9%, p=0.82). DISCUSSION In our study, the presence of GI manifestations in COVID-19 at the time of admission was not associated with increased mortality, LOS, or mechanical ventilation.", "doc_id": "5psze32l"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Early Clinical and CT Manifestations of Coronavirus Disease 2019 (COVID-19) Pneumonia.", "abstract": "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.", "doc_id": "8q6p7495"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "[Clinical features of 2019 novel coronavirus pneumonia in the early stage from a fever clinic in Beijing].", "abstract": "Objective: To summarize and analyze the clinical and imaging characteristics of patients with 2019 novel coronavirus pneumonia in the early stage in Beijing. Methods: A retrospective analysis of clinical and imaging data of 9 patients with 2019 novel coronavirus infection diagnosed in one fever clinicic in Beijing from January 18, 2020 to February 3, 2020. Results: 5 male and 4 female was included in those 9 patients, whose median age was 36 years, and the age range from 15 to 49 years. 8 of these patients had no underlying disease and one suffered from diabetes. 7 patients had a history of travel to Wuhan City or Hubei Province, and one patient was a medical staff. Two family clustered was found. The incubation period was 1 to 6 days. The clinical manifestations were fever in 8 cases (8/9) , dry cough in 5 cases (5/9) , pharyngalgia in 4 cases (4/9) , fatigue in 4 cases (4/9) , body soreness in 4 cases (4/9) , and blocked or watery nose in 1 case (1/9) . Six patients (6/9) had abnormal cell peripheral blood, of which 3 (3/9) had an increased monocyte count, 2 (2/9) had a reduced lymphocyte, and 1 (1/9) had an increased leukocyte count, while the 3 patients had normal cell blood routines. The median of CRP was 16.3 mg/L, including 5 patients with slightly elevated (5/9) , 4 patients with normal values (4/9) . the results of procalcitonin test were negative in5 patients. Three patients were examined by chest X-ray examination, one of which was normal, one case showed infiltrates of right upper lung, and another showed in right lower lung. All patients underwent chest HRCT. And 7 cases (7/9) showed multiple ground glass exudation, including 5 cases (5/7) involved bilateral lungs, 2 cases (2/7) involved unilateral lung, 3 cases (3/7) with patchy consolidation, and 2 cases (2/9) showed no abnormality. Conclusions: The patents with 2019 novel coronavirus pneumonia in this study generally have an epidemiological history. The clinical manifestations are fever and cough. Peripheral white blood cell counts were most normal And PCT were all negative. Chest HRCT manifested as multiple ground-glass opacities with partly consolidation. Some patients had normal chest radiographs but HRCT showed pneumonia. Some patients had no pneumonia on chest HRCT.", "doc_id": "0ymzuhi0"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Diagnostic and clinical significance of \"atypical\" symptoms in coronavirus disease 2019.", "abstract": "", "doc_id": "5apubuuv"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Gastrointestinal symptoms as the first, atypical indication of SARS-CoV-2 infection.", "abstract": "", "doc_id": "17ugnbd0"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Anosmia Is a Key Symptom of COVID-19 Infection and Should Be Used as a Diagnostic Tool.", "abstract": "Based on observations described in our letter, we can draw the following conclusions: (1) anosmia must imperatively be added to the list of specific symptoms of COVID-19 infection, (2) anosmia can serve as a free and specific diagnostic tool for developing countries currently affected by the pandemic, (3) the mechanisms of COVID-19 anosmia seem not to directly involve nasal obstruction but rather seem to be related to damage the olfactory neuroepithelium.", "doc_id": "aeu9e7vf"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "[Using the big data ofinternet to understand coronavirus disease 2019's symptom characteristics: a big data study].", "abstract": "Objective: Analyzing the symptom characteristics of Coronavirus Disease 2019(COVID-19) to improve its prevention. Methods: Using Baidu Index Platform (http://index.baidu.com) and the website of Chinese Center for Disease Control and Prevention as data resources to obtain the search volume (SV) of keywords for symptoms associated with COVID-19 from January 1 to February 20 in each year from 2017 to 2020, in Hubei province and other top 10 impacted provinces in China and the epidemic data. Data of 2020 were compared with the previous three years. Data of Hubei province were compared with confirmed cases. The differences and characteristics of the SV of COVID-19-related symptoms, and the correlation between the SV of COVID-19 and new confirmed or suspected cases were analyzed and the hysteresis effects were discussed. Results: Compared the data from January 1 to February 20, 2020, with the SV for the same period of previous three years, Hubei's SV for cough, fever, diarrhea, chest tightness, dyspnea and other symptoms were significantly increased. The total SV of lower respiratory symptoms was significantly higher than that of upper respiratory symptoms (P<0.001). The SV of COVID-19 in Hubei province was significantly correlated with new confirmed or suspected cases (R(confirmed) = 0.723, R(suspected) = 0.863, all P < 0.001). The results of the distributed lag model suggested that the patients who retrieved relevant symptoms on the Internet may begin to see a doctor in 2-3 days later and be diagnosed in 3-4 days later. Conclusions: The total SV of lower respiratory symptoms is higher than that of upper respiratory symptoms, and the SV of diarrhea also increased significantly. It warns us to pay attention to not only the symptoms of lower respiratory tract, but also the gastrointestinal symptoms, especially diarrhea in patients with COVID-19. There is a relationship between Internet retrieval behavior and the number of new confirmed or suspected cases. Big data has a certain role in the early warning of infectious diseases.", "doc_id": "551a8lsf"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Gustatory Dysfunction as an Early Symptom in COVID-19 Screening.", "abstract": "The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from Wuhan, China in December 2019 leads to the present coronavirus disease 2019 (COVID-19) pandemic. The various symptoms identified for COVID-19 are fever, dry cough, sore throat, dyspnea, fatigue, myalgia, and headache. Olfactory and gustatory dysfunctions are emerging as a new symptom more in the European patients. Taste disturbances are common in various oral and systemic diseases. Varying severity and onset of taste disturbances are reported in COVID-19 positive patients in this pandemic. But a sudden onset of taste disturbances without an established and recognized cause should raise suspicion of COVID-19. This article will analyze the various studies focusing on taste disturbances as a reliable early symptom for COVID-19 screening.", "doc_id": "432jmxik"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Early Insights into Immune Responses during COVID-19.", "abstract": "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.", "doc_id": "1mhxy9hh"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Olfactory and rhinological evaluations in SARS-CoV-2 patients complaining of olfactory loss.", "abstract": "Since December 2019, a novel coronavirus SARS-CoV-2 (Covid-19) outbreak emerged in China and spread rapidly in several countries. As of April 5, 2020, 1.218.474 cases were confirmed with 65.884 deaths worldwide (1). The clinical manifestations of Covid-19 range from asymptomatic carrier status to severe pneumonia. In a study of 7,736 Covid-19 patients in China, of all the clinical symptoms, hyposmia was not reported in any patient(2). Anyway, it is now clear that olfactory dysfunction may also be present in these patients(3) as the only or prevalent manifestation(4).", "doc_id": "66gu5af1"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "The Clinical Manifestations and Chest Computed Tomography Findings of Coronavirus Disease 2019 (COVID-19) Patients in China: A Proportion Meta-Analysis", "abstract": "OBJECTIVES: The objectives of this study were to identify the clinical features and chest computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) patients and to compare the characteristics of patients diagnosed in Wuhan and in other areas of China by integrating the findings reported in previous studies METHODS: We conducted a proportion meta-analysis to integrate the results of previous studies identified in online databases, and subsequently compared the overlapping of 95% confidence intervals (CIs) between locations of diagnosis The heterogeneity of the results of the included studies was also demonstrated RESULTS: Nine studies with level IV evidence were considered to be eligible for the meta-analysis, and a comparative analysis was only possible between patients diagnosed in Wuhan and outside of Wuhan in China Fever (84 8%;95% CI, 78 5% to 90 1%) was identified as the most common clinical manifestation in all COVID-19 patients, and signs of respiratory infection were also frequently present in these patients When comparing the clinical features according to the location of diagnosis, fever and dyspnea were less frequent in patients diagnosed outside of Wuhan (fever: 78 1%;95% CI, 73 2% to 82 7%;dyspnea: 3 80%;95% CI, 0 13% to 12 22%) than in patients diagnosed in Wuhan (fever: 91 7%;95% CI, 88 0% to 94 8%;dyspnea: 21 1%;95% CI, 13 2% to 30 3%) The chest CT findings exhibited no significant differences between the groups CONCLUSION: Fever was found to be the most common symptom in COVID-19, and respiratory infection signs were also commonly present Fever and dyspnea were less frequently observed in the patients diagnosed outside of Wuhan, which should be considered in COVID-19 screening programs These results may be attributable to the earlier diagnosis of the disease and the younger age of patients outside of Wuhan although further analysis is needed The role of chest CT in COVID-19 diagnosis is inconclusive based on this study", "doc_id": "7oaerpee"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "A COVID-19 outbreak in a rheumatology department upon the early days of the pandemic", "abstract": "Objectives: To describe our experience with a coronavirus disease 2019 (COVID-19) outbreak within a large rheumatology department, early in the pandemic. Methods: Symptomatic and asymptomatic healthcare workers (HCWs) had a naso-oropharyngeal swab for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and were followed clinically. Reverse transcription polymerase-chain reaction (RT-PCR) was repeated to document cure, and serological response was assessed. Patients with risk contacts within the department in the 14 days preceding the outbreak were screened for COVID-19 symptoms. Results: 14/34 HCWs (41%; 40{+/-}14 years, 71% female) tested positive for SARS-CoV-2, and 11/34 (32%) developed symptoms but were RT-PCR-negative. Half of RT-PCR-positive HCWs did not report fever, cough, or dyspnoea before testing, which were absent in 3/14 cases (21%). Mild disease prevailed (79%), but 3 HCWs had moderate disease requiring further assessment, which excluded severe complications. Nevertheless, symptom duration (28{+/-}18 days), viral shedding (31{+/-}10 days post-symptom onset, range 15-51) and work absence (29{+/-}28 days) were prolonged. 13/14 (93%) of RT-PCR-positive and none of the RT-PCR-negative HCWs had a positive humoral response, with higher IgG-index in individuals over 50 years (14.5{+/-}7.7 vs 5.0{+/-}4.4, p=0.012). Of 617 rheumatic patients, 8 (1.3%) developed COVID-19 symptoms (1/8 hospitalisation, 8/8 complete recovery), following a consultation/procedure with an asymptomatic (7/8) or mildly-symptomatic (1/8) HCW. Conclusions: A COVID-19 outbreak can occur among HCWs and rheumatic patients, swiftly spreading over the presymptomatic stage. Mild disease without typical symptoms should be recognised, and may evolve with delayed viral shedding, prolonged recovery, and adequate immune response in most individuals.", "doc_id": "4qlwf00l"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Symptom clusters in Covid19: A potential clinical prediction tool from the COVID Symptom study app", "abstract": "As no one symptom can predict disease severity or the need for dedicated medical support in COVID-19, we asked if documenting symptom time series over the first few days informs outcome. Unsupervised time series clustering over symptom presentation was performed on data collected from a training dataset of completed cases enlisted early from the COVID Symptom Study Smartphone application, yielding six distinct symptom presentations. Clustering was validated on an independent replication dataset between May 1- May 28th, 2020. Using the first 5 days of symptom logging, the ROC-AUC of need for respiratory support was 78.8%, substantially outperforming personal characteristics alone (ROC-AUC 69.5%). Such an approach could be used to monitor at-risk patients and predict medical resource requirements days before they are required.", "doc_id": "2leg4980"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "ACUTE VISION LOSS IN A PATIENT WITH COVID-19", "abstract": "To date, there have been reports of neurologic manifestations in Covid-19 patients including ischemic strokes, Guillain-Barre Syndrome and anosmia. In this case report, we report a patient who presented with dysosmia, dysgeusia along with monocular peripheral vision loss after being diagnosed with Covid-19.", "doc_id": "csj9yf02"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Alteration of consciousness as initial presentation in COVID-19: Observation", "abstract": "", "doc_id": "2g2n4s8c"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Predictive value of sudden olfactory loss in the diagnosis of COVID-19", "abstract": "Introduction: Recent reports suggest that sudden smell loss might be a symptom of SARS-CoV-2 infection. The aim of this study was to investigate the frequency of olfactory loss in an out-patient population who presented to a coronavirus testing center during a 2-week period and to evaluate the diagnostic value of the symptom sudden smell loss for screening procedures. Methods: In this cross-sectional controlled cohort study, 500 patients who presented with symptoms of a common cold to a corona testing center and fulfilled corona testing criteria, completed a standardized diagnostic questionnaire which included the patients main symptoms, time course and an additional self-assessment of the patients current smell, taste function and nasal breathing compared to the level before onset of symptoms. Results: Out of the 500 patients, 69 presented with olfactory loss. Twenty-two of them subsequently tested positive for SARS-CoV-2. Only twelve out of the patients without olfactory loss tested positive, resulting in a frequency of 64.7% for the symptom sudden smell loss in COVID-19 patients. Compared to COVID-19 patients without smell loss, they were significantly younger and less severely affected. Changes in nasal airflow were significantly more pronounced in SARS-CoV-2 negative patients with olfactory complaints compared to the patients with smell loss who were tested positive for SARS-CoV-2. By excluding patients with a blocked nose, the symptom sudden smell loss can be attested a high specificity (97%) and a sensitivity of 65% with a PPV of 63% and NPV of 97% for COVID-19. Conclusion: Considering the high frequency of smell loss in non-hospitalized COVID-19 patients, acute olfactory impairment should be included in the WHO symptoms list and should be recognized as an early symptom of the disease. In contrast to other acute viral smell impairment, COVID-19 associated smell loss seems to be only rarely accompanied by a severely blocked nose.", "doc_id": "aox5dqxn"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Cerebral venous thrombosis: A typical presentation of COVID-19 in the young", "abstract": "Objective: Identify clinical and radiographic features of venous infarct as a presenting feature of COVID-19 in the young. Background: SARS-CoV-2 infection causes hypercoagulability and inflammation leading to venous thrombotic events (VTE). Although elderly patients with comorbidities are at higher risk, COVID-19 may also cause VTE in a broader patient population without these risks. Neurologic complications and manifestations of COVID-19, including neuropathies, seizures, strokes and encephalopathy usually occur in severe established cases of COVID-19 infection who primarily present with respiratory distress. Case description: Case report of a 29-year-old woman, with no significant past medical history or comorbidities, presenting with new onset seizures. Further questioning revealed a one-week history of headaches, low-grade fever, mild cough and shortness of breath, diagnosed as COVID-19. Imaging revealed a left temporoparietal hemorrhagic venous infarction with left transverse and sigmoid sinus thrombosis treated with full dose anticoagulation and antiepileptics. Conclusion: Although elderly patients with comorbidities are considered highest risk for COVID-19 neurologic complications, usually when systemic symptoms are severe, this case report emphasizes that young individuals are at risk for VTE with neurologic complications even when systemic symptoms are mild, likely induced by COVID-19 associated hypercoagulable state.", "doc_id": "7i81cm5y"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "[SARS-CoV-2 infection with gastrointestinal symptoms as the first manifestation in a neonate].", "abstract": "Since December 2019, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has occurred in Wuhan, Hubei Province, China. The infected cases were noted mostly in adults, but rarely reported in children, especially neonates. Most children with SARS-CoV-2 infection present mainly with respiratory symptoms, but less commonly with gastrointestinal symptoms, and tend to have mild clinical symptoms. A neonate with SARS-CoV-2 infection, who had vomiting and milk refusal as the first symptom, was recently admitted to Wuhan Children's Hospital. After two weeks of treatment, the patient recovered gradually and was discharged. Here, this case is reported to improve the understanding of SARS-CoV-2 infection in neonates.", "doc_id": "02ejyglj"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "[Anosmia and ageusia as primary symptoms of COVID-19].", "abstract": "This case report describes a physician in the early 30ies with subjective anosmia and ageusia as the major presenting symptoms of COVID-19. Apart from a week of slightly runny nose when coming from cold to warm air, the only symptom was a sudden onset of persistent anosmia and ageusia. Two weeks after normalisation of the mild sino-nasal symptoms, the patient was tested positive for SARS-CoV-2, and anosmia was verified with Sniffin' Sticks tests. Hypogeusia was verified with taste screening and two validated taste tests. Olfactory and gustatory loss may be underestimated symptoms of COVID-19.", "doc_id": "6kne981m"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms", "abstract": "OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5\u00b0C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.", "doc_id": "93egl14x"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "\u00e5\u0084\u00bf\u00e7\u00ab\u00a52019\u00e5\u0086 \u00e7\u008a\u00b6\u00e7\u0097 \u00e6\u00af\u0092\u00e7\u0097 \u00e6\u0082\u00a3\u00e8\u0080 \u00e7\u009a\u0084\u00e8\u0083\u00b8\u00e9\u0083\u00a8CT\u00e8\u00a1\u00a8\u00e7\u008e\u00b0\u00e5\u0092\u008c\u00e4\u00b8\u00b4\u00e5\u00ba\u008a\u00e7\u0089\u00b9\u00e5\u00be\u0081./ \u00e5\u0084\u00bf\u00e7\u00ab\u00a52019\u00e5\u0086 \u00e7\u008a\u00b6\u00e7\u0097 \u00e6\u00af\u0092\u00e7\u0097 \u00e6\u0082\u00a3\u00e8\u0080 \u00e7\u009a\u0084\u00e8\u0083\u00b8\u00e9\u0083\u00a8CT\u00e8\u00a1\u00a8\u00e7\u008e\u00b0\u00e5\u0092\u008c\u00e4\u00b8\u00b4\u00e5\u00ba\u008a\u00e7\u0089\u00b9\u00e5\u00be\u0081./ Chest CT findings and clinical features of coronavirus disease 2019 in children", "abstract": "OBJECTIVES: To describe the CT features and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19). METHODS: A total of 9 COVID-19 infected pediatric patients were included in this study. Clinical history, laboratory examination, and detailed CT imaging features were analyzed. All patients underwent the first CT scanning on the same day of being diagnosed by real-time reverse-transcription polymerase chain reaction (rRT-PCR). A low-dose CT scan was performed during follow-up. RESULTS: All the child patients had positive results. Four patients had cough and one patient had fever. One patient presented both cough and fever. Two children presented other symptoms like sore throat and stuffy nose. One child showed no clinical symptom. Five patients had positive initial CT findings with subtle lesions like ground-glass opacity (GGO) or spot-like mixed consolidation. Three patients were reported with negative results in the initial and follow-up CT examination. One patient was reported with initial negative CT findings but turning positive during the first follow-up. All patients had absorbed lesions on follow-up CT images after treatment. CONCLUSIONS: Pediatric COVID-19 patients have certain imaging and clinical features as well as disease prognosis. Children with COVID-19 tend to have normal or subtle CT findings and relatively better outcome.", "doc_id": "2a6l14f1"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Epidemiologic and clinical characteristics of 10 children with coronavirus disease 2019 in Changsha, China", "abstract": "BACKGROUND: The outbreak of a new coronavirus, first reported in Wuhan, China, is spreading around the world. Information on the characteristics of children with Coronavirus Disease 2019 (COVID-19) is limited. METHODS: In this retrospective study, we recruited 10 children infected with SARS-COV-2 from January 27 to March 10, 2020, in Changsha, China. We report the epidemiological, clinical, laboratory, and high-resolution CT findings for these children. Qualitative descriptive analysis was used to describe the key results. RESULTS: Ten children were included. Three were male and seven were female. Three were from Wuhan, Hubei Province, and seven were from Changsha. All had a history of close contact with adults with COVID-19 before the onset of disease. Clinical manifestations included fever in four cases, respiratory symptoms in three cases, febrile convulsions in one case, vomiting in one case, abdominal pain in one case, and asymptomatic infection in two cases. All the children tested positive for nucleic acid in throat swabs at admission. Stool swabs of three cases were positive for nucleic acid after several days of fever. In nine children, blood routine results were normal, whereas in one case the white blood cell count was elevated. In four cases, CT findings of the lungs showed light ground-glass opacities, one case showed changes similar to bronchopneumonia, and the remaining cases were normal. All were treated with symptomatic support without complications. CONCLUSION: Our findings indicate that intrafamily transmission may be the main form of transmission of COVID-19 in children, and persistent intestinal excretion of virus is another characteristic among children. The results of stool swab tests should be considered for discharge and release from isolation.", "doc_id": "1ysxsj2n"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Clinical characteristics and drug therapies in patients with the common-type coronavirus disease 2019 in Hunan, China", "abstract": "Background Clinical characteristics of patients with the coronavirus disease 2019 (COVID-19) may present differently within and outside the epicenter of Wuhan, China. More clinical investigations are needed. Objective The study was aimed to describe the clinical characteristics, laboratory parameters, and therapeutic methods of COVID-19 patients in Hunan, China. Setting The First Hospital of Changsha, First People's Hospital of Huaihua, and the Central Hospital of Loudi, Hunan province, China. Methods This was a retrospective multi-center case-series analysis. Patients with confirmed COVID-19 diagnosis hospitalized at the study centers from January 17 to February 10, 2020, were included. The following data were obtained from electronic medical records: demographics, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings, computer tomography scans, and treatment measures. Main outcome measure Epidemiological, clinical, laboratory, and radiological characteristics and treatments. Results A total of 54 patients were included (51 had the common-type COVID-19, three had the severe-type), the median age was 41, and 52% of them were men. The median time from the first symptoms to hospital admission was seven days. Among patients with the common-type COVID-19, the median length of stay was nine days, and 21 days among patients with severe COVID-19. The most common symptoms at the onset of illness were fever (74.5%), cough (56.9%), and fatigue (43.1%) among patients in the common-type group. Fourteen patients (37.8%) had a reduced WBC count, 23 (62.2%) had reduced eosinophil ratio, and 21 (56.76%) had decreased eosinophil count. The most common patterns on chest-computed tomography were ground-glass opacity (52.2%) and patchy bilateral shadowing (73.9%). Pharmacotherapy included recombinant human interferon α2b, lopinavir/ritonavir, novaferon, antibiotics, systematic corticosteroids and traditional Chinese medicine prescription. The outcome of treatment indicated that in patients with the common-type COVID-19, interferon-α2b, but not novaferon, had some benefits, antibiotics treatment was not needed, and corticosteroids should be used cautiously. Conclusion As of February 10, 2020, the symptoms of COVID-19 patients in Hunan province were relatively mild comparing to patients in Wuhan, the epicenter. We observed some treatment benefits with interferon-α2b and corticosteroid therapies but not with novaferon and antibiotic treatment in our study population.", "doc_id": "5cxb9ktc"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Probability of symptoms and critical disease after SARS-CoV-2 infection", "abstract": "We quantified the probability of developing symptoms (respiratory or fever \\geq 37.5 {\\deg}C) and critical disease (requiring intensive care or resulting in death) of SARS-CoV-2 positive subjects. 5,484 contacts of SARS-CoV-2 index cases detected in Lombardy, Italy were analyzed, and positive subjects were ascertained via nasal swabs and serological assays. 73.9% of all infected individuals aged less than 60 years did not develop symptoms (95% confidence interval: 71.8-75.9%). The risk of symptoms increased with age. 6.6% of infected subjects older than 60 years had critical disease, with males at significantly higher risk.", "doc_id": "2uiffl46"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "The implications of preliminary screening and diagnosis: Clinical characteristics of 33 mild patients with SARS-CoV-2 infection in Hunan, China", "abstract": "BACKGROUND: In December 2019, coronavirus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. The disease has rapidly spread from Wuhan to other regions. OBJECTIVES: To describe the clinical manifestations and epidemiological characteristics of patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in Hunan Province in 2020. STUDY DESIGN: From January 19 to February 7, 2020, 33 patients with positive in nucleic acid test of pharyngeal swab were retrospectively collected and analyzed. RESULTS: There are 33 COVID-19 patients (16 male, 17 female), and the median age was 46 years. Nineteen patients (48 %) were associated with a family cluster outbreak. Seventeen patients (52 %) had traveled or lived in Hubei Province. These patients are early mild cases, most common symptoms are fever [23 (70 %)] and cough [13 (39 %)]. Most patients' white blood cell counts are normal, while they manifest as significant reduction in lymphocytes [17/28 (61 %)]. The levels of c-reactive protein and erythrocyte sedimentation rate suggest a typical viral infection. Procalcitonin did not increase and D-dimer increased slightly. Lactate dehydrogenase (LDH) levels have elevated in most patients. CT images of these patients showed bilateral multiple plaques or nodular ground-glass opacities (68.4 %). Fecal nucleic acid results were positive in eight COVID-19 patients accompanied with diarrhea. Tear nucleic acid results were negative in six COVID-19 patients. And four asymptomatic patients were infected with SARS-CoV-2. CONCLUSIONS: The clinical symptoms, laboratory results and imaging reports of patients with COVID-19 in Hunan area are significantly different from those in Wuhan area. For non-Wuhan epidemic areas, more attention should be paid to nucleic acid test results of throat swabs and stools, and it is not easily to diagnose based on clinical symptoms and CT results. Reduced whole blood lymph count can be used as an adjuvant diagnosis of early SARS-CoV-2 infection. Attention should be paid to asymptomatic carriers, which is of great significance for the control of the global epidemic.", "doc_id": "5hdyu886"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Upper airway symptoms in coronavirus disease 2019 (COVID-19)", "abstract": "", "doc_id": "db7zcdyh"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Clinical and epidemiological characteristics of 1420 European patients with mild-to-moderate coronavirus disease 2019", "abstract": "BACKGROUND: The clinical presentation of European patients with mild-to-moderate COVID-19 infection is still unknown. OBJECTIVE: To study the clinical presentation of COVID-19 in Europe. METHODS: Patients with positive diagnosis of COVID-19 were recruited from 18 European hospitals. Epidemiological and clinical data were obtained through a standardized questionnaire. Bayesian analysis was used for analysing the relationship between outcomes. RESULTS: A total of 1,420 patients completed the study (962 females, 30.7% of healthcare workers). The mean age of patients was 39.17 \u00b1 12.09 years. The most common symptoms were headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), myalgia (62.5%), rhinorrhea (60.1%), gustatory dysfunction (54.2%) and sore throat (52.9%). Fever was reported by 45.4%. The mean duration of COVID-19 symptoms of mild-to-moderate cured patients was 11.5 \u00b1 5.7 days. The prevalence of symptoms significantly varied according to age and sex. Young patients more frequently had ear, nose and throat complaints, whereas elderly individuals often presented fever, fatigue and loss of appetite. Loss of smell, headache, nasal obstruction and fatigue were more prevalent in female patients. The loss of smell was a key symptom of mild-to-moderate COVID-19 patients and was not associated with nasal obstruction and rhinorrhea. Loss of smell persisted at least 7 days after the disease in 37.5% of cured patients. CONCLUSION: The clinical presentation of mild-to-moderate COVID-19 substantially varies according to the age and the sex characteristics of patients. Olfactory dysfunction seems to be an important underestimated symptom of mild-to-moderate COVID-19 that needs to be recognized as such by the WHO.", "doc_id": "4ofl66rt"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Association of Digestive Symptoms and Hospitalization in Patients With SARS-CoV-2 Infection", "abstract": "INTRODUCTION: High rates of concurrent gastrointestinal manifestations have been noted in patients with corona virus disease 2019 (COVID-19); however, the association between these digestive manifestations and need for hospitalization has not been established. METHODS: This is a retrospective review of consecutive patients diagnosed with COVID-19. A total of 207 patients were identified; 34.5% of patients noted concurrent gastrointestinal symptoms, with 90% of gastrointestinal symptoms being mild. RESULTS: In a multivariate regression model controlled for demographics and disease severity, an increased risk of hospitalization was noted in patients with any digestive symptom (adjusted odds ratio 4.84, 95% confidence interval: 1.68-13.94). DISCUSSION: The presence of digestive symptoms in COVID-19 is associated with a need for hospitalization.", "doc_id": "59k4c0ts"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Sniffing out the evidence; It's now time for public health bodies recognize the link between COVID-19 and smell and taste disturbance", "abstract": "Since the outbreak of the pandemic, anecdotal observations have been accumulating rapidly that sudden anosmia and dysgeusia are peculiar symptoms associated with the COVID-19 infection. Prof C. Hopkins, as President of British Rhinological Society, published a letter describing \"the loss of sense of smell as a marker of COVID-19 infection\" and proposed that adults presenting with anosmia but no other symptoms should self-isolate for seven days. The Hopkins team published the first case report and case series as well as other evidence that isolated sudden onset anosmia (ISOA), should be considered highly suspicious for SARS-CoV-2(1). Subsequently, a larger series of 2428 patients presenting with new onset anosmia during the COVID-19 pandemic has been reported, of whom 16% report loss of sense of smell as an isolated symptom. Only 51% reported the recognized symptoms of cough or fever. A major limitation of this series however, was a lack of access to testing to confirm the COVID-19 status of the patients(2); in the 80 who had been tested 74% were positive. In the same way, the American Academy of Otolaryngology-head and neck surgery (AA0-HNS) proposed \"that anosmia could be added to the list of screening tools for possible COVID-19 infection. More, they warrant serious consideration for self-isolation and testing those patients".", "doc_id": "3xccfhd9"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Gastrointestinal Symptoms and outcomes in hospitalized COVID-19 patients", "abstract": "INTRODUCTION: Gastrointestinal (GI) symptoms are increasingly being recognized in coronavirus disease 2019 (COVID-19). It is unclear if the presence of GI symptoms is associated with poor outcomes in COVID-19. We aim to assess if GI symptoms could be used for prognostication in hospitalized patients with COVID-19. METHODS: We retrospectively analyzed patients admitted to a tertiary medical center in Brooklyn, NY, from March 18, 2020, to March 31, 2020, with COVID-19. The patients' medical charts were reviewed for the presence of GI symptoms at admission, including nausea, vomiting, diarrhea, and abdominal pain. COVID-19 patients with GI symptoms (cases) were compared with COVID-19 patients without GI symptoms (control). RESULTS: A total of 150 hospitalized COVID-19 patients were included, of which 31 (20.6%) patients had at least one or more of the GI symptoms (cases). They were compared with the 119 COVID-19 patients without GI symptoms (controls). The average age among cases was 57.6 years (SD 17.2) and, control was 63.3 years (SD 14.6). No statistically significant difference was noted in comorbidities and laboratory findings. The primary outcome was mortality, which did not differ between cases and controls (41.9% vs. 37.8%, p=0.68). No statistically significant differences were noted in secondary outcomes, including the length of stay (LOS, 7.8 days vs. 7.9 days, p=0.87) and need for mechanical ventilation (29% vs. 26.9%, p=0.82). DISCUSSION: In our study, the presence of GI manifestations in COVID-19 at the time of admission was not associated with increased mortality, LOS, or mechanical ventilation.", "doc_id": "dlbpa2nw"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias", "abstract": "BACKGROUND: A novel coronavirus (2019-nCoV) has raised world concern since it emerged in Wuhan Hubei China in December, 2019. The infection may result into severe pneumonia with clusters illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias. METHODS: Nineteen 2019-nCoV pneumonia (NCOVID-19) and fifteen other pneumonia patients (NON-NCOVID-19) in out of Hubei places were involved in this study. Both NCOVID-19 and NON-NCOVID-19 patients were confirmed to be infected in throat swabs or/and sputa with or without 2019-nCoV by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the difference between NCOVID-19 and NON-NCOVID-19. RESULTS: All patients had a history of exposure to confirmed case of 2019-nCoV or travel to Hubei before illness. The median duration, respectively, was 8 (IQR:6~11) and 5 (IQR:4~11) days from exposure to onset in NCOVID-19 and NON-NCOVID-19. The clinical symptoms were similar between NCOVID-19 and NON-NCOVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) NCOVID-19 but 4 (26.67%) NON-NCOVID-19 patients had bilateral involvement while 17 (89.47%) NCOVID-19 but 1 (6.67%) NON-NCOVID-19 patients had multiple mottling and ground-glass opacity of chest CT images. Compared to NON-NCOVID-19, NCOVID-19 present remarkably more abnormal laboratory tests including AST, ALT, \u00ce\u00b3-GT, LDH and α-HBDH. CONCLUSION: The 2019-nCoV infection caused similar onsets to other pneumonias. CT scan may be a reliable test for screening NCOVID-19 cases. Liver function damage is more frequent in NCOVID-19 than NON-NCOVID-19 patients. LDH and α-HBDH may be considerable markers for evaluation of NCOVID-19.", "doc_id": "bveq7kpp"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "A case of COVID-19 patient with the diarrhea as initial symptom and literature review", "abstract": "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.", "doc_id": "0ylislv9"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Epidemiology and Clinical Characteristics of COVID-19", "abstract": "Since December 2019, there has been an outbreak of a novel coronavirus (COVID-19) infection in Wuhan, China. Meanwhile, the outbreak also drew attention and concern from the World Health Organization (WHO). COVID-19 is another human infectious disease caused by coronavirus. The transmission of COVID-19 is potent and the infection rate is fast. Since there is no specific drug for COVID-19, the treatment is mainly symptomatic supportive therapy. In addition, it should be pointed out that patients with severe illness need more aggressive treatment and meticulous care. Recently, accurate RNA detection has been decisive for the diagnosis of COVID-19. The development of highly sensitive RT-PCR has facilitated epidemiological studies that provide insight into the prevalence, seasonality, clinical manifestations and course of COVID-19 infection. In this review, we summarize the epidemiology and characteristics of COVID-19.", "doc_id": "0uvzy48c"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Symptom Cluster of ICU Nurses Treating COVID-19 Pneumonia Patients in Wuhan, China", "abstract": "BACKGROUND: In treating highly infectious coronavirus disease-19 (COVID-19) pneumonia, intensive care unit (ICU) nurses face a high risk of developing somatic symptom disorder (SSD).The symptom clusters in one population may show overlaps and involvements, a phenomenon that should be deliberately resolved to improve the management efficiency. OBJECTIVES: The present study aims to investigate the symptoms and causes of SSD of ICU nurses treating COVID-19 pneumonia. The research results are expected to provide evidence for the establishment of a better management strategy. METHODS: This study enrolled a total of 140 ICU nurses who were selected by Jiangsu Province Hospital to work in Wuhan (the epicenter of the COVID-19 epidemic in China) on February 3, 2020. A questionnaire, Somatic symptom disorders for ICU nurses in Wuhan No. 1 Hospital, was designed based on the International Classification of Functioning, Disability and Health. Exploratory factor analysis was performed to cluster the symptoms and logistic regression analysis to find the risk factors of the symptoms. RESULTS: Five major symptoms were chest discomfort and palpitation (31.4%), dyspnea (30.7%), nausea (21.4%), headache (19.3%), and dizziness (17.9%). In exploratory factor analysis, the symptoms were classified into three clusters: Cluster A of breathing and sleep disturbances (dizziness, sleepiness, and dyspnea); Cluster B of gastrointestinal complaints and pain (nausea and headache), and Cluster C of general symptoms (xerostomia, fatigue, as well as chest discomfort and palpitation). In Cluster A, urine/feces splash, sex, and sputum splash were independent predictive factors. In Cluster B, fall of protective glasses and urine/feces splash were independent predictive factors. In Cluster C, urine/feces splash and urine/feces clearance were independent predictive factors. CONCLUSION: The ICU nurses in Wuhan showed varying and overlapping SSDs. These SSDs could be classified into three symptom clusters. Based on the characteristics of their SSDs, specific interventions could be implemented to safeguard the health of ICU nurses.", "doc_id": "cljv4lz9"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province", "abstract": "BACKGROUND: The 2019 novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak. METHODS: Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens. RESULTS: None of the 137 patients (61 males, 76 females, aged 20-83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea. CONCLUSIONS: The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.", "doc_id": "4670hs1r"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Epidemiological and initial clinical characteristics of patients with family aggregation of COVID-19", "abstract": "BACKGROUND: Since December 2019, a new outbreak of the coronavirus disease 2019 (COVID-19) in Wuhan (Hubei, China) and rapidly spread throughout China, however, confirmed cases are still increasing worldwide. OBJECTIVES: To investigate the epidemiological history and initial clinical characteristics of 10 patients with family aggregation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Western Chongqing, China. STUDY DESIGN: Ten patients positive for SARS-CoV-2 nucleic acid detection by real time Reverse Transcription-Polymerase Chain Reaction (RT-PCR), were collected from The People's Hospital of Dazu District, Chongqing. Epidemiological data and laboratory and imaging results were collected on the first day of admission, and analyzed based on the Diagnosis and Treatment Guideline for COVID-19 (5th edition, China). RESULTS: Of the 10 cases, case A had a history of a temporary stay in Wuhan and transmitted the virus to the others through family gathering, living together, and sharing vehicles. The average age was 56.5 years (\u00b1 11.16), six patients were males, and the incubation period was 2-14 days. Dry cough was the main symptom, followed by fever and fatigue. Most patients were clinically classified as ordinary-type, with three cases being severe-type. Chest computed tomography results were nonspecific, mainly with ground-glass attenuation and/or shadow images. Extensive lesion distribution was seen in severe cases. CD4+ lymphocyte counts were 61, 180, and 348 cells/uL in severe-type patients, respectively. Notably, viral nucleic acid values in nasopharyngeal swabs were lower (19, 25, and 26) than those of ordinary-type patients, suggesting a higher viral load. Neutrophil-lymphocyte ratio (NLR) was also higher in severe-type patients CONCLUSIONS: Initial examination results of lower CD4+ lymphocyte counts and RT-PCR-CT values coupled with higher NLR may indicate the severity of COVID-19 infection for these family clusters.", "doc_id": "24wyajfj"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Clinical and radiological features of novel coronavirus pneumonia", "abstract": "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.", "doc_id": "8nnc5qkq"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "[Clinical features of 2019 novel coronavirus pneumonia in the early stage from a fever clinic in Beijing]", "abstract": "Objective: To summarize and analyze the clinical and imaging characteristics of patients with 2019 novel coronavirus pneumonia in the early stage in Beijing. Methods: A retrospective analysis of clinical and imaging data of 9 patients with 2019 novel coronavirus infection diagnosed in one fever clinicic in Beijing from January 18, 2020 to February 3, 2020. Results: 5 male and 4 female was included in those 9 patients, whose median age was 36 years, and the age range from 15 to 49 years. 8 of these patients had no underlying disease and one suffered from diabetes. 7 patients had a history of travel to Wuhan City or Hubei Province, and one patient was a medical staff. Two family clustered was found. The incubation period was 1 to 6 days. The clinical manifestations were fever in 8 cases (8/9) , dry cough in 5 cases (5/9) , pharyngalgia in 4 cases (4/9) , fatigue in 4 cases (4/9) , body soreness in 4 cases (4/9) , and blocked or watery nose in 1 case (1/9) . Six patients (6/9) had abnormal cell peripheral blood, of which 3 (3/9) had an increased monocyte count, 2 (2/9) had a reduced lymphocyte , and 1 (1/9) had an increased leukocyte count, while the 3 patients had normal cell blood routines. The median of CRP was 16.3 mg/L, including 5 patients with slightly elevated (5/9) , 4 patients with normal values (4/9) . the results of procalcitonin test were negative in5 patients. Three patients were examined by chest X-ray examination, one of which was normal, one case showed infiltrates of right upper lung, and another showed in right lower lung. All patients underwent chest HRCT. And 7 cases (7/9) showed multiple ground glass exudation, including 5 cases (5/7) involved bilateral lungs, 2 cases (2/7) involved unilateral lung, 3 cases (3/7) with patchy consolidation, and 2 cases (2/9) showed no abnormality. Conclusions: The patents with 2019 novel coronavirus pneumonia in this study generally have an epidemiological history. The clinical manifestations are fever and cough. Peripheral white blood cell counts were most normal And PCT were all negative. Chest HRCT manifested as multiple ground-glass opacities with partly consolidation. Some patients had normal chest radiographs but HRCT showed pneumonia. Some patients had no pneumonia on chest HRCT.", "doc_id": "34vw7ttc"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Clinical Insights into the Gastrointestinal Manifestations of COVID-19", "abstract": "The month of December 2019 became a critical part of the time of humanity when the first case of coronavirus disease 2019 (COVID-19) was reported in the Wuhan, Hubei Province in China. As of April 13th, 2020, there have been approximately 1.9 million cases and 199,000 deaths across the world, which were associated with COVID-19. The COVID-19 is the seventh coronavirus to be identified to infect humans. In the past, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome were the two coronaviruses that infected humans with a high fatality, particularly among the elderly. Fatalities due to COVID-19 are higher in patients older than 50 years of age or those with multimorbid conditions. The COVID-19 is mainly transmitted through respiratory droplets, with the most common symptoms being high fever, cough, myalgia, atypical symptoms included sputum production, headache, hemoptysis and diarrhea. However, the incubation period can range from 2 to 14 days without any symptoms. It is particularly true with gastrointestinal (GI) symptoms in which patients can still shed the virus even after pulmonary symptoms have resolved. Given the high percentage of COVID-19 patients that present with GI symptoms (e.g., nausea and diarrhea), screening patients for GI symptoms remain essential. Recently, cases of fecal-oral transmission of COVID-19 have been confirmed in the USA and China, indicating that the virus can replicate in both the respiratory and digestive tract. Moreover, the epidemiology, clinical characteristics, diagnostic procedures, treatments and prevention of the gastrointestinal manifestations of COVID-19 remain to be elucidated.", "doc_id": "43ngt2qc"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "COVID-19 is a Real Headache!", "abstract": "After the emergence of a novel coronavirus named SARS-CoV-2, coronavirus disease 2019 (COVID-19) was initially characterized by fever, sore throat, cough, and dyspnea, mainly manifestations of respiratory system. However, other manifestations such as headache, abdominal pain, diarrhea, loss of taste and smell were added to the clinical spectrum, during the course of the COVID-19 pandemic. The reports on the neurological findings are increasing rapidly and headache seems to be the leader on the symptom list. Headache was reported in 11%-34% of the hospitalized COVID-19 patients, but clinical features of these headaches were totally missing in available publications. According to our initial experience, significant features of headache presentation in the symptomatic COVID-19 patients were new-onset, moderate-severe, bilateral headache with pulsating or pressing quality in the temporoparietal, forehead or periorbital region. The most striking features of the headache were sudden to gradual onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID-19. Symptomatic COVID-19 patients, around 6%-10%, also reported headache as a presenting symptom. The possible pathophysiological mechanisms of headache include activation of peripheral trigeminal nerve endings by the SARS-CoV-2 directly or through the vasculopathy and/or increased circulating pro-inflammatory cytokines and hypoxia. We concluded that as a common non-respiratory symptom of COVID-19, headache should not be overlooked, and its characteristics should be recorded with scrutiny.", "doc_id": "a722r9va"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Novel coronavirus pneumonia combined with viral conjunctivitis: three cases report/ \u4e2d\u534e\u5b9e\u9a8c\u773c\u79d1\u6742\u5fd7", "abstract": "Since January 2020, as ophthalmologists working at the center of the novel coronavirus pneumonia (NCP) outbreak in Wuhan, China, we found 3 cases in 30 NCP patients with binocular conjunctivitis. Of them, one case visited for conjunctivitis as a first symptom and then diagnosed as NCP, and two cases visited for binocular conjunctivitis during the NCP onset. In 3 patients, conjunctivitis was manifested as signs of viral conjunctivitis from mild to moderate. Their symptoms of two patients disappeared after treatment with antiviral eyedrops for 7 to 10 days and another patient died of NCP. Interestingly,although we detected positive viral nucleic acid in the conjunctiva sacs of 2 of other 27 NCP patients by using swabs and RT-PCR technology, no conjunctivitis occurred in these two patients.", "doc_id": "4alt7h2y"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "COVID-19: Focus on the lungs but do not forget the gastrointestinal tract", "abstract": "The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared in the last weeks as global pandemic. Currently affecting more than 5 000 000 individuals worldwide, COVID-19 is most commonly associated with symptoms caused by the acute respiratory distress syndrome (ARDS). As the number of infected individuals increases, we are learning that not only lungs, but also other organs can be affected by the virus. The gastrointestinal symptoms, for example diarrhoea, vomiting, nausea or abdominal pain, are frequent in patients with COVID-19. Moreover, alimentary tract symptoms may precede the respiratory presentation of SARS-CoV-2 infection. This can lead to delayed diagnosis and inappropriate management of infected patients. In addition, SARS-CoV-2 nucleic acid can be detected in faeces of infected patients and rectal swabs are even reported to remain positive for a longer period of time than nasopharyngeal swabs. Here, we aim to provide an update on the gastrointestinal involvement of COVID-19 presenting the symptoms that can be encountered in infected patients. We address the role of angiotensin-converting enzyme 2 (ACE2), as a functional receptor for SARS-CoV-2, which also was found in the gastrointestinal tract. Finally, we briefly discuss faecal shedding of SARS-CoV-2 and its potential role in the pathogenesis of the disease.", "doc_id": "6d4ygjfa"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Neurological manifestations and neuro-invasive mechanisms of the severe acute respiratory syndrome coronavirus type 2", "abstract": "BACKGROUND AND PURPOSE: Infections with coronaviruses are not always confined to the respiratory tract and various neurological manifestations have been reported. The aim of this study was to perform a review to describe neurological manifestations in patients with COVID-19 and possible neuro-invasive mechanisms of Sars-CoV-2. METHODS: PubMed, Web of Science and COVID-dedicated databases were searched for the combination of COVID-19 terminology and neurology terminology up to 10 May 2020. Social media channels were followed up between 15 March and 10 May 2020 for postings with the same scope. Neurological manifestations were extracted from the identified papers and combined to provide a useful summary for the neurologist in clinical practice. RESULTS: Neurological manifestations potentially related to COVID-19 have been reported in large studies, case series and case reports and include acute cerebrovascular diseases, impaired consciousness, cranial nerve manifestations and autoimmune disorders such as the Guillain-Barr\u00e9 syndrome often present in patients with more severe COVID-19. Cranial nerve symptoms such as olfactory and gustatory dysfunctions are highly prevalent in patients with mild to moderate COVID-19 even without associated nasal symptoms and often present in an early stage of the disease. CONCLUSION: Physicians should be aware of the neurological manifestations in patients with COVID-19, especially when rapid clinical deterioration occurs. The neurological symptoms in COVID-19 patients may be due to direct viral neurological injury or indirect neuroinflammatory and autoimmune mechanisms. No antiviral treatments against the virus or vaccines for its prevention are available and the long-term consequences of the infection on human health remain uncertain especially with regard to the neurological system.", "doc_id": "6krqeqva"} {"topic_name": "coronavirus early symptoms", "topic_id": "26", "title": "Coronavirus disease 2019 presenting with conjunctivitis as the first symptom", "abstract": "", "doc_id": "9c38uqr9"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic Patients with Novel Coronavirus Disease (COVID-19)", "abstract": "", "doc_id": "1ix7mtxd"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Characteristics of SARS-CoV-2 isolated from asymptomatic carrier in Tokyo.", "abstract": "", "doc_id": "d43l86od"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "[Potential false-positive rate among the 'asymptomatic infected individuals' in close contacts of COVID-19 patients].", "abstract": "Objective: As the prevention and control of COVID-19continues to advance, the active nucleic acid test screening in the close contacts of the patients has been carrying out in many parts of China. However, the false-positive rate of positive results in the screening has not been reported up to now. But to clearify the false-positive rate during screening is important in COVID-19 control and prevention. Methods: Point values and reasonable ranges of the indicators which impact the false-positive rate of positive results were estimated based on the information available to us at present. The false-positive rate of positive results in the active screening was deduced, and univariate and multivariate-probabilistic sensitivity analyses were performed to understand the robustness of the findings. Results: When the infection rate of the close contacts and the sensitivity and specificity of reported results were taken as the point estimates, the positive predictive value of the active screening was only 19.67%, in contrast, the false-positive rate of positive results was 80.33%. The multivariate-probabilistic sensitivity analysis results supported the base-case findings, with a 75% probability for the false-positive rate of positive results over 47%. Conclusions: In the close contacts of COVID-19 patients, nearly half or even more of the 'asymptomatic infected individuals' reported in the active nucleic acid test screening might be false positives.", "doc_id": "5t4twnpm"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "[Asymptomatic and pre-symptomatic cases of COVID-19 contribution to spreading the epidemic and need for targeted control strategies].", "abstract": "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.", "doc_id": "ghasrwqc"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Pre-Procedural Surveillance Testing for SARS-CoV-2 in an Asymptomatic Population in the Seattle Region Shows Low Rates of Positivity.", "abstract": "Seattle region hospitals have been impacted for several months by community spread of the coronavirus disease of 2019 (COVID-19).\u2026.", "doc_id": "5t62i01v"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Comparison of clinical and epidemiological characteristics of asymptomatic and symptomatic SARS-CoV-2 infection: A multi-center study in Sichuan Province, China.", "abstract": "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.", "doc_id": "gqb0rr5t"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Covid-19: Nine in 10 pregnant women with infection when admitted for delivery are asymptomatic, small study finds.", "abstract": "", "doc_id": "baiim35r"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "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.", "abstract": "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.", "doc_id": "coac0tz3"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "[Analysis of the first cluster of cases in a family of COVID-19 in Gansu Province].", "abstract": "The epidemiological history and clinical characteristics of 7 cases of COVID-19 and 1 case of close contact in the first family aggregation epidemic of COVID-19 in Gansu Province were analyzed. The first patient A developed on January 22, 2020, with a history of residence in Wuhan, and confirmed severe cases of NCP on January 24, 2020; patient B, on January 23, 2020, diagnosed on January 31, severe cases; patient C, asymptomatic, diagnosed on January 27; patient D, asymptomatic, diagnosed on January 27; patient E, on January 24, diagnosed on January 28; patient F, asymptomatic, diagnosed on January 31; Patient G was asymptomatic and was diagnosed on January 31. In close contact, H was asymptomatic, PCR test was negative and asymptomatic, and he was discharged early. Among the 7 patients, 1 case died of (B) aggravation, and the other patients' condition was effectively controlled after active treatment. Except for the discharged cases, 5 cases were positive for COVID-19 specific IgM antibody and 1 case was negative. In this clustering outbreak, 4 patients remained asymptomatic, but PCR and IgM antibodies were positive, indicating that asymptomatic patients may be the key point to control the epidemic. Specific IgM antibody screening for patients whose pharyngeal swab nucleic acid test is negative but with ground glass-like lung lesions is very important for early detection and early isolation.", "doc_id": "lnb1e9iy"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "[Screening and management of asymptomatic infection of corona virus disease 2019 (COVID-19)].", "abstract": "To date, the controlling of outbreak of corona virus disease 2019 (COVID-19) has entered into a critical period in China. Recently, work resumption and public place is planning to open outside of Hubei, suggesting an uncertain and complex development of the epidemic in the next stage. Few days ago, we conducted a study on the epidemiological and clinical characteristics of asymptomatic infections of COVID-19, and found them might be the infection source. We believe that the findings are critical for developing public health intervention strategies for controlling COVID-19 infection in the future. Screening among the high-risk population and improving the sensitivity of measurement may contribute to the detection and management of asymptomatic infection.", "doc_id": "hkm8yspk"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Delivery in asymptomatic Italian woman with SARS-CoV-2 infection", "abstract": "", "doc_id": "jnq52q6v"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Profiling pre-symptomatic and asymptomatic cases with confirmed SARS-CoV-2 infection in Mexico City", "abstract": "IMPORTANCE: Asymptomatic SARS-CoV-2 infections are potential sources for transmission; characterization of these cases has not been conducted in most low/middle income countries, including Mexico. OBJECTIVE: To profile pre-symptomatic/asymptomatic SARS-CoV-2 infections in Mexico City, its associated comorbidities and outcomes. DESIGN: Prospective observational study SETTING: Subjects assessed by convenience sampling within the National Epidemiological Surveillance System in Mexico City. PARTICIPANTS: Subjects with and without respiratory and non-respiratory symptoms (RS, NRS, respectively) assessed for SARS-CoV-2 using real time RT-PCR from nasopharyngeal swabs. OUTCOMES: Severe COVID-19, intensive care unit admission, 30-day mortality and their outcomes in cases RS or NRS and asymptomatic cases. RESULTS: Amongst 60121 cases with confirmed SARS-CoV-2 infection as of July 1st, 2020, we identified 5982 cases without RS (9.9%) and 2452 who were asymptomatic at first evaluation (4.1%). Compared to cases with RS, NRS and asymptomatic cases were younger and had lower rates of comorbidities. Cases with NRS had higher rates of severe COVID-19 outcomes including hospitalization, ICU admission, and intubation (p<0.001). Mortality was higher for cases with NRS (HR 3.13, 95%CI 1.80-5.45) or RS (HR 7.58, 95%CI 4.56-12.58) compared to asymptomatic cases, adjusted for age, sex and comorbidities. Predictors for mortality in cases without RS included older age, previous exposure to suspected viral infection cases, comorbidities, presence of NRS and vomiting. For asymptomatic SARS-Co-V-2 infections, chronic kidney disease, previous exposure with suspected infection cases and older age were predictors for lethality. CONCLUSIONS AND RELEVANCE: Definition of pre-symptomatic/asymptomatic cases has relevant implications for SARS-CoV-2 infection outcomes. Older age and comorbidity impact on the probability of developing severe complications for cases who were asymptomatic or had only NRS at evaluation and were sent for domiciliary treatment. Extending testing for detection of asymptomatic cases must be considered in Mexico to better understand the impact of the pandemic.", "doc_id": "2umm65yq"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "A simple SIR model with a large set of asymptomatic infectives", "abstract": "There is increasing evidence that one of the most difficult problems in trying to control the ongoing COVID-19 epidemic is the presence of a large cohort of asymptomatic infectives. We develop a SIR-type model taking into account the presence of asymptomatic, or however undetected, infective, and the substantially long time these spend being infective and not isolated. We discuss how a SIR-based prediction of the epidemic course based on early data but not taking into account the presence of a large set of asymptomatic infectives would give wrong estimate of very relevant quantities such as the need of hospital beds, the time to the epidemic peak, and the number of people which are left untouched by the first wave and thus in danger in case of a second epidemic wave. In the second part of the note, we apply our model to the COVID-19 epidemics in Italy. We obtain a good agreement with epidemiological data; according to the best fit of epidemiological data in terms of this model, only 10\\% of infectives in Italy is symptomatic.", "doc_id": "32qxyxgj"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Visualizing the invisible: The effect of asymptomatic transmission on the outbreak dynamics of COVID-19", "abstract": "Understanding the outbreak dynamics of the COVID-19 pandemic has important implications for successful containment and mitigation strategies. Recent studies suggest that the population prevalence of SARS-CoV-2 antibodies, a proxy for the number of asymptomatic cases, could be an order of magnitude larger than expected from the number of reported symptomatic cases. Knowing the precise prevalence and contagiousness of asymptomatic transmission is critical to estimate the overall dimension and pandemic potential of COVID-19. However, at this stage, the effect of the asymptomatic population, its size, and its outbreak dynamics remain largely unknown. Here we use reported symptomatic case data in conjunction with antibody seroprevalence studies, a mathematical epidemiology model, and a Bayesian framework to infer the epidemiological characteristics of COVID-19. Our model learns, in real time, the time-varying contact rate of the outbreak, and projects the temporal evolution and credible intervals of the effective reproduction number and the symptomatic, asymptomatic, and recovered populations. Our study reveals that the outbreak dynamics of COVID-19 are sensitive to three parameters: the effective reproduction number, the ratio between the symptomatic and asymptomatic populations, and the infectious periods of both groups. For three distinct locations, Santa Clara County (CA, USA), New York City (NY, USA), and Heinsberg (NRW, Germany), our model estimates the fraction of the population that has been infected and recovered by May 13, 2020 to 6.2% (95% CI: 3.3%-9.0%), 22.7% (95% CI: 15.7%-29.8%), and 20.5% (95% CI: 17.0%-24.3%). Our method traces the initial outbreak date in Santa Clara County back to January 20, 2020 (95% CI: January 16, 2020 - January 24, 2020). Our results could significantly change our understanding and management of the COVID-19 pandemic: A large asymptomatic population will make isolation, containment, and tracing of individual cases challenging. Instead, if needed, managing community transmission through increasing population awareness, promoting physical distancing, and encouraging behavioral changes could become more relevant.", "doc_id": "1lq1n4hd"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic COVID-19 Have Longer Treatment Cycle Than Moderate Type of Confirmed Patients", "abstract": "IMPORTANCE A kind of pneumonia caused by unknown causes that occurred in Wuhan, Hubei, China in December 2019, was reported as a result of novel coronavirus infection on January 7, 2020, and then WHO named it \"COVID-19\". The comparison of epidemiological and clinical characteristics for those patients between asymptomatic COVID-19 infections and moderate type of confirmed cases is limited. OBJECTIVE To compare the difference of epidemiology and clinical characteristics between asymptomatic COVID-19 infections and moderate type of confirmed cases. DESIGN, SETTING, AND PARTICIPANTS Retrospective, single-center cohort study of COVID-19 involving 52 infections of both 26 asymptomatic and 26 moderate type of confirmed cases in the recovery stage at Guizhou Provincial Staff Hospital in Guiyang, China, from January 29, to March 31, 2020; final date of follow-up was April 22. This study was registered in Chinese Clinical Trial Registry Center. EXPOSURES Documented the asymptomatic COVID-19 infections and moderate type of confirmed cases. MAIN OUTCOMES AND MEASURES Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Epidemiological and clinical characteristics of asymptomatic COVID-19 infections and moderate type of confirmed cases were compared. RESULTS The median treatment cycle of asymptomatic COVID-19 infections was 16 days (interquartile range, 11-20 days) and longer than 13 days (interquartile range, 10-15 days) of moderate type of confirmed cases (p=0.049). The median incubation period of asymptomatic COVID-19 infections was 10 days (interquartile range, 0-21 days), while the control group was 7 days (interquartile range, 1-15 days) (p=0.27). On the initial chest computerized tomography (CT) check, 18 (69.2%, 18/26) asymptomatic COVID-19 infections were no imaging changes, which was of no significance compared with 12 (46.2%, 12/26) patients with moderate type of confirmed patients (p=0.092). CONCLUSIONS AND RELEVANCE In this single-center study, we found that asymptomatic COVID-19 infections have longer treatment cycle than those moderate type of confirmed cases.", "doc_id": "6vxc7wv0"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "The prevalence of antibodies to SARS-CoV-2 in asymptomatic healthcare workers with intensive exposure to COVID-19", "abstract": "The prevalence of asymptomatic SARS-CoV-2 infection in healthcare workers with intensive exposure to COVID-19 is unclear. In this study, we investigated the seroprevalence of SARS-CoV-2 in 797 asymptomatic healthcare workers with intensive exposure to COVID-19 patients in Wuhan, China. Positive IgG was detected from 35 asymptomatic healthcare workers, and the prevalence of antibodies to SARS-CoV-2 in asymptomatic healthcare workers was 4.39% (35/797). None of them developed COVID-19 until May 15. 33 of them have performed at least one chest CT scan showing no viral pneumonia features, and 16 have finished at least one-time SARS-CoV-2 RNA detection with negative results. When contacting with the patients, 15 of them dressed with full personal protective equipment (PPE), and 16 worn N95 mask and gown. To the best of our knowledge, this is the first investigation reported that the seroprevalence of SARS-CoV-2 was 4.39% in asymptomatic healthcare workers with applied PPE in a high epidemic area, which may provide useful information of estimating asymptomatic infection rate in general population.", "doc_id": "9e8ra3sa"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "The natural history and transmission potential of asymptomatic SARS-CoV-2 infection", "abstract": "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 centre 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 10th and April 4th, 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.", "doc_id": "js5my502"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission", "abstract": "Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3-week period (April 2020), 1,032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19) >7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B{middle dot}1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.", "doc_id": "dqc3qsw0"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Chest Computed Tomography Findings in Asymptomatic Patients with COVID-19", "abstract": "Background: Little is known about the damage to the respiratory system in asymptomatic patients with coronavirus disease (COVID-19). Objective: Herein, we evaluated the findings of chest computed tomography (CT) and radiography in patients with COVID-19 who were asymptomatic. Methods: We retrospectively investigated patients with a confirmed diagnosis of COVID-19 but who did not show any symptoms. Among the 139 patients with COVID-19 who were hospitalized, 10 (7.2%) were asymptomatic. Their chest CT and radiographic findings were analyzed. Results: In the results, all patients (100%) had ground glass opacity (GGO) on chest CT. Further, the GGO lesions were predominantly distributed peripherally and posteriorly in all patients. In 9 (90%) patients, the GGO lesions were combined with reticular opacity. Air-bronchogram due to bronchiolectasis surrounded by GGO was observed in 8 patients (80%). Additionally, the lung lesions were dominant on the right side in all patients. Conclusions: In conclusion, considering our results that the lung is affected in asymptomatic patients, it will be necessary to extend the indications of COVID-19 testing for effective management of COVID-19 during the pandemic.", "doc_id": "4hfmst53"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic animal traders prove positive for SARS virus.", "abstract": "", "doc_id": "8goh28zu"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Seroprevalence of IgG antibodies to SARS-coronavirus in asymptomatic or subclinical population groups.", "abstract": "We systematically reviewed the current understanding of human population immunity against SARS-CoV in different groups, settings and geography. Our meta-analysis, which included all identified studies except those on wild animal handlers, yielded an overall seroprevalence of 0.10% [95% confidence interval (CI) 0.02-0.18]. Health-care workers and others who had close contact with SARS patients had a slightly higher degree of seroconversion (0.23%, 95% CI 0.02-0.45) compared to healthy blood donors, others from the general community or non-SARS patients recruited from the health-care setting (0.16%, 95% CI 0-0.37). When analysed by the two broad classes of testing procedures, it is clear that serial confirmatory test protocols resulted in a much lower estimate (0.050%, 95% CI 0-0.15) than single test protocols (0.20%, 95% CI 0.06-0.34). Potential epidemiological and laboratory pitfalls are also discussed as they may give rise to false or inconsistent results in measuring the seroprevalence of IgG antibodies to SARS-CoV.", "doc_id": "j8ta21zr"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "COVID-19 Pneumonia in Asymptomatic Trauma Patients; Report of 8 Cases.", "abstract": "We are currently involved in the novel coronavirus 2019 (COVID-19) pandemic. A considerable number of COVID-19 infected cases are asymptomatic but they can transmit the disease to others, especially healthcare workers. In this study, we reported 8 incidentally detected cases of COVID-19 pneumonia in chest computed tomography (CT) scan of patients referred to emergency department following multiple trauma without any respiratory symptoms.", "doc_id": "ldamulbe"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Epidemiological and clinical features of asymptomatic patients with SARS-CoV-2 infection", "abstract": "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.", "doc_id": "dud6dzp6"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "COVID-19: asymptomatic carrier transmission is an underestimated problem", "abstract": "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.", "doc_id": "32jaz3vz"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic and Human-to-Human Transmission of SARS-CoV-2 in a 2-Family Cluster, Xuzhou, China", "abstract": "We report epidemiologic, laboratory, and clinical findings for 7 patients with 2019 novel coronavirus disease in a 2-family cluster. Our study confirms asymptomatic and human-to-human transmission through close contacts in familial and hospital settings. These findings might also serve as a practical reference for clinical diagnosis and medical treatment.", "doc_id": "axg1t0ue"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic COVID-19 infection in late pregnancy indicated no vertical transmission", "abstract": "This study is to investigate the clinical characteristics of late pregnancy with asymptomatic 2019 novel coronavirus disease (COVID-19) infection, evaluate the outcome of maternal and fetal prognosis, and identify the evidence of intrauterine vertical transmission. A 22-years-old pregnant woman with asymptomatic COVID-19 infection who was admitted to our hospital on 11 February 2020 was enrolled in this study. Clinical data including laboratory test results and chest computed tomography (CT) scanning were collected and reviewed. Diagnosis of late pregnancy with asymptomatic COVID-19 infection was made. Lumbar anesthesia for cesarean section was performed and a female baby was delivered uneventfully, with the Apgar score of 9 to 10 points. Three times of COVID-19 nucleic acid test for the baby was negative after delivery. The puerpera returned to normal after the operation and two times of throat swab COVID-19 nucleic acid test were all negative after antiviral therapy. We reported an asymptomatic COVID-19 pregnant woman with detailed clinical information and our result indicated that for late pregnant women with asymptomatic COVID-19 infection, there might be no intrauterine infection caused by vertical transmission.", "doc_id": "j20vjioo"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Hazardous Postoperative Outcomes of Unexpected COVID-19 Infected Patients: A Call for Global Consideration of Sampling All Asymptomatic Patients Before Surgical Treatment", "abstract": "", "doc_id": "1txzs78c"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Intraoperative Diagnosis of Coronavirus Disease 2019 in an Asymptomatic Patient: A Case Report", "abstract": "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.", "doc_id": "d06wt817"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic COVID-19 infection in pregnant woman in the third trimester: a case report/ \u4e2d\u534e\u56f4\u4ea7\u533b\u5b66\u6742\u5fd7", "abstract": "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'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.", "doc_id": "c4r277bi"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic patients as a source of COVID-19 infections: A systematic review and meta-analysis", "abstract": "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\u00ae and Google\u00ae (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 \u00b1 17.17 years) than patients with abnormal radiology (39.14 \u00b1 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.", "doc_id": "59a0v3sg"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic COVID-19 Patients Can Contaminate Their Surroundings: an Environment Sampling Study", "abstract": "The contamination of patients' surroundings by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains understudied. We sampled the surroundings and the air of six negative-pressure non-intensive care unit (non-ICU) rooms in a designated isolation ward in Chengdu, China, that were occupied by 13 laboratory-confirmed coronavirus disease 2019 (COVID-19) patients who had returned from overseas travel, including 2 asymptomatic patients. A total of 44 of 112 (39.3%) surface samples were positive for SARS-CoV-2 as detected by real-time PCR, suggesting extensive contamination, although all of the air samples were negative. In particular, in a single room occupied by an asymptomatic patient, four sites were SARS-CoV-2 positive, highlighting that asymptomatic COVID-19 patients do contaminate their surroundings and impose risks for others with close contact. Placement of COVID-19 patients in rooms with negative pressure may bring a false feeling of safety, and the importance of rigorous environment cleaning should be emphasized.IMPORTANCE Although it has been well recognized that the virus SARS-CoV-2, the causative agent of COVID-19, can be acquired by exposure to fomites, surprisingly, the contamination of patients' surroundings by SARS-CoV-2 is largely unknown, as there have been few studies. We performed an environmental sampling study for 13 laboratory-confirmed COVID-19 patients and found extensive contamination of patients' surroundings. In particular, we found that asymptomatic COVID-19 patients contaminated their surroundings and therefore imposed risks for other people. Environment cleaning should be emphasized in negative-pressure rooms. The findings may be useful to guide infection control practice to protect health care workers.", "doc_id": "azwu5ay9"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Comparison of clinical and epidemiological characteristics of asymptomatic and symptomatic SARS-CoV-2 infection: A multi-center study in Sichuan Province, China", "abstract": "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.", "doc_id": "h3fnztro"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Covid-19: Nine in 10 pregnant women with infection when admitted for delivery are asymptomatic, small study finds", "abstract": "", "doc_id": "3zyyjtkc"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "The time scale of asymptomatic transmission affects estimates of epidemic potential in the COVID-19 outbreak", "abstract": "The role of asymptomatic carriers in transmission poses challenges for control of the COVID-19 pandemic. Study of asymptomatic transmission and implications for surveillance and disease burden are ongoing, but there has been little study of the implications of asymptomatic transmission on dynamics of disease. We use a mathematical framework to evaluate expected effects of asymptomatic transmission on the basic reproduction number R0 (i.e., the expected number of secondary cases generated by an average primary case in a fully susceptible population) and the fraction of new secondary cases attributable to asymptomatic individuals. If the generation-interval distribution of asymptomatic transmission differs from that of symptomatic transmission, then estimates of the basic reproduction number which do not explicitly account for asymptomatic cases may be systematically biased. Specifically, if asymptomatic cases have a shorter generation interval than symptomatic cases, R0 will be over-estimated, and if they have a longer generation interval, R0 will be under-estimated. Estimates of the realized proportion of asymptomatic transmission during the exponential phase also depend on asymptomatic generation intervals. Our analysis shows that understanding the temporal course of asymptomatic transmission can be important for assessing the importance of this route of transmission, and for disease dynamics. This provides an additional motivation for investigating both the importance and relative duration of asymptomatic transmission.", "doc_id": "b2f0pn3l"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "The relative transmissibility of asymptomatic COVID-19 infections among close contacts", "abstract": "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.", "doc_id": "cca7gzjq"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "How the asymptomatic population is influencing the COVID-19 outbreak in India?", "abstract": "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.", "doc_id": "2ohq74mq"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Challenges of managing the asymptomatic carriers of SARS-CoV-2", "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 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.", "doc_id": "27z0z409"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Covid-19: identifying and isolating asymptomatic people helped eliminate virus in Italian village", "abstract": "", "doc_id": "jf91xz2x"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, China", "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.", "doc_id": "ffs350f2"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic transmission during the COVID-19 pandemic and implications for public health strategies", "abstract": "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.", "doc_id": "6ua5txjc"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic COVID-19: What the Neuroradiologist Needs to Know about Pulmonary Manifestations", "abstract": "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.", "doc_id": "5j6uu16i"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "The assessment of transmission efficiency and latent infection period on asymptomatic carriers of SARS-CoV-2 infection", "abstract": "Few studies aimed on the transmission efficiency of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A follow-up study was performed on 147 asymptomatic carriers in Anhui Province. Of 147 asymptomatic carriers, 50.0% were male, 50.3% cases were older than 40 years, and 43.8% were farmers, 68.7% cases were from north of Anhui Province. There were 16 asymptomatic carriers developed illness in the following 14 days isolated observation, and diagnosed as confirmed cases. The possible latent infection period was evaluated ranged from one to five days before onset, and the median time was two days. The second attack rate of 16 confirmed cases whom transferred from asymptomatic carriers was 9.7% (23/236), while 131 asymptomatic carriers caused 2.6% (24/914) close contacts infection, there was a significant difference of second attack rate among two groups (P\u00ef\u00bc\u009c0.001). Our study indicated that COVID-19 cases are contagious during the incubation period, and the close contact screening should be covered the incubation period. Furthermore, the transmission efficiency of asymptomatic carriers was lower than that of confirmed cases.", "doc_id": "2d21mbr5"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "FDG PET/CT Findings in an Asymptomatic Case of Confirmed COVID-19", "abstract": "In the current and rapidly worsening pandemic, patients with COVID-19 may undergo imaging with FDG PET/CT. Because a significant proportion of infected patients may be asymptomatic, incidental discovery on a PET/CT scan performed for unrelated reasons can occur. Because of the highly infectious nature of this agent, it is important that interpreting physicians be aware of the typical imaging findings to identify potentially affected patients. We present the case of an asymptomatic patient referred for FDG PET/CT imaging of a lung nodule who demonstrated the typical CT findings of COVID-19 infection and was subsequently found to be positive on testing.", "doc_id": "9j8apdl6"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Covid-19: four fifths of cases are asymptomatic, China figures indicate", "abstract": "", "doc_id": "ai1x7cue"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "An Asymptomatic Patient with COVID-19", "abstract": "", "doc_id": "a235uvsc"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan, China", "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\u00b110.82 days, and was significantly longer in progression patients (28.60\u00b17.55 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.", "doc_id": "5daqr7ff"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic case of Covid-19 in an infant with cystic fibrosis", "abstract": "", "doc_id": "g3bcykft"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic cases with SARS-CoV-2 infection", "abstract": "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.", "doc_id": "0r8vo1fa"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Epidemiological and Clinical Characteristics of 26 Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Carriers", "abstract": "BACKGROUND: We retrospectively analyzed 26 persistently asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carriers. METHODS: Epidemiological and clinical characteristics from the 26 asymptomatic patients with positive results for SARS-CoV-2 ribonucleic acid testing were obtained. RESULTS: Twenty-two patients (84.6%) correlated with clustering occurrence. The median period from contact to diagnosis and the last positive nucleic acid test was 19 (8-24 days) and 21.5 days (10-36 days), respectively. The median period from diagnosis to negative nucleic acid test was significantly different between patients with normal or atypical chest computed tomography (CT) findings (n\u00e2\u0080 =\u00e2\u0080 16, 61.5%; 7.5 days [2-20 days]) and patients with typical ground-glass or patchy opacities on CT (n\u00e2\u0080 =\u00e2\u0080 10, 38.5%; 12.5 days [8-22 days]; P\u00e2\u0080 <\u00e2\u0080 .01). Seven patients (70.0%) with initial positive nucleic acid test results had a negative result simultaneously with improved CT findings. Obvious improvement in CT findings was observed in 3 patients (30.0%) despite positive nucleic acid test results. CONCLUSIONS: In asymptomatic patients, changes in biochemical and inflammatory variables are small and changes on chest CT can occur. It is worth noting that the long existence of SARS-CoV-2 in some asymptomatic patients and false-negative results need to be considered in SARS-CoV-2 nucleic acid test.", "doc_id": "j7l6yomy"} {"topic_name": "coronavirus asymptomatic", "topic_id": "27", "title": "Asymptomatic SARS-CoV-2 Infection in Household Contacts of a Healthcare Provider, Wuhan, China", "abstract": "We found that all 5 asymptomatic household contacts of a Wuhan, China, physician with coronavirus disease had severe acute respiratory syndrome coronavirus 2 detected by PCR. The index patient and 2 contacts also had abnormal chest computed tomography scans. Asymptomatic infected household contacts of healthcare workers with coronavirus disease might be underrecognized.", "doc_id": "3as2o2y5"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Hydroxychloroquine-associated QT interval prolongation", "abstract": "", "doc_id": "79ruujhu"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Hydroxychloroquine: Corrected QT interval prolongation, first degree atrioventricular block and left bundle branch block during an off-label treatment with hydroxychloroquine for COVID-19 pneumonia: 3 case reports", "abstract": "", "doc_id": "cpkmdhup"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Hydroxychloroquine: QTc prolongation following off-label-use: case report", "abstract": "", "doc_id": "0piwihfs"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Hydroxychloroquine and Potential Drug Interactions in Older Adults", "abstract": "", "doc_id": "2s4yspi3"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Repurposing of well-known medications as antivirals: hydroxychloroquine and chloroquine; from HIV-1 infection to COVID-19.", "abstract": "INTRODUCTION Chloroquine (CQ) and hydroxychloroquine (HCQ), originally were prescribed for prevention or treatment of malaria, but now successfully are used in several rheumatologic diseases. In addition, in recent decades considering their immunomodulatory effects, high tolerably and low cost, they are evaluated for various viral infections from HIV to COVID-19. AREAS COVERED In this review we tried to summarize all available studies on HCQ and CQ efficacy for management of viral infections and the probable mechanisms of action. The data were collected by searching \"Hydroxychloroquine\", \"Choloroquine\", \"Viral infection\", and names of various viral infections in PubMed/MEDLINE, Scopus, and Google Scholar databases from commencement to June 2020. Out of 95 search results, 74 most relevant works were gathered. EXPERT OPINION HCQ/CQ showed acceptable efficacy in HIV especially as an adjuvant treatment beside routine HAART. However, for some viral infections such as ZIKA, EBOLA, SARS-CoV and MERS-CoV, human studies are lacking. In the COVID-19 pandemic, in vitro and preliminary human studies showed encouraging findings. However, later well-designed trials and retrospective studies with large sample size, not only reported non-significant efficacy but also showed more cardiac adverse reactions. Alkalinisation of acid vesicles is the most important mechanism of action.", "doc_id": "1x5bhtx7"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Research towards treating COVID-19.", "abstract": "", "doc_id": "5j40679w"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).", "abstract": "Importance Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. Objective To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. Design, Setting, and Participants This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. Main Outcomes and Measures Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. Results Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (3%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. Conclusions and Relevance In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.", "doc_id": "2qwk2z22"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Caution Needed on the Use of Chloroquine and Hydroxychloroquine for Coronavirus Disease 2019.", "abstract": "", "doc_id": "1na6ony7"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Covid-19: US gives emergency approval to hydroxychloroquine despite lack of evidence.", "abstract": "", "doc_id": "cdx5glzj"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Hydroxychloroquine against COVID-19: A critical appraisal of the existing evidence.", "abstract": "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.", "doc_id": "an28gfe4"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Hydroxychloroquine reduces the risk of covid-19 in patients with rheumatic diseases: myth or reality?", "abstract": "", "doc_id": "1z9n6hyl"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Facts and myths: Efficacies of repurposing chloroquine and hydroxychloroquine for the treatment of COVID-19.", "abstract": "The emergence of coronavirus disease 2019 (COVID-19) is caused by the 2019 novel coronavirus (2019-nCoV). The 2019-nCoV first broke out in Wuhan and subsequently spreads worldwide owing to its extreme transmission efficiency. The fact that the COVID-19 cases and mortalities are reported in globally and the WHO has declared this outbreak as the pandemic. The international health authorities have focused on rapid diagnosis and isolation of patients as well as search for therapies able to counter the disease severity. Due to the lack of known specific, effective and proven therapies as well as the situation of public-health emergency, drug repurposing appears to be the best armour to find therapeutic solution against 2019-nCoV infection. Repurposing anti-malarial drugs, chloroquine (CQ)/ hydroxychloroquine (HCQ) have shown efficacy to inhibit most coronaviruses, including SARS-CoV-1 coronavirus. These CQ analogues have shown potential efficacy to inhibit 2019-nCoV in vitro that lead to focus in several future clinical trials. This review discusses the possible effective roles and mechanisms of CQ analogues for interfering with the 2019-nCoV replication cycle and infection.", "doc_id": "6itoktmg"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Annals On Call - COVID-19: Is Chloroquine the Answer?", "abstract": "", "doc_id": "1b4qkn36"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Chloroquine and hydroxychloroquine to treat COVID-19: between hope and caution.", "abstract": "", "doc_id": "awhpp498"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Evidence of protective effect of hydroxychloroquine to prevent COVID-19.", "abstract": "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].\"", "doc_id": "4ch5dmj8"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "An independent appraisal and re-analysis of hydroxychloroquine treatment trial for COVID-19.", "abstract": "", "doc_id": "2clz993c"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin.", "abstract": "", "doc_id": "766c0l35"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring", "abstract": "Background: Despite a paucity of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected COVID-19. Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods: We performed a case series of COVID-19 positive/suspected patients admitted between 2/1/2020 and 4/4/2020 who were treated with azithromycin, hydroxychloroquine or a combination. We evaluated baseline and post-medication QT interval (QTc, Bazett) using 12-lead ECGs. Critical QTc prolongation was defined as: a) maximum QTc [\u2265]500 ms (if QRS <120 ms) or QTc [\u2265]550 (if QRS [\u2265]120 ms) and b) increased QTc of [\u2265]60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Results: Of 490 COVID-19 positive/suspected patients, 314 (64%) received either/both drugs, and 98 (73 COVID-19 positive, 25 suspected) met study criteria (age 62{+/-}17 yrs, 61% male). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448{+/-}29 ms and increased to 459{+/-}36ms (p=0.005) with medications. Significant prolongation was observed only in men (18{+/-}43 ms vs -0.2{+/-}28 ms in women, p=0.02). 12% of patients reached critical QTc prolongation. In a multivariable logistic regression, age, sex, Tisdale score, Elixhauser score, and baseline QTc were not associated with critical QTc prolongation (p>0.14). Changes in QTc were highest with the combination compared to either drug, with many-fold greater prolongation with the combination vs. azithromycin alone (17{+/-}39 vs. 0.5{+/-}40 ms, p=0.07). No patients manifested torsades de pointes. Conclusions: Overall, 12% of patients manifested critical QTc interval prolongation, and traditional risk indices failed to flag these patients. With the drug combination, QTc prolongation was several-fold higher compared to azithromycin alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients with these drugs should be carefully assessed prior to use.", "doc_id": "6qz40fnv"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Hydroxychloroquine and azithromycin as potential treatments for COVID-19;clinical status impacts the outcome", "abstract": "", "doc_id": "84ci8h6p"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "A short therapeutic regimen based on hydroxychloroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissions and complications.", "abstract": "The new SARS-CoV-2 infection named COVID-19 has severely hit our Health System. At the time of writing this paper no medical therapy is officially recommended or has shown results in improving the outcomes in COVID-19 patients. With the aim of diminishing the impact in Hospital admissions and reducing the number of medical complications, we implemented a strategy based on a Hospital Home-Care Unit (HHCU) using an easy-to-use treatment based on an oral administration regimen outside the hospital with hydroxychloroquine (HCQ) plus azithromycin (AZM) for a short period of 5 days. Patients and methods: Patients [\u2265] 18 years old visiting the emergency room at the Hospital Universitario San Pedro de Logrono (La Rioja) between March, 31st and April, 12th diagnosed with COVID-19 with confirmed SARS-CoV-2 infection by a specific PCR, as follows: Patients with pneumonia (CURB [\u2264] 1) who did not present severe comorbidities and had no processes that contraindicated this therapeutic regime. Olygosimptomatic patients without pneumonia aged [\u2265] 55 years. Patients [\u2265] 18 years old without pneumonia with significant comorbidities. We excluded patients with known allergies to some of the antimicrobials used and patients treated with other drugs that increase the QTc or with QTc >450msc. The therapeutic regime was: HCQ 400 mg every twice in a loading dose followed by 200 mg twice for 5 days, plus AZM 500 mg on the first day followed by 250 mg daily for 5 days. A daily telephone follow-up was carried out from the hospital by the same physician. The end-points of our study were: 1.- To measure the need for hospital admission within 15 days after the start of treatment. 2.- To measure the need to be admitted to the intensive care unit (ICU) within 15 days after the start of the treatment. 3.- To describe the severity of the clinical complications developed. 4.- To measure the mortality within 30 days after starting treatment (differentiating if the cause is COVID-19 or something else). 5.-To describe the safety and adverse effects of the therapeutic regime. Results: During the 13 days studied a total of 502 patients were attended in the emergency room due to COVID-19. Forty-two were sent at home; 80 were attended by the HHCU (patients on this study) and 380 were admitted to the Hospital. In our series there were a group of 69 (85.18%) patients diagnosed with pneumonia (37 males and 32 females). Most of them, 57 (82.60%) had a CURB65 score of <1 (average age 49) and 12 (17.40%) a CURB score of 1 (average age 63). Eighteen (22.50%) of the pneumonia patients also had some morbidity as a risk factor. 11 patients (13.75%) without pneumonia were admitted to the HHCU because comorbidities or age [\u2265] 55 years. Six patients with pneumonia had to be hospitalized during the observation period, 3 of them because side effects and 3 because of worsening. One of these patients, with morbid obesity and asthma, had clinical worsening needing mechanical ventilation at ICU and developed acute distress respiratory syndrome. With the exception of the patient admitted to the ICU, the rest of the patients were discharged at home in the following 8 days (3 to 8 days). Twelve patients (15%), 11 of whom had pneumonia, experienced side effects affecting mainly the digestive. In another patient a QTc interval prolongation (452 msc) was observed. In total 3 of these patients had to be admitted in the Hospital, 2 because of vomiting and 1 because a QTc interval lengthening. None of the patients needed to stop the HCQ or AZM and all the 80 patients finished the therapeutic strategy. From the group without pneumonia only a patient developed diarrhea that did not require hospitalization or stop the medication. Conclusions: Our strategy has been associated with a reduction in the burden of hospital pressure, and it seems to be successful in terms of the number of patients who have developed serious complications and / or death. None of the patients died in the studied period and only 6 have to be admitted in conventional hospitalization area.", "doc_id": "2igc5wzx"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxychloroquine therapy", "abstract": "Background: Hydroxychloroquine is currently being tested as post-exposure prophylaxis against coronavirus disease 2019 (COVID-19) in several ongoing clinical trials. Objective: To compare the incidence of COVID-19 in Spanish patients with autoimmune rheumatic diseases treated with and without hydroxychloroquine. Methods: Retrospective electronic record review, from February 27th to April 16th, of patients with autoimmune inflammatory diseases followed at two academic tertiary care hospitals in Seville, Spain. The cumulative incidence of COVID-19, confirmed or suspected, was compared between patients with and without hydroxychloroquine as part of their treatment of autoimmune inflammatory diseases. Results: Among 722 included subjects, 290 (40%) were receiving hydroxychloroquine. During the seven-week study period, five (1.7% [95% CI: 0.5%-4.0%] cases of COVID-19 were registered among patients with hydroxychloroquine and five (1.2% [0.4%-2.7%]) (p=0.523) in without hydroxychloroquine. COVID-19 was confirmed by PCR in one (0.3%, 95% CI 0.008-1.9%) patient with hydroxychloroquine and two (0.5%, 95% CI 0.05%-1.6%) without hydroxychloroquine (p=1.0). One patient on hydroxychloroquine and two subjects without hydroxychloroquine were admitted to the hospital, none of them required to be transferred to the intensive care unit and no patient died during the episode. Conclusions: The incidence and severity of COVID-19 among patients with autoimmune rheumatic diseases with and without hydroxychloroquine was not significantly different. Hydroxychloroquine does not seem to be an appropriate therapy for post-exposure prophylaxis against COVID-19.", "doc_id": "9whgh5b3"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "A recommendation for the use of chloroquine, hydroxychloroquine, primaquine, or tafenoquine for prophylaxis against the 2019 novel coronavirus (COVID-19) with note to the ophthalmic considerations", "abstract": "With the ongoing pandemic of infectious disease termed coronavirus disease 2019 (COVID-19) caused by the novel coronavirus identified as severe acute respiratory syndrome coronavirus 2 (SARS-C0V-2), prevention of infection and spread is critical in preventing morbidity and mortality. Prophylaxis, specifically chemoprophylaxis, is particularly critical to breaking the spread and rapid rate of increase of SARS-CoV-2. Pre-exposure and post-exposure prophylaxis are both required components of this public health measure. As the use of anti-malarial agents, specifically the 4-aminoquinolones, chloroquine and hydroxychloroquine, for the treatment of SARS-CoV-2 is now being reported, attention must be turned to their role in the chemoprophylaxis of SARS-CoV-2. In a search of the peer-reviewed medical literature (using MEDLINE and cross-referenced literature), this report is first peer-reviewed publication to present the use of these anti-malarial agents as prophylaxis against SARS-CoV-2. The ophthalmic consideration of the use of these drugs is highlighted in this report.", "doc_id": "2m08hkb7"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Outcomes of Hydroxychloroquine Treatment Among Hospitalized COVID-19 Patients in the United States- Real-World Evidence From a Federated Electronic Medical Record Network", "abstract": "On March 28, 2020, in response to the rapidly accelerating COVID-19 pandemic, U.S FDA issued emergency use authorization for hydroxychloroquine (HCQ) in hospitalized COVID-19 patients based on limited in-vitro and anecdotal clinical data. Analysis of the accumulated real-world data utilizing electronic medical records (EMR) could indicate HCQ therapy benefits as we await the results of clinical trials. However, any such analysis of retrospective observational data should account for variables such as demographics and comorbidities that could affect treatment strategies or outcomes. Therefore, we report the outcomes of HCQ treatment in a propensity-matched cohort of COVID-19 hospitalized patients. Our analysis of a large retrospective cohort of hospitalized COVID-19 patients treated with HCQ did not show benefits in mortality or the need for mechanical ventilation when compared to a matched cohort of patients who did not receive HCQ.", "doc_id": "ax4aw25i"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "QT Interval Prolongation and Torsade De Pointes in Patients with COVID-19 treated with Hydroxychloroquine/Azithromycin", "abstract": "Background: The emergence of the COVID-19 pandemic has resulted in over two million affected and over 150 thousand deaths to date. There is no known effective therapy for the disease. Initial reports suggesting the potential benefit of Hydroxychloroquine/Azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns regarding the potential risk of QT prolongation and induction of torsade de pointes (TdP). Methods: This is a multicenter retrospective study of 251 patients with COVID-19 treated with HY/AZ. We reviewed ECG tracings from baseline and until 3 days after completion of therapy to determine the progression of QTc and incidence of arrhythmia and mortality. Results: QTc prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc prolongation to > 500 ms, a known marker of high risk for TdP had developed in 15.9% of patients. One patient developed TdP requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc of patients exhibiting QTc prolongation of > 60 ms was normal. Conclusion: The combination of HY/AZ significantly prolongs the QTc in patients with COVID-19. This prolongation may be responsible for life threating arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in lights of its unproven efficacy. Strict QTc monitoring should be performed if the regimen is given.", "doc_id": "0sy3j2oc"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis", "abstract": "Abstract Importance The antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as a potential treatment for COVID-19 due their effect on several cellular processes that impact viral replication. Although more than 100 ongoing trials are testing their efficacy, CQ and HCQ are being used widely in clinical practice, exposing COVID-19 patients to potentially significant cardiac adverse effects. Objective To systematically review the literature and estimate the risk of cardiac toxicity in patients receiving CQ or HCQ for COVID-19. Data Sources A systematic search was conducted on May 27, 2020 of Ovid EBM Reviews, Ovid Embase (1974+), Ovid Medline (1946+ including epub ahead of print, in-process & other non-indexed citations), Scopus (1970+) and Web of Science (1975+) and preprint servers (Medrvix and ResearchSquare) and manual search of references lists. Study Selection Studies that included COVID-19 patients treated with CQ or HCQ, with or without azithromycin, were included as follows: (1) COVID-19 patient population, (2) the study included more than 10 patients receiving either one of the medications, (3) reported electrocardiographic changes and/or cardiac arrhythmias. Data Extraction and Synthesis Study characteristics and endpoints incidence were extracted. Due to the very low incidence of torsades de pointes (TdP) and other endpoints (rare events), the arcsine transformation was used to obtain a pooled estimate of the different incidences using a random-effects meta-analysis. Meta-regression analyses were used to assess whether the incidence of different endpoints significantly varied by multiple study-level variables specified a priori. Main Outcomes and Measures Pooled Incidence of: (1) change in QTc value from baseline [\u2265] 60 ms, (2) QTc [\u2265] 500 ms, (3) the composite of endpoint 1 and 2, (4) TdP arrhythmia or ventricular tachycardia (VT) or cardiac arrest, (5) discontinuation of treatment due to drug-induced QT prolongation or arrhythmias. Results A total of 19 studies with a total of 5652 patients were included. All included studies were of high methodological quality in terms of exposure ascertainment or outcome assessment. Among 2719 patients treated with CQ or HCQ, only two episodes of TdP were reported; the pooled incidence of TdP arrhythmia or VT or cardiac arrest was 3 per 1000, 95% CI (0-21), I2=96%, 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5%, 95% CI (1-11), I2=98%. The pooled incidence of change in QTc from baseline of [\u2265] 60 ms was 7%, 95% CI (3-14), I2=94% (12 studies of 2008 patients). The pooled incidence of QTc [\u2265] 500 ms was 6%, 95% CI (2-12), I2=95% (16 studies of 2317 patients). Among 11 studies of 3127 patients, the pooled incidence of change in QTc from baseline of [\u2265] 60 ms or QTc [\u2265] 500 ms was 9%, 95% CI (3-17), I2=97%. Mean/median age, coronary artery disease, hypertension, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations explained between-studies heterogeneity. Conclusions and Relevance Treatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation, which is a harbinger for drug-induced TdP/VT or cardiac arrest. CQ/HCQ use resulted in a relatively higher incidence of TdP as compared to drugs withdrawn from the market for this particular adverse effect. Therefore, these agents should be used only in the context of randomized clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring.", "doc_id": "62j81bq3"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Comparative in vitro transcriptomic analyses of COVID-19 candidate therapy hydroxychloroquine suggest limited immunomodulatory evidence of SARS-CoV-2 host response genes", "abstract": "Hydroxychloroquine (HCQ) has emerged as a potential and controversial antiviral candidate therapy for COVID-19. While many clinical trials are underway to test the efficacy of HCQ as a treatment for COVID-19, underlying mechanisms of HCQ in the setting of COVID-19 remain unclear. Hence, we examined differential gene expression signatures of HCQ exposure, in vitro SARS-CoV-2 infection, and host signatures of COVID-19 in blood, bronchoalveolar lavage, and postmortem lung to evaluate whether HCQ transcriptome signatures associate with restoration of SARS-CoV-2-related host transcriptional responses. Here, we show that 24 hours of in vitro treatment of peripheral blood mononuclear cells(PBMC) with HCQ significantly impacted transcription of 16 genes involved in immune regulation and lipid metabolism. Using transcriptome data from in vitro SARS-CoV-2 infected NHBE and A549 cells and PBMC derived from confirmed COVID-19 infected patients, we determined that only 0.24% of the COVID-19 PBMC differentially expressed gene set and 0.39% of the in vitro SARS-CoV-2 cells differentially expressed gene set overlapped with HCQ-related differentially expressed genes. Moreover, we observed that HCQ treatment significantly impacted transcription of 159 genes in human primary monocyte-derived macrophages involved in cholesterol biosynthetic process and chemokine activity. Notably, when we compared the macrophage HCQ-related gene lists with genes transcriptionally altered during SARS-CoV-2 infection and in bronchoalveolar lavage of COVID-19+ patients, the CXCL6 gene was impacted in all three transcriptional signatures revealing evidence in favor of chemokine modulation. HCQ-related transcriptional changes minimally overlapped with host genes altered in postmortem lung biopsies from COVID-19 participants. These results may provide insight into the immunomodulation mechanisms of HCQ treatment in the setting of COVID-19 and suggest HCQ is not a panacea to SARS-CoV-2 infection.", "doc_id": "30x26ip7"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients", "abstract": "Background: COVID-19 has rapidly emerged as a pandemic infection that has caused significant mortality and economic losses. Potential therapies and means of prophylaxis against COVID-19 are urgently needed to combat this novel infection. As a result of in vitro evidence suggesting zinc sulfate may be efficacious against COVID-19, our hospitals began using zinc sulfate as add-on therapy to hydroxychloroquine and azithromycin. We performed a retrospective observational study to compare hospital outcomes among patients who received hydroxychloroquine and azithromycin plus zinc versus hydroxychloroquine and azithromycin alone. Methods: Data was collected from electronic medical records for all patients being treated with admission dates ranging from March 2, 2020 through April 5, 2020. Initial clinical characteristics on presentation, medications given during the hospitalization, and hospital outcomes were recorded. Patients in the study were excluded if they were treated with other investigational medications. Results: The addition of zinc sulfate did not impact the length of hospitalization, duration of ventilation, or ICU duration. In univariate analyses, zinc sulfate increased the frequency of patients being discharged home, and decreased the need for ventilation, admission to the ICU, and mortality or transfer to hospice for patients who were never admitted to the ICU. After adjusting for the time at which zinc sulfate was added to our protocol, an increased frequency of being discharged home (OR 1.53, 95% CI 1.12-2.09) reduction in mortality or transfer to hospice remained significant (OR 0.449, 95% CI 0.271-0.744). Conclusion: This study provides the first in vivo evidence that zinc sulfate in combination with hydroxychloroquine may play a role in therapeutic management for COVID-19.", "doc_id": "4pcv1i3i"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Antimalarial drugs put to the test for COVID-19", "abstract": "Over 200,000 people worldwide could receive the old antimalarial drugs chloroquine and hydroxychloroquine across more than 130 clinical trials designed to treat or prevent COVID-19, according to the US clinical trials database A small study in March suggested that hydroxychloroquine plus the antibiotic azithromycin helped people with COVID-19 recover faster President Donald J Trump touted hydroxychloroquine\u2019s potential in the following weeks, spurring huge demand for the drug While some doctors prescribed it without proof, others scrambled to construct clinical studies to assess the drug\u2019s efficacy The earliest results are discouraging A team of investigators in Brazil gave chloroquine to 81 hospitalized patients;32% of those who received high doses died, compared with 15% who received the low dose (medRxiv 2020, DOI: 10 1101/2020 04 07 20056424) Separately, data analyzed from 368 people with COVID-19 at hospitals run by the US Veterans Health Administration revealed that 28% who received hydroxychloroquine and 22% who got that View: PDF ;Full Text HTML", "doc_id": "063hs3u1"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Perspectives on repositioning chloroquine and hydroxychloroquine for the treatment of Covid-19", "abstract": "Coronavirus disease 2019 (COVID-19) is now spreading as a pandemic ravaging the whole world In the absence of a vaccine and an effective antiviral chemotherapy, there is currently an intense global interest in repositioning chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) to combat the pandemic CQ has been used for decades for the treatment and prophylaxis against malaria in endemic countries It is readily available and has also been manufactured in these countries CQ is cheap, stable under field conditions and has been well tolerated as an antimalarial This experience could be adapted to deploy CQ or HCQ for prophylaxis or treatment of COVID19 if strong evidence could be generated for these uses We believe that well-designed drug trials should be initiated in malaria-endemic countries, taking into account the local context of the epidemic and the capacity of the health system in combating it In this paper, we are presenting the current status of evidence for using CQ and HCQ against COVID19", "doc_id": "85g1tp38"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Influence of conflicts of interest on public positions in the COVID-19 era, the case of Gilead Sciences", "abstract": "Fundings and gifts from the pharmaceutical industry have an influence on the decisions made by physicians and medical experts In the context of the COVID-19 epidemic, several treatments are available to treat patients infected with the virus Some are protected by patents, such as remdesivir, others are not, such as hydroxychloroquine We wanted to observe the possible correlation between the fact, for an academic doctor in infectious diseases, of having benefited from funding by Gilead Sciences, producer of remdesivir, and the public positions taken by this doctor towards hydroxychloroquine Our results show a correlation (correlation coefficient = 1) between the amount received from the Gilead Sciences company and public opposition to the use of hydroxychloroquine in France This should open up the debate on the role of the interest links of doctors with pharmaceutical companies in the medical and scientific public debate", "doc_id": "7873jkzh"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Former FDA leaders decry emergency authorization of malaria drugs for coronavirus", "abstract": "The recent Food and Drug Administration (FDA) emergency use authorization (EUA) for two malaria drugs to treat COVID-19, based on thin evidence of efficacy, has jeopardized research to learn the drugs\u2019 real value against the pandemic coronavirus, say former agency executives under President Donald Trump and former President Barack Obama They also charge that the 28 March EUA for chloroquine phosphate and hydroxychloroquine sulfate undermines FDA\u2019s scientific authority because it appeared to be a response not to scientific evidence, but to fervent advocacy of the drugs by Trump and other political figures FDA has multiple mechanisms to allow the use of unapproved, experimental drugs for small numbers of desperately ill patients outside of clinical trials Because chloroquine and hydroxychloroquine are approved for malaria, doctors could prescribe them \u201coff label\u201d for COVID-19 patients even without the EUA Since Trump first endorsed the drugs on 19 March, however, shortages have been reported, depriving some people with autoimmune disorders such as lupus who also depend on hydroxychloroquine The EUA will immediately add tens of millions of doses of the drugs for distribution to hospitalized COVID-19 patients through health care centers", "doc_id": "bnq02x8q"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study", "abstract": "Background: There is conflicting data regarding the use of hydroxychloroquine (HCQ) in COVID-19 hospitalized patients Objective: To assess the efficacy of HCQ in increasing SARS-CoV-2 viral clearance Design: Retrospective observational study Setting: Cleveland Clinic Abu Dhabi Participants: Hospitalized adult patients with confirmed SARS-CoV-2 infection Intervention: None Measurements: The primary outcome was the time from a confirmed positive nasopharyngeal swab to turn negative. A negative nasopharyngeal swab conversion was defined as a confirmed SARS-CoV-2 case followed by two negative results using RT-PCR assay with samples obtained 24 hours apart Results: 34 confirmed COVID-19 patients were included. Nineteen (55.9%) patients presented with symptoms, and 14 (41.2%) had pneumonia. Only 21 (61.8%) patients received HCQ. The time to SARS-CoV-2 negativity nasopharyngeal test was significantly longer in patients who received HCQ compared to those who did not receive HCQ (17 [13-21] vs. 10 [4-13] days, p=0.023). HCQ was independently associated with time to negativity test after adjustment for potential confounders (symptoms, pneumonia or oxygen therapy) in multivariable linear regression analysis. On day 14, 47.8% (14/23) patients tested negative in the HCQ group compared to 90.9% (10/11) patients who did not receive HCQ (p=0.016). Limitations: Small sample size and retrospective design with a potential risk of selection bias Conclusion: HCQ was associated with a slower viral clearance in COVID-19 patients with mild to moderate disease. Data from ongoing randomized clinical trials with HCQ should provide a definitive answer regarding the efficacy and safety of this treatment.", "doc_id": "9b88lizj"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "[Potential harms associated with 4-aminoquinoline treatment].", "abstract": "Hydroxychloroquine and chloroquine are currently being evaluated as treatment against COVID-19. These drugs are associated with some potential harms, including QTc-interval prolongation, hypoglycaemia, severe skin reactions and psychiatric effects. Use of hydroxychloroquine or chloroquine should be reserved to current indications or clinical trials, as recommended by several governmental medical products agencies.", "doc_id": "8wgg86qc"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Hydroxychloroquine for COVID-19: What is our Current State of Knowledge?", "abstract": "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.", "doc_id": "b6aeu1ph"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Risk of using hydroxychloroquine as a treatment of COVID-19", "abstract": "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.", "doc_id": "ccbcpfaz"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "COVID-19 in Patient with Sarcoidosis Receiving Long-Term Hydroxychloroquine Treatment, France, 2020", "abstract": "Because of in vitro studies, hydroxychloroquine is under evaluation as a preexposure or postexposure prophylaxis for coronavirus disease (COVID-19) and as a possible COVID-19 curative treatment. We report a case of COVID-19 in a patient with sarcoidosis who was receiving long-term hydroxychloroquine treatment, despite adequate plasma concentrations.", "doc_id": "d612wsh3"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State", "abstract": "Importance: Hydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events. Objective: To describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19. Design, Setting, and Participants: Retrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020. Exposures: Receipt of both hydroxychloroquine and azithromycin, hydroxychloroquine alone, azithromycin alone, or neither. Main Outcomes and Measures: Primary outcome was in-hospital mortality. Secondary outcomes were cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation). Results: Among 1438 hospitalized patients with a diagnosis of COVID-19 (858 [59.7%] male, median age, 63 years), those receiving hydroxychloroquine, azithromycin, or both were more likely than those not receiving either drug to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O2 saturation lower than 90%, and aspartate aminotransferase greater than 40 U/L. Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). In logistic models, compared with patients receiving neither drug cardiac arrest was significantly more likely in patients receiving hydroxychloroquine + azithromycin (adjusted OR, 2.13 [95% CI, 1.12-4.05]), but not hydroxychloroquine alone (adjusted OR, 1.91 [95% CI, 0.96-3.81]) or azithromycin alone (adjusted OR, 0.64 [95% CI, 0.27-1.56]), . In adjusted logistic regression models, there were no significant differences in the relative likelihood of abnormal electrocardiogram findings. Conclusions and Relevance: Among patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. However, the interpretation of these findings may be limited by the observational design.", "doc_id": "2bl0q0b1"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Eritema multiforme inducido por hidroxicloroquina en paciente con COVID-19./ Eritema multiforme inducido por hidroxicloroquina en paciente con COVID-19./ Hydroxychloroquine-induced erythema multiforme in a patient with COVID-19", "abstract": "", "doc_id": "1zutvba1"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Chloroquine and hydroxychloroquine for COVID-19: A word of caution", "abstract": "", "doc_id": "8qohdj5i"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "COVID-19 coronavirus research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine", "abstract": "OBJECTIVES/BACKGROUND AND OBJECTIVES: Prior epidemics of high-mortality human coronaviruses, such as the acute respiratory syndrome coronavirus (SARS-CoV or SARS-1) in 2003, have driven the characterization of compounds that could be possibly active against the currently emerging novel coronavirus SARS-CoV-2 (COVID-19). Presently, no approved treatment or prophylaxis is available for COVID-19. We comment on the existing COVID-19 research methodologies in general and the published reporting. Given the media attention and claims of effectiveness, we chose chloroquine and hydroxychloroquine, in combination with azithromycin, as an area of COVID-19 research to examine. METHODS/STUDY DESIGN AND SETTING: MEDLINE and EMBASE electronic databases were searched from 2019 to present (April 3rd, 2020) using a mix of keywords such as COVID-19 and chloroquine and hydroxychloroquine. We also searched the largest clinical medicine preprint repository, medRxiv.org. RESULTS: We found 6 studies, 3 randomized control trials and 3 observational studies, focusing on chloroquine and hydroxychloroquine (with azithromycin). We critically appraised the evidence. CONCLUSION: We found that the COVID-19 research methodology is very poor in the area of chloroquine/hydroxychloroquine research. In screening the literature, we observed the same across COVID-19 research in relation to potential treatments. The reporting is very poor and sparse, and patient-important outcomes needed to discern decision-making priorities are not reported. We do understand the barriers to perform rigorous research in health care settings overwhelmed by a novel deadly disease. However, this emergency pandemic situation does not transform flawed methods and data into credible results. The adequately powered, comparative, and robust clinical research that is needed for optimal evidence-informed decision-making remains absent in COVID-19.", "doc_id": "5w1q57v2"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Recommendations for the measurement of the QT interval during the use of drugs for COVID-19 infection treatment. Updatable in accordance with the availability of new evidence", "abstract": "COVID-19 infection has shown rapid growth worldwide, and different therapies have been proposed for treatment, in particular, the combination of immune response modulating drugs such as chloroquine and hydroxychloroquine (antimalarials) alone or in combination with azithromycin. Although the clinical evidence supporting their use is scarce, the off label use of these drugs has spread very quickly in face of the progression of the epidemic and the high mortality rate in susceptible populations. However, these medications can pathologically prolong the QT interval and lead to malignant ventricular arrhythmias such that organized guidance on QT evaluation and management strategies are important to reduce morbidity associated with the potential large-scale use.", "doc_id": "2dlkd91k"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Of chloroquine and COVID-19", "abstract": "Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.", "doc_id": "cht8jcpc"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19)", "abstract": "Importance: Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. Objective: To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. Design, Setting, and Participants: This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. Main Outcomes and Measures: Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. Results: Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (3%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. Conclusions and Relevance: In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.", "doc_id": "9ojr7oic"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Chloroquine and Hydroxychloroquine in the Era of SARS - CoV2: Caution on Their Cardiac Toxicity", "abstract": "", "doc_id": "6brgbjol"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Does pandemic justify the use of hydroxychloroquine for treatment and prevention of COVID-19 in India?", "abstract": "", "doc_id": "12ikum8s"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Antiretroviral HIV drugs in COVID-19 research: promises and risks. An opinion piece", "abstract": "The unprecedented global scale of COVID-19 globally has triggered a race to discover interventions to reduce associated morbidity and mortality and rapid release of research findings prior to any degree of critical review. As with previous novel infection outbreaks, antiretrovirals are just one drug class that has been held up as a potential strategy for prophylaxis and treatment with scant evidence and risk of harm. Here we summarise the evidence for antiretrovirals to treat COVID-19 and, as a drug that has also been studied in HIV, hydroxychloroquine, and flag some of the pitfalls of using therapies that have not been evaluated robustly.", "doc_id": "2vik7mwl"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Can hydroxychloroquine protect patients with rheumatic diseases from COVID-19? Response to: 'Does hydroxychloroquine prevent the transmission of COVID-19?' by Heldwein and Calado and 'SLE, hydroxychloroquine and no SLE patients with COVID-19: a comment' by Joob and Wiwanitkit", "abstract": "", "doc_id": "dam2gyoe"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "CORRIGENDUM to Emergency Approval of Chloroquine and Hydroxychloroquine for Treatment of COVID-19 (updated to Emergency Authorization of Chloroquine and Hydroxychloroquine for Treatment of COVID-19)", "abstract": "", "doc_id": "4jyy8498"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Hydroxychloroquine against COVID-19: A critical appraisal of the existing evidence", "abstract": "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.", "doc_id": "5jafu8tw"} {"topic_name": "coronavirus hydroxychloroquine", "topic_id": "28", "title": "Serious adverse drug reactions with hydroxychloroquine: a pharmacovigilance study in Vigibase\u00ae", "abstract": "", "doc_id": "2hwnocp4"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Structure-based drug designing and immunoinformatics approach for SARS-CoV-2", "abstract": "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.", "doc_id": "ty27die9"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "The COVID-19 Gene and Drug Set Library", "abstract": "The coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 (COVID-19) pandemic has received rapid response by the research community to offer suggestions for repurposing of approved drugs as well as to improve our understanding of the COVID-19 viral life cycle molecular mechanisms. In a short period, tens of thousands of research preprints and other publications have emerged including those that report lists of experimentally validated drugs and compounds as potential COVID-19 therapies. In addition, gene sets from interacting COVID-19 virus-host proteins and differentially expressed genes when comparing infected to uninfected cells are being published at a fast rate. To organize this rapidly accumulating knowledge, we developed the COVID-19 Gene and Drug Set Library (https://amp.pharm.mssm.edu/covid19/), a collection of gene and drug sets related to COVID-19 research from multiple sources. The COVID-19 Gene and Drug Set Library is delivered as a web-based interface that enables users to view, download, analyze, visualize, and contribute gene and drug sets related to COVID-19 research. To evaluate the content of the library, we performed several analyses including comparing the results from 6 in-vitro drug screens for COVID-19 repurposing candidates. Surprisingly, we observe little overlap across these initial screens. The most common and unique hit across these screen is mefloquine, a malaria drug that should receive more attention as a potential therapeutic for COVID-19. Overall, the library of gene and drug sets can be used to identify community consensus, make researchers and clinicians aware of the development of new potential therapies, as well as allow the research community to work together towards a cure for COVID-19.", "doc_id": "ps7nl8ns"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Coronavirus disease 2019: a clinical review.", "abstract": "In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in Wuhan, China, and it subsequently spread in many countries around the world. Many efforts have been applied to control and prevent the spread of COVID-19, and many scientific studies have been conducted in a short period of time. Here we present an overview of the viral structure, pathogenesis, diagnosis, and clinical features of COVID-19 based on the current state of knowledge, and we compare its clinical characteristics with SARS and Middle East Respiratory Syndrome (MERS). Current researches on potentially effective treatment alternatives are discussed. We hope this review can help medical workers and researchers around the world contain the current COVID-19 pandemic.", "doc_id": "xzylsle9"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications.", "abstract": "Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID-19. By describing the life cycle of the newly emergent coronavirus, SARS-CoV-2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID-19. Moreover, we propose that Niemann-Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS-CoV-2, by highlighting key established features of the disorder that together result in an \"unfavorable\" host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID-19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC-like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID-19.", "doc_id": "5t1mefcs"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Novel Drugs Targeting the SARS-CoV-2/COVID-19 Machinery.", "abstract": "Like other human pathogenic viruses, coronavirus SARS-CoV-2 employs sophisticated macromolecular machines for viral host cell entry, genome replication and protein processing. Such machinery encompasses SARS-CoV-2 envelope spike (S) glycoprotein required for host cell entry by binding to the ACE2 receptor, viral RNA-dependent RNA polymerase (RdRp) and 3-chymotrypsin-like main protease (3Clpro/Mpro). Under the pressure of the accelerating COVID-19 pandemic caused by the outbreak of SARSCoV- 2 in Wuhan, China in December 2019, novel and repurposed drugs were recently designed and identified for targeting the SARS-CoV-2 reproduction machinery, with the aim to limit spread of SARS-CoV-2 and morbidity and mortality of the COVID-19 pandemic.", "doc_id": "91pm9ffj"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Repurposing Nimesulide, a Potent Inhibitor of the B0AT1 Subunit of the SARS-CoV-2 Receptor, as a Therapeutic Adjuvant of COVID-19.", "abstract": "The global pandemic caused by the SARS-CoV-2 infection is a health emergency that needs to be addressed immediately. The international scientific community, following World Health Organization (WHO) indications, launched different trials for testing drugs putatively able to block the SARS-CoV-2 infection or treat the COVID-19 disease symptoms. In parallel, studies devoted to a better understanding of SARS-CoV-2 biology are in the course for designing an effective vaccine. One of the human membrane proteins known to be docked by the virus is angiotensin-converting enzyme 2 (ACE2), proposed to be responsible for viral entry in target cells. Recently, the 3D structure of ACE2 has been obtained, showing its physical interaction with B0AT1 (SLC6A19), a plasma membrane transporter involved in the trafficking of amino acids in cells. The receptor targeted by SARS-CoV-2 is a supercomplex formed by a dimer of ACE2-B0AT1, in which ACE2 binds the viral protein and B0AT1 stabilizes the heterodimer. As a serendipity occurrence, nimesulide was shown to abolish the transport function of B0AT1. Here we suggest including nimesulide in the list of drugs to be tested for the identification of co-adjuvants in the treatment of COVID-19.", "doc_id": "62iqyk0r"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Structural Basis of the SARS-CoV-2/SARS-CoV Receptor Binding and Small-Molecule Blockers as Potential Therapeutics.", "abstract": "Over the past two decades, deadly coronaviruses have caused major challenges to public health, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2, 2019) pandemic. The path for virus invasion into humans and other hosts is mediated by \"host-pathogen\" interactions, specifically, virus-receptor binding. An in-depth understanding of the virus-receptor binding mechanism is a prerequisite for the discovery of vaccines, antibodies, and/or small-molecule inhibitors that can interrupt this interaction and prevent or cure infection. In this review, we discuss the viral entry mechanism, the known structural aspects of virus-receptor interactions (SARS-CoV-2 S/humanACE2, SARS-CoV S/humanACE2, and MERS-CoV S/humanDPP4), the key protein domains and amino acid residues involved in binding, and the small-molecule inhibitors and other drugs that have (as of June, 2020) exhibited therapeutic potential. Specifically, we review the potential clinical utility of two transmembrane serine protease 2 (TMPRSS2)-targeting protease inhibitors, nafamostat mesylate and camostat mesylate, as well as two novel potent fusion inhibitors and the repurposed Ebola drug, remdesivir, which is specific to RdRp, against human coronaviruses, including SARS-CoV-2. This article has been accepted for publication on June 23, 2020. Changes may still occur before final publication. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "doc_id": "tw2nls29"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Therapeutic dilemma in the repression of severe acute respiratory syndrome coronavirus-2 proteome.", "abstract": "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.", "doc_id": "btk6u9j4"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Coronavirus puts drug repurposing on the fast track.", "abstract": "", "doc_id": "l76lspvx"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "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.", "abstract": "A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has expanded the number of highly pathogenic coronaviruses affecting humans. The 2019-nCoV 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 2019-nCoV 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 2019-nCoV; 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 2019-nCoV, and that domain 288-330 of S1 protein from the 2019-nCoV represents promising therapeutic and/or vaccine target.", "doc_id": "vogum3ir"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Biophysical modeling of the SARS-CoV-2 viral cycle reveals ideal antiviral targets", "abstract": "Effective therapies for COVID-19 are urgently needed. Presently there are more than 800 COVID-19 clinical trials globally, many with drug combinations, resulting in an empirical process with an enormous number of possible combinations. To identify the most promising potential therapies, we developed a biophysical model for the SARS-CoV-2 viral cycle and performed a sensitivity analysis for individual model parameters and all possible pairwise parameter changes (162 = 256 possibilities). We found that model-predicted virion production is fairly insensitive to changes in most viral entry, assembly, and release parameters, but highly sensitive to some viral transcription and translation parameters. Furthermore, we found a cooperative benefit to pairwise targeting of transcription and translation, predicting that combined targeting of these processes will be especially effective in inhibiting viral production.", "doc_id": "rbvpwe90"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Lessons learned from SARS-CoV and MERS-CoV: FDA-approved Abelson tyrosine-protein kinase 2 inhibitors may help us combat SARS-CoV-2", "abstract": "", "doc_id": "50yohq7p"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Glycoinformatics approach for identifying target positions to inhibit initial binding of SARS-CoV-2 S1 protein to the host cell", "abstract": "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 \u03b1-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.", "doc_id": "x8jgcqts"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Identifying SARS-CoV-2 entry inhibitors through drug repurposing screens of SARS- S and MERS-S pseudotyped particles", "abstract": "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.", "doc_id": "n1aphggl"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Network pharmacology studies on the effect of Chai-Ling decoction in coronavirus disease 2019", "abstract": "Background: Chai-Ling decoction (CLD), derived from a modification of Xiao-Chai-Hu (XCH) decoction and Wu-Ling-San (WLS) decoction, has been used to treat the early-stage of coronavirus disease 2019 (COVID-19). However, the mechanisms of CLD in COVID-19 remain unknown. In this study, the potential mechanisms of CLD in COVID-19 were preliminarily investigated based on network pharmacology and molecular docking method. Methods: Initially, the active components and targets of CLD were screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper database. The targets of COVID-19 were obtained from GeneCards database. The protein-protein interaction network was established using STRING database to analyze the key targets. Gene Oncology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes analysis were also conducted to evaluate the pathways related to the targets of CLD on COVID-19. Moreover, the compound-target-pathway network was established using Cytoscape 3.2.7. Subsequently, the molecular docking method was performed to select the active compounds with high binding affinity on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2), which is the key target of SARS-CoV-2 in entering target cells. The possible binding sites were also visualized by a three-dimensional graph. Results: Network pharmacology analysis showed that there were 106 active components and 160 targets of CLD. Additionally, 251 targets related to COVID-19 were identified, and 24 candidates of CLD on COVID-19 were selected. A total of 283 GO terms of CLD on COVID-19 were identified, and 181 pathways were screened based on GO and Kyoto Encyclopedia of Genes and Genomes analyses. CLD might alleviate the inflammatory response and improve lung injury to treat COVID-19 through interleukin 17 signaling, T helper cell 17 differentiation, tumor necrosis factor signaling, and hypoxia inducible factor-1 signaling. Besides, molecular docking indicated that beta-sitosterol, kaempferol, and stigmasterol were the top three candidates in CLD with the highest affinity to SARS-CoV-2 and ACE2. Conclusion: Our study identifies the potential mechanisms of CLD on COVID-19 and beta-sitosterol, kaempferol, and stigmasterol may be the key compounds that exert antiviral effects against SARS-CoV-2.", "doc_id": "xaindhzs"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "An update on therapeutic repurposing strategies for COVID-19", "abstract": "The severe acute respiratory syndrome coronavirus 2, well known as COVID-19 has become the current health distress to the entire world. In the pandemic scenario the research on the rapid development of new drug molecules is highly risky and tedious process. The current COVID-19 emergency demands an urgent development of possible strategies to protect people at high risk of infection and hence the drug repurposing became an emerging approach to fight COVID-19. This review summarizes an update on various therapeutic strategies with special attention on repurposing of drugs to fight against SARS-CoV-2 worldwide. The investigation of existing drugs for new therapeutic purposes is one line of scientific research followed to develop safe and effective COVID-19 treatments. Broad-spectrum antiviral agents (BSAAs) that have been believed to be safe through testing on early phase clinical trials have been hyped as good drug repurposing candidates. Broad-spectrum antiviral drugs such as Ribavirin, Umifenovir were advised for COVID-19 treatment. Some antibiotics may be repurposed as COVID-19 treatments such as teicoplanin, oritavancin, dalbavancin, monensin and azithromycin. Ivermectin an antiparasitic is recently repurposed. Hydroxychloroquine and chloroquine, having immunomodulating effect on humans, have been shown to have antiviral activity at starting and post-entry stages of the SARS-CoV-2 infection. There is a need for global health emergency to call for a courageous, global response at the political and governmental levels. Therefore, the regulatory agencies must act swiftly to lessen any financial obstacles involving private companies and update guidelines for drug licenses by repurposing if necessary.", "doc_id": "9idkf0i9"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV", "abstract": "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\u20133. 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.", "doc_id": "zf096duh"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Targeted Oxidation Strategy (TOS) for Potential Inhibition of Coronaviruses by Disulfiram \u2014 a 70-Year Old Anti-Alcoholism Drug", "abstract": "In the new millennium, the outbreak of new coronavirus has happened three times: SARS-CoV, MERS-CoV, and 2019-nCoV Unfortunately, we still have no pharmaceutical weapons against the diseases caused by these viruses The pandemic of 2019-nCoV reminds us of the urgency to search new drugs with totally different mechanism that may target the weaknesses specific to coronaviruses Herein, we disclose a new targeted oxidation strategy (TOS II) leveraging non-covalent interactions potentially to oxidize and inhibit the activities of cytosolic thiol proteins via thiol/thiolate oxidation to disulfide (TOD) Quantum mechanical calculations show encouraging results supporting the feasibility to selectively oxidize thiol of targeted proteins via TOS II even in relatively reducing cytosolic microenvironments Molecular docking against the two thiol proteases Mpro and PLpro of 2019-nCoV provide evidence to support a TOS II mechanism for two experimentally identified anti-2019-nCoV disulfide oxidants: disulfiram and PX-12 Remarkably, disulfiram is an anti-alcoholism drug approved by FDA 70 years ago, thus it can be immediately used in phase III clinical trial for anti-2019-nCoV treatment Finally, a preliminary list of promising TOS II drug candidates targeting the two thiol proteases of 2019-nCoV are proposed upon virtual screening of 32143 disulfides", "doc_id": "7dah95yc"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "COVID-19: Living through Another Pandemic", "abstract": "Novel beta-coronavirus SARS-CoV-2 is the pathogenic agent responsible for coronavirus disease-2019 (COVID-19), a globally pandemic infectious disease. Due to its high virulence and the absence of immunity among the general population, SARS-CoV-2 has quickly spread to all countries. This pandemic highlights the urgent unmet need to expand and focus our research tools on what are considered \"neglected infectious diseases\" and to prepare for future inevitable pandemics. This global emergency has generated unprecedented momentum and scientific efforts around the globe unifying scientists from academia, government and the pharmaceutical industry to accelerate the discovery of vaccines and treatments. Herein, we shed light on the virus structure and life cycle and the potential therapeutic targets in SARS-CoV-2 and briefly refer to both active and passive immunization modalities, drug repurposing focused on speed to market, and novel agents against specific viral targets as therapeutic interventions for COVID-19.", "doc_id": "m4gq1z41"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications", "abstract": "Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID-19. By describing the life cycle of the newly emergent coronavirus, SARS-CoV-2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID-19. Moreover, we propose that Niemann-Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS-CoV-2, by highlighting key established features of the disorder that together result in an \"unfavorable\" host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID-19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC-like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID-19.", "doc_id": "7rsx6cah"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "The Landscape of Human Cancer Proteins Targeted by SARS-CoV-2", "abstract": "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.", "doc_id": "2cvvkrx9"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Repurposing cefuroxime for treatment of COVID-19: a scoping review of in silico studies", "abstract": "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 19 (COVID-19), is a novel human Coronavirus that is responsible for about 300,000 deaths worldwide. To date, there is no confirmed treatment or vaccine prevention strategy against COVID-19. Due to the urgent need for effective treatment, drug repurposing is regarded as the immediate option. Potential drugs can often be identified via in silico drug screening experiments. Consequently, there has been an explosion of in silico experiments to find drug candidates or investigate anecdotal claims. One drug with several anecdotal accounts of benefit is Cefuroxime. The aim of this study was to identify and summarize in silico evidence for possible activity of Cefuroxime against SARS-CoV-2.To this end, we performed a scoping review of literature of in silico drug repurposing experiments for SARS-CoV-2 using PRISMA-ScR. We searched Medline, Embase, Scopus, Web of Knowledge, and Google Scholar for original studies published between 1st Feb, 2020 and 15th May, 2020 that screened drug libraries, and identified Cefuroxime as a top-ranked potential inhibitor drug against SARS-CoV-2 proteins. Six studies were identified. These studies reported Cefuroxime as a potential inhibitor of 3 key SARS-CoV-2 proteins; main protease, RNA dependent RNA polymerase, and ACE2-Spike complex. We provided a summary of the methodology and findings of the identified studies. Our scoping review identified significant in silico evidence that Cefuroxime may be a potential multi-target inhibitor of SARS-CoV-2. Further in vitro and in vivo studies are required to evaluate the potential of Cefuroxime for COVID-19.Communicated by Ramaswamy H. Sarma.", "doc_id": "xui8cfzv"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "The pharmacological development of direct acting agents for emerging needed therapy against SARS-CoV-2", "abstract": "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.", "doc_id": "d978skhv"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Network Medicine Framework for Identifying Drug Repurposing Opportunities for COVID-19", "abstract": "The COVID-19 pandemic demands the rapid identification of drug-repurpusing candidates. In the past decade, network medicine had developed a framework consisting of a series of quantitative approaches and predictive tools to study host-pathogen interactions, unveil the molecular mechanisms of the infection, identify comorbidities as well as rapidly detect drug repurpusing candidates. Here, we adapt the network-based toolset to COVID-19, recovering the primary pulmonary manifestations of the virus in the lung as well as observed comorbidities associated with cardiovascular diseases. We predict that the virus can manifest itself in other tissues, such as the reproductive system, and brain regions, moreover we predict neurological comorbidities. We build on these findings to deploy three network-based drug repurposing strategies, relying on network proximity, diffusion, and AI-based metrics, allowing to rank all approved drugs based on their likely efficacy for COVID-19 patients, aggregate all predictions, and, thereby to arrive at 81 promising repurposing candidates. We validate the accuracy of our predictions using drugs currently in clinical trials, and an expression-based validation of selected candidates suggests that these drugs, with known toxicities and side effects, could be moved to clinical trials rapidly.", "doc_id": "b36wi464"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus", "abstract": "OBJECTIVE: In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia. METHODS: There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction. In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb. RESULTS: Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response. CONCLUSION: Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.", "doc_id": "hedqnoma"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Potential therapeutic targets and promising drugs for combating SARS-CoV-2", "abstract": "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.", "doc_id": "zl1d3gf2"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Novel Drugs Targeting the SARS-CoV-2/COVID-19 Machinery", "abstract": "Like other human pathogenic viruses, coronavirus SARS-CoV-2 employs sophisticated macromolecular machines for viral host cell entry, genome replication and protein processing. Such machinery encompasses SARS-CoV-2 envelope spike (S) glycoprotein required for host cell entry by binding to the ACE2 receptor, viral RNA-dependent RNA polymerase (RdRp) and 3-chymotrypsin-like main protease (3Clpro/Mpro). Under the pressure of the accelerating COVID-19 pandemic caused by the outbreak of SARSCoV- 2 in Wuhan, China in December 2019, novel and repurposed drugs were recently designed and identified for targeting the SARS-CoV-2 reproduction machinery, with the aim to limit spread of SARS-CoV-2 and morbidity and mortality of the COVID-19 pandemic.", "doc_id": "pqooh65g"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Perspectives for repurposing drugs for the coronavirus disease 2019", "abstract": "The newly emerged 2019 novel coronavirus (CoV), named as severe acute respiratory syndrome CoV-2 (SARS-CoV-2), like SARS-CoV (now, SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV), has been associated with high infection rates with over 36,405 deaths. In the absence of approved marketed drugs against coronaviruses, the treatment and management of this novel CoV disease (COVID-19) worldwide is a challenge. Drug repurposing that has emerged as an effective drug discovery approach from earlier approved drugs could reduce the time and cost compared to de novo drug discovery. Direct virus-targeted antiviral agents target specific nucleic acid or proteins of the virus while host-based antivirals target either the host innate immune responses or the cellular machineries that are crucial for viral infection. Both the approaches necessarily interfere with viral pathogenesis. Here we summarize the present status of both virus-based and host-based drug repurposing perspectives for coronaviruses in general and the SARS-CoV-2 in particular.", "doc_id": "hcj8fylw"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China", "abstract": "A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain, providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s).", "doc_id": "t9gbq4yu"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "COVID-19 Drug Discovery Using Intensive Approaches", "abstract": "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.", "doc_id": "64ff1ksc"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Predicting potential drug targets and repurposable drugs for COVID-19 via a deep generative model for graphs", "abstract": "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.", "doc_id": "2lmwnfda"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Structural Basis of the SARS-CoV-2/SARS-CoV Receptor Binding and Small-Molecule Blockers as Potential Therapeutics", "abstract": "Over the past two decades, deadly coronaviruses have caused major challenges to public health, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2, 2019) pandemic. The path for virus invasion into humans and other hosts is mediated by \"host-pathogen\" interactions, specifically, virus-receptor binding. An in-depth understanding of the virus-receptor binding mechanism is a prerequisite for the discovery of vaccines, antibodies, and/or small-molecule inhibitors that can interrupt this interaction and prevent or cure infection. In this review, we discuss the viral entry mechanism, the known structural aspects of virus-receptor interactions (SARS-CoV-2 S/humanACE2, SARS-CoV S/humanACE2, and MERS-CoV S/humanDPP4), the key protein domains and amino acid residues involved in binding, and the small-molecule inhibitors and other drugs that have (as of June, 2020) exhibited therapeutic potential. Specifically, we review the potential clinical utility of two transmembrane serine protease 2 (TMPRSS2)-targeting protease inhibitors, nafamostat mesylate and camostat mesylate, as well as two novel potent fusion inhibitors and the repurposed Ebola drug, remdesivir, which is specific to RdRp, against human coronaviruses, including SARS-CoV-2. This article has been accepted for publication on June 23, 2020. Changes may still occur before final publication. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "doc_id": "nbc07tf7"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Protein-ligand interaction study to identify potential dietary compounds binding at the active site of therapeutic target proteins of SARS-CoV-2", "abstract": "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.", "doc_id": "28wu1oyy"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin", "abstract": "The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health.Communicated by Ramaswamy H. Sarma.", "doc_id": "bha6pl7o"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Molecular Investigation of SARS-CoV-2 Proteins and Their Interactions with Antiviral Drugs", "abstract": "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.", "doc_id": "jg9vlpu1"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Coronavirus membrane fusion mechanism offers a potential target for antiviral development", "abstract": "The coronavirus disease 2019 (COVID-19) pandemic has focused attention on the need to develop effective therapies against the causative agent, SARS-CoV-2, and also against other pathogenic coronaviruses (CoV) that have emerged in the past or might appear in future. Researchers are therefore focusing on steps in the CoV replication cycle that may be vulnerable to inhibition by broad-spectrum or specific antiviral agents. The conserved nature of the fusion domain and mechanism across the CoV family make it a valuable target to elucidate and develop pan-CoV therapeutics. In this article, we review the role of the CoV spike protein in mediating fusion of the viral and host cell membranes, summarizing the results of research on SARS-CoV, MERS-CoV, and recent peer-reviewed studies of SARS-CoV-2, and suggest that the fusion mechanism be investigated as a potential antiviral target. We also provide a supplemental file containing background information on the biology, epidemiology, and clinical features of all human-infecting coronaviruses, along with a phylogenetic tree of these coronaviruses.", "doc_id": "ktkq5cmt"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Identification of a druggable binding pocket in the spike protein reveals a key site for existing drugs potentially capable of combating Covid-19 infectivity", "abstract": "BACKGROUND: Following the recent outbreak of the new coronavirus pandemic (Covid-19), the rapid determination of the structure of the homo-trimeric spike glycoprotein has prompted the study reported here. The aims were to identify potential \"druggable\" binding pockets in the protein and, if located, to virtual screen pharmaceutical agents currently in use for predicted affinity to these pockets which might be useful to restrict, reduce, or inhibit the infectivity of the virion. RESULTS: Our analyses of this structure have revealed a key potentially druggable pocket where it might be viable to bind pharmaceutical agents to inhibit its ability to infect human cells. This pocket is found at the inter-chain interface that exists between two domains prior to the virion binding to human Angiotensin Converting Enzyme 2 (ACE2) protein. One of these domains is the highly mobile receptor binding domain, which must move into position to interact with ACE2, which is an essential feature for viral entry to the host cell. Virtual screening with a library of purchasable drug molecules has identified pharmaceuticals currently in use as prescription and over the counter medications that, in silico, readily bind into this pocket. CONCLUSIONS: This study highlights possible drugs already in use as pharmaceuticals that may act as agents to interfere with the movements of the domains within this protein essential for the infectivity processes and hence might slow, or even halt, the infection of host cells by this new coronavirus. As these are existing pharmaceuticals already approved for use in humans, this knowledge could accelerate their roll-out, through repurposing, for affected individuals and help guide the efforts of other researchers in finding effective treatments for the disease.", "doc_id": "9wac5sfz"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Attacking COVID-19 Progression using Multi-Drug Therapy for Synergetic Target Engagement", "abstract": "COVID-19 is a devastating respiratory and inflammatory illness caused by a new coronavirus that is rapidly spreading throughout the human population. Over the past 6 months, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has already infected over 11.6 million (25% located in United States) and killed more than 540K people around the world. As we face one of the most challenging times in our recent history, there is an urgent need to identify drug candidates that can attack SARS-CoV-2 on multiple fronts. We have therefore initiated a computational dynamics drug pipeline using molecular modeling, structure simulation, docking and machine learning models to predict the inhibitory activity of several million compounds against two essential SARS-CoV-2 viral proteins and their host protein interactors; S/Ace2, Tmprss2, Cathepsins L and K, and Mpro to prevent binding, membrane fusion and replication of the virus, respectively. All together we generated an ensemble of structural conformations that increase high quality docking outcomes to screen over>6 million compounds including all FDA-approved drugs, drugs under clinical trial (>3000) and an additional>30 million selected chemotypes from fragment libraries. Our results yielded an initial set of 350 high value compounds from both new and FDA-approved compounds that can now be tested experimentally in appropriate biological model systems. We anticipate that our results will initiate screening campaigns and accelerate the discovery of COVID-19 treatments.", "doc_id": "4qyrtzhu"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "COVID-19: Drug Targets and Potential Treatments", "abstract": "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.", "doc_id": "f6xhrpi8"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Tackling SARS-CoV-2: proposed targets and repurposed drugs", "abstract": "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.", "doc_id": "4tis2he4"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes", "abstract": "In December 2019, COVID-19 epidemic was described in Wuhan, China, and the infection has spread widely affecting hundreds of thousands. Herein, an effort was made to identify commercially available drugs in order to repurpose them against coronavirus by the means of structure-based virtual screening. In addition, ZINC15 library was used to identify novel leads against main proteases. Human TMPRSS2 3D structure was first generated using homology modeling approach. Our molecular docking study showed four potential inhibitors against Mpro enzyme, two available drugs (Talampicillin and Lurasidone) and two novel drug-like compounds (ZINC000000702323 and ZINC000012481889). Moreover, four promising inhibitors were identified against TMPRSS2; Rubitecan and Loprazolam drugs, and compounds ZINC000015988935 and ZINC000103558522. ADMET profile showed that the hits from our study are safe and drug-like compounds. Furthermore, molecular dynamic (MD) simulation and binding free energy calculation using the MM-PBSA method was performed to calculate the interaction energy of the top-ranked drugs.Communicated by Ramaswamy H. Sarma.", "doc_id": "f74u6ddy"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Targeting the entry step of SARS-CoV-2: a promising therapeutic approach", "abstract": "", "doc_id": "g98idtmf"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Plausible mechanisms of Niclosamide as an antiviral agent against COVID-19", "abstract": "Abstract Corona virus disease 2019 (COVID-19) pandemic caused 18 440 deaths world wide as of 25 March 2020 and posing a serious threat to public health. There is a need, therefore, for effective therapeutic strategies to cure this disease. However, high attrition rates, substantial costs and slow pace are the major limitations of novel drug discovery. Drug repurposing, by employing \u2018old\u2019 drugs to treat \u2018new\u2019 diseases is an attractive approach in drug discovery. Niclosamide (NIC) is an approved anti-helminthic drug with diverse antiviral mechanisms. In this work we hypothesize, the potential antiviral mechanisms of NIC against COVID-19.", "doc_id": "zfe4lbr0"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Pulmonary delivery of nanostructured lipid carriers for effective repurposing of salinomycin as an antiviral agent", "abstract": "Coronavirus disease outbreak caused a severe public health burden all over the world. Salinomycin (SAL) is a broad-spectrum antibiotic that had drawn attention in selective targeting of cancer and viral infections. Recent drug screen identified SAL as a potent antiviral agent against SARS-CoV-2. In this review we discuss the potential of pulmonary delivery of SAL using nanostructured lipid carriers (NLCs) against SARS-CoV-2.", "doc_id": "8lgkeeqq"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "SARS-CoV-2 infection of kidney organoids prevented with soluble human ACE2", "abstract": "", "doc_id": "ejy8gtof"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "The SARS coronavirus nucleocapsid protein \u2013 Forms and functions", "abstract": "Abstract The nucleocapsid phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV N protein) packages the viral genome into a helical ribonucleocapsid (RNP) and plays a fundamental role during viral self-assembly. It is a protein with multifarious activities. In this article we will review our current understanding of the N protein structure and its interaction with nucleic acid. Highlights of the progresses include uncovering the modular organization, determining the structures of the structural domains, realizing the roles of protein disorder in protein\u2013protein and protein\u2013nucleic acid interactions, and visualizing the ribonucleoprotein (RNP) structure inside the virions. It was also demonstrated that N-protein binds to nucleic acid at multiple sites with a coupled-allostery manner. We propose a SARS-CoV RNP model that conforms to existing data and bears resemblance to the existing RNP structures of RNA viruses. The model highlights the critical role of modular organization and intrinsic disorder of the N protein in the formation and functions of the dynamic RNP capsid in RNA viruses. This paper forms part of a symposium in Antiviral Research on \u201cFrom SARS to MERS: 10years of research on highly pathogenic human coronaviruses.\u201d", "doc_id": "6fue84x6"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein", "abstract": "", "doc_id": "7y2lvd25"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "The signal peptide as a new target for drug design", "abstract": "Abstract Many current and potential drug targets are membrane-bound or secreted proteins that are expressed and transported via the Sec61 secretory pathway. They are targeted to translocon channels across the membrane of the endoplasmic reticulum (ER) by signal peptides (SPs), which are temporary structures on the N-termini of their nascent chains. During translation, such proteins enter the lumen and membrane of the ER by a process known as co-translational translocation. Small molecules have been found that interfere with this process, decreasing protein expression by recognizing the unique structures of the SPs of particular proteins. The SP may thus become a validated target for designing drugs for numerous disorders, including certain hereditary diseases.", "doc_id": "oh85yi49"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Adamantanes might be protective from COVID-19 in patients with neurological diseases: multiple sclerosis, parkinsonism and cognitive impairment", "abstract": "Abstract Facing the outbreak of coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need to find protective or curable drugs to prevent or to stop the course of the coronavirus SARS-CoV-2 infection. Recent evidence accumulates that adamantanes, widely used in different neurological diseases, could be repurposed for COVID-19. We hereby report on a questionnaire-based study performed to assess severity of COVID-19 in patients suffering from multiple sclerosis (n=10), Parkinson's disease (n=5) or cognitive impairment (n=7). In all patients infection with SARS-CoV-2 was confirmed by rtPCR of nasopharyngeal swabs. They were receiving treatment with either amantadine (n=15) or memantine (n=7) in stable registered doses. All of them had two-week quarantine since documented exposure and none of them developed clinical manifestations of infectious disease. They also did not report any significant changes in neurological status in the course of primary nervous system disease. Above results warrant further studies on protective effects of adamantanes against COVID-19 manifestation, especially in subjects suffering from neurological disease.", "doc_id": "vaq0kwln"} {"topic_name": "coronavirus drug repurposing", "topic_id": "29", "title": "Can beta-adrenergic blockers be used in the treatment of COVID-19?", "abstract": "", "doc_id": "ya7sy0cu"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Duration of antibiotic therapy in critically ill patients: a randomized controlled trial of a clinical and C-reactive protein-based protocol versus an evidence-based best practice strategy without biomarkers", "abstract": "BACKGROUND: The rational use of antibiotics is one of the main strategies to limit the development of bacterial resistance. We therefore sought to evaluate the effectiveness of a C-reactive protein-based protocol in reducing antibiotic treatment time in critically ill patients. METHODS: A randomized, open-label, controlled clinical trial conducted in two intensive care units of a university hospital in Brazil. Critically ill infected adult patients were randomly allocated to (i) intervention to receive antibiotics guided by daily monitoring of CRP levels and (ii) control to receive antibiotics according to the best practices for rational use of antibiotics. RESULTS: One hundred thirty patients were included in the CRP (n = 64) and control (n = 66) groups. In the intention-to-treat analysis, the median duration of antibiotic therapy for the index infectious episode was 7.0 (5.0\u20138.8) days in the CRP and 7.0 (7.0\u201311.3) days in the control (p = 0.011) groups. A significant difference in the treatment time between the two groups was identified in the curve of cumulative suspension of antibiotics, with less exposure in the CRP group only for the index infection episode (p = 0.007). In the per protocol analysis, involving 59 patients in each group, the median duration of antibiotic treatment was 6.0 (5.0\u20138.0) days for the CRP and 7.0 (7.0\u201310.0) days for the control (p = 0.011) groups. There was no between-group difference regarding the total days of antibiotic exposure and antibiotic-free days. CONCLUSIONS: Daily monitoring of CRP levels may allow early interruption of antibiotic therapy in a higher proportion of patients, without an effect on total antibiotic consumption. The clinical and microbiological relevance of this finding remains to be demonstrated. TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT02987790. Registered 09 December 2016.", "doc_id": "xoygeing"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Benefit-risk assessment for remdesivir in COVID-19", "abstract": "", "doc_id": "7xci160l"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Recommandations EMA sur l\u2019usage compassionnel du remdesivir", "abstract": "", "doc_id": "bpkc94al"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Br\u00e8ves : En savoir plus sur le remdesivir", "abstract": "", "doc_id": "mun50en6"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment", "abstract": "[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.", "doc_id": "kq77whdx"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Remdesivir: Various toxicities: 4 case reports", "abstract": "", "doc_id": "e2fv14wl"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Five reasons why data on compassionate use of remdesivir deserved publication (and are worth reading).", "abstract": "", "doc_id": "m8c4h7og"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Quantification of plasma remdesivir and its metabolite GS-441524 using liquid chromatography coupled to tandem mass spectrometry. Application to a Covid-19 treated patient.", "abstract": "Objectives A method based on liquid chromatography coupled to triple quadrupole mass spectrometry detection using 50 \u00b5L of plasma was developed and fully validated for quantification of remdesivir and its active metabolites GS-441524. Methods A simple protein precipitation was carried out using 75 \u00b5L of methanol containing the internal standard (IS) remdesivir-13C6 and 5 \u00b5L ZnSO4 1 M. After separation on Kinetex\u00ae 2.6 \u00b5m Polar C18 100A LC column (100 \u00d7 2.1 mm i.d.), both compounds were detected by a mass spectrometer with electrospray ionization in positive mode. The ion transitions used were m/z 603.3 \u2192 m/z 200.0 and m/z 229.0 for remdesivir, m/z 292.2 \u2192 m/z 173.1 and m/z 147.1 for GS-441524 and m/z 609.3 \u2192 m/z 206.0 for remdesivir-13C6. Results Calibration curves were linear in the 1-5000 \u03bcg/L range for remdesivir and 5-2500 for GS-441524, with limit of detection set at 0.5 and 2 \u03bcg/L and limit of quantification at 1 and 5 \u03bcg/L, respectively. Precisions evaluated at 2.5, 400 and 4000 \u03bcg/L for remdesivir and 12.5, 125, 2000 \u03bcg/L for GS-441524 were lower than 14.7% and accuracy was in the [89.6-110.2%] range. A slight matrix effect was observed, compensated by IS. Higher stability of remdesivir and metabolite was observed on NaF-plasma. After 200 mg IV single administration, remdesivir concentration decrease rapidly with a half-life less than 1 h while GS-441524 appeared rapidly and decreased slowly until H24 with a half-life around 12 h. Conclusions This method would be useful for therapeutic drug monitoring of these compounds in Covid-19 pandemic.", "doc_id": "kplplr6a"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Remdesivir for the Treatment of Covid-19 - Preliminary Report.", "abstract": "", "doc_id": "40vtvseh"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Hopes rise on coronavirus drug remdesivir.", "abstract": "", "doc_id": "j40u05z6"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "The role of remdesivir in South Africa: preventing COVID-19 deaths through increasing ICU capacity.", "abstract": "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.", "doc_id": "7gzem1s5"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review.", "abstract": "The need for proven disease-specific treatments for the novel pandemic coronavirus SARS-CoV-2 necessitates a worldwide search for therapeutic options. Since the SARS-CoV-2 virus shares extensive homology with SARS-CoV and MERS-CoV, effective therapies for SARS-CoV and MERS-CoV may also have therapeutic potential for the current COVID-19 outbreak. To identify therapeutics that might be repositioned for treatment of the SARS-CoV-2 disease COVID-19, we strategically reviewed the literature to identify existing therapeutics with evidence of efficacy for the treatment of the three coronaviruses that cause severe respiratory illness (SARS-CoV, MERS-CoV, and SARS-CoV-2). Mechanistic and in vitro analyses suggest multiple promising therapeutic options with potential for repurposing to treat patients with COVID-19. Therapeutics with particularly high potential efficacy for repurposing include camostat mesylate, remdesivir, favipiravir, tocilizumab, baricitinib, convalescent plasma, and humanized monoclonal antibodies. Camostat mesylate has shown therapeutic potential, likely by preventing viral entry into epithelial cells. In early research, the targeted antivirals remdesivir and favipiravir appear to benefit patients by decreasing viral replication; clinical trials suggest that remdesivir speeds recovery from COVID-19. Tocilizumab and baricitinib appear to improve mortality by preventing a severe cytokine storm. Convalescent plasma and humanized monoclonal antibodies offer passive immunity and decreased recovery time. This review highlights potential therapeutic options that may be repurposed to treat COVID-19 and suggests opportunities for further research.", "doc_id": "inibtytf"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Antivirals for COVID-19.", "abstract": "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.", "doc_id": "eaqxifxu"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir.", "abstract": "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.", "doc_id": "bz1lz2ze"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Remdesivir for 5 or 10 Days in Patients with Severe Covid-19.", "abstract": "BACKGROUND Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). METHODS We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. RESULTS In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). CONCLUSIONS In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).", "doc_id": "zbi0llig"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Hints of hope with remdesivir.", "abstract": "", "doc_id": "o4m1pun6"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Remdesivir in covid-19.", "abstract": "", "doc_id": "m2k6usaz"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Tocilizumab and Remdesivir in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19).", "abstract": "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.", "doc_id": "tdfqhty8"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Successful treatment of patients severely ill with COVID-19.", "abstract": "", "doc_id": "b83u3zl1"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Efficacy of remdesivir in a rhesus macaque model of MERS-CoV infection.", "abstract": "", "doc_id": "vs6rh9i9"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Covid-19: Remdesivir is helpful but not a wonder drug, say researchers.", "abstract": "", "doc_id": "ujvei43u"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Efficacy of remdesivir in COVID-19 patients with a simulated two-arm controlled study", "abstract": "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.", "doc_id": "qpa6tk6v"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "The role of remdesivir in South Africa: preventing COVID-19 deaths through increasing ICU capacity", "abstract": "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.", "doc_id": "sqjaembq"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Impacts of remdesivir on dynamics and efficacy stratified by the severity of COVID-19: a simulated two-arm controlled study", "abstract": "Background: The impact of remdesivir on length of stay of hospitalization, high-risk state, and death stratified by the severity of COVID-19 at enrollment is controversial. Methods: We applied a simulated two-arm controlled study design to the data on compassionate use of remdesivir as a secondary analysis. Dynamics of risk states and death from COVID-19 patients defined by the six-point disease severity recommended by the WHO R&D and the time to discharge from hospital were used to evaluate the efficacy of remdesivir treatment compared with standard care. Results: Stratified by the risk state at enrollment, low-risk patients exhibited the highest efficacy of remdesivir in reducing subsequent progression to high-risk state by 67% (relative risk (RR)=0.33,95% CI: 0.30-0.35) and further to death by 55% (RR=0.45, 95%CI: 0.39-0.50). For the medium-risk patients, less but still statistically significant efficacy results were noted in reducing progression to high-risk state by 52% (RR=0.48, 95% CI: 0.45-0.51) and further to death by 40% (RR=0.60, 95% CI:0.54-0.66). High-risk state patients treated with remdesivir led to a 25% statistically significant reduction in death (RR=0.75, 95% CI: 0.69-0.82). Regarding the outcome of discharge, remdesivir treatment was most effective for medium-risk patients at enrollment (RR: 1.41, 95% CI: 1.35-1.47) followed by high- (RR=1.34, 95% CI: 1.27-1.42) and low-risk patients (RR=1.28, 95% CI: 1.25-1.31). Conclusion: Our results with a simulated two-arm controlled study have provided a new insight into the precision treatment of remdesivir for COVID-19 patients based on risk-stratified efficacy.", "doc_id": "4od9gu6y"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "What could remdesivir data tell us about tackling COVID-19?", "abstract": "In the coming weeks, the world will get a sense of whether Gilead Sciences\u2019 remdesivir, an antiviral developed for Ebola, is useful against the novel coronavirus With the coronavirus pandemic spiraling\u2014during the week of March 30, worldwide infections crossed 900,000 and deaths exceeded 45,000\u2014initial 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\u2019t 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\u2019s experimental drug When a new infectious disease threatens", "doc_id": "svp32re6"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Foundational research and NIH funding enabling Emergency Use Authorization of remdesivir for COVID-19", "abstract": "Emergency Use Authorization for remdesivir months after discovery of COVID19 is unprecedented. Typically, decades of research and public sector funding are required to establish the mature body of foundational research requisite for efficient, targeted drug discovery and development. This work quantifies the body of research related to the biological target of remdesivir, RNA-dependent RNA polymerase (RdRp), or parent chemical structure, nucleoside analogs (NcAn), through 2019, as well as NIH funding for this research from 2000 to 2019. There were 6,567 RdRp related publications in PubMed, including 1,263 with NIH support, and 11,073 NcAn-related publications, including 2,319 with NIH support. NIH support for RdRp research comprised 2,203 Project Years with Costs of $1,875 million. NIH support for NcAn research comprised 4,607 Project Years with Costs of $4,612 million. Research Project grants accounted for 63% and 48% of Project Years for RdRp and NcAn respectively, but only 19% and 12% of Project Costs. Analytical modeling of research maturation estimates that RdRp and NcAn research passed an established maturity threshold in 2008 and 1994 respectively. Of 97 investigational compounds targeting RdRp since 1989, the three authorized for use entered clinical trials after both thresholds. This work demonstrates the scale of foundational research on the biological target and parent chemical structure of remdesivir that supported its discovery and development for COVID19. This work identifies $6.5 billion in NIH funding for research leading to remdesivir, underscoring the role of public sector investments in basic research and research infrastructure that underlie new drugs and the response to emergent disease.", "doc_id": "rt5yi5hc"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Use of Remdesivir in the Management of COVID-19: A Systematic Review on Current Evidences.", "abstract": "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.", "doc_id": "x89iy0m2"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Remdesivir for the Treatment of Covid-19 - Preliminary Report", "abstract": "", "doc_id": "zlmv67ia"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Remdesivir as a possible therapeutic option for the COVID-19", "abstract": "", "doc_id": "wcdq0fqj"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Compassionate Use of Remdesivir in Covid-19", "abstract": "", "doc_id": "11wfbtbc"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Hopes rise for coronavirus drug remdesivir", "abstract": "", "doc_id": "67i1yt74"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Compassionate Use of Remdesivir for Patients with Severe Covid-19", "abstract": "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.).", "doc_id": "kxds6r7t"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit", "abstract": "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.", "doc_id": "r0znh1bi"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Rapid review for the anti-coronavirus effect of remdesivir", "abstract": "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.", "doc_id": "a0drmmf7"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Repurposing Therapeutics for Potential Treatment of SARS-CoV-2: A Review", "abstract": "The need for proven disease-specific treatments for the novel pandemic coronavirus SARS-CoV-2 necessitates a worldwide search for therapeutic options. Since the SARS-CoV-2 virus shares extensive homology with SARS-CoV and MERS-CoV, effective therapies for SARS-CoV and MERS-CoV may also have therapeutic potential for the current COVID-19 outbreak. To identify therapeutics that might be repositioned for treatment of the SARS-CoV-2 disease COVID-19, we strategically reviewed the literature to identify existing therapeutics with evidence of efficacy for the treatment of the three coronaviruses that cause severe respiratory illness (SARS-CoV, MERS-CoV, and SARS-CoV-2). Mechanistic and in vitro analyses suggest multiple promising therapeutic options with potential for repurposing to treat patients with COVID-19. Therapeutics with particularly high potential efficacy for repurposing include camostat mesylate, remdesivir, favipiravir, tocilizumab, baricitinib, convalescent plasma, and humanized monoclonal antibodies. Camostat mesylate has shown therapeutic potential, likely by preventing viral entry into epithelial cells. In early research, the targeted antivirals remdesivir and favipiravir appear to benefit patients by decreasing viral replication; clinical trials suggest that remdesivir speeds recovery from COVID-19. Tocilizumab and baricitinib appear to improve mortality by preventing a severe cytokine storm. Convalescent plasma and humanized monoclonal antibodies offer passive immunity and decreased recovery time. This review highlights potential therapeutic options that may be repurposed to treat COVID-19 and suggests opportunities for further research.", "doc_id": "fy8tyj9a"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Efficacy of remdesivir in patients with COVID-19: a protocol for systematic review and meta-analysis of randomised controlled trials", "abstract": "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.", "doc_id": "kcrmi3x8"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "What Do We Know About Remdesivir Drug Interactions?", "abstract": "", "doc_id": "wn0o7422"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "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", "abstract": "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\u00e2\u0080\u00afdays after initiation of remdesivir, was transitioned to room air 24\u00e2\u0080\u00afh later, and discharged at the completion of remdesivir therapy.", "doc_id": "6wwmbgw7"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Statistical Issues and Lessons Learned from COVID-19 Clinical Trials with Lopinavir-Ritonavir and Remdesivir", "abstract": "BACKGROUND: Recently, three randomized clinical trials on COVID-19 treatments were completed, one for lopinavir-ritonavir and two for remdesivir. One trial reported that remdesivir was superior to placebo in shortening the time to recovery, while the other two showed no benefit of the treatment under investigation. OBJECTIVE: From statistical perspectives, we identify several key issues in the design and analysis of three COVID-19 trials and reanalyze the data from the cumulative incidence curves in the three trials using more appropriate statistical methods. METHODS: The lopinavir-ritonavir trial enrolled 39 additional patients due to insignificant results after the sample size reached the planned number, which led to inflation of the type I error rate. The remdesivir trial of Wang et al. failed to reach the planned sample size due to a lack of eligible patients, while the bootstrap method was used to predict the quantity of clinical interest conditionally and unconditionally if the trial had continued to reach the originally planned sample size. Moreover, we used a terminal (or cure) rate model and a model-free metric known as the restricted mean survival time or the restricted mean time to improvement (RMTI) to analyze the reconstructed data. The remdesivir trial of Beigel et al. reported the median recovery time of the remdesivir and placebo groups and the rate ratio for recovery, while both quantities depend on a particular time point representing local information. We use the restricted mean time to recovery (RMTR) as a global and robust measure for efficacy. RESULTS: For the lopinavir-ritonavir trial, with the increase of sample size from 160 to 199, the type I error rate was inflated from 0.05 to 0.071. The difference of RMTIs between the two groups evaluated at day 28 was -1.67 days (95% CI [-3.62, 0.28]; P=.09) in favor of lopinavir-ritonavir but not statistically significant. For the remdesivir trial of Wang et al., the difference of RMTIs at day 28 was -0.89 day (95% CI [-2.84, 1.06]; P=.37). The planned sample size was 453, yet only 236 patients were enrolled. The conditional prediction shows that the HR estimates would reach statistical significance if the target sample size had been maintained. For the remdesivir trial of Beigel et al., the difference of RMTRs between the remdesivir and placebo groups at day 30 was -2.7 days (95% CI [-4.0, -1.2]; P<.001), confirming the superiority of remdesivir. The difference in the recovery time at the 25th percentile (95% CI [-3, 0]; P=.65) was insignificant, while the differences manifested to be statistically significant at larger percentiles. CONCLUSIONS: Based on the statistical issues and lessons learned from the recent three clinical trials on COVID-19 treatments, we suggest more appropriate approaches for the design and analysis for ongoing and future COVID-19 trials.", "doc_id": "6jo4308s"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More", "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 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.", "doc_id": "8n6eybze"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir", "abstract": "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.", "doc_id": "ygbfvjz8"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Early experience with remdesivir in SARS-CoV-2 pneumonia", "abstract": "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.", "doc_id": "mp3qb33p"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Remdesivir for 5 or 10 Days in Patients with Severe Covid-19", "abstract": "BACKGROUND: Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). METHODS: We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. RESULTS: In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). CONCLUSIONS: In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).", "doc_id": "pibcxe1x"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Arguments in favour of remdesivir for treating SARS-CoV-2 infections", "abstract": "", "doc_id": "107lb1bd"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Hints of hope with remdesivir", "abstract": "", "doc_id": "df11ovar"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Remdesivir in covid-19", "abstract": "", "doc_id": "928lhz2l"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "That Escalated Quickly: Remdesivir's Place in Therapy for COVID-19", "abstract": "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.", "doc_id": "ioqvxhar"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Pharmacokinetics of remdesivir and GS-441524 in two critically ill patients who recovered from COVID-19", "abstract": "BACKGROUND: Remdesivir is a prodrug of the nucleoside analogue GS-441524 and is under evaluation for treatment of SARS-CoV-2-infected patients. OBJECTIVES: To evaluate the pharmacokinetics of remdesivir and GS-441524 in plasma, bronchoalveolar aspirate (BAS) and CSF in two critically ill COVID-19 patients. METHODS: Remdesivir was administered at 200 mg loading dose on the first day followed by 12 days of 100 mg in two critically ill patients. Blood samples were collected immediately after (C0) and at 1 (C1) and 24 h (C24) after intravenous administration on day 3 until day 9. BAS samples were collected on Days 4, 7 and 9 from both patients while one CSF on Day 7 was obtained in one patient. Remdesivir and GS-441524 concentrations were measured in these samples using a validated UHPLC-MS/MS method. RESULTS: We observed higher concentrations of remdesivir at C0 (6- to 7-fold higher than EC50 from in vitro studies) and a notable decay at C1. GS-441524 plasma concentrations reached a peak at C1 and persisted until the next administration. Higher concentrations of GS-441524 were observed in the patient with mild renal dysfunction. Mean BAS/plasma concentration ratios of GS-441524 were 2.3% and 6.4% in Patient 1 and Patient 2, respectively. The CSF concentration found in Patient 2 was 25.7% with respect to plasma. GS-441524 levels in lung and CNS suggest compartmental differences in drug exposure. CONCLUSIONS: We report the first pharmacokinetic evaluation of remdesivir and GS-441524 in recovered COVID-19 patients. Further study of the pharmacokinetic profile of remdesivir, GS-441524 and the intracellular triphosphate form are required.", "doc_id": "vachz4i9"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Tocilizumab and Remdesivir in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19)", "abstract": "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.", "doc_id": "d4tc2xe7"} {"topic_name": "coronavirus remdesivir", "topic_id": "30", "title": "Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs Against Human Coronavirus 229E (HCoV-229E)", "abstract": "Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5'-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. The study revealed that remdesivir exhibited an EC50 value of 0.07 \u00b5M against HCoV-229E with TC50 of > 2.00 \u00b5M against MRC-5 cells. Parent NRTIs were found to be inactive against (HCoV-229E) at tested concentrations. Among all the NRTIs and 5'-O-fatty acyl conjugates of NRTIs, 5'-O-tetradecanoyl ester conjugate of FTC showed modest activity with EC50 and TC50 values of 72.8 \u00b5M and 87.5 \u00b5M, respectively. These data can be used for the design of potential compounds against other coronaviruses.", "doc_id": "7wiirvox"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "COVID-19, a far cry from the influenza", "abstract": "", "doc_id": "nux0uy7b"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "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.", "abstract": "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.", "doc_id": "1n5ej08f"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Potential impact of seasonal forcing on a SARS-CoV-2 pandemic.", "abstract": "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.", "doc_id": "28sgnyh1"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "INFECTIONS IN PREGNANCY WITH COVID-19 AND OTHER RESPIRATORY RNA VIRUS DISEASES ARE RARELY, IF EVER, TRANSMITTED TO THE FETUS: EXPERIENCES WITH CORONAVIRUSES, HPIV, hMPV RSV, AND INFLUENZA.", "abstract": "SARS-CoV-2, the agent of COVID-19, is similar to two other coronaviruses, SARS-CoV and MERS-CoV, in causing life-threatening maternal respiratory infections and systemic complications. Because of global concern for potential intrauterine transmission of SARS-CoV-2 from pregnant women to their infants, this report analyzes the effects on pregnancy of infections caused by SARS-CoV-2 and other respiratory RNA viruses, and examines the frequency of maternal-fetal transmission with SARS-CoV-2, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, respiratory syncytial virus (RSV), parainfluenza (HPIV) and metapneumovirus (hMPV). There have been no confirmed cases of intrauterine transmission reported with COVID-19 or any other coronavirus infections. Influenza virus, despite causing approximately one billion annual infections globally, has only a few cases of confirmed or suspected intrauterine fetal infections reported. RSV is in an unusual cause of illness among pregnant women, and with the exception of one premature infant with congenital pneumonia, no other cases of maternal-fetal infection are described. Parainfluenza virus and human metapneumovirus can produce symptomatic maternal infections but do not cause intrauterine fetal infection. In summary, it appears that the absence thus far of maternal-fetal transmission of the SARS-CoV-2 virus during the COVID-19 pandemic is similar to other coronaviruses, and is also consistent with the extreme rarity of suggested or confirmed cases of intrauterine transmission of other respiratory RNA viruses. This observation has important consequences for pregnant women as it appears that if intrauterine transmission of SARSCoV-2 does eventually occur, it will be a rare event. Potential mechanisms of fetal protection from maternal viral infections are also discussed.", "doc_id": "xmg9tnda"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "[Comparison of pathological changes and pathogenic mechanisms caused by H1N1 influenza virus, highly pathogenic H5N1 avian influenza virus, SARS-CoV, MERS-CoV and 2019-nCoV coronavirus].", "abstract": "\u6211\u56fd\u6b66\u6c49\u51fa\u73b0\u7684\u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u80ba\u708e\u75ab\u60c5\u7ecf\u8fc7\u8fc5\u901f\u53d1\u5c55\u5df2\u5bf9\u5168\u56fd\u9020\u6210\u4e25\u91cd\u5f71\u54cd\uff0c\u4f46\u5230\u76ee\u524d\u4e3a\u6b62\u5bf9\u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u80ba\u708e\u75c5\u7406\u53d8\u5316\u548c\u53d1\u75c5\u673a\u5236\u5374\u77e5\u4e4b\u751a\u5c11\u3002\u672c\u6587\u603b\u7ed3\u91cd\u75c7\u6d41\u611f\u75c5\u6bd2H1N1\u3001\u9ad8\u81f4\u75c5\u6027\u79bd\u6d41\u611f\u75c5\u6bd2H5N1\u3001SARS-CoV\u3001MERS-CoV\u53ca2019-nCoV\u51a0\u72b6\u75c5\u6bd2\u51e0\u79cd\u5f15\u8d77\u91cd\u5927\u75ab\u60c5\u75c5\u6bd2\u611f\u67d3\u6027\u75be\u75c5\u7684\u75c5\u7406\u6539\u53d8\uff0c\u5c38\u68c0\u80ba\u7ec4\u7ec7\u5747\u8868\u73b0\u4e3a\u5f25\u6f2b\u6027\u80ba\u6ce1\u635f\u4f24\uff08diffuse alveolar damage\uff0cDAD\uff09\uff0c\u4f46\u4e0d\u540c\u75c5\u6bd2\u5f15\u8d77\u7684\u75c5\u7406\u8868\u73b0\u5b58\u5728\u5dee\u5f02\uff0c\u91cd\u75c7\u6d41\u611f\u75c5\u6bd22009 H1N1\u75c5\u6bd2\u4e0e\u53d7\u4f53\u03b1-2,6-SA\u53ca\u03b1-2,3-SA\u7ed3\u5408\uff0c\u9664DAD\u75c5\u53d8\u5916\uff0c\u5e38\u4f34\u6709\u4e0a\u547c\u5438\u9053\u3001\u6c14\u7ba1\u3001\u652f\u6c14\u7ba1\u548c\u7ec6\u652f\u6c14\u7ba1\u7684\u708e\u6027\u75c5\u53d8\uff0c\u4e14\u8f83\u6613\u5408\u5e76\u7ec6\u83cc\u611f\u67d3\u3002\u9ad8\u81f4\u75c5\u6027\u79bd\u6d41\u611f\u75c5\u6bd2H5N1\u4e3b\u8981\u7ed3\u5408\u03b1-2,3-SA\u53d7\u4f53\uff0c\u4e3b\u8981\u7d2f\u53ca\u80ba\u6ce1\u4e0a\u76ae\u53ca\u7ec6\u652f\u6c14\u7ba1\uff0c\u5c11\u89c1\u4e0a\u547c\u5438\u9053\u53ca\u6c14\u7ba1\u3001\u652f\u6c14\u7ba1\u75c5\u53d8\uff0c\u5e38\u4f34\u5c40\u7076\u80ba\u51fa\u8840\u53ca\u80ba\u7ec4\u7ec7\u574f\u6b7b\u3002\u673a\u5316\u53ca\u7ea4\u7ef4\u5316\u8f83\u5c11\u89c1\u3002SARS-CoV\u901a\u8fc7\u7ed3\u5408\u8840\u7ba1\u7d27\u5f20\u7d20\u8f6c\u6362\u91762\uff08ACE2\uff09\u8fdb\u5165\u7ec6\u80de\uff0c\u75c5\u53d8\u4e0e\u75c5\u7a0b\u76f8\u5173\uff0cDAD\u6e17\u51fa\u671f\u4e00\u822c\u89c1\u4e8e\u75c5\u7a0b10\uff5e14 d\u6b7b\u4ea1\u60a3\u8005\u3002\u75c5\u7a0b\u5927\u4e8e10 d\u60a3\u8005\u8868\u73b0\u4e3aDAD\u673a\u5316\u671f\uff0c\u5e76\u5e38\u4f34\u6709\u95ed\u585e\u6027\u7ec6\u652f\u6c14\u7ba1\u708e\u4f34\u673a\u5316\u6027\u80ba\u708e\u6837\u6539\u53d8\u53ca\u80ba\u6ce1\u8154\u5185\u663e\u8457\u591a\u6838\u5de8\u7ec6\u80de\u3002SARS-CoV\u53caH5N1\u611f\u67d3\u60a3\u8005\u80ba\u5916\u5668\u5b98\u5747\u53ef\u89c1\u813e\u548c\u6dcb\u5df4\u7ed3\u5185\u6dcb\u5df4\u7ec6\u80de\u8017\u7aed\u3001\u6025\u6027\u80be\u5c0f\u7ba1\u574f\u6b7b\u3001\u9aa8\u9ad3\u5185\u566c\u8840\u7ec6\u80de\u73b0\u8c61\u3002.", "doc_id": "b28sdgvk"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "A Comparison of Clinical and Chest CT Findings in Patients With Influenza A (H1N1) Virus Infection and Coronavirus Disease (COVID-19).", "abstract": "OBJECTIVE. The purpose of this study was to compare clinical and chest CT findings in patients with influenza A (H1N1) pneumonia and coronavirus disease (COVID-19) pneumonia. MATERIALS AND METHODS. Thirty patients with diagnosed influenza A (H1N1) virus infection (group A) and 30 patients with diagnosed COVID-19 (group B) were retrospectively enrolled in the present study. The clinical characteristics and chest CT findings of the two groups were compared. RESULTS. Fever, cough, expectoration, and dyspnea were the main symptoms in both groups with viral pneumonia, with cough and expectoration more frequently found in group A. Lymphopenia, an elevated C-reactive protein level, and an increased erythrocyte sedimentation rate were common laboratory test findings in the two groups. The median time from symptom onset to CT in group A and group B was 6 and 15 days, respectively, and the median total CT score of the pulmonary lobes involved was 6 and 13, respectively. Linear opacification, crazy-paving sign, vascular enlargement, were more common in group B. In contrast, bronchiectasis and pleural effusion were more common in group A. Other common CT features, including peripheral or peribronchovascular distribution, ground-glass opacities (GGOs), consolidation, subpleural line, air bronchogram, and bronchial distortion, did not show statistical significance. CONCLUSION. On CT, the significant differences between influenza A (H1N1) pneumonia and COVID-19 pneumonia were findings of linear opacification, crazy-paving sign, vascular enlargement, pleural thickening, and pleural effusion, which were more common in patients with COVID-19 pneumonia, and bronchiectasis and pleural effusion, which were more common in patients with influenza A (H1N1) pneumonia. Other imaging findings, including peripheral or peribronchovascular distribution, ground-glass opacities (GGO), consolidation, subpleural line, air bronchogram, and bronchial distortion, were not significantly different between the two patient groups.", "doc_id": "1qjmktdl"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Pollen Explains Flu-Like and COVID-19 Seasonality", "abstract": "Current models for flu-like epidemics insufficiently explain multi-cycle seasonality. Meteorological factors alone do not predict seasonality, given substantial climate differences between countries that are subject to flu-like epidemics or COVID-19. Pollen is documented to be antiviral and allergenic, play a role in immuno-activation, and seems to create a bio-aerosol lowering the reproduction number of flu-like viruses. Therefore, we hypothesize that pollen may explain the seasonality of flu-like epidemics including COVID-19. We tested the Pollen-Flu Seasonality Theory for 2016-2020 flu-like seasons, including COVID-19, in The Netherlands with its 17 million inhabitants. We combined changes in flu-like incidence per 100K/Dutch citizens (code: ILI) with weekly pollen counts and meteorological data for the same period. Finally, a discrete, predictive model is tested using pollen and meteorological threshold values displaying inhibitory effects on flu-like incidence. We found a highly significant inverse association of r(224)= -.38 between pollen and changes in flu-like incidence corrected for incubation period, confirming our expectations for the 2019/2020 COVID-19 season. We found that our predictive model has the highest inverse correlation with changes in flu-like incidence of r(222) = -.48 (p < .001) when pollen thresholds of 610 total pollen grains/m3 per week, 120 allergenic pollen grains/m3 per week, and a solar radiation threshold of 510 J/cm2 are passed. The passing of at least the pollen thresholds, preludes the beginning and end of flu-like seasons. Solar radiation is a supportive factor, temperature makes no difference, and relative humidity associates even with flu-like incidence increases. We conclude that pollen is a predictor for the inverse seasonality of flu-like epidemics including COVID-19, and solar radiation is a co-inhibitor. The observed seasonality of COVID-19 during Spring, suggests that COVID-19 may revive in The Netherlands after week 33, the start being preceded by the relative absence of pollen, and follows standard pollen-flu seasonality patterns.", "doc_id": "8ndl8zjz"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Chest Computed Tomography Findings in COVID-19 and Influenza: A Narrative Review", "abstract": "Objective The COVID-19 pandemic and annual influenza epidemic are responsible for thousands of deaths globally With a similarity in clinical as well as laboratory findings, there is a need to differentiate these two conditions on chest CT scan This paper attempts to use existing literature to draw out differences in chest CT findings in COVID-19 and influenza Methods A search was conducted using PubMed 17 original studies on chest CT findings in COVID-19 and influenza were identified for full-text review and data analysis Findings COVID-19 and influenza share similar chest CT findings The differences found show that COVID-19 ground-glass opacities are usually peripherally located with the lower lobes being commonly involved, while influenza has a central, peripheral, or random distribution usually affecting the five lobes Vascular engorgement, pleural thickening, and subpleural lines were reported in COVID-19 patients In contrast, pneumomediastinum and pneumothorax were reported only in studies on influenza Conclusion and Relevance COVID-19 and influenza have overlapping chest CT features with few differences which can assist in telling apart the two pathologies Additional studies are needed to further define the differences and degree between COVID-19 and influenza Copyright \u00a9 2020 Stephen O Onigbinde et al", "doc_id": "27dmsmbu"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Risk stratification of hospitalized COVID-19 patients through comparative studies of laboratory results with influenza", "abstract": "Background The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 overlaps with the flu season. Methods We compared clinical and laboratory results from 719 influenza and 973 COVID-19 patients from January to April 2020. We compiled laboratory results from the first 14 days of the hospitalized patients using parameters that are most significantly different between COVID-19 and influenza and hierarchically clustered COVID-19 patients based on these data. The clinical outcomes were compared among different clusters. Results Temporal analyses of laboratory results revealed that compared to influenza, patients with COVID-19 exhibited a continued increase in the white blood cell count, rapid decline of hemoglobin, more rapid increase in blood urea nitrogen (BUN) and D-dimer, and higher level of alanine transaminase, C-reactive protein, ferritin, and fibrinogen. Using these results, we sub-classified the COVID-19 patients into 5 clusters through a hierarchical clustering analysis. We then reviewed the medical record of these patients and risk stratified them based on the clinical outcomes. The cluster with the highest risk showed 27.8% fatality, 94% ICU admission, 94% intubation, and 28% discharge rates compared to 0%, 38%, 22%, and 88% in the lowest risk cluster, respectively. Patients in the highest risk cluster had leukocytosis including neutrophilia and monocytosis, severe anemia, higher BUN, creatinine, D-dimer, alkaline phosphatase, bilirubin, and troponin. Conclusions There are significant differences in the clinical and laboratory courses between COVID-19 and influenza. Risk stratification in hospitalized COVID-19 patients using laboratory data could be useful to predict clinical outcomes and pathophysiology of these patients.", "doc_id": "p38x1q8s"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "The Epidemic Severity Index: Estimating Relative Local Severity of Novel Disease Outbreaks", "abstract": "Determining the severity of a novel pathogen in the early stages is difficult in the absence of reliable data. The pattern of outbreaks for COVID-19 across the globe have differed markedly above and below +40N latitudes, suggesting very different levels of severity, but countries worldwide have implemented the same lockdown strategies. Existing methods for estimating severity appear not to have been useful in informing strategic decisions, possibly due to mismatches between the data required and those available, overly sophisticated methods with undesirable biases, or perhaps confusion and uncertainly generated by the wide range of estimates these methods produced early on. The Epidemic Severity Index (ESI) is a simple, robust method for estimating the local severity of novel epidemic outbreaks using early and widely-available data and that does not depend on any estimated values. ESI allows rapid, meaningful comparisons across territories that can be tracked as the outbreaks unfold. The ESI quantifies severity relative to a parameterised baseline rather than attempting to estimate values for infection fatality rates, case fatality rates or transmission rates. The relative nature of the ESI sidesteps any problems of confidence associated with absolute rate estimation methods and offers immediate practical strategic value.", "doc_id": "7ml79gku"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Room Temperature Isothermal Colorimetric Padlock Probe Rolling Circle Amplification for Viral RNA Detection", "abstract": "Seasonal flu and pandemics, which account for millions of infections and hundreds of thousands of deaths, require rapid and reliable detection mechanisms for preventive and therapeutic measures. Current methods of viral detection have limitations in speed, accuracy, accessibility, and usability. This project presents a novel, widely applicable viral diagnosis that uses a modified version of the traditional rolling circle amplification (RCA) to be sensitive, specific, direct, colorimetric, and operable at room temperature. We are specifically aiming to detect SARS-CoV-2, Influenza A (H1N1pdm09), and Influenza B (Victoria Lineage). Results using synthetic viral DNA sequences show that the diagnostic test could take as fast as 30 minutes and detect up to picomolar concentrations of DNA strands. The next step for this project is to test the assay with synthetic viral RNA to verify the results. We envision that the implementation of this type of diagnostic test could allow faster responses to outbreaks of related viruses and quicker societal recovery.", "doc_id": "86dzod5b"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Differentiating between 2019 novel coronavirus pneumonia and influenza using a nonspecific laboratory marker-based dynamic nomogram", "abstract": "Background. There is currently a lack of nonspecific laboratory indicators as a quantitative standard to distinguish between the 2019 coronavirus disease (COVID-19) and an influenza A or B virus infection. Thus, the aim of this study was to establish a nomogram to detect COVID-19. Methods. A nomogram was established using data collected from 457 patients (181 with COVID-19 and 276 with influenza A or B infection) in China. The nomogram used age, lymphocyte percentage, and monocyte count to differentiate COVID-19 from influenza. Results. Our nomogram predicted probabilities of COVID-19 with an area under the receiver operating characteristic curve of 0.913 (95% confidence interval [CI], 0.883-0.937), greater than that of the lymphocyte:monocyte ratio (0.849; 95% CI, 0.812-0.880; P = .0007), lymphocyte percentage (0.808; 95% CI, 0.768-0.843; P < .0001), monocyte count (0.780; 95% CI, 0.739-0.817; P < .0001), or age (0.656; 95% CI, 0.610-0.699; P < .0001). The predicted probability conformed to the real observation outcomes of COVID-19, according to the calibration curves. Conclusions. We found that age, lymphocyte percentage, and monocyte count are risk factors for the early-stage prediction of patients infected with the 2019 novel coronavirus. As such, our research provides a useful test for doctors to differentiate COVID-19 from influenza.", "doc_id": "d118to5c"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Analysis of Covid-19 and non-Covid-19 viruses including influenza viruses to see the influence of intensive preventive measures among Japanese", "abstract": "Severe acute respiratory coronavirus 2 (SARS-CoV-2) spread and cause death in worldwide. The preventative measures and infection control are underway throughout the society and there are signs of convergence in some areas. Other viruses as well as SARS-CoV-2 cause cold-like symptoms and spread in winter. However, it is unclear to what extent SARS-CoV-2, influenza virus and other causative viruses have been prevailed since the preventative measures were implemented. In this study, we conducted multiples PCR and quantitative reverse transcription PCR using nasal swabs from 191 patients with cold-like symptoms in Japan to reveal the causative viruses. As a result, at least one virus were detected in 40 out of 191 (21%) patients. Of these, we frequently identified the human rhinovirus / enterovirus (5.8%, n=11), SARS-CoV-2 (4.2%, n=8) and human metapneumovirus (3.7%, n=7). On the other hand, no influenza virus was detected. These results shows the prevalence of causative viruses after the social preventative measures and implies the difference of infectivity between SARS-CoV-2 and influenza virus.", "doc_id": "otjctvr8"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Performance of suspected influenza case definitionbefore and during the COVID-19 pandemic", "abstract": "Background: The influenza-related burden remains high and the COVID-19 pandemic may difficult its accurate surveillance. This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. Methods: A cross-sectional analysis of a cohort study took place and cases fulfilling the suspected case criteria (n = 20,511), and with laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection were analyzed. Results: A high sensitivity and modest specificity were documented, and this later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the Area Under the Receiver Operating Characteristics among the analyzed periods. Conclusions: The evaluated case definition remains to be a cost-effective alternative to identify patients who may benefit from influenza-specific antiviral drugs, even during the COVID-19 global outbreak.", "doc_id": "5unh2a3f"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Early surveillance and public health emergency disposal measures between novel coronavirus disease 2019 and avian influenza in China: a case-comparison study", "abstract": "Background: The novel coronavirus disease 2019 (COVID-19) outbreak is spreading rapidly throughout China and the world. Hence, early surveillance and public health emergency disposal are considered crucial to curb this emerging infectious disease. However, studies that investigated the early surveillance and public health emergency disposal for the prevention and control of the COVID-19 outbreak in China are relatively few. We aimed to compare the strengths and weaknesses of early surveillance and public health emergency disposal for prevention and control between COVID-19 and H7N9 avian influenza, which was commended by the international community, in China. Methods: A case-comparison study was conducted using a set of six key time nodes to form a reference framework for evaluating early surveillance and public health emergency disposal between H7N9 avian influenza (2013) in Shanghai, China and COVID-19 in Wuhan, China. Findings: A report to the local Center for Disease Control and Prevention, China, for the first hospitalized patient was sent after 6 and 20 days for H7N9 avian influenza and COVID-19, respectively. In contrast, the pathogen was identified faster in the case of COVID-19 than in the case of H7N9 avian influenza (12 days vs. 31 days). The government response regarding COVID-19 was 10 days later than that regarding avian influenza. The entire process of early surveillance and public health emergency disposal lasted 5 days longer in COVID-19 than in H7N9 avian influenza (46 days vs. 41 days). Conclusions: The identification of the unknown pathogen improved in China between the outbreaks of avian influenza and COVID-19. The longer emergency disposal period in the case of COVID-19 could be attributed to the government's slower response to the epidemic. Improving public health emergency management could lessen the adverse social effects of emerging infectious diseases and public health crisis in the future.", "doc_id": "j40zj4al"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Genetic analysis of the novel SARS-CoV-2 host receptor TMPRSS2 in different populations", "abstract": "The infection coronavirus disease 2019 (COVID-19) is caused by a virus classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At cellular level, virus infection initiates with binding of viral particles to the host surface cellular receptor angiotensin converting enzyme 2 (ACE2). SARS-CoV-2 engages ACE2 as the entry receptor and employs the cellular serine protease 2 (TMPRSS2) for S protein priming. TMPRSS2 activity is essential for viral spread and pathogenesis in the infected host. Understanding how TMPRSS2 protein expression in the lung varies in the population could reveal important insights into differential susceptibility to influenza and coronavirus infections. Here, we systematically analyzed coding-region variants in TMPRSS2 and the eQTL variants, which may affect the gene expression, to compare the genomic characteristics of TMPRSS2 among different populations. Our findings suggest that the lung-specific eQTL variants may confer different susceptibility or response to SARS-CoV-2 infection from different populations under the similar conditions. In particular, we found that the eQTL variant rs35074065 is associated with high expression of TMPRSS2 but with a low expression of the interferon (IFN)-\u03b1/\u03b2-inducible gene, MX1, splicing isoform. Thus, these subjects could account for a more susceptibility either to viral infection or to a decrease in cellular antiviral response.", "doc_id": "gzy4yud3"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Using EpiRank for Analyzing Emerging Coronavirus Epidemic Patterns", "abstract": "Huang et al. (2019) used their EpiRank algorithm, which emphasizes forward-and-backward commuter flow between homes and workplaces, to analyze the distribution patterns of two infectious diseases in Taiwan: the 2009-H1N1 influenza virus and the widespread emergence of the 2000-2008 type 71 enterovirus (EV). As this article was being prepared, the spreading mechanism of the novel coronavirus disease now designated as COVID-19 had yet to be identified, but according to the American Centers for Disease Control, its spreading mechanism and patterns are likely more similar to influenza than to other coronaviruses such as Severe Acute Respiratory Syndrome (SARS-CoV-1) or Middle East Respiratory Syndrome (MERS-CoV). To consider potential COVID-19 spatial patterns, we applied EpiRank to the 2003 SARS outbreak in north Taiwan for comparison with H1N1 and EV. SARS was found to be less contagious than H1N1 or EV, but with a significantly higher fatality rate. The characteristics of these diseases determined their specific spatial spreading patterns, as reflected in the different effects of forward and backward commuting movement. Our motivation is to highlight these differences and to illustrate EpiRank spatial patterns for the 2003 SARS outbreak for comparison with EpiRank-determined distributions for the H1N1 and EV outbreaks. Our results indicate that the daytime parameter (i.e., forward movement effect) range was slightly higher (0.5-0.55) for the SARS outbreak than for either the influenza (0.4-0.5) or EV (0.3-0.5) outbreaks, suggesting that the forward-and-backward movements of individuals between residential and core urban areas with concentrated populations were equally important regarding the spread of SARS. While COVID-19 might resemble either SARS or H1N1 in terms of spatial spreading, its daytime parameter is likely somewhere in-between, with backward movement being dominant (similar to H1N1) or with forward and backward movement being equally important (similar to SARS). Building on Huang et al. (2019) paper, we present an estimated risk distribution pattern for the Taipei Metropolitan Area for a daytime parameter of 0.55.", "doc_id": "xj0h9o2v"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "COVID-19: Tracking the Pandemic with A Simple Curve Approximation Tool (SCAT)", "abstract": "Background In the current COVID-19 pandemic, much focus is put on 'flattening the curve'. This epidemiological 'curve' refers to the cases versus time graph, which shows the rise of a disease to its peak before descending. The aim in a pandemic is to flatten this curve by reducing the peak and spreading out the timeline. However, the models used to predict this curve are often not clearly outlined, no model parameters are given, and models are not tested against real data. This lack of detail makes it difficult to recreate the curve. What is much needed is a simple tool for approximating the curve to allow ideas to be tested and comparisons made. Methods This work presents a Simple Curve Approximation Tool (SCAT) which can be used by anyone. This tool allows the user to approximate and draw the curve and allows testing of assumptions, trajectories and the wildly varying figures reported in the media. The mathematics behind SCAT is clearly outlined here but understanding of this is not required. SCAT is provided online as a downloadable MS Excel workbook with some sample cases shown. Throughout this work, the parameters used are specified so that all results can be easily reproduced. Findings Although not intended as a prediction tool, SCAT has achieved less than 0.5 % error in short-term forward prediction. It also shows a very significant improvement on the pandemic exponential approximations found throughout media reporting. As a comparison tool, it highlights obvious differences between COVID-19 and other diseases, such as influenza, and between countries at different stages of the pandemic (China, Italy and the UK are used here for demonstration purposes). Interpretation SCAT allows for quick approximation of the curve and creates meaningful comparisons and understandable visualisations for COVID-19 and other diseases. Funding None.", "doc_id": "6kl6uso6"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Excess cases of influenza suggest an earlier start to the coronavirus epidemic in Spain than official figures tell us: an analysis of primary care electronic medical records from over 6 million people from Catalonia", "abstract": "Objectives: There is uncertainty about when the first cases of COVID-19 appeared in Spain, as asymptomatic patients can transmit the virus. We aimed to determine whether influenza diagnoses masked early COVID-19 cases and, if so, estimate numbers of undetected COVID-19 cases in a large database of primary-care records covering >6 million people in Catalonia. Design: Time-series study of influenza and COVID-19 cases, using all influenza seasons from autumn-winter 2010-2011 to autumn-winter 2019-2020. Setting: Primary care, Catalonia, Spain. Participants: People registered in one of the contributing primary-care practices, covering >6 million people and >85% of the population. Main outcome measures: Weekly new cases of influenza and COVID-19 diagnosed in primary care. Analyses: Daily counts of both cases were computed using the total cases recorded over the previous 7 days to avoid weekly effects on recording practice. Epidemic curves were characterised for the 2010-2011 to 2019-2020 influenza seasons. Influenza seasons with a similar epidemic curve and peak case number as the 2019-2020 season were used to model predictions for 2019-2020. ARIMA models were fitted to the included influenza seasons, overall and stratified by age, to estimate expected case numbers. Daily excess influenza cases were defined as the number of observed minus expected cases. Results: Four influenza season curves (2011-2012, 2012-2013, 2013-2014, and 2016-2017) were used to estimate the number of expected cases of influenza in 2019-2020. Between 4 February 2020 and 20 March 20202, 8,017 (95% CI: 1,841 to 14,718) excess influenza cases were identified. This excess was highest in the 15-64 age group. Conclusions: COVID-19 cases may have been present in the Catalan population when the first imported case was reported on 25 February 2020. COVID-19 carriers may have been misclassified as influenza diagnoses in primary care, boosting community transmission before public health measures were taken. In future, the surveillance of excess influenza cases using widely available primary-care electronic medical records could help detect new outbreaks of COVID-19 or other influenza-like illness-causing pathogens. Earlier detection would allow public health responses to be initiated earlier than during the current crisis.", "doc_id": "ye6k6cf8"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Social Distancing and Personal Protective Measures Decrease Influenza Morbidity and Mortality", "abstract": "Seasonal influenza (flu) is an underappreciated source of disease morbidity and mortality worldwide. While vaccination remains the cornerstone of influenza prevention, common measures practiced during the COVID-19 pandemic such as social distancing, the use of protective face masks, and frequent hand washing are rarely utilized during flu season. In this investigation, we examined the effect of these preventative measures in decreasing influenza burden this year. We examined three countries with major COVID-19 outbreaks i.e. China, Italy and the United States, and compared the flu activity this year to the average of the last 4 years (2015-2019). We found that this year in China and Italy, there was a significantly steeper decline of flu cases than average, which correlated with an increase in positive COVID-19 case reports in those countries. These \"averted\" cases can be translated into a substantial decrease in morbidity and mortality. As such, we conclude that the current COVID-19 pandemic is a reminder that behavioral measures can decrease the burden of communicable respiratory infections, and these measures should be adopted to an extent during normal influenza season.", "doc_id": "jitmsez2"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Understanding dynamics of pandemics", "abstract": "Along the centuries, novel strain of virus such as influenza produces pandemics which increase illness, death and disruption in the countries. Spanish flu in 1918, Asian flu in 1957, Hong Kong flu in 1968 and swine flu in 2009 were known pandemic which had various characteristics in terms of morbidity and mortality. A current pandemic is caused by novel corona virus originated from China. COVID-19 pandemic is very similar to Spanish, Hong Kong, Asian and swine influenza pandemics in terms of spreading to world by the mobilized people. Burden of pandemic is considered in terms of disease transmissibility and the growth rate of epidemic and duration of pandemic can be calculated by transmissibility characteristic. The case definition, finding out cases and first case cluster, proper treatment, sufficient stockpiles of medicine and population cooperation with the containment strategy should be considered for reduction of burden of pandemic.", "doc_id": "rjdb1qrt"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "COVID-19 pneumonia: CT findings of 122 patients and differentiation from influenza pneumonia", "abstract": "OBJECTIVES: To investigate the clinical and chest CT characteristics of COVID-19 pneumonia and explore the radiological differences between COVID-19 and influenza. MATERIALS AND METHODS: A total of 122 patients (61 men and 61 women, 48 \u00b1 15 years) confirmed with COVID-19 and 48 patients (23 men and 25 women, 47 \u00b1 19 years) confirmed with influenza were enrolled in the study. Thin-section CT was performed. The clinical data and the chest CT findings were recorded. RESULTS: The most common symptoms of COVID-19 were fever (74%) and cough (63%), and 102 patients (83%) had Wuhan contact. Pneumonia in 50 patients with COVID-19 (45%) distributed in the peripheral regions of the lung, while it showed mixed distribution in 26 patients (74%) with influenza (p = 0.022). The most common CT features of the COVID-19 group were pure ground-glass opacities (GGO, 36%), GGO with consolidation (51%), rounded opacities (35%), linear opacities (64%), bronchiolar wall thickening (49%), and interlobular septal thickening (66%). Compared with the influenza group, the COVID-19 group was more likely to have rounded opacities (35% vs. 17%, p = 0.048) and interlobular septal thickening (66% vs. 43%, p = 0.014), but less likely to have nodules (28% vs. 71%, p < 0.001), tree-in-bud sign (9% vs. 40%, p < 0.001), and pleural effusion (6% vs. 31%, p < 0.001). CONCLUSIONS: There are significant differences in the CT manifestations of patients with COVID-19 and influenza. Presence of rounded opacities and interlobular septal thickening, with the absence of nodules and tree-in-bud sign, and with the typical peripheral distribution, may help us differentiate COVID-19 from influenza. KEY POINTS: \u00e2\u0080\u00a2 Typical CT features of COVID-19 include pure ground-glass opacities (GGO), GGO with consolidation, rounded opacities, bronchiolar wall thickening, interlobular septal thickening, and a peripheral distribution. \u00e2\u0080\u00a2 Presence of rounded opacities and interlobular septal thickening, with the absence of nodules and tree-in-bud sign, and with the typical peripheral distribution, may help us differentiate COVID-19 from influenza.", "doc_id": "wjb7ltjx"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Characteristic CT findings distinguishing 2019 novel coronavirus disease (COVID-19) from influenza pneumonia", "abstract": "OBJECTIVES: To investigate the different CT characteristics which may distinguish influenza from 2019 coronavirus disease (COVID-19). METHODS: A total of 13 confirmed patients with COVID-19 were enrolled from January 16, 2020, to February 25, 2020. Furthermore, 92 CT scans of confirmed patients with influenza pneumonia, including 76 with influenza A and 16 with influenza B, scanned between January 1, 2019, to February 25, 2020, were retrospectively reviewed. Pulmonary lesion distributions, number, attenuation, lobe predomination, margin, contour, ground-glass opacity involvement pattern, bronchial wall thickening, air bronchogram, tree-in-bud sign, interlobular septal thickening, intralobular septal thickening, and pleural effusion were evaluated in COVID-19 and influenza pneumonia cohorts. RESULTS: Peripheral and non-specific distributions in COVID-19 showed a markedly higher frequency compared with the influenza group (p < 0.05). Most lesions in COVID-19 showed balanced lobe localization, while in influenza pneumonia they were predominantly located in the inferior lobe (p < 0.05). COVID-19 presented a clear lesion margin and a shrinking contour compared with influenza pneumonia (p < 0.05). COVID-19 had a patchy or combination of GGO and consolidation opacities, while a cluster-like pattern and bronchial wall thickening were more frequently seen in influenza pneumonia (p < 0.05). The lesion number and attenuation, air bronchogram, tree-in-bud sign, interlobular septal thickening, and intralobular septal thickening were not significantly different between the two groups (all p > 0.05). CONCLUSIONS: Though viral pneumonias generally show similar imaging features, there are some characteristic CT findings which may help differentiating COVID-19 from influenza pneumonia. KEY POINTS: \u00e2\u0080\u00a2 CT can play an early warning role in the diagnosis of COVID-19 in the case of no epidemic exposure. \u00e2\u0080\u00a2 CT could be used for the differential diagnosis of influenza and COVID-19 with satisfactory accuracy. \u00e2\u0080\u00a2 COVID-19 had a patchy or combination of GGO and consolidation opacities with peripheral distribution and balanced lobe predomination.", "doc_id": "6m8xicjc"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "COVID-19: A promising cure for the global panic", "abstract": "The novel Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, which is the causative agent of a potentially fatal disease that is of great global public health concern. The outbreak of COVID-19 is wreaking havoc worldwide due to inadequate risk assessment regarding the urgency of the situation. The COVID-19 pandemic has entered a dangerous new phase. When compared with SARS and MERS, COVID-19 has spread more rapidly, due to increased globalization and adaptation of the virus in every environment. Slowing the spread of the COVID-19 cases will significantly reduce the strain on the healthcare system of the country by limiting the number of people who are severely sick by COVID-19 and need hospital care. Hence, the recent outburst of COVID-19 highlights an urgent need for therapeutics targeting SARS-CoV-2. Here, we have discussed the structure of virus; varying symptoms among COVID-19, SARS, MERS and common flu; the probable mechanism behind the infection and its immune response. Further, the current treatment options, drugs available, ongoing trials and recent diagnostics for COVID-19 have been discussed. We suggest traditional Indian medicinal plants as possible novel therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways.", "doc_id": "pbxs2hmz"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Comparison of Hospitalized Patients With ARDS Caused by COVID-19 and H1N1", "abstract": "BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses. RESEARCH QUESTION: The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS. STUDY DESIGN AND METHODS: This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared. RESULTS: The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the H1N1 cohort (P < .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P < .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P < .05). The Pao2/Fio2 of 198.5 mm Hg in the COVID-19 cohort was significantly higher than the Pao2/Fio2 of 107.0 mm Hg in the H1N1 cohort (P < .001). Ground-glass opacities was more common in patients with COVID-19 than in patients with H1N1 (P < .001). There was a greater variety of antiviral therapies administered to COVID-19 patients than to H1N1 patients. The in-hospital mortality of patients with COVID-19 was 28.8%, whereas that of patients with H1N1 was 34.7% (P = .483). SOFA score-adjusted mortality of H1N1 patients was significantly higher than that of COVID-19 patients, with a rate ratio of 2.009 (95% CI, 1.563-2.583; P < .001). INTERPRETATION: There were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.", "doc_id": "csexhq9q"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "COVID-19 versus seasonal influenza 2019-2020: USA", "abstract": "Severe mitigation efforts in the USA to reduce the incidence of COVID-19 infections have led to a massive rise in unemployment, social disruption, and appear to be leading to a severe economic depression. In contrast, no such interventions were regarded as necessary to manage seasonal influenza in 2019-2020. Another mitigation approach is proposed for COVID-19 that would allow society to function and yet should still be effective.", "doc_id": "9lakd5pl"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "The epidemiology and clinical characteristics of co-infection of SARS-CoV-2 and influenza viruses in patients during COVID-19 outbreak", "abstract": "In this study, we performed a single-centred study of 307 SARS-CoV-2 infected patients. It was found that co-infection of SARS-CoV-2 and influenza virus was common during COVID-19 outbreak. And patients co-infected with SARS-CoV-2 and influenza B virus have a higher risk of developing poor outcomes so a detection of both viruses was recommended during COVID-19 outbreak. This article is protected by copyright. All rights reserved.", "doc_id": "8dds3rkn"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Comparison of Hospitalized Patients with pneumonia caused by COVID-19 and influenza A in children under 5 years", "abstract": "BACKGROUND: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in Wuhan, considerable attention has been paid on its epidemiology and clinical characteristics in children patients. However, it is also crucial for clinicians to differentiate COVID-19 from other respiratory infectious diseases, such as influenza viruses. METHODS: This was a retrospective study. Two group of COVID-19 patients (n=57) and influenza A patients (n=59) were enrolled. We analyzed and compared their clinical manifestations, imaging characteristics and treatments. RESULTS: The proportions of cough (70.2%), fever (54.4%) and gastrointestinal symptoms (14.1%) in COVID-19 patients were lower than those of influenza A patients (98.3%, P<0.001; 84.7%, P<0.001; and 35.6%, P=0.007; respectively). In addition, COVID-19 patients showed significantly lower levels of leukocytes (7.87 vs. 9.89\u00d7109/L, P=0.027), neutrophils (2.43 vs. 5.16\u00d7109/L, P<0.001), C-reactive protein (CRP; 3.7 vs. 15.1mg/L, P=0.001) and procalcitonin (PCT; 0.09 vs. 0.68mm/h, P<0.001), while lymphocyte levels (4.58 vs. 3.56\u00d7109/L; P=0.006) were significantly higher compared with influenza A patients. In terms of CT imaging, ground-glass opacification in chest CT was more common in COVID-19 patients than in influenza A patients (42.1% vs. 15%, P=0.032). In contrast, consolidation was more common in influenza A patients (25%) than that in COVID-19 patients (5.2%, P=0.025). CONCLUSION: The clinical manifestations and laboratory tests of COVID-19 children are milder than those of influenza A children under 5 years. Additionally, imaging results more commonly presented as ground-glass opacities in COVID-19 patients.", "doc_id": "qapadc6p"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Positive effects of COVID-19 control measures on influenza prevention", "abstract": "Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become a pandemic threat to the whole world. At the same time, influenza virus has been active, with influenza virus and SARS-CoV-2 sharing the same transmission routes. This article aims to alert clinicians of the presence of co-infection with these two viruses and to describe the effect of the measures taken to fight COVID-19 on influenza prevention and control.", "doc_id": "mqzxvp6n"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "INFECTIONS IN PREGNANCY WITH COVID-19 AND OTHER RESPIRATORY RNA VIRUS DISEASES ARE RARELY, IF EVER, TRANSMITTED TO THE FETUS: EXPERIENCES WITH CORONAVIRUSES, HPIV, hMPV RSV, AND INFLUENZA", "abstract": "SARS-CoV-2, the agent of COVID-19, is similar to two other coronaviruses, SARS-CoV and MERS-CoV, in causing life-threatening maternal respiratory infections and systemic complications. Because of global concern for potential intrauterine transmission of SARS-CoV-2 from pregnant women to their infants, this report analyzes the effects on pregnancy of infections caused by SARS-CoV-2 and other respiratory RNA viruses, and examines the frequency of maternal-fetal transmission with SARS-CoV-2, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, respiratory syncytial virus (RSV), parainfluenza (HPIV) and metapneumovirus (hMPV). There have been no confirmed cases of intrauterine transmission reported with COVID-19 or any other coronavirus infections. Influenza virus, despite causing approximately one billion annual infections globally, has only a few cases of confirmed or suspected intrauterine fetal infections reported. RSV is in an unusual cause of illness among pregnant women, and with the exception of one premature infant with congenital pneumonia, no other cases of maternal-fetal infection are described. Parainfluenza virus and human metapneumovirus can produce symptomatic maternal infections but do not cause intrauterine fetal infection. In summary, it appears that the absence thus far of maternal-fetal transmission of the SARS-CoV-2 virus during the COVID-19 pandemic is similar to other coronaviruses, and is also consistent with the extreme rarity of suggested or confirmed cases of intrauterine transmission of other respiratory RNA viruses. This observation has important consequences for pregnant women as it appears that if intrauterine transmission of SARSCoV-2 does eventually occur, it will be a rare event. Potential mechanisms of fetal protection from maternal viral infections are also discussed.", "doc_id": "twm32weg"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan", "abstract": "BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CO-V-2), was first reported in Wuhan, Hubei province, China has now rapidly spread over 50 countries. For the prevention and control of infection, Taiwan Centers for Disease Control initiated testing of SARS-CoV-2 on January 24th 2020 for persons suspected with this disease. Until February 28th, 43 flu-like symptomatic patients were screened in China Medical University Hospital. METHODS: Two patients were confirmed positive for SARS-CoV-2 infection by rRT-PCR as COVID-19 patients A and B. Causative pathogens for included patients were detected using FilmArray™ Respiratory Panel. We retrospectively analyzed the clinical presentations, laboratory data, radiologic findings, and travel and exposure contact histories, of the COVID-19 patients in comparison to those with other respiratory infections. RESULTS: Through contact with Taiwan No. 19 case patient on 27th January, COVID-19 patients A and B were infected. Both patients had no identified comorbidities and developed mild illness with temporal fever, persistent cough, and lung interstitial infiltrates. Owing to the persistence of positive SARS-CoV-2 in respiratory specimen, the two COVID-19 patients are still in the isolation rooms despite recovery until 10th of March. The results of FilmArrayTM Respiratory Panel revealed 22 of the 41 non-COVID-19 patients were infected by particular pathogens. In general, seasonal respiratory pathogens are more prevalent than SARS-CoV-2 in symptomatic patients in non- COVID-19 endemic area during the flu season. Since all patients shared similar clinical and laboratory findings, expanded surveillance of detailed exposure history for suspected patients and application of rapid detection tools are highly recommended.", "doc_id": "ryojd2b3"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Comparative review of respiratory diseases caused by coronaviruses and influenza A viruses during epidemic season", "abstract": "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.", "doc_id": "gc3iq0wp"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "How coronavirus lockdowns stopped flu in its tracks", "abstract": "", "doc_id": "0wxf08hc"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Does this patient have COVID-19? A practical guide for the internist", "abstract": "Coronavirus disease 2019 (COVID-19) is currently causing a pandemic and will likely persist in endemic form in the foreseeable future. Physicians need to correctly approach this new disease, often representing a challenge in terms of differential diagnosis. Although COVID-19 lacks specific signs and symptoms, we believe internists should develop specific skills to recognize the disease, learning its 'semeiotic'. In this review article, we summarize the key clinical features that may guide in differentiating a COVID-19 case, requiring specific testing, from upper respiratory and/or influenza-like illnesses of other aetiology. We consider two different clinical settings, where availability of the different diagnostic strategies differs widely: outpatient and inpatient. Our reasoning highlights how challenging a balanced approach to a patient with fever and flu-like symptoms can be. At present, clinical workup of COVID-19 remains a hard task to accomplish. However, knowledge of the natural history of the disease may aid the internist in putting common and unspecific symptoms into the correct clinical context.", "doc_id": "evv73ry1"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Echoes of 2009 H1N1 Influenza Pandemic in the COVID Pandemic", "abstract": "The severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV2) pandemic that has engulfed the globe has had incredible effects on health care systems and economic activity. Social distancing and school closures have played a central role in public health efforts to counter the coronavirus disease 2019 (COVID)-19 pandemic. The most recent global pandemic prior to COVID-19 was the 2009 pandemic, hemagglutinin type 1 and neuraminidase type 1 (H1N1) influenza. The course of events in 2009 offer some rich lessons that could be applied to the current COVID-19 pandemic. This commentary highlights some of the most relevant points and a discussion of possible outcomes of the COVID-19 pandemic.", "doc_id": "gyimko76"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "[Comparison of pathological changes and pathogenic mechanisms caused by H1N1 influenza virus, highly pathogenic H5N1 avian influenza virus, SARS-CoV, MERS-CoV and 2019-nCoV]", "abstract": "", "doc_id": "mz8g2u0v"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Characteristics of respiratory virus infection during the outbreak of 2019 novel coronavirus in Beijing", "abstract": "BACKGROUND: Coronavirus disease 2019 (COVID-19) is spreading. Here, we summarized the composition of pathogens in fever clinic patients and analyzed the characteristics of different respiratory viral infections. METHODS: Retrospectively collected patients with definite etiological results using nasal and pharyngeal swabs in a fever clinic. RESULTS: Overall, 1860 patients were screened, and 136 patients were enrolled. 72 (52.94%) of them were diagnosed as influenza (Flu) A virus infection. 32 (23.53%) of them were diagnosed as Flu B virus infection. 18 (13.24%) and 14 (10.29%) of them were diagnosed as COVID-19 and respiratory syncytial virus (RSV) infections, respectively. The COVID-19 group had a higher rate of contact with the epidemic area within 14 days and of clustering onset than other groups. Fever was the most common symptom in these patients. The ratio of fever to the highest temperature was higher in Flu A virus infection patients than in COVID-19 patients. COVID-19 patients had a lower white blood cell count and neutrophil count than Flu A virus and RSV infection groups, but higher lymphocyte count than Flu A and B virus infection groups. The COVID-19 group (83.33%) had a higher rate of pneumonia in chest CT scans than Flu A and B virus infection groups. CONCLUSIONS: Influenza viruses accounted for a large proportion of respiratory virus infection even during the epidemic of COVID-19 in Beijing. No single symptom or laboratory finding was suggestive of a specific respiratory virus; however, epidemic history was significant for the screening of COVID-19.", "doc_id": "eu79h4ee"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "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", "abstract": "", "doc_id": "kz0mas3w"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "A Comparison of Clinical and Chest CT Findings in Patients With Influenza A (H1N1) Virus Infection and Coronavirus Disease (COVID-19)", "abstract": "OBJECTIVE. The purpose of this study was to compare clinical and chest CT findings in patients with influenza A (H1N1) pneumonia and coronavirus disease (COVID-19) pneumonia. MATERIALS AND METHODS. Thirty patients with diagnosed influenza A (H1N1) virus infection (group A) and 30 patients with diagnosed COVID-19 (group B) were retrospectively enrolled in the present study. The clinical characteristics and chest CT findings of the two groups were compared. RESULTS. Fever, cough, expectoration, and dyspnea were the main symptoms in both groups with viral pneumonia, with cough and expectoration more frequently found in group A. Lymphopenia, an elevated C-reactive protein level, and an increased erythrocyte sedimentation rate were common laboratory test findings in the two groups. The median time from symptom onset to CT in group A and group B was 6 and 15 days, respectively, and the median total CT score of the pulmonary lobes involved was 6 and 13, respectively. Linear opacification, crazy-paving sign, vascular enlargement, were more common in group B. In contrast, bronchiectasis and pleural effusion were more common in group A. Other common CT features, including peripheral or peribronchovascular distribution, ground-glass opacities (GGOs), consolidation, subpleural line, air bronchogram, and bronchial distortion, did not show statistical significance. CONCLUSION. On CT, the significant differences between influenza A (H1N1) pneumonia and COVID-19 pneumonia were findings of linear opacification, crazy-paving sign, vascular enlargement, pleural thickening, and pleural effusion, which were more common in patients with COVID-19 pneumonia, and bronchiectasis and pleural effusion, which were more common in patients with influenza A (H1N1) pneumonia. Other imaging findings, including peripheral or peribronchovascular distribution, ground-glass opacities (GGO), consolidation, subpleural line, air bronchogram, and bronchial distortion, were not significantly different between the two patient groups.", "doc_id": "y7c0ynin"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Could enhanced influenza and pneumococcal vaccination programs help limit the potential damage from SARS-CoV-2 to fragile health systems of southern hemisphere countries this winter?", "abstract": "", "doc_id": "881eg8v3"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Comparison of short-term mortality between mechanically ventilated patients with COVID-19 and influenza in a setting of sustainable healthcare system", "abstract": "", "doc_id": "zn0msy5w"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Characteristics of and Public Health Emergency Responses to COVID-19 and H1N1 Outbreaks: A Case-Comparison Study", "abstract": "Background: Recently, the novel coronavirus disease (COVID-19) has already spread rapidly as a global pandemic, just like the H1N1 swine influenza in 2009. Evidences have indicated that the efficiency of emergency response was considered crucial to curb the spread of the emerging infectious disease. However, studies of COVID-19 on this topic are relatively few. Methods: A qualitative comparative study was conducted to compare the timeline of emergency responses to H1N1 (2009) and COVID-19, by using a set of six key time nodes selected from international literature. Besides, we also explored the spread speed and peak time of COVID-19 and H1N1 swine influenza by comparing the confirmed cases in the same time interval. Results: The government\u2019s entire emergency responses to the epidemic, H1N1 swine influenza (2009) completed in 28 days, and COVID-19 (2019) completed in 46 days. Emergency responses speed for H1N1 was 18 days faster. As for the epidemic spread speed, the peak time of H1N1 came about 4 weeks later than that of COVID-19, and the H1N1 curve in America was flatter than COVID-19 in China within the first four months after the disease emerged. Conclusions: The speed of the emergency responses to H1N1 was faster than COVID-19, which might be an important influential factor for slowing down the arrival of the peak time at the beginning of the epidemic. Although COVID-19 in China is coming to an end, the government should improve the public health emergency system, in order to control the spread of the epidemic and lessen the adverse social effects in possible future outbreaks.", "doc_id": "mz9goiqk"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "An international characterisation of patients hospitalised with COVID-19 and a comparison with those previously hospitalised with influenza", "abstract": "Background To better understand the profile of individuals with severe coronavirus disease 2019 (COVID-19), we characterised individuals hospitalised with COVID-19 and compared them to individuals previously hospitalised with influenza. Methods We report the characteristics (demographics, prior conditions and medication use) of patients hospitalised with COVID-19 between December 2019 and April 2020 in the US (Columbia University Irving Medical Center [CUIMC], STAnford Medicine Research data Repository [STARR-OMOP], and the Department of Veterans Affairs [VA OMOP]) and Health Insurance Review & Assessment [HIRA] of South Korea. Patients hospitalised with COVID-19 were compared with patients previously hospitalised with influenza in 2014-19. Results 6,806 (US: 1,634, South Korea: 5,172) individuals hospitalised with COVID-19 were included. Patients in the US were majority male (VA OMOP: 94%, STARR-OMOP: 57%, CUIMC: 52%), but were majority female in HIRA (56%). Age profiles varied across data sources. Prevalence of asthma ranged from 7% to 14%, diabetes from 18% to 43%, and hypertensive disorder from 22% to 70% across data sources, while between 9% and 39% were taking drugs acting on the renin-angiotensin system in the 30 days prior to their hospitalisation. Compared to 52,422 individuals hospitalised with influenza, patients admitted with COVID-19 were more likely male, younger, and, in the US, had fewer comorbidities and lower medication use. Conclusions Rates of comorbidities and medication use are high among individuals hospitalised with COVID-19. However, COVID-19 patients are more likely to be male and appear to be younger and, in the US, generally healthier than those typically admitted with influenza.", "doc_id": "xd3bf11a"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Active surveillance documents rates of clinical care seeking due to respiratory illness", "abstract": "BACKGROUND: Respiratory viral infections are a leading cause of disease worldwide. However, the overall community prevalence of infections has not been properly assessed, as standard surveillance is typically acquired passively among individuals seeking clinical care. METHODS: We conducted a prospective cohort study in which participants provided daily diaries and weekly nasopharyngeal specimens that were tested for respiratory viruses. These data were used to analyze healthcare seeking behavior, compared with cross\u2010sectional ED data and NYC surveillance reports, and used to evaluate biases of medically attended ILI as signal for population respiratory disease and infection. RESULTS: The likelihood of seeking medical attention was virus\u2010dependent: higher for influenza and metapneumovirus (19%\u201020%), lower for coronavirus and RSV (4%), and 71% of individuals with self\u2010reported ILI did not seek care and half of medically attended symptomatic manifestations did not meet the criteria for ILI. Only 5% of cohort respiratory virus infections and 21% of influenza infections were medically attended and classifiable as ILI. We estimated 1 ILI event per person/year but multiple respiratory infections per year. CONCLUSION: Standard, healthcare\u2010based respiratory surveillance has multiple limitations. Specifically, ILI is an incomplete metric for quantifying respiratory disease, viral respiratory infection, and influenza infection. The prevalence of respiratory viruses, as reported by standard, healthcare\u2010based surveillance, is skewed toward viruses producing more severe symptoms. Active, longitudinal studies are a helpful supplement to standard surveillance, can improve understanding of the overall circulation and burden of respiratory viruses, and can aid development of more robust measures for controlling the spread of these pathogens.", "doc_id": "14n4szd1"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Coronavirus Disease 2019 (COVID-19): A critical care perspective beyond China", "abstract": "", "doc_id": "oe7adj91"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "This really is nothing like flu", "abstract": "Those downplaying the coronavirus ignore our lack of immunity and vaccines", "doc_id": "t9u7d029"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Clinical features of COVID-19 and influenza: A comparative study on Nord Franche-Comte cluster", "abstract": "Clinical descriptions about influenza-like illnesses (ILI) in COVID-19 seem non-specific. We aimed to compare the clinical features of COVID-19 and influenza. We retrospectively investigated the clinical features and outcomes of confirmed cases of COVID-19 and influenza in Nord Franche-Comt\u00e9 Hospital between February 26(th) and March 14(th) 2020. We used SARS-CoV-2 RT-PCR and influenza virus A/B RT-PCR in respiratory samples to confirm the diagnosis. We included 124 patients. The mean age was 59(\u00b119[19-98]) years with 69% female. 70 patients with COVID-19 and 54 patients with influenza A/B. Regarding age, sex and comorbidities, no differences were found between the two groups except a lower Charlson index in COVID-19 group (2[\u00b12.5] vs 3[\u00b12.4],p=0.003). Anosmia (53% vs 17%,p<0.001), dysgeusia (49% vs 20%,p=0.001), diarrhea (40% vs 20%,p=0.021), frontal headache (26% vs 9%,p=0.021) and bilateral cracklings sounds (24% vs 9%,p=0.034) were statistically more frequent in COVID-19. Sputum production (52% vs 29%,p=0.010), dyspnea (59% vs 34%,p=0.007), sore throat (44% vs 20%,p=0.006), conjunctival hyperhemia (30% vs 4%,p<0.001), tearing (24% vs 6%,p=0.004), vomiting (22% vs 3%,p=0.001) and rhonchi sounds (17% vs 1%,p=0.002) were more frequent with influenza infection. We described several clinical differences which can help the clinicians during the co-circulation of influenza and SARS-CoV-2.", "doc_id": "2pmpspuj"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "The dynamic effects of infectious disease outbreaks: The case of pandemic influenza and human coronavirus", "abstract": "Pandemic influenza is a regularly recurring form of infectious disease; this work analyses its economic effects. Like many other infectious diseases influenza pandemics are usually of short, sharp duration. Human coronavirus is a less regularly recurring infectious disease. The human coronavirus pandemic of 2019 (COVID-19) has presented with seemingly high transmissibility and led to extraordinary socioeconomic disruption due to severe preventative measures by governments. To understand and compare these events, epidemiological and economic models are linked to capture the transmission of a pandemic from regional populations to regional economies and then across regional economies. In contrast to past pandemics, COVID-19 is likely to be of longer duration and more severe in its economic effects given the greater uncertainty surrounding its nature. The analysis indicates how economies are likely to be affected due to the risk-modifying behaviour in the form of preventative measures taken in response to the latest novel pandemic virus.", "doc_id": "k7yxpl56"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "COVID-19 versus seasonal influenza 2019\u20132020: USA", "abstract": "Severe mitigation efforts in the USA to reduce the incidence of COVID-19 infections have led to a massive rise in unemployment, social disruption, and appear to be leading to a severe economic depression. In contrast, no such interventions were regarded as necessary to manage seasonal influenza in 2019\u20132020. Another mitigation approach is proposed for COVID-19 that would allow society to function and yet should still be effective.", "doc_id": "yf06vblx"} {"topic_name": "difference between coronavirus and flu", "topic_id": "31", "title": "Social distancing measures: evidence of interruption of seasonal influenza activity and early lessons of the SARS-CoV-2 pandemic", "abstract": "", "doc_id": "b003vcdc"} {"topic_name": "coronavirus subtypes", "topic_id": "32", "title": "Genomic epidemiology put to the test against COVID-19", "abstract": "In early April, a paper published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) raised the eyebrows of a number of genomic epidemiologists It suggested that there were three distinct variants of the novel coronavirus, SARS-CoV-2, spreading in different regions of the world\u2014one predominantly in Australia and North America, one in China, and one in Europe It also suggested that the variant circulating in North America and Australia was older than the one that appeared in Wuhan, China, at the end of December (Proc Natl Acad Sci U S A 2020, DOI: 10 1073/pnas 2004999117) If this were true, the outbreak of COVID-19, the disease caused by the virus, would have started outside Wuhan, which contradicts scientific consensus Some genomic epidemiologists, who track the genomes of pathogens to understand how diseases spread, thought that although the data the PNAS paper used were sound, the paper\u2019s analytical View: PDF ;Full Text HTML", "doc_id": "cccqcfgq"} {"topic_name": "coronavirus subtypes", "topic_id": "32", "title": "Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction", "abstract": "The emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests the possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect these variants. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variants as an attenuated vaccine or laboratory tool should be evaluated.", "doc_id": "mgsaoz3j"} {"topic_name": "coronavirus subtypes", "topic_id": "32", "title": "Bayesian phylodynamic inference on the temporal evolution and global transmission of SARS-CoV-2", "abstract": "", "doc_id": "jnkszwea"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "In silico identification of vaccine targets for 2019-nCoV.", "abstract": "Background: The newly identified coronavirus known as 2019-nCoV has posed a serious global health threat. According to the latest report (18-February-2020), it has infected more than 72,000 people globally and led to deaths of more than 1,016 people in China. Methods: The 2019 novel coronavirus proteome was aligned to a curated database of viral immunogenic peptides. The immunogenicity of detected peptides and their binding potential to HLA alleles was predicted by immunogenicity predictive models and NetMHCpan 4.0. Results: We report in silico identification of a comprehensive list of immunogenic peptides that can be used as potential targets for 2019 novel coronavirus (2019-nCoV) vaccine development. First, we found 28 nCoV peptides identical to Severe acute respiratory syndrome-related coronavirus (SARS CoV) that have previously been characterized immunogenic by T cell assays. Second, we identified 48 nCoV peptides having a high degree of similarity with immunogenic peptides deposited in The Immune Epitope Database (IEDB). Lastly, we conducted a de novo search of 2019-nCoV 9-mer peptides that i) bind to common HLA alleles in Chinese and European population and ii) have T Cell Receptor (TCR) recognition potential by positional weight matrices and a recently developed immunogenicity algorithm, iPred, and identified in total 63 peptides with a high immunogenicity potential. Conclusions: Given the limited time and resources to develop vaccine and treatments for 2019-nCoV, our work provides a shortlist of candidates for experimental validation and thus can accelerate development pipeline.", "doc_id": "z20po3eq"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "An Immunoinformatics Study to Predict Epitopes in the Envelope Protein of SARS-COV-2", "abstract": "COVID-19 is a new viral emergent human disease caused by a novel strain of Coronavirus. This virus has caused a huge problem in the world as millions of the people are affected with this disease in the entire world. We aimed to design a peptide vaccine for COVID-19 particularly for the envelope protein using computational methods to predict epitopes inducing the immune system and can be used later to create a new peptide vaccine that could replace conventional vaccines. A total of available 370 sequences of SARS-CoV-2 were retrieved from NCBI for bioinformatics analysis using Immune Epitope Data Base (IEDB) to predict B and T cells epitopes. Then we docked the best predicted CTL epitopes with HLA alleles. CTL cell epitopes namely interacted with MHC class I alleles and we suggested them to become universal peptides based vaccine against COVID-19. Potentially continuous B cell epitopes were predicted using tools from IEDB. The Allergenicity of predicted epitopes was analyzed by AllerTOP tool and the coverage was determined throughout the worlds. We found these CTL epitopes to be T helper epitopes also. The B cell epitope, SRVKNL and T cell epitope, FLAFVVFLL were suggested to become a universal candidate for peptide-based vaccine against COVID-19. We hope to confirm our findings by adding complementary steps of both in vitro and in vivo studies to support this new universal predicted candidate.", "doc_id": "ss6g3jkg"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "Multi-Antigenic Virus-like Particle of SARS CoV-2 produced in Saccharomyces cerevisiae as a vaccine candidate", "abstract": "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\u2122) 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 \u201cCorona\u201d like morphology, and uniform size distribution.", "doc_id": "1q71gjwt"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19", "abstract": "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.", "doc_id": "jgbjxgh1"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability", "abstract": "The rapid spread of SARS-CoV-2 has a significant impact on global health, travel and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated neutralizing antibodies from convalescent COVID-19 patients using a SARS-CoV-2 stabilized prefusion spike protein. Several of these antibodies were able to potently inhibit live SARS-CoV-2 infection at concentrations as low as 0.007 \u00b5g/mL, making them the most potent human SARS-CoV-2 antibodies described to date. Mapping studies revealed that the SARS-CoV-2 spike protein contained multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as previously undefined non-RBD epitopes. In addition to providing guidance for vaccine design, these mAbs are promising candidates for treatment and prevention of COVID-19.", "doc_id": "fgzrhs2i"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "Design of an Epitope-Based Peptide Vaccine against the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): A Vaccine Informatics Approach", "abstract": "The recurrent and recent global outbreak of SARS-COV-2 has turned into a global concern which has infected more than one million people all over the globe, and this number is increasing in hours. Unfortunate no vaccine or specific treatment is available, which make it more deadly. An immunoinformatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. In this study, we have identified a total of 15 antigenic peptides (including T and B Cells) in the surface glycoprotein of SARS-CoV-2 which found to be 100% conserved with other SARS coronaviruses. Furthermore, the population coverage analysis has found that CD4+ T-cell peptides showed higher cumulative population coverage over to CD8+ peptides in the 16 different geographical regions in the world. Notably, only 09 out of 15 peptides (LTDEMIAQY, IRASANLAA, FGAISSVLN, VKQLSSNFG, FAMQMAYRF, FGAGAALQ, VITPGTNTS, WTAGAAAYY and QTQTNSPRRARS) that have 80% - 90% identity with experimentally identified epitopes of different organisms including SARS-CoV and this will likely be beneficial for a quick progression of the vaccine design. Moreover, docking analysis suggested that these peptides are tightly bound in the groove of HLA molecules which can induce the T-cell response. Overall this study allows us to determine potent peptide antigen targets in surface glycoprotein on intuitive grounds which open up a new horizon in COVID-19 research. However, this study needs experimental validation by in vitro and in vivo.", "doc_id": "vsw5kuth"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "A candidate modified-live bovine coronavirus vaccine: safety and immunogenicity evaluation.", "abstract": "A modified-live vaccine against the respiratory form of bovine coronavirus (BCoV) infection was developed by progressive attenuation of a respiratory strain (438/06-TN). The vaccine was found to be safe as four colostrum-deprived newborn calves remained healthy after oronasal administration of ten doses of the vaccine. The immunogenicity of the vaccine was assessed by intramuscular injection of one vaccine dose to 30 BCoV-antibody negative 2-3-month-old calves. At 30 days post-vaccination, all vaccinated calves displayed high antibody titres against BCoV. Sequence analysis of the S gene of wild-type and cell-adapted 438/06-TN strain detected 10 nucleotide changes, 9 of which were non-synonymous.", "doc_id": "emcx33um"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "Current Status of Epidemiology, Diagnosis, Therapeutics, and Vaccines for Novel Coronavirus Disease 2019 (COVID-19)", "abstract": "Coronavirus disease 2019 (COVID-19), which causes serious respiratory illness such as pneumonia and lung failure, was first reported in Wuhan, the capital of Hubei, China. The etiological agent of COVID-19 has been confirmed as a novel coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is most likely originated from zoonotic coronaviruses, like SARS-CoV, which emerged in 2002. Within a few months of the first report, SARS-CoV-2 had spread across China and worldwide, reaching a pandemic level. As COVID-19 has triggered enormous human casualties and serious economic loss posing global threat, an understanding of the ongoing situation and the development of strategies to contain the virus's spread are urgently needed. Currently, various diagnostic kits to test for COVID-19 are available and several repurposing therapeutics for COVID-19 have shown to be clinically effective. In addition, global institutions and companies have begun to develop vaccines for the prevention of COVID-19. Here, we review the current status of epidemiology, diagnosis, treatment, and vaccine development for COVID-19.", "doc_id": "vaovwwkp"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "Design of a Multiepitope-Based Peptide Vaccine against the E Protein of Human COVID-19: An Immunoinformatics Approach", "abstract": "Background: A new endemic disease has spread across Wuhan City, China, in December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a \"public-health emergency of international concern\" due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus, the objective of this study is to design a multiepitope peptide vaccine against COVID-19 using an immunoinformatics approach. Method: Several techniques facilitating the combination of the immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T-cell epitope-based peptide vaccine using the envelope protein of 2019-nCoV as a target. Results: Extensive mutations, insertion, and deletion were discovered with comparative sequencing in the COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively. Conclusion: The T-cell epitope-based peptide vaccine was designed for COVID-19 using the envelope protein as an immunogenic target. Nevertheless, the proposed vaccine rapidly needs to be validated clinically in order to ensure its safety and immunogenic profile to help stop this epidemic before it leads to devastating global outbreaks.", "doc_id": "74kzoxi9"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "Reverse vaccinology approach to design a novel multi-epitope vaccine candidate against COVID-19: an in silico study", "abstract": "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.", "doc_id": "rwtv6yys"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "In silico identification of vaccine targets for 2019-nCoV", "abstract": "Background: The newly identified coronavirus known as 2019-nCoV has posed a serious global health threat. According to the latest report (18-February-2020), it has infected more than 72,000 people globally and led to deaths of more than 1,016 people in China. Methods: The 2019 novel coronavirus proteome was aligned to a curated database of viral immunogenic peptides. The immunogenicity of detected peptides and their binding potential to HLA alleles was predicted by immunogenicity predictive models and NetMHCpan 4.0. Results: We report in silico identification of a comprehensive list of immunogenic peptides that can be used as potential targets for 2019 novel coronavirus (2019-nCoV) vaccine development. First, we found 28 nCoV peptides identical to Severe acute respiratory syndrome-related coronavirus (SARS CoV) that have previously been characterized immunogenic by T cell assays. Second, we identified 48 nCoV peptides having a high degree of similarity with immunogenic peptides deposited in The Immune Epitope Database (IEDB). Lastly, we conducted a de novo search of 2019-nCoV 9-mer peptides that i) bind to common HLA alleles in Chinese and European population and ii) have T Cell Receptor (TCR) recognition potential by positional weight matrices and a recently developed immunogenicity algorithm, iPred, and identified in total 63 peptides with a high immunogenicity potential. Conclusions: Given the limited time and resources to develop vaccine and treatments for 2019-nCoV, our work provides a shortlist of candidates for experimental validation and thus can accelerate development pipeline.", "doc_id": "9q1zvoc1"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "High throughput and comprehensive approach to develop multiepitope vaccine against minacious COVID-19", "abstract": "The ongoing enigmatic COVID-19 outbreak, first reported from Wuhan, China, on last day of the year 2019, which has spread to 213 countries, territories/areas till 28th April 2020, threatens hundreds of thousands human souls. This devastating viral infection has stimulated the urgent development of viable vaccine against COVID-19 across the research institutes around the globe. The World Health Organization (WHO) has also confirmed that the recent pandemic is causing Public Health Emergency of International apprehension. Moreover, the earlier two pathogenic SARS-CoV and MERS-CoV and many others yet to be identified pose a universal menace. Here, in this piece of work, we have utilized an in silico structural biology and advanced immunoinformatic strategies to devise a multi-epitope subunit vaccine against ongoing COVID-19 infection. The engineered vaccine sequence is adjuvanted with \u00df-3 defensin and comprised of B-cell epitopes, HTL epitopes and CTL epitopes. This is very likely that the vaccine will be able to elicit the strong immune response. Further, specific binding of the engineered vaccine and immune cell receptor TLR3 was estimated by molecular interaction studies. Strong interaction in the binding groove as well as good docking scores affirmed the stringency of engineered vaccine. The interaction is stable with minimal deviation in root-mean square deviation and root-mean-square fluctuation was confirmed by the molecular dynamics simulation experiment. The immune-simulation by C-ImmSim server, which mimics the natural immune environment, yielded more potent immune response data of B-cells, Th cells, Tc cells and IgG for vaccine. The encouraging data obtained from the various in-silico works indicated this vaccine as an effective therapeutic against COVID-19.", "doc_id": "s67xk5tm"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "The development of vaccines against SARS corona virus in mice and SCID-PBL/hu mice", "abstract": "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.", "doc_id": "blnn9q3r"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "Robust computational design and evaluation of peptide vaccines for cellular immunity with application to SARS-CoV-2", "abstract": "We present a combinatorial machine learning method to evaluate and optimize peptide vaccine formulations, and we find for SARS-CoV-2 that it provides superior predicted display of viral epitopes by MHC class I and MHC class II molecules over populations when compared to other candidate vaccines. Our method is robust to idiosyncratic errors in the prediction of MHC peptide display and considers target population HLA haplotype frequencies during optimization. To minimize clinical development time our methods validate vaccines with multiple peptide presentation algorithms to increase the probability that a vaccine will be effective. We optimize an objective function that is based on the presentation likelihood of a diverse set of vaccine peptides conditioned on a target population HLA haplotype distribution and expected epitope drift. We produce separate peptide formulations for MHC class I loci (HLA-A, HLA-B, and HLA-C) and class II loci (HLA-DP, HLA-DQ, and HLA-DR) to permit signal sequence based cell compartment targeting using nucleic acid based vaccine platforms. Our SARS-CoV-2 MHC class I vaccine formulations provide 93.21% predicted population coverage with at least five vaccine peptide-HLA hits on average in an individual (\u2265 1 peptide 99.91%) with all vaccine peptides perfectly conserved across 4,690 geographically sampled SARS-CoV-2 genomes. Our MHC class II vaccine formulations provide 90.17% predicted coverage with at least five vaccine peptide-HLA hits on average in an individual with all peptides having observed mutation probability \u2264 0.001. We evaluate 29 previously published peptide vaccine designs with our evaluation tool with the requirement of having at least five vaccine peptide-HLA hits per individual, and they have a predicted maximum of 58.51% MHC class I coverage and 71.65% MHC class II coverage given haplotype based analysis. We provide an open source implementation of our design methods (OptiVax), vaccine evaluation tool (EvalVax), as well as the data used in our design efforts.", "doc_id": "10ucu0lt"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "Ensuring global access to COVID-19 vaccines", "abstract": "", "doc_id": "b4zibmi1"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "COVID-19: The race for a vaccine", "abstract": "", "doc_id": "j17lomkk"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "Disease X ver1.0: COVID-19", "abstract": "The SARS-Cov2 has presented the world with a novel pandemic challenge requiring a rapid response. This article provides a May 2020 snapshot from Professor Paul Young, who is part of a group working with urgency on Australia\u2019s leading COVID-19 candidate vaccine.", "doc_id": "4lruc5or"} {"topic_name": "coronavirus vaccine candidates", "topic_id": "33", "title": "Design of multi epitope-based peptide vaccine against E protein of human COVID-19: An immunoinformatics approach", "abstract": "Background New endemic disease has been spread across Wuhan City, China on December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a \u201cpublic-health emergency of international concern\u201d due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus the objective of this study is to design a multi epitope peptide vaccine against COVID-19 using immunoinformatics approach. Method Several techniques facilitating the combination of immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T cell epitopes-based peptide vaccine using the envelope protein of 2019-nCoV as a target. Results Extensive mutations, insertion and deletion were discovered with comparative sequencing in COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively. Conclusion T cell epitopes-based peptide vaccine was designed for COVID-19 using envelope protein as an immunogenic target. Nevertheless, the proposed vaccine is rapidly needed to be validated clinically in order to ensure its safety, immunogenic profile and to help on stopping this epidemic before it leads to devastating global outbreaks.", "doc_id": "6ojmmmuj"} {"topic_name": "coronavirus recovery", "topic_id": "34", "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.", "abstract": "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.", "doc_id": "bpiiddi7"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "[Comparison of Recovery Phase CT Features between Mild/moderate and Severe/critical Coronavirus Disease 2019 Patients].", "abstract": "Objective To investigate the computed tomographc(CT)features of mild/moderate and severe/critical cases of coronavirus disease 2019(COVID-19)in the recovery phase. Methods Totally 63 discharged patients in Wuhan,China,who underwent both chest CT and reverse transcription-polymerase chain reaction(RT-PCR)from February 1 to February 29,2020,were included.With RT-PCR as a gold standard,the performance of chest CT in diagnosing COVID-19 was assessed.Patients were divided into mild/moderate and severe/critical groups according to the disease conditions,and clinical features such as sex,age,symptoms,hospital stay,comorbidities,and oxygen therapy were collected.CT images in the recovery phase were reviewed in terms of time from onset,CT features,location of lesions,lobe score,and total CT score. Results There were 37 patients in the mild/moderate group and 26 in the severe/critical group. Compared with the mild/moderate patients,the severe/critical patients had older age [(43\u00b116) years vs. (52\u00b116) years; t=2.10, P=0.040], longer hospital stay [(15\u00b16)d vs. (19\u00b17)d; t=2.70, P=0.009], higher dyspnea ratio (5.41% vs. 53.85%; \u03c72=18.90, P<0.001), lower nasal oxygen therapy ratio (81.08% vs. 19.23%;\u03c72=23.66, P<0.001), and higher bi-level positive airway pressure ventilation ratio (0 vs. 57.69%; \u03c72=25.62, P<0.001). Time from onset was (23\u00b16) days in severe/critical group, significantly longer than that in mild/moderate group [(18\u00b17) days] (t=3.40, P<0.001). Severe/critical patients had significantly higher crazy-paving pattern ratio (46.15% vs.10.81%;\u03c72=4.24, P=0.039) and lower ground-glass opacities ratio (15.38% vs. 67.57%; \u03c72=16.74, P<0.001) than the mild/moderate patients. The proportion of lesions in peripheral lung was significantly higher in mild/moderate group than in severe/critical group (78.38% vs.34.61%; \u03c72=13.43, P<0.001), and the proportion of diffusely distributed lesions was significantly higher in severe/critical group than in mild/moderate group (65.38% vs.10.81%; \u03c72=20.47, P<0.001). Total CT score in severe/critical group was also significantly higher in severe/critical group than in mild/moderate group [11 (8,17) points vs. 7 (4,9) points; Z=3.81, P<0.001]. Conclusions The CT features in the recovery stage differ between mild/moderate and severe/critical COVID-19 patients.The lung infiltration is remarkably more severe in the latter.", "doc_id": "osgc4bm8"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Coronaviruses and the cardiovascular system: acute and long-term implications.", "abstract": "", "doc_id": "14mp0824"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Patients who have recovered from covid-19: issuing certificates and offering voluntary registration.", "abstract": "", "doc_id": "0hr744mg"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "[Advances in the research of mechanism of pulmonary fibrosis induced by Corona Virus Disease 2019 and the corresponding therapeutic measures].", "abstract": "The Corona Virus Disease 2019 (COVID-19) outbroke in Wuhan, China in December 2019 and the severe acute respiratory syndrome (SARS) outbroke in Guangzhou, China in 2003 were caused by highly pathogenic coronaviruses with high homology. Since the 2019 novel coronavirus has strong transmissibility and progress rapidly. It has caused negative social effects and massive economic damage on a global scale. While there is currently no vaccine or effective drugs. Pulmonary fibrosis is a pulmonary disease with progressive fibrosis, which is the main factor leading to pulmonary dysfunction and quality of life decline in SARS survivors after recovery. Extensive epidemiological, viral immunological, and current clinical evidences support the possibility that pulmonary fibrosis may be one of the major complications in COVID-19 patients. Although there are no reports on the mechanism of COVID-19 inducing pulmonary fibrosis, based on the existing theoretical basis, we focus on the possible mechanism of COVID-19 sustained lung damaging, the key role of abnormal immune mechanism in the initiation and promotion of pulmonary fibrosis, and the corresponding therapeutic measures.", "doc_id": "cmde6yx9"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Consideration of prevention and management of long-term consequences of post-acute respiratory distress syndrome in patients with COVID-19.", "abstract": "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.", "doc_id": "3xfhjddg"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Rehab facilities face COVID-19 crunch as more patients recover.", "abstract": "", "doc_id": "9p6lc8km"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Prevalence and Recovery From Olfactory and Gustatory Dysfunctions in Covid-19 Infection: A Prospective Multicenter Study.", "abstract": "BACKGROUND Covid-19 is defined by an association of multiple symptoms, including frequently reported olfactory and gustatory disorders. OBJECTIVE The main purpose of this study was to analyze the prevalence of these neurosensory impairments in patients with Covid-19, and to assess short-term recovery. METHODS We performed a multicenter case series study during the Covid-19 epidemic. All patients presenting a RT-PCR-confirmed SARS-CoV-2 infection were included, whether hospitalized or treated at home. To analyze the prevalence and features of olfactory and gustatory dysfunctions, a phone interview was conducted 5 days after the positive PCR result. The questionnaire was submitted again 10 days later to patients having reported olfactory and gustatory disorders, in order to assess their recovery. RESULTS 115 patients were included in our study. 81 patients (70%) reported olfactory and gustatory disorders without nasal obstruction or rhinorrhea. These impairments were more frequently reported in the female population, young people, and house-bound patients with mild symptomatic forms. Short-term recovery assessed at Day 15 was complete for 64% of the patients, and incomplete in 33%. Median recovery time was 15 days (4-27 days) after olfactory or gustatory symptom onset. CONCLUSION Olfactory and gustatory dysfunctions related to Covid-19 are frequently reported and prevalent in mild symptomatic forms of the disease. Recovery in most cases seems rapid and complete.", "doc_id": "czb53bpp"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Adjustment outcomes in Chinese patients following one-month recovery from severe acute respiratory syndrome in Hong Kong.", "abstract": "This study aimed to examine the short-term adjustment outcomes including distress, self-esteem, and quality of life among Chinese patients after 1-month recovery from severe acute respiratory syndrome (SARS) in Hong Kong and to investigate the predictive abilities of a set of selected variables on the outcomes. At 1-month recovery, 100 SARS survivors (mean age = 37; 66 women) and 184 community subjects completed self-administered questionnaires. In the General Health Questionnaire-28, 61% of the SARS survivors were identified as distressed cases under a conservative cutoff score of 6. Compared with the community sample, SARS survivors had significantly more distress and poor quality of life. Being a healthcare worker, severity of SARS symptoms, steroid dosage, and social support accounted for a portion of variances of different measures. Early psychiatric screening and intervention may be beneficial for the adjustment of SARS survivors after short-term recovery. Future research on the long-term impact of SARS is recommended.", "doc_id": "ysiuvdc8"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "[Rehabilitation is crucial for severe COVID-19 survivors].", "abstract": "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.", "doc_id": "jud53dmv"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Incomplete and late recovery of sudden olfactory dysfunction in COVID-19", "abstract": "INTRODUCTION: Sudden olfactory dysfunction is a new symptom related to COVID-19, with little data on its duration or recovery rate. OBJECTIVE: To characterize patients with sudden olfactory dysfunction during the COVID-19 pandemic, especially their recovery data. METHODS: An online survey was conducted by the Brazilian Society of Otorhinolaryngology and Cervico-Facial Surgery, and Brazilian Academy of Rhinology, including doctors who assessed sudden olfactory dysfunction patients starting after February 1st, 2020. Participants were posteriorly asked by e-mail to verify data on the recovery of sudden olfactory loss and test for COVID-19 at the end of the data collection period. RESULTS: 253 sudden olfactory dysfunction patients were included, of which 59.1% were females with median age of 36 years, with a median follow-up period of 31 days. 183 patients (72.3%) had been tested for COVID-19, and of those 145 (79.2%) tested positive. Patients that tested positive for COVID-19 more frequently showed non-specific inflammatory symptoms (89.7% vs. 73.7%; p=0.02), a lower rate of total recovery of sudden olfactory dysfunction (52.6% vs. 70.3%; p=0.05) and a longer duration to achieve total recovery (15 days vs. 10 days; p=0.0006) than the ones who tested negative for COVID-19. Considering only positive-COVID-19 patients, individuals with sudden hyposmia completely recovered more often than the ones with sudden anosmia (68.4% vs. 50.0%; p=0.04). CONCLUSION: Positive-COVID-19 patients with sudden olfactory dysfunction showed lower total recovery rate and longer duration than negative-COVID-19 patients. Additionally, total recovery was seen more frequently in positive-COVID-19 patients with sudden hyposmia than the ones with sudden anosmia.", "doc_id": "diui92j4"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Considerations for Postacute Rehabilitation for Survivors of COVID-19", "abstract": "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.", "doc_id": "7l17lern"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "The War on COVID-19 Pandemic: Role of Rehabilitation Professionals and Hospitals", "abstract": "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.", "doc_id": "hc7dndxt"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Long term complications and rehabilitation of COVID-19 patients", "abstract": "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.", "doc_id": "gnc0x3hi"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Preliminary detection of lung hypoperfusion in discharged Covid-19 patients during recovery", "abstract": "", "doc_id": "1its28tm"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Immediate and long-term consequences of COVID-19 infections for the development of neurological disease", "abstract": "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.", "doc_id": "ds12pmp1"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Olfactory and gustatory dysfunctions in 100 patients hospitalized for COVID-19: sex differences and recovery time in real-life", "abstract": "PURPOSE: COVID-19 displays a variety of clinical manifestations; in pauci-symptomatic patients olfactory (OD) and gustatory dysfunctions (GD) may represent the first or only symptom. This topic is currently arousing great interest, and a growing number of papers are being published. Aim of this study is to investigate the timing of recovery from OD and GD in a real-life population hospitalized for COVID-19. METHODS: We followed up by a phone interview the first 100 patients discharged a month earlier from three Italian non-intensive care wards. RESULTS: All 100 patients were Caucasian, mean age was 65 years, 60% were males. Forty-two patients (mean age 63 years) experienced subjective chemosensory dysfunctions (29 OD and 41 GD): the male/female ratio was 2:1; 83% reported a complete or near complete recovery at follow-up. The recovery rate was not significantly different between males and females. The mean duration of OD and GD was 18 and 16 days, respectively. The mean recovery time from OD or GD resulted significantly longer for females than for males (26 vs 14 days, P = 0.009). Among the 42 symptomatic, the mean age of males was significantly higher than that of females (66 vs 57 years, P = 0.04), while the opposite was observed in the 58 asymptomatic patients (60 vs 73 years, P = 0.0018). CONCLUSIONS: Recovery from OD or GD was rapid, occurring within 4 weeks in most patients. Chemosensory dysfunctions in women was less frequent, but longer lasting. The value of our study is its focus on a population of hospitalized patients significantly older than those previously described, and the additional data on gender differences.", "doc_id": "tgo40n0j"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "[Advances in the research of mechanism of pulmonary fibrosis induced by Corona Virus Disease 2019 and the corresponding therapeutic measures]", "abstract": "The Corona Virus Disease 2019 (COVID-19) outbroke in Wuhan, China in December 2019 and the severe acute respiratory syndrome (SARS) outbroke in Guangzhou, China in 2003 were caused by highly pathogenic coronaviruses with high homology. Since the 2019 novel coronavirus has strong transmissibility and progress rapidly. It has caused negative social effects and massive economic damage on a global scale. While there is currently no vaccine or effective drugs. Pulmonary fibrosis is a pulmonary disease with progressive fibrosis, which is the main factor leading to pulmonary dysfunction and quality of life decline in SARS survivors after recovery. Extensive epidemiological, viral immunological, and current clinical evidences support the possibility that pulmonary fibrosis may be one of the major complications in COVID-19 patients. Although there are no reports on the mechanism of COVID-19 inducing pulmonary fibrosis, based on the existing theoretical basis, we focus on the possible mechanism of COVID-19 sustained lung damaging, the key role of abnormal immune mechanism in the initiation and promotion of pulmonary fibrosis, and the corresponding therapeutic measures.", "doc_id": "kzifv9df"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Successful treatment of severe COVID-19 pneumonia in a liver transplant recipient", "abstract": "Coronavirus disease 2019 (COVID-19) pandemic spreads rapidly and may be an increasing challenge for transplant community. Clinical data on COVID-19 infection in transplant population is very limited. Herein we presented the clinical course and outcome of a 50-year-old male post liver transplantation who contracted COVID-19, with subsequent infection of his wife. The process of illness was representative. A therapeutic regime with temporary immunosuppression withdrawal and systemic low-dose corticosteroid as principle was involved in the management of the patient which made him recover from severe COVID-19 pneumonia.", "doc_id": "0kthumgi"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "The effect of massage on the quality of life in patients recovering from COVID-19: A systematic review protocol", "abstract": "BACKGROUND: There is a worldwide outbreak of covid-19, and as the number of patients increases, more and more patients are recovering. Massage is used as an alternative therapy. Currently, there are no relevant articles for systematic review. METHODS: We will search the randomized controlled trials related to acupuncture therapy and postoperative anorectal diseases from inception to January 2020. The following database is our focus area: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan-Fang Database. All published randomized controlled trials in English or Chinese related to massage for COVID-19 will be included. Primary outcome asthe influence of massage on the quality of life of convalescent patients. Secondary outcomes were accompanying symptoms (such as myalgia, expectoration, stuffiness, runny nose, pharyngalgia, anhelation, chest distress, dyspnea, crackles, headache, nausea, vomiting, anorexia, diarrhea) disappear rate, negative COVID-19 results rate on 2 consecutive occasions (not on the same day), average hospitalization time, clinical curative effect, and improved quality of life. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide evidence to judge whether massage is an effective intervention on the quality of life in patients recovering. PROSPERO REGISTRATION NUMBER: CRD42020181398.", "doc_id": "yqge5668"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Impaired pulmonary function in discharged patients with COVID-19: More work ahead", "abstract": "", "doc_id": "tnrveryw"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "De Novo Status Epilepticus in patients with COVID-19", "abstract": "Neurological complications are increasingly recognized with SARS-CoV-2, the causative pathogen for COVID-19. We present a single-center retrospective case series reporting the EEG and outcome of de novo status epilepticus (SE) in two African-American women with laboratory-confirmed SARS-CoV-2 virus. SE was the initial presentation in one asymptomatic individual. Patient 2 had COVID-19 pneumonia, and fluctuating mental status that raised the suspicion of subclinical SE. The patient with older age and higher comorbidities failed to recover from the viral illness that has no definitive treatment.", "doc_id": "1idyb9cg"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Recovery from the coronavirus disease-2019 (COVID-19) in two patients with coexisted (HIV) infection", "abstract": "", "doc_id": "dafuxkbf"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "WITHDRAWN: Analysis of thin-section CT in patients with coronavirus disease (COVID-19) after hospital discharge", "abstract": "", "doc_id": "7i75vs1i"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Long-term conditions and severe acute respiratory syndrome SARS-CoV-2 (COVID-19)", "abstract": "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.", "doc_id": "s6oi477q"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Follow-up studies in COVID-19 recovered patients - is it mandatory?", "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.", "doc_id": "uqhaxqqh"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review", "abstract": "Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing human coronavirus disease 2019 (COVID-19), which has now spread into a worldwide pandemic. The pulmonary manifestations of COVID-19 have been well described in the literature. Two similar human coronaviruses that cause Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1) are known to cause disease in the central and peripheral nervous systems. Emerging evidence suggests COVID-19 has neurologic consequences as well. Observations: This review serves to summarize available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system, and describe the range of clinical neurological complications that have been reported thus far in COVID-19 and their potential pathogenesis. Viral neuroinvasion may be achieved by several routes, including transsynaptic transfer across infected neurons, entry via the olfactory nerve, infection of vascular endothelium, or leukocyte migration across the blood-brain barrier. The most common neurologic complaints in COVID-19 are anosmia, ageusia, and headache, but other diseases, such as stroke, impairment of consciousness, seizure, and encephalopathy, have also been reported. Conclusions and Relevance: Recognition and understanding of the range of neurological disorders associated with COVID-19 may lead to improved clinical outcomes and better treatment algorithms. Further neuropathological studies will be crucial to understanding the pathogenesis of the disease in the central nervous system, and longitudinal neurologic and cognitive assessment of individuals after recovery from COVID-19 will be crucial to understand the natural history of COVID-19 in the central nervous system and monitor for any long-term neurologic sequelae.", "doc_id": "1z6l12ks"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study", "abstract": "BACKGROUND: The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019. This study was performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19). METHODS: Clinical data were collected from two tertiary hospitals in Wuhan. A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and we compare them with recovered patients (recovered group). Continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed by χ test or Fisher exact test as appropriate. RESULTS: Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients. The median age of the death group was older than the recovered group (69 [62, 74] vs. 40 [33, 57] years, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a9.738, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001). More patients in the death group had underlying diseases (72.5% vs. 41.4%, χ\u00e2\u0080\u008a=\u00e2\u0080\u008a22.105, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001). Patients in the death group had a significantly longer time of illness onset to hospitalization (10.0 [6.5, 12.0] vs. 7.0 [5.0, 10.0] days, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a3.216, P\u00e2\u0080\u008a=\u00e2\u0080\u008a0.001). On admission, the proportions of patients with symptoms of dyspnea (70.6% vs. 19.0%, χ\u00e2\u0080\u008a=\u00e2\u0080\u008a60.905, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001) and expectoration (32.1% vs. 12.1%, χ\u00e2\u0080\u008a=\u00e2\u0080\u008a13.250, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001) were significantly higher in the death group. The blood oxygen saturation was significantly lower in the death group (85 [77, 91]% vs. 97 [95, 98]%, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a10.625, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001). The white blood cell (WBC) in death group was significantly higher on admission (7.23 [4.87, 11.17] vs. 4.52 [3.62, 5.88] \u00d710/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a7.618, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001). Patients in the death group exhibited significantly lower lymphocyte count (0.63 [0.40, 0.79] vs. 1.00 [0.72, 1.27] \u00d710/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a8.037, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001) and lymphocyte percentage (7.10 [4.45, 12.73]% vs. 23.50 [15.27, 31.25]%, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a10.315, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001) on admission, and the lymphocyte percentage continued to decrease during hospitalization (7.10 [4.45, 12.73]% vs. 2.91 [1.79, 6.13]%, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a5.242, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001). Alanine transaminase (22.00 [15.00, 34.00] vs. 18.70 [13.00, 30.38] U/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a2.592, P\u00e2\u0080\u008a=\u00e2\u0080\u008a0.010), aspartate transaminase (34.00 [27.00, 47.00] vs. 22.00 [17.65, 31.75] U/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a7.308, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001), and creatinine levels (89.00 [72.00, 133.50] vs. 65.00 [54.60, 78.75] \u00b5mol/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a6.478, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001) were significantly higher in the death group than those in the recovered group. C-reactive protein (CRP) levels were also significantly higher in the death group on admission (109.25 [35.00, 170.28] vs. 3.22 [1.04, 21.80] mg/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a10.206, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001) and showed no significant improvement after treatment (109.25 [35.00, 170.28] vs. 81.60 [27.23, 179.08] mg/L, Z\u00e2\u0080\u008a=\u00e2\u0080\u008a1.219, P\u00e2\u0080\u008a=\u00e2\u0080\u008a0.233). The patients in the death group had more complications such as acute respiratory distress syndrome (ARDS) (89.9% vs. 8.6%, χ\u00e2\u0080\u008a=\u00e2\u0080\u008a148.105, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001), acute cardiac injury (59.6% vs. 0.9%, χ\u00e2\u0080\u008a=\u00e2\u0080\u008a93.222, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001), acute kidney injury (18.3% vs. 0%, χ\u00e2\u0080\u008a=\u00e2\u0080\u008a23.257, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001), shock (11.9% vs. 0%, χ\u00e2\u0080\u008a=\u00e2\u0080\u008a14.618, P\u00e2\u0080\u008a<\u00e2\u0080\u008a0.001), and disseminated intravascular coagulation (DIC) (6.4% vs. 0%, χ\u00e2\u0080\u008a=\u00e2\u0080\u008a7.655, P\u00e2\u0080\u008a=\u00e2\u0080\u008a0.006). CONCLUSIONS: Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels. More patients in the death group had complications such as ARDS, acute cardiac injury, acute kidney injury, shock, and DIC.", "doc_id": "en413zlr"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Influencia de la infecci\u00f3n SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiqui\u00e1tricas: \u00bfuna pandemia demorada?/ Influencia de la infecci\u00f3n SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiqui\u00e1tricas: \u00bfuna pandemia demorada?/ Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic?", "abstract": "INTRODUCTION: SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100 000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. DEVELOPMENT: We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. CONCLUSIONS: SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.", "doc_id": "0xkz36bj"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Behavioral Health and Response for COVID-19", "abstract": "Research from financial stress, disasters, pandemics, and other extreme events, suggests that behavioral health will suffer, including anxiety, depression, and posttraumatic stress symptoms. Furthermore, these symptoms are likely to exacerbate alcohol or drug use, especially for those vulnerable to relapse. The nature of coronavirus disease 2019 (COVID-19) and vast reach of the virus, leave many unknows for the repercussions on behavioral health, yet existing research suggests that behavioral health concerns should take a primary role in response to the pandemic. We propose a 4-step services system designed for implementation with a variety of different groups and reserves limited clinical services for the most extreme reactions. While we can expect symptoms to remit overtime, many will also have longer-term or more severe concerns. Behavioral health interventions will likely need to change overtime and different types of interventions should be considered for different target groups, such as for those who recover from COVID-19, health-care professionals, and essential personnel; and the general public either due to loss of loved ones or significant life disruption. The important thing is to have a systematic plan to support behavioral health and to engage citizens in prevention and doing their part in recovery by staying home and protecting others.", "doc_id": "8kp07f7i"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "SARS-CoV-2 turned positive in a discharged patient with COVID-19 arouses concern regarding the present standards for discharge", "abstract": "An outbreak of coronavirus disease (COVID-19) in Wuhan, China caused by SARS-CoV-2 has led to a serious epidemic in China and other countries, resulting in worldwide concern. With active efforts of prevention and control, more and more patients are being discharged. However, how to manage these patients normatively is still challenging. This paper reports an asymptomatic discharged patient with COVID-19 who retested positive for SARS-CoV-2, which arouses concern regarding the present discharge standards of COVID-19.", "doc_id": "7jakv2ge"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Establishment of a COVID-19 Recovery Unit in a Veteran Affairs (VA) Post-Acute Facility", "abstract": "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.", "doc_id": "3thnu3kk"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "The impact of nutrition on COVID-19 susceptibility and long-term consequences", "abstract": "While all groups are affected by the COVID-19 pandemic, the elderly, underrepresented minorities, and those with underlying medical conditions are at the greatest risk. The high rate of consumption of diets high in saturated fats, sugars, and refined carbohydrates (collectively called Western diet, WD) worldwide, contribute to the prevalence of obesity and type 2 diabetes, and could place these populations at an increased risk for severe COVID-19 pathology and mortality. WD consumption activates the innate immune system and impairs adaptive immunity, leading to chronic inflammation and impaired host defense against viruses. Furthermore, peripheral inflammation caused by COVID-19 may have long-term consequences in those that recover, leading to chronic medical conditions such as dementia and neurodegenerative disease, likely through neuroinflammatory mechanisms that can be compounded by an unhealthy diet. Thus, now more than ever, wider access to healthy foods should be a top priority and individuals should be mindful of healthy eating habits to reduce susceptibility to and long-term complications from COVID-19.", "doc_id": "b999y89f"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Proyecci\u00f3n epidemiol\u00f3gica de COVID-19 en Chile basado en el modelo SEIR generalizado y el concepto de recuperado./ [An epidemiological forecast of COVID-19 in Chile based on the generalized SEIR model and the concept of recovered]", "abstract": "The COVID-19 pandemic declared by the World Health Organization (WHO) has generated a wide-ranging debate regarding epidemiological forecasts and the global implications. With the data obtained from the Chilean Ministry of Health (MINSAL), a prospective study was carried out using the generalized SEIR model to estimate the course of COVID-19 in Chile. Three scenarios were estimated: Scenario 1 with official MINSAL data; scenario 2 with official MINSAL data and recovery criteria proposed by international organizations of health; and scenario 3 with official MINSAL data, recovery criteria proposed by international organizations of health, and without considering deaths in the total recovered. There are considerable differences between scenario 1 compared to 2 and 3 in the number of deaths, active patients, and duration of the disease. Scenario 3, considered the most adverse, estimates a total of 11,000 infected people, 1,151 deaths, and that the peak of the disease will occur in the first days of May. We concluded that the concept of recovered may be decisive for the epidemiological forecasts of COVID-19 in Chile.", "doc_id": "agsowv3x"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "La r\u00e9habilitation: indispensable pour les survivants d'un COVID-19 s\u00e9v\u00e8re./ [Rehabilitation is crucial for severe COVID-19 survivors]", "abstract": "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.", "doc_id": "6ztf2n5w"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Involvement of the Nervous System in SARS-CoV-2 Infection", "abstract": "As a severe and highly contagious infectious disease, coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several case reports have demonstrated that the respiratory system is the main target in patients with COVID-19, but the disease is not limited to the respiratory system. Case analysis indicated that the nervous system can be invaded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that 36.4% of COVID-19 patients had neurological symptoms. Importantly, the involvement of the CNS may be associated with poor prognosis and disease worsening. Here, we discussed the symptoms and evidence of nervous system involvement (directly and indirectly) caused by SARS-CoV-2 infection and possible mechanisms. CNS symptoms could be a potential indicator of poor prognosis; therefore, the prevention and treatment of CNS symptoms are also crucial for the recovery of COVID-19 patients.", "doc_id": "9fwttpfb"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Rehab facilities face COVID-19 crunch as more patients recover", "abstract": "", "doc_id": "mrjd1lp0"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "A Contemporary Review of Neurological Sequelae of COVID-19", "abstract": "Coronavirus 2019 (COVID-19) is currently the center of what has become a public health crisis. While the virus is well-known for its trademark effects on respiratory function, neurological damage has been reported to affect a considerable proportion of severe cases. To characterize the neuro-invasive potential of this disease, a contemporary review of COVID-19 and its neurological sequelae was conducted using the limited, but growing, literature that is available. These neurological squeal are based on the manifestations that the virus has on normal central and peripheral nervous system function. The authors present the virology of the SARS-CoV-2 agent by analyzing its classification as an enveloped, positive-stranded RNA virus. A comprehensive timeline is then presented, indicating the progression of the disease as a public health threat. Furthermore, underlying chronic neurological conditions potentially lead to more adverse cases of COVID-19. SARS-CoV-2 may reach ACE2 receptors on neuronal tissue through mode of the general circulation. The CNS may also be susceptible to an immune response where a \u201ccytokine storm\u201d can manifest into neural injury. Histological evidence is provided, while symptoms such as headache and vertigo are highlighted as CNS manifestations of COVID-19. Treatment of these symptoms is addressed with paracetamol being recommended as a possible, but not conclusive, treatment to some CNS symptoms. The authors then discuss the peripheral nervous system sequelae and COVID's impact on causing chemosensory dysfunction starting with viral attack on olfactory sensory neurons and cells types within the lining of the nose. Histological evidence is also provided while symptoms such as anosmia and ageusia are characterized as PNS manifestations. Possible treatment options for these symptoms are then addressed as a major limitation, as anecdotal, and not conclusive evidence can be made. Finally, preventive measures of the neurological sequelae are addressed using a multidirectional approach. Postmortem examinations of the brains of COVID-19 patients are suggested as being a possible key to formulating new understandings of its neuropathology. Lastly, the authors suggest a more comprehensive neurological follow-up of recovered patients, in order to better characterize the neurological sequelae of this illness.", "doc_id": "411qyubx"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Anxiety persists after recovery from acquired COVID-19 in anaesthesiologists", "abstract": "", "doc_id": "bv6g9px3"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Positive SARS-CoV-2 RNA recurs repeatedly in a case recovered from COVID-19: dynamic results from 108 days of follow-up", "abstract": "The evidence of long-term clinical dynamic on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA re-positive case are less. We performed a 108 days follow-up on dynamic clinical presentations in a case, who hospitalized three times due to the positive recurrence of SARS-CoV-2 RNA after discharge, to understand the prognosis of the 2019-Coronavirus disease (COVID-19). In this case, positive SARS-CoV-2 recurred even after apparent recovery (normal CT imaging, no clinical symptoms, negative SARS-CoV-2 on stool sample and negative serum IgM test) from COVID-19, viral shedding duration lasted for 65 days, the time from symptom onset to disappearance was up to 95 days. Erythrocyte-associated indicators, liver function and serum lipid metabolism presented abnormal throughout during the observation period. Awareness of atypical presentations such as this one is important to prompt the improvement of the management of COVID-19.", "doc_id": "pen037ms"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Liver Injury in Critically Ill and Non-critically Ill COVID-19 Patients: A Multicenter, Retrospective, Observational Study", "abstract": "Background: Liver injury commonly occurs in patients with COVID-19. There is limited data describing the course of liver injury occurrence in patients with different disease severity, and the causes and risk factors are unknown. We aim to investigate the incidence, characteristics, risk factors, and clinical outcomes of liver injury in patients with COVID-19. Methods: This retrospective observational study was conducted in three hospitals (Zhejiang, China). From January 19, 2020 to February 20, 2020, patients confirmed with COVID-19 (\u226518 years) and without liver injury were enrolled and divided into non-critically ill and critically ill groups. The incidence and characteristics of liver injury were compared between the two groups. Demographics, clinical characteristics, treatments, and treatment outcomes between patients with or without liver injury were compared within each group. The multivariable logistic regression model was used to explore the risk factors for liver injury. Results: The mean age of 131 enrolled patients was 51.2 years (standard deviation [SD]: 16.1 years), and 70 (53.4%) patients were male. A total of 76 patients developed liver injury (mild, 40.5%; moderate, 15.3%; severe, 2.3%) with a median occurrence time of 10.0 days. Critically ill patients had higher and earlier occurrence (81.5 vs. 51.9%, 12.0 vs. 5.0 days; p < 0.001), greater injury severity (p < 0.001), and slower recovery (50.0 vs. 61.1%) of liver function than non-critically ill patients. Multivariable regression showed that the number of concomitant medications (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.05\u20131.21) and the combination treatment of lopinavir/ritonavir and arbidol (OR: 3.58, 95% CI: 1.44\u20139.52) were risk factors for liver injury in non-critically ill patients. The metabolism of arbidol can be significantly inhibited by lopinavir/ritonavir in vitro (p < 0.005), which may be the underlying cause of drug-related liver injury. Liver injury was related to increased length of hospital stay (mean difference [MD]: 3.2, 95% CI: 1.3\u20135.2) and viral shedding duration (MD: 3.0, 95% CI: 1.0\u20134.9). Conclusions: Critically ill patients with COVID-19 suffered earlier occurrence, greater injury severity, and slower recovery from liver injury than non-critically ill patients. Drug factors were related to liver injury in non-critically ill patients. Liver injury was related to prolonged hospital stay and viral shedding duration in patients with COVID-19. Clinical Trial Registration: World Health Organization International Clinical Trials Registry Platform, ChiCTR2000030593. Registered March 8, 2020.", "doc_id": "2jv7xkfn"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Comment on \u201cHearing loss and COVID-19: A note\u201d", "abstract": "", "doc_id": "axddll4d"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Potentially irreversible olfactory and gustatory impairments in COVID-19: indolent vs. fulminant SARS-CoV-2 neuroinfection", "abstract": "", "doc_id": "jhv8mtvn"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Subjective smell and taste changes during the COVID-19 pandemic: Short term recovery", "abstract": "Since the COVID-19 pandemic began, many individuals have reported acute loss of smell and taste. In order to better characterize all patients with these symptoms, a longitudinal national survey was created. Since April 10, 2020, 549 completed the initial survey, with 295 completing 14-day, and 202 completing 1-month follow up surveys. At 1-month follow-up, 67.1% reported a return to \u201cvery good\u201d or \u201cgood\u201d smell, and 73.1% reported a return to \u201cvery good\u201d or \u201cgood\u201d taste. Chemosensory changes are a cardinal sign of COVID-19. Fortunately, our data, representing a large longitudinal study of patients experiencing smell and taste losses during the COVID-19 pandemic, indicates that the majority appear to recover within a month.", "doc_id": "hwd9xjnn"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Concern coronavirus may trigger post-viral fatigue syndromes", "abstract": "", "doc_id": "r9y9acz4"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "COVID-19: The potential treatment of pulmonary fibrosis associated with SARS-CoV-2 infection", "abstract": "In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. COVID-19 has spread rapidly over several months, affecting patients across all age groups and geographic areas. The disease has a diverse course; patients may range from asymptomatic to those with respiratory failure, complicated by acute respiratory distress syndrome (ARDS). One possible complication of pulmonary involvement in COVID-19 is pulmonary fibrosis, which leads to chronic breathing difficulties, long-term disability and affects patients\u2019 quality of life. There are no specific mechanisms that lead to this phenomenon in COVID-19, but some information arises from previous severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) epidemics. The aim of this narrative review is to present the possible causes and pathophysiology of pulmonary fibrosis associated with COVID-19 based on the mechanisms of the immune response, to suggest possible ways of prevention and treatment.", "doc_id": "4b45gh77"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "The COVID-19 rehabilitation pandemic(1)", "abstract": "The coronavirus disease 2019 (COVID-19) pandemic and the response to the pandemic are combining to produce a tidal wave of need for rehabilitation. Rehabilitation will be needed for survivors of COVID-19, many of whom are older, with underlying health problems. In addition, rehabilitation will be needed for those who have become deconditioned as a result of movement restrictions, social isolation, and inability to access healthcare for pre-existing or new non-COVID-19 illnesses. Delivering rehabilitation in the same way as before the pandemic will not be practical, nor will this approach meet the likely scale of need for rehabilitation. This commentary reviews the likely rehabilitation needs of older people both with and without COVID-19 and discusses how strategies to deliver effective rehabilitation at scale can be designed and implemented in a world living with COVID-19.", "doc_id": "j6kis5b5"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Olfactory dysfunction in recovered COVID\u201019 patients", "abstract": "", "doc_id": "133u377v"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "A Case of COVID-19 Infection With Delayed Thromboembolic Complication on Warfarin", "abstract": "Novel coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented threat to humanity with more than eight million infections and 450,000 deaths reported worldwide so far. The spectrum of the disease varies from mild asymptomatic infection to severe disease with rapid progression to acute respiratory distress syndrome and multiorgan failure. It is associated with a prothrombotic state and hence there is a risk of thromboembolic complications in critically ill patients, even after recovery. However, the duration of prothrombotic risk after recovery is yet to be determined. We present the case of a 78-year-old man with a history of atrial fibrillation on warfarin who had been recently discharged to a nursing home after recovering from COVID-19 pneumonia and presented to the emergency department a month later with worsening shortness of breath and cough. He was found to have worsening respiratory failure with multiple segmental pulmonary emboli, despite being on warfarin, and supratherapeutic international normalized ratio (INR). He required mechanical ventilation and was started on steroids and therapeutic enoxaparin anticoagulation. This case highlights the risk of delayed thromboembolic complications in patients with COVID-19 infection and the need to identify the subgroup of patients with a higher risk of thromboembolism, such as discharges to nursing homes and those in need of oxygen requirement; and those with underlying comorbid conditions that may require anticoagulation for a longer duration. The role of heparin is being increasingly investigated in patients with COVID-19 infection; however, the role of other anticoagulants such as warfarin is yet to be defined.", "doc_id": "rhoo2k3r"} {"topic_name": "coronavirus recovery", "topic_id": "34", "title": "Analysis of thin-section CT in patients with coronavirus disease (COVID-19) after hospital discharge", "abstract": "PURPOSE: To analyze clinical and thin-section computed tomographic (CT) data from the patients with coronavirus disease (COVID-19) to predict the development of pulmonary fibrosis after hospital discharge. MATERIALS AND METHODS: Fifty-nine patients (31 males, 28 females; mean age: 41 years, range: 25 to 70 years) with confirmed COVID-19 infection performed follow-up thin-section CT of the thorax. After 31.5 days of hospital admission, the results of thin-section CT were analyzed for parenchymal abnormality (ground-glass opacification, interstitial thickening, and consolidation) and evidence of fibrosis (parenchymal band, traction bronchiectasis, and irregular interfaces). Patients were analyzed based on the evidence of fibrosis and divided into two groups, group A (with CT evidence of fibrosis) and group B (without CT evidence of fibrosis). Patient demographics, length of stay (LOS), rate of intensive care unit (ICU) admission, peak C-reactive protein level, and CT score were compared between the two groups. RESULTS: Among the 59 patients, 89.8% (53/59) patients had a typical transition from early phase to advanced phase and advanced phase to dissipating phase. Out of 59 patients, 39% (23/59) patients developed fibrosis (group A), whereas 61% (36/59) patients did not show definite fibrosis (group B). Patients in group A were older (mean age, 45.4 vs. 33.8 years), with longer LOS (19.1 vs. 15.0 days), higher rate of ICU admission (21.7% (5/23) vs. 5.6% (2/36)), higher peak C-reactive protein level (30.7 vs. 18.1 mg/L), and higher maximal CT score (5.2 vs. 4.0) than those in group B. CONCLUSIONS: Pulmonary fibrosis may develop early in patients with COVID-19 after hospital discharge. Older patients with severe illness during treatment were more prone to develop fibrosis according to thin-section CT results.", "doc_id": "ptlh8oqx"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "The American Heart Association COVID-19 CVD Registry powered by Get With The Guidelines\u00ae.", "abstract": "Background: In response to the public health emergency created by the COVID-19 pandemic, American Heart Association volunteers and staff aimed to rapidly develop and launch a resource for the medical and research community to expedite scientific advancement through shared learning, quality improvement, and research. In less than 4 weeks after it was first announced on April 3, 2020, AHA's COVID-19 CVD Registry powered by Get With The Guidelines\u00ae (GWTG) received its first clinical records. Methods and Results: Participating hospitals are enrolling consecutive hospitalized patients with active COVID-19 disease, regardless of CVD status. This hospital quality improvement program will allow participating hospitals and health systems to evaluate patient-level data including mortality rates, intensive care unit (ICU) bed days, and ventilator days from individual review of electronic medical records of sequential adult patients with active COVID-19 infection. Participating sites can leverage these data for onsite, rapid quality improvement and benchmarking versus other institutions. After 9 weeks, more than 130 sites have enrolled in the program and more than 4,000 records have been abstracted in the national dataset. Additionally, the aggregate dataset will be a valuable data resource for the medical research community. Conclusions: The AHA COVID-19 CVD Registry will support greater understanding of the impact of COVID-19 on cardiovascular disease and will inform best practices for evaluation and management of patients with COVID-19.", "doc_id": "2071y2x8"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "COVID-19 Government Response Event Dataset (CoronaNet v.1.0).", "abstract": "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.", "doc_id": "4dgvuaxr"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "A New Resource for Genomics and Precision Health Information and Publications on the Investigation and Control of COVID-19 and other Coronaviruses", "abstract": "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", "doc_id": "1s0hhx71"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "FakeCovid -- A Multilingual Cross-domain Fact Check News Dataset for COVID-19", "abstract": "In this paper, we present a first multilingual cross-domain dataset of 5182 fact-checked news articles for COVID-19, collected from 04/01/2020 to 15/05/2020. We have collected the fact-checked articles from 92 different fact-checking websites after obtaining references from Poynter and Snopes. We have manually annotated articles into 11 different categories of the fact-checked news according to their content. The dataset is in 40 languages from 105 countries. We have built a classifier to detect fake news and present results for the automatic fake news detection and its class. Our model achieves an F1 score of 0.76 to detect the false class and other fact check articles. The FakeCovid dataset is available at Github.", "doc_id": "9it9pgq1"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Benchmarking Deep Learning Models and Automated Model Design for COVID-19 Detection with Chest CT Scans", "abstract": "COVID-19 pandemic has spread all over the world for months. As its transmissibility and high pathogenicity seriously threaten people's lives, the accurate and fast detection of the COVID-19 infection is crucial. Although many recent studies have shown that deep learning based solutions can help detect COVID-19 based on chest CT scans, there lacks a consistent and systematic comparison and evaluation on these techniques. In this paper, we first build a clean and segmented CT dataset called Clean-CC-CCII by fixing the errors and removing some noises in a large CT scan dataset CC-CCII with three classes: novel coronavirus pneumonia (NCP), common pneumonia (CP), and normal controls (Normal). After cleaning, our dataset consists of a total of 340,190 slices of 3,993 scans from 2,698 patients. Then we benchmark and compare the performance of a series of state-of-the-art (SOTA) 3D and 2D convolutional neural networks (CNNs). The results show that 3D CNNs outperform 2D CNNs in general. With extensive effort of hyperparameter tuning, we find that the 3D CNN model DenseNet3D121 achieves the highest accuracy of 88.63% (F1-score is 88.14% and AUC is 0.940), and another 3D CNN model ResNet3D34 achieves the best AUC of 0.959 (accuracy is 87.83% and F1-score is 86.04%). We further demonstrate that the mixup data augmentation technique can largely improve the model performance. At last, we design an automated deep learning methodology to generate a lightweight deep learning model MNas3DNet41 that achieves an accuracy of 87.14%, F1-score of 87.25%, and AUC of 0.957, which are on par with the best models made by AI experts. The automated deep learning design is a promising methodology that can help health-care professionals develop effective deep learning models using their private data sets. Our Clean-CC-CCII dataset and source code are available at: https://github.com/arthursdays/HKBU_HPML_COVID-19.", "doc_id": "c079r94n"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "COVID-19 Mobility Data Collection of Seoul, South Korea", "abstract": "The relationship between pandemic and human mobility has received considerable attention from scholars, as investigating such relationship can provide an indication of how human mobility changes in response to a public health crisis or whether reduced mobility contributes to preventing the spread of an infectious disease. While several studies attempted to unveil this relationship, no studies have focused on changes in mobility pattern at a finer scale utilizing high-resolution datasets. To address the complex association between pandemic's spread and human mobility, this paper presents two categories of mobility datasets-trip mode and trip purpose-that concern nearly 10 million citizens' movements during the first 100 days of COVID-19 in Seoul, South Korea, where no major lockdown has been imposed. We curate hourly data of subway ridership, traffic volume and population present count at selected points of interests. The results to be derived from the presented datasets can be used as an important reference for public health decision making in the post COVID-19 era.", "doc_id": "r0j0368k"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Exploring Epidemiological Behavior of Novel Coronavirus Outbreak through the Development and Analysis of COVID-19 Daily Dataset in Bangladesh", "abstract": "Globally, there is an obvious concern about the fact that the evolving 2019-nCoV coronavirus is a worldwide public health threat. The appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019 triggered a major global epidemic, which is now a major community health issue. As of April 17, 2020, according to Institute of Epidemiology, Disease Control and Research (IEDCR) Bangladesh has reported 1838 confirmed cases in between 8 March to 17 April 2020, with > 4.08% of mortality rate and >3.15% of recovery rate. COVID-19 outbreak is evolving so rapidly in Bangladesh; therefore, the availability of epidemiological data and its sensible analysis are essential to direct strategies for situational awareness and intervention. This article presents an exploratory data analysis approach to collect and analyze COVID-19 data on epidemiological outbreaks based on first publicly available COVID-19 Daily Dataset of Bangladesh. Various publicly open data sources on the outbreak of COVID-19 provided by the IEDCR, World Health Organization (WHO), Directorate General of Health Services (DGHS), and Ministry of Health and Family Welfare (MHFW) of Bangladesh have been used in this research. A Visual Exploratory Data Analysis (V-EDA) techniques have been followed in this research to understand the epidemiological characteristics of COVID-19 outbreak in different districts of Bangladesh in between 8 March 2020 to 12 April 2020 and these findings were compared with those of other countries. In all, this is extremely important to promptly spread information to understand the risks of this pandemic and begin containment activities in the country.", "doc_id": "bce1oeyl"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "A structured open dataset of government interventions in response to COVID-19", "abstract": "In response to the COVID-19 pandemic, governments have implemented a wide range of nonpharmaceutical interventions (NPIs). Monitoring and documenting government strategies during the COVID-19 crisis is crucial to understand the progression of the epidemic. Following a content analysis strategy of existing public information sources, we developed a specific hierarchical coding scheme for NPIs. We generated a comprehensive structured dataset of government interventions and their respective timelines of implementation. To improve transparency and motivate collaborative validation process, information sources are shared via an open library. We also provide codes that enable users to visualise the dataset. Standardization and structure of the dataset facilitate inter-country comparison and the assessment of the impacts of different NPI categories on the epidemic parameters, population health indicators, the economy, and human rights, among others. This dataset provides an in-depth insight of the government strategies and can be a valuable tool for developing relevant preparedness plans for pandemic. We intend to further develop and update this dataset on a weekly basis until the end of December 2020.", "doc_id": "byr1qy54"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Associations between COVID-19 infection, tobacco smoking and nicotine use, common respiratory conditions and inhaled corticosteroids: a prospective QResearch-Case Mix Programme data linkage study January-May 2020", "abstract": "Introduction Epidemiological and laboratory research seems to suggest that smoking and perhaps nicotine alone could reduce the severity of COVID-19. Likewise, there is some evidence that inhaled corticosteroids could also reduce its severity, opening the possibility that nicotine and inhaled steroids could be used as treatments. Methods In this prospective cohort study, we will link English general practice records from the QResearch database to Public Health England's database of SARS-CoV-2 positive tests, Hospital Episode Statistics, admission to intensive care units, and death from COVID-19 to identify our outcomes: hospitalisation, ICU admission, and death due to COVID. Using Cox regression, we will perform sequential adjustment for potential confounders identified by separate directed acyclic graphs to: 1. Assess the association between smoking and COVID-19 disease severity, and how that changes on adjustment for smoking-related comorbidity. 2. More closely characterise the association between smoking and severe COVID-19 disease by assessing whether the association is modified by age (as a proxy of length of smoking), gender, ethnic group, and whether people have asthma or COPD. 3. Assess for evidence of a dose-response relation between smoking intensity and disease severity, which would help create a case for causality. 4. Examine the association between former smokers who are using NRT or are vaping and disease severity. 5. Examine whether pre-existing respiratory disease is associated with severe COVID-19 infection. 6. Assess whether the association between chronic obstructive pulmonary disease (COPD) and asthma and COVID-19 disease severity is modified by age, gender, ethnicity, and smoking status. 7. Assess whether the use of inhaled corticosteroids is associated with severity of COVID-19 disease. 8. To assess whether the association between use of inhaled corticosteroids and severity of COVID-19 disease is modified by the number of other airways medications used (as a proxy for severity of condition) and whether people have asthma or COPD. Conclusions This representative population sample will, to our knowledge, present the first comprehensive examination of the association between smoking, nicotine use without smoking, respiratory disease, and severity of COVID-19. We will undertake several sensitivity analyses to examine the potential for bias in these associations.", "doc_id": "hlqqkn31"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "MosMedData: Chest CT Scans with COVID-19 Related Findings", "abstract": "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.", "doc_id": "doazmz7c"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Mining Twitter Data on COVID-19 for Sentiment analysis and frequent patterns Discovery", "abstract": "A study with a societal objective was carried out on people exchanging on social networks and more particularly on Twitter to observe their feelings on the COVID-19. A dataset of more than 600,000 tweets with hashtags like COVID and coronavirus posted between February 27, 2020 and March 25, 2020 was built. An exploratory treatment of the number of tweets posted by country, by language and other parameters revealed an overview of the apprehension of the pandemic around the world. A sentiment analysis was elaborated on the basis of the tweets posted in English because these constitute the great majority. On the other hand, the FP-Growth algorithm was adapted to the tweets in order to discover the most frequent patterns and its derived association rules, in order to highlight the tweeters insights relatively to COVID-19.", "doc_id": "iah8zka4"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "On the Generation of Medical Dialogues for COVID-19", "abstract": "Under the pandemic of COVID-19, people experiencing COVID19-related symptoms or exposed to risk factors have a pressing need to consult doctors. Due to hospital closure, a lot of consulting services have been moved online. Because of the shortage of medical professionals, many people cannot receive online consultations timely. To address this problem, we aim to develop a medical dialogue system that can provide COVID19-related consultations. We collected two dialogue datasets - CovidDialog - (in English and Chinese respectively) containing conversations between doctors and patients about COVID-19. On these two datasets, we train several dialogue generation models based on Transformer, GPT, and BERT-GPT. Since the two COVID-19 dialogue datasets are small in size, which bear high risk of overfitting, we leverage transfer learning to mitigate data deficiency. Specifically, we take the pretrained models of Transformer, GPT, and BERT-GPT on dialog datasets and other large-scale texts, then finetune them on our CovidDialog datasets. Experiments demonstrate that these approaches are promising in generating meaningful medical dialogue about COVID-19. But more advanced approaches are needed to build a fully useful dialogue system that can offer accurate COVID-related consultations. The data and code are available at https://github.com/UCSD-AI4H/COVID-Dialogue", "doc_id": "tprgbl51"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Online COVID-19 diagnosis with chest CT images: Lesion-attention deep neural networks", "abstract": "Chest (computed tomography) CT scanning is one of the most important technologies for COVID-19 diagnosis in the current clinical practice, which motivates more concerted efforts in developing AI-based diagnostic tools to alleviate the enormous burden on the medical system. We develop a lesion-attention deep neural network (LA-DNN) to predict COVID-19 positive or negative with a richly annotated chest CT image dataset. The CT image dataset contains 746 public chest CT images of COVID-19 patients collected from over 760 preprints, and the data annotations are accompanied with the textual radiology reports. We extract two types of important information from these annotations: One is the flag of whether an image indicates a positive or negative case of COVID-19, and the other is the description of five lesions on the CT images associated with the positive cases. The proposed data-driven LA-DNN model focuses on the primary task of binary classification for COVID-19 diagnosis, while an auxiliary multi-label learning task is implemented simultaneously to draw the model's attention to the five lesions of COVID-19 during the training. The joint task learning process makes it a highly sample-efficient deep model that can learn COVID-19 radiology features effectively with very limited samples. The experimental results show that the area under the curve (AUC) and sensitivity (recall) for the diagnosis of COVID-19 patients are 91.2% and 85.7% respectively, which reach the clinical standards for practical use. An online system has been developed for fast online diagnoses using CT images at the web address https://www.covidct.cn/.", "doc_id": "nvmon1sm"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Sample-Efficient Deep Learning for COVID-19 Diagnosis Based on CT Scans", "abstract": "Coronavirus disease 2019 (COVID-19) has infected more than 1.3 million individuals all over the world and caused more than 106,000 deaths. One major hurdle in controlling the spreading of this disease is the inefficiency and shortage of medical tests. There have been increasing efforts on developing deep learning methods to diagnose COVID-19 based on CT scans. However, these works are difficult to reproduce and adopt since the CT data used in their studies are not publicly available. Besides, these works require a large number of CTs to train accurate diagnosis models, which are difficult to obtain. In this paper, we aim to address these two problems. We build a publicly-available dataset containing hundreds of CT scans positive for COVID-19 and develop sample-efficient deep learning methods that can achieve high diagnosis accuracy of COVID-19 from CT scans even when the number of training CT images are limited. Specifically, we propose an Self-Trans approach, which synergistically integrates contrastive self-supervised learning with transfer learning to learn powerful and unbiased feature representations for reducing the risk of overfitting. Extensive experiments demonstrate the superior performance of our proposed Self-Trans approach compared with several state-of-the-art baselines. Our approach achieves an F1 of 0.85 and an AUC of 0.94 in diagnosing COVID-19 from CT scans, even though the number of training CTs is just a few hundred.", "doc_id": "l3f469ht"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "A citizen science initiative for open data and visualization of COVID-19 outbreak in Kerala, India", "abstract": "India, the second most populated country in the world, reported its first COVID-19 case in the state of Kerala with a travel history from Wuhan. Subsequently, a surge of cases was observed in the state mainly through the individuals who traveled from Europe and the Middle East to Kerala, thus initiating an outbreak. Since public awareness through dissemination of reliable information plays a significant role in controlling the spread of the disease, the Department of Health Services, Government of Kerala initially released daily updates through daily textual bulletins. However, this unstructured data requires refinement and enrichment for upstream applications, such as visualization, and/or analysis. Here we reported a citizen science initiative that leveraged publicly available and crowd-verified data on COVID-19 outbreak in Kerala from the government bulletins, supplemented with the information from media outlets to generate reusable datasets. This data was further used to provide real-time analysis, and daily updates of COVID-19 cases in Kerala, through a user-friendly bilingual dashboard (https://covid19kerala.info/) for non-specialists. We ensured longevity and reusability of the dataset by depositing it in a public repository, aligning with open source principles for future analytical efforts. Finally, to show the scope of the sourced data, we also provided a snapshot of outbreak trends and demographic characteristics of the individuals affected with COVID-19 in Kerala during the first 99 days of the outbreak.", "doc_id": "nbzbmrsd"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Public Opinions towards COVID-19 in California and New York on Twitter", "abstract": "Background: With the pandemic of COVID-19 and the release of related policies, discussions about the COVID-19 are widespread online. Social media becomes a reliable source for understanding public opinions toward this virus outbreak. Objective: This study aims to explore public opinions toward COVID-19 on social media by comparing the differences in sentiment changes and discussed topics between California and New York in the United States. Methods: A dataset with COVID-19-related Twitter posts was collected from March 5, 2020 to April 2, 2020 using Twitter streaming API. After removing any posts unrelated to COVID-19, as well as posts that contain promotion and commercial information, two individual datasets were created based on the geolocation tags with tweets, one containing tweets from California state and the other from New York state. Sentiment analysis was conducted to obtain the sentiment score for each COVID-19 tweet. Topic modeling was applied to identify top topics related to COVID-19. Results: While the number of COVID-19 cases increased more rapidly in New York than in California in March 2020, the number of tweets posted has a similar trend over time in both states. COVID-19 tweets from California had more negative sentiment scores than New York. There were some fluctuations in sentiment scores in both states over time, which might correlate with the policy changes and the severity of COVID-19 pandemic. The topic modeling results showed that the popular topics in both California and New York states are similar, with \"protective measures\" as the most prevalent topic associated with COVID-19 in both states. Conclusions: Twitter users from California had more negative sentiment scores towards COVID-19 than Twitter users from New York. The prevalent topics about COVID-19 discussed in both states were similar with some slight differences.", "doc_id": "onipxf2z"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "CoV2ID: Detection and Therapeutics Oligo Database for SARS-CoV-2", "abstract": "The ability to detect the SARS-CoV-2 in a widespread epidemic is crucial for screening of carriers and for the success of quarantine efforts. Methods based on real-time reverse transcription polymerase chain reaction (RT-qPCR) and sequencing are being used for virus detection and characterization. However, RNA viruses are known for their high genetic diversity which poses a challenge for the design of efficient nucleic acid-based assays. The first SARS-CoV-2 genomic sequences already showed novel mutations, which may affect the efficiency of available screening tests leading to false-negative diagnosis or inefficient therapeutics. Here we describe the CoV2ID (http://covid.portugene.com/), a free database built to facilitate the evaluation of molecular methods for detection of SARS-CoV-2 and treatment of COVID-19. The database evaluates the available oligonucleotide sequences (PCR primers, RT-qPCR probes, etc.) considering the genetic diversity of the virus. Updated sequences alignments are used to constantly verify the theoretical efficiency of available testing methods. Detailed information on available detection protocols are also available to help laboratories implementing SARS-CoV-2 testing.", "doc_id": "mg2dziuw"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "CORD-19: The Covid-19 Open Research Dataset.", "abstract": "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.", "doc_id": "pt8nh7wx"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "A large-scale COVID-19 Twitter chatter dataset for open scientific research -- an international collaboration.", "abstract": "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.", "doc_id": "1lisdjpm"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "COVID-19-CT-CXR: a freely accessible and weakly labeled chest X-ray and CT image collection on COVID-19 from biomedical literature.", "abstract": "The latest threat to global health is the COVID-19 outbreak. Although there exist large datasets of chest X-rays (CXR) and computed tomography (CT) scans, few COVID-19 image collections are currently available due to patient privacy. At the same time, there is a rapid growth of COVID-19-relevant articles in the biomedical literature. Here, we present COVID-19-CT-CXR, a public database of COVID-19 CXR and CT images, which are automatically extracted from COVID-19-relevant articles from the PubMed Central Open Access (PMC-OA) Subset. We extracted figures, associated captions, and relevant figure descriptions in the article and separated compound figures into subfigures. We also designed a deep-learning model to distinguish them from other figure types and to classify them accordingly. The final database includes 1,327 CT and 263 CXR images (as of May 9, 2020) with their relevant text. To demonstrate the utility of COVID-19-CT-CXR, we conducted four case studies. (1) We show that COVID-19-CT-CXR, when used as additional training data, is able to contribute to improved DL performance for the classification of COVID-19 and non-COVID-19 CT. (2) We collected CT images of influenza and trained a DL baseline to distinguish a diagnosis of COVID-19, influenza, or normal or other types of diseases on CT. (3) We trained an unsupervised one-class classifier from non-COVID-19 CXR and performed anomaly detection to detect COVID-19 CXR. (4) From text-mined captions and figure descriptions, we compared clinical symptoms and clinical findings of COVID-19 vs. those of influenza to demonstrate the disease differences in the scientific publications. We believe that our work is complementary to existing resources and hope that it will contribute to medical image analysis of the COVID-19 pandemic. The dataset, code, and DL models are publicly available at https://github.com/ncbi-nlp/COVID-19-CT-CXR.", "doc_id": "uqfygev4"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study", "abstract": "BACKGROUND: Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain. METHODS: During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies. FINDINGS: The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020. Data lock for this report was on April 26, 2020. During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies. Median patient age was 71 years (range 23-94; IQR 58-79). Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis. The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years. INTERPRETATION: To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy. FUNDING: None.", "doc_id": "2i3iv0sz"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Dataset on dynamics of Coronavirus on Twitter", "abstract": "In this data article, we provide a dataset of 8,982,694 Twitter posts around the coronavirus health global crisis. The data were collected through the Twitter REST API search. We used the rtweet R package to download raw data. The term searched was \"Coronavirus\" which included the word itself and its hashtag version. We collected the data over 23 days, from January 21 to February 12, 2020. The dataset is multilingual, prevailing English, Spanish, and Portuguese. We include a new variable created from other four variables; it is called \"type\" of tweets, which is useful for showing the diversity of tweets and the dynamics of users on Twitter. The dataset comprises seven databases which can be analysed separately. On the other hand, they can be crossed to set other researches, among them, trends and relevance of different topics, types of tweets, the embeddedness of users and their profiles, the retweets dynamics, hashtag analysis, as well as to perform social network analysis. This dataset can attract the attention of researchers related to different fields on knowledge, such as data science, social science, network science, health informatics, tourism, infodemiology, and others.", "doc_id": "lwipyymp"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Monitoring Depression Trend on Twitter during the COVID-19 Pandemic", "abstract": "The COVID-19 pandemic has severely affected people's daily lives and caused tremendous economic loss worldwide. However, its influence on people's mental health conditions has not received as much attention. To study this subject, we choose social media as our main data resource and create by far the largest English Twitter depression dataset containing 2,575 distinct identified depression users with their past tweets. To examine the effect of depression on people's Twitter language, we train three transformer-based depression classification models on the dataset, evaluate their performance with progressively increased training sizes, and compare the model's\"tweet chunk\"-level and user-level performances. Furthermore, inspired by psychological studies, we create a fusion classifier that combines deep learning model scores with psychological text features and users' demographic information and investigate these features' relations to depression signals. Finally, we demonstrate our model's capability of monitoring both group-level and population-level depression trends by presenting two of its applications during the COVID-19 pandemic. We hope this study can raise awareness among researchers and the general public of COVID-19's impact on people's mental health.", "doc_id": "qgjtnpd3"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Conversations and Medical News Frames on Twitter: Infodemiological Study on COVID-19 in South Korea", "abstract": "BACKGROUND: SARS-CoV-2 (severe acute respiratory coronavirus 2) was spreading rapidly in South Korea at the end of February 2020 following its initial outbreak in China, making Korea the new center of global attention. The role of social media amid the current coronavirus disease (COVID-19) pandemic has often been criticized, but little systematic research has been conducted on this issue. Social media functions as a convenient source of information in pandemic situations. OBJECTIVE: Few infodemiology studies have applied network analysis in conjunction with content analysis. This study investigates information transmission networks and news-sharing behaviors regarding COVID-19 on Twitter in Korea. The real time aggregation of social media data can serve as a starting point for designing strategic messages for health campaigns and establishing an effective communication system during this outbreak. METHODS: Korean COVID-19-related Twitter data were collected on February 29, 2020. Our final sample comprised of 43,832 users and 78,233 relationships on Twitter. We generated four networks in terms of key issues regarding COVID-19 in Korea. This study comparatively investigates how COVID-19-related issues have circulated on Twitter through network analysis. Next, we classified top news channels shared via tweets. Lastly, we conducted a content analysis of news frames used in the top-shared sources. RESULTS: The network analysis suggests that the spread of information was faster in the Coronavirus network than in the other networks (Corona19, Shincheon, and Daegu). People who used the word \"Coronavirus\" communicated more frequently with each other. The spread of information was faster, and the diameter value was lower than for those who used other terms. Many of the news items highlighted the positive roles being played by individuals and groups, directing readers' attention to the crisis. Ethical issues such as deviant behavior among the population and an entertainment frame highlighting celebrity donations also emerged often. There was a significant difference in the use of nonportal (n=14) and portal news (n=26) sites between the four network types. The news frames used in the top sources were similar across the networks (P=.89, 95% CI 0.004-0.006). Tweets containing medically framed news articles (mean 7.571, SD 1.988) were found to be more popular than tweets that included news articles adopting nonmedical frames (mean 5.060, SD 2.904; N=40, P=.03, 95% CI 0.169-4.852). CONCLUSIONS: Most of the popular news on Twitter had nonmedical frames. Nevertheless, the spillover effect of the news articles that delivered medical information about COVID-19 was greater than that of news with nonmedical frames. Social media network analytics cannot replace the work of public health officials; however, monitoring public conversations and media news that propagates rapidly can assist public health professionals in their complex and fast-paced decision-making processes.", "doc_id": "8ravbor6"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Open access institutional and news media tweet dataset for COVID-19 social science research", "abstract": "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.", "doc_id": "5o12mbut"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Targeting SARS-CoV-2 with AI- and HPC-enabled Lead Generation: A First Data Release", "abstract": "Researchers across the globe are seeking to rapidly repurpose existing drugs or discover new drugs to counter the the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One promising approach is to train machine learning (ML) and artificial intelligence (AI) tools to screen large numbers of small molecules. As a contribution to that effort, we are aggregating numerous small molecules from a variety of sources, using high-performance computing (HPC) to computer diverse properties of those molecules, using the computed properties to train ML/AI models, and then using the resulting models for screening. In this first data release, we make available 23 datasets collected from community sources representing over 4.2 B molecules enriched with pre-computed: 1) molecular fingerprints to aid similarity searches, 2) 2D images of molecules to enable exploration and application of image-based deep learning methods, and 3) 2D and 3D molecular descriptors to speed development of machine learning models. This data release encompasses structural information on the 4.2 B molecules and 60 TB of pre-computed data. Future releases will expand the data to include more detailed molecular simulations, computed models, and other products.", "doc_id": "h23w89h2"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "TICO-19: the Translation Initiative for Covid-19", "abstract": "The COVID-19 pandemic is the worst pandemic to strike the world in over a century. Crucial to stemming the tide of the SARS-CoV-2 virus is communicating to vulnerable populations the means by which they can protect themselves. To this end, the collaborators forming the Translation Initiative for COvid-19 (TICO-19) have made test and development data available to AI and MT researchers in 35 different languages in order to foster the development of tools and resources for improving access to information about COVID-19 in these languages. In addition to 9 high-resourced,\"pivot\"languages, the team is targeting 26 lesser resourced languages, in particular languages of Africa, South Asia and South-East Asia, whose populations may be the most vulnerable to the spread of the virus. The same data is translated into all of the languages represented, meaning that testing or development can be done for any pairing of languages in the set. Further, the team is converting the test and development data into translation memories (TMXs) that can be used by localizers from and to any of the languages.", "doc_id": "31ybxjjx"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Chaos game representation dataset of SARS-CoV-2 genome", "abstract": "As of April 16, 2020, the novel coronavirus disease (called COVID-19) spread to more than 185 countries/regions with more than 142,000 deaths and more than 2,000,000 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, digital signal processing, and machine learning techniques and algorithms. However, to make feasible this approach, it is necessary to transform the nucleotide sequences string to numerical values representation. Thus, the dataset provides a chaos game representation (CGR) of SARS-CoV-2 virus nucleotide sequences. The dataset provides the CGR of 100 instances of SARS-CoV-2 virus, 11540 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).", "doc_id": "luhvbwgv"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Early Outbreak Detection for Proactive Crisis Management Using Twitter Data: COVID-19 a Case Study in the US", "abstract": "During a disease outbreak, timely non-medical interventions are critical in preventing the disease from growing into an epidemic and ultimately a pandemic. However, taking quick measures requires the capability to detect the early warning signs of the outbreak. This work collects Twitter posts surrounding the 2020 COVID-19 pandemic expressing the most common symptoms of COVID-19 including cough and fever, geolocated to the United States. Through examining the variation in Twitter activities at the state level, we observed a temporal lag between the rises in the number of symptom reporting tweets and officially reported positive cases which varies between 5 to 19 days.", "doc_id": "ad5avzd6"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Document Classification for COVID-19 Literature", "abstract": "The global pandemic has made it more important than ever to quickly and accurately retrieve relevant scientific literature for effective consumption by researchers in a wide range of fields. We provide an analysis of several multi-label document classification models on the LitCovid dataset, a growing collection of 8,000 research papers regarding the novel 2019 coronavirus. We find that pre-trained language models fine-tuned on this dataset outperform all other baselines and that the BioBERT and novel Longformer models surpass all others with almost equivalent micro-F1 and accuracy scores of around 81% and 69% on the test set. We evaluate the data efficiency and generalizability of these models as essential features of any system prepared to deal with an urgent situation like the current health crisis. Finally, we explore 50 errors made by the best performing models on LitCovid documents and find that they often (1) correlate certain labels too closely together and (2) fail to focus on discriminative sections of the articles; both of which are important issues to address in future work. Both data and code are available on GitHub.", "doc_id": "elphxl9s"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Viral and host factors related to the clinical outcome of COVID-19", "abstract": "In December 2019, coronavirus disease 2019 (COVID-19), which is caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan (Hubei province, China)1; it soon spread across the world. In this ongoing pandemic, public health concerns and the urgent need for effective therapeutic measures require a deep understanding of the epidemiology, transmissibility and pathogenesis of COVID-19. Here we analysed clinical, molecular and immunological data from 326 patients with confirmed SARS-CoV-2 infection in Shanghai. The genomic sequences of SARS-CoV-2, assembled from 112 high-quality samples together with sequences in the Global Initiative on Sharing All Influenza Data (GISAID) dataset, showed a stable evolution and suggested that there were two major lineages with differential exposure history during the early phase of the outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes. Lymphocytopenia, especially reduced CD4+ and CD8+ T cell counts upon hospital admission, was predictive of disease progression. High levels of interleukin (IL)-6 and IL-8 during treatment were observed in patients with severe or critical disease and correlated with decreased lymphocyte count. The determinants of disease severity seemed to stem mostly from host factors such as age and lymphocytopenia (and its associated cytokine storm), whereas viral genetic variation did not significantly affect outcomes.", "doc_id": "vhwghd5n"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "An Interactive Online Dashboard for Tracking COVID-19 in U.S. Counties, Cities, and States in Real Time", "abstract": "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.", "doc_id": "9kb1tt5d"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Emergence of a Novel Coronavirus (COVID-19): Protocol for Extending Surveillance Used by the Royal College of General Practitioners Research and Surveillance Centre and Public Health England", "abstract": "BACKGROUND: The Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) have successfully worked together on the surveillance of influenza and other infectious diseases for over 50 years, including three previous pandemics. With the emergence of the international outbreak of the coronavirus infection (COVID-19), a UK national approach to containment has been established to test people suspected of exposure to COVID-19. At the same time and separately, the RCGP RSC's surveillance has been extended to monitor the temporal and geographical distribution of COVID-19 infection in the community as well as assess the effectiveness of the containment strategy. OBJECTIVES: The aims of this study are to surveil COVID-19 in both asymptomatic populations and ambulatory cases with respiratory infections, ascertain both the rate and pattern of COVID-19 spread, and assess the effectiveness of the containment policy. METHODS: The RCGP RSC, a network of over 500 general practices in England, extract pseudonymized data weekly. This extended surveillance comprises of five components: (1) Recording in medical records of anyone suspected to have or who has been exposed to COVID-19. Computerized medical records suppliers have within a week of request created new codes to support this. (2) Extension of current virological surveillance and testing people with influenza-like illness or lower respiratory tract infections (LRTI)-with the caveat that people suspected to have or who have been exposed to COVID-19 should be referred to the national containment pathway and not seen in primary care. (3) Serology sample collection across all age groups. This will be an extra blood sample taken from people who are attending their general practice for a scheduled blood test. The 100 general practices currently undertaking annual influenza virology surveillance will be involved in the extended virological and serological surveillance. (4) Collecting convalescent serum samples. (5) Data curation. We have the opportunity to escalate the data extraction to twice weekly if needed. Swabs and sera will be analyzed in PHE reference laboratories. RESULTS: General practice clinical system providers have introduced an emergency new set of clinical codes to support COVID-19 surveillance. Additionally, practices participating in current virology surveillance are now taking samples for COVID-19 surveillance from low-risk patients presenting with LRTIs. Within the first 2 weeks of setup of this surveillance, we have identified 3 cases: 1 through the new coding system, the other 2 through the extended virology sampling. CONCLUSIONS: We have rapidly converted the established national RCGP RSC influenza surveillance system into one that can test the effectiveness of the COVID-19 containment policy. The extended surveillance has already seen the use of new codes with 3 cases reported. Rapid sharing of this protocol should enable scientific critique and shared learning. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18606.", "doc_id": "vchsm0cr"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "CORD19STS: COVID-19 Semantic Textual Similarity Dataset", "abstract": "In order to combat the COVID-19 pandemic, society can benefit from various natural language processing applications, such as dialog medical diagnosis systems and information retrieval engines calibrated specifically for COVID-19. These applications rely on the ability to measure semantic textual similarity (STS), making STS a fundamental task that can benefit several downstream applications. However, existing STS datasets and models fail to translate their performance to a domain-specific environment such as COVID-19. To overcome this gap, we introduce CORD19STS dataset which includes 13,710 annotated sentence pairs collected from COVID-19 open research dataset (CORD-19) challenge. To be specific, we generated one million sentence pairs using different sampling strategies. We then used a finetuned BERT-like language model, which we call Sen-SCI-CORD19-BERT, to calculate the similarity scores between sentence pairs to provide a balanced dataset with respect to the different semantic similarity levels, which gives us a total of 32K sentence pairs. Each sentence pair was annotated by five Amazon Mechanical Turk (AMT) crowd workers, where the labels represent different semantic similarity levels between the sentence pairs (i.e. related, somewhat-related, and not-related). After employing a rigorous qualification tasks to verify collected annotations, our final CORD19STS dataset includes 13,710 sentence pairs.", "doc_id": "eozy4ng5"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Open access epidemiological data from the COVID-19 outbreak", "abstract": "", "doc_id": "4c0vh2h1"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "COVID-19 Image Data Collection", "abstract": "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.", "doc_id": "53aq480d"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Weibo-COV: A Large-Scale COVID-19 Social Media Dataset from Weibo", "abstract": "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.", "doc_id": "1bjt64o7"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Dashboard of sentiment in Austrian social media during COVID-19", "abstract": "To track online emotional expressions of the Austrian population close to real-time during the COVID-19 pandemic, we build a self-updating monitor of emotion dynamics using digital traces from three different data sources. This enables decision makers and the interested public to assess issues such as the attitude towards counter-measures taken during the pandemic and the possible emergence of a (mental) health crisis early on. We use web scraping and API access to retrieve data from the news platform derstandard.at, Twitter and a chat platform for students. We document the technical details of our workflow in order to provide materials for other researchers interested in building a similar tool for different contexts. Automated text analysis allows us to highlight changes of language use during COVID-19 in comparison to a neutral baseline. We use special word clouds to visualize that overall difference. Longitudinally, our time series show spikes in anxiety that can be linked to several events and media reporting. Additionally, we find a marked decrease in anger. The changes last for remarkably long periods of time (up to 12 weeks). We discuss these and more patterns and connect them to the emergence of collective emotions. The interactive dashboard showcasing our data is available online under http://www.mpellert.at/covid19_monitor_austria/. Our work has attracted media attention and is part of an web archive of resources on COVID-19 collected by the Austrian National Library.", "doc_id": "mjtlhh5e"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "MosMedData: Chest CT Scans With COVID-19 Related Findings Dataset", "abstract": "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", "doc_id": "0b8250y7"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Understanding the perception of COVID-19 policies by mining a multilanguage Twitter dataset", "abstract": "The objective of this work is to explore popular discourse about the COVID-19 pandemic and policies implemented to manage it. Using Natural Language Processing, Text Mining, and Network Analysis to analyze corpus of tweets that relate to the COVID-19 pandemic, we identify common responses to the pandemic and how these responses differ across time. Moreover, insights as to how information and misinformation were transmitted via Twitter, starting at the early stages of this pandemic, are presented. Finally, this work introduces a dataset of tweets collected from all over the world, in multiple languages, dating back to January 22nd, when the total cases of reported COVID-19 were below 600 worldwide. The insights presented in this work could help inform decision makers in the face of future pandemics, and the dataset introduced can be used to acquire valuable knowledge to help mitigate the COVID-19 pandemic.", "doc_id": "uwrotzhk"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Coswara -- A Database of Breathing, Cough, and Voice Sounds for COVID-19 Diagnosis", "abstract": "The COVID-19 pandemic presents global challenges transcending boundaries of country, race, religion, and economy. The current gold standard method for COVID-19 detection is the reverse transcription polymerase chain reaction (RT-PCR) testing. However, this method is expensive, time-consuming, and violates social distancing. Also, as the pandemic is expected to stay for a while, there is a need for an alternate diagnosis tool which overcomes these limitations, and is deployable at a large scale. The prominent symptoms of COVID-19 include cough and breathing difficulties. We foresee that respiratory sounds, when analyzed using machine learning techniques, can provide useful insights, enabling the design of a diagnostic tool. Towards this, the paper presents an early effort in creating (and analyzing) a database, called Coswara, of respiratory sounds, namely, cough, breath, and voice. The sound samples are collected via worldwide crowdsourcing using a website application. The curated dataset is released as open access. As the pandemic is evolving, the data collection and analysis is a work in progress. We believe that insights from analysis of Coswara can be effective in enabling sound based technology solutions for point-of-care diagnosis of respiratory infection, and in the near future this can help to diagnose COVID-19.", "doc_id": "mza4x7h1"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Psychometric Analysis and Coupling of Emotions Between State Bulletins and Twitter in India during COVID-19 Infodemic", "abstract": "COVID-19 infodemic has been spreading faster than the pandemic itself. The misinformation riding upon the infodemic wave poses a major threat to people's health and governance systems. Since social media is the largest source of information, managing the infodemic not only requires mitigating of misinformation but also an early understanding of psychological patterns resulting from it. During the COVID-19 crisis, Twitter alone has seen a sharp 45% increase in the usage of its curated events page, and a 30% increase in its direct messaging usage, since March 6th 2020. In this study, we analyze the psychometric impact and coupling of the COVID-19 infodemic with the official bulletins related to COVID-19 at the national and state level in India. We look at these two sources with a psycho-linguistic lens of emotions and quantified the extent and coupling between the two. We modified path, a deep skip-gram based open-sourced lexicon builder for effective capture of health-related emotions. We were then able to capture the time-evolution of health-related emotions in social media and official bulletins. An analysis of lead-lag relationships between the time series of extracted emotions from official bulletins and social media using Granger's causality showed that state bulletins were leading the social media for some emotions such as Medical Emergency. Further insights that are potentially relevant for the policymaker and the communicators actively engaged in mitigating misinformation are also discussed. Our paper also introduces CoronaIndiaDataset2, the first social media based COVID-19 dataset at national and state levels from India with over 5.6 million national and 2.6 million state-level tweets. Finally, we present our findings as COVibes, an interactive web application capturing psychometric insights captured upon the CoronaIndiaDataset, both at a national and state level.", "doc_id": "g1u3xyzj"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Spatial-Temporal Dataset of COVID-19 Outbreak in China", "abstract": "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.", "doc_id": "0is1vyhy"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Can AI help in screening Viral and COVID-19 pneumonia?", "abstract": "Coronavirus disease (COVID-19) is a pandemic disease, which has already caused thousands of causalities and infected several millions of people worldwide. Any technological tool enabling rapid screening of the COVID-19 infection with high accuracy can be crucially helpful to healthcare professionals. The main clinical tool currently in use for the diagnosis of COVID-19 is the Reverse transcription polymerase chain reaction (RT-PCR), which is expensive, less-sensitive and requires specialized medical personnel. X-ray imaging is an easily accessible tool that can be an excellent alternative in the COVID-19 diagnosis. This research was taken to investigate the utility of artificial intelligence (AI) in the rapid and accurate detection of COVID-19 from chest X-ray images. The aim of this paper is to propose a robust technique for automatic detection of COVID-19 pneumonia from digital chest X-ray images applying pre-trained deep-learning algorithms while maximizing the detection accuracy. A public database was created by the authors combining several public databases and also by collecting images from recently published articles. The database contains a mixture of 423 COVID-19, 1485 viral pneumonia, and 1579 normal chest X-ray images. Transfer learning technique was used with the help of image augmentation to train and validate several pre-trained deep Convolutional Neural Networks (CNNs). The networks were trained to classify two different schemes: i) normal and COVID-19 pneumonia; ii) normal, viral and COVID-19 pneumonia with and without image augmentation. The classification accuracy, precision, sensitivity, and specificity for both the schemes were 99.7%, 99.7%, 99.7% and 99.55% and 97.9%, 97.95%, 97.9%, and 98.8%, respectively.", "doc_id": "iilujjvc"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Knowledge synthesis from 100 million biomedical documents augments the deep expression profiling of coronavirus receptors", "abstract": "The COVID-19 pandemic demands assimilation of all available biomedical knowledge to decode its mechanisms of pathogenicity and transmission. Despite the recent renaissance in unsupervised neural networks for decoding unstructured natural languages, a platform for the real-time synthesis of the exponentially growing biomedical literature and its comprehensive triangulation with deep omic insights is not available. Here, we present the nferX platform for dynamic inference from over 45 quadrillion possible conceptual associations extracted from unstructured biomedical text, and their triangulation with Single Cell RNA-sequencing based insights from over 25 tissues. Using this platform, we identify intersections between the pathologic manifestations of COVID-19 and the comprehensive expression profile of the SARS-CoV-2 receptor ACE2. We find that tongue keratinocytes and olfactory epithelial cells are likely under-appreciated targets of SARS-CoV-2 infection, correlating with reported loss of sense of taste and smell as early indicators of COVID-19 infection, including in otherwise asymptomatic patients. Airway club cells, ciliated cells and type II pneumocytes in the lung, and enterocytes of the gut also express ACE2. This study demonstrates how a holistic data science platform can leverage unprecedented quantities of structured and unstructured publicly available data to accelerate the generation of impactful biological insights and hypotheses.", "doc_id": "dtnuet6c"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "An updated analysis of turning point, duration and attack rate of COVID-19 outbreaks in major Western countries with data of daily new cases", "abstract": "As coronavirus spreads around the world, the study of its effects is of great practical significance. We collated data on daily new cases of the COVID-19 outbreaks in the six Western countries of the Group of Seven and the dates of governments' interventions. We studied the periods before and after the dates of major governments' interventions integrally based on a segmented Poisson model. The relevant results are published in the paper of \"Predicting turning point, duration and attack rate of COVID - 19 outbreaks in major Western countries\" [1]. Our method can be used to update prediction daily as COVID-19 outbreaks evolve. In this article, we illustrate an updated analysis with our method to facilitate reproducibility. Both datasets used and updated are provided.", "doc_id": "bycyzejg"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "Racism is a Virus: Anti-Asian Hate and Counterhate in Social Media during the COVID-19 Crisis", "abstract": "The spread of COVID-19 has sparked racism, hate, and xenophobia in social media targeted at Chinese and broader Asian communities. However, little is known about how racial hate spreads during a pandemic and the role of counterhate speech in mitigating the spread. Here we study the evolution and spread of anti-Asian hate speech through the lens of Twitter. We create COVID-HATE, the largest dataset of anti-Asian hate and counterhate spanning three months, containing over 30 million tweets, and a social network with over 87 million nodes. By creating a novel hand-labeled dataset of 2,400 tweets, we train a text classifier to identify hate and counterhate tweets that achieves an average AUROC of 0.852. We identify 891,204 hate and 200,198 counterhate tweets in COVID-HATE. Using this data to conduct longitudinal analysis, we find that while hateful users are less engaged in the COVID-19 discussions prior to their first anti-Asian tweet, they become more vocal and engaged afterwards compared to counterhate users. We find that bots comprise 10.4% of hateful users and are more vocal and hateful compared to non-bot users. Comparing bot accounts, we show that hateful bots are more successful in attracting followers compared to counterhate bots. Analysis of the social network reveals that hateful and counterhate users interact and engage extensively with one another, instead of living in isolated polarized communities. Furthermore, we find that hate is contagious and nodes are highly likely to become hateful after being exposed to hateful content. Importantly, our analysis reveals that counterhate messages can discourage users from turning hateful in the first place. Overall, this work presents a comprehensive overview of anti-Asian hate and counterhate content during a pandemic. The COVID-HATE dataset is available at http://claws.cc.gatech.edu/covid.", "doc_id": "l9mutkby"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "TweetsCOV19 -- A Knowledge Base of Semantically Annotated Tweets about the COVID-19 Pandemic", "abstract": "Publicly available social media archives facilitate research in the social sciences and provide corpora for training and testing a wide range of machine learning, NLP and information retrieval methods. With respect to the recent outbreak of COVID-19, online discourse on Twitter reflects public opinion and perception related to the pandemic itself as well as mitigating measures and their societal impact. Understanding such discourse, its evolution and interdependencies with real-world events or (mis)information can foster valuable insights. On the other hand, such corpora are crucial facilitators for computational methods addressing tasks such as sentiment analysis, event detection or entity recognition. However, obtaining, archiving and semantically annotating large amounts of tweets is costly. In this paper, we describe TweetsCOV19, a publicly available knowledge base of currently more than 8 million tweets, spanning the period Oct'19-Apr'20. Metadata about the tweets as well as extracted entities, hashtags, user mentions, sentiments, and URLs are exposed using established RDF/S vocabularies, providing an unprecedented knowledge base for a range of knowledge discovery tasks. Next to a description of the dataset and its extraction and annotation process, we present an initial analysis, use cases and usage of the corpus.", "doc_id": "aj2kscs9"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "The COronavirus Pandemic Epidemiology (COPE) Consortium: A Call to Action", "abstract": "The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.", "doc_id": "8byzhm1d"} {"topic_name": "coronavirus public datasets", "topic_id": "35", "title": "NAIST COVID: Multilingual COVID-19 Twitter and Weibo Dataset", "abstract": "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.", "doc_id": "o8b1rtux"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Rapid Structure-Based Screening Informs Potential Agents for Coronavirus Disease (COVID-19) Outbreak", "abstract": "Coronavirus Disease 2019 (COVID-19), caused by the novel coronavirus, has spread rapidly across China. Consequently, there is an urgent need to sort and develop novel agents for the prevention and treatment of viral infections. A rapid structure-based virtual screening is used for the evaluation of current commercial drugs, with structures of human angiotensin converting enzyme II (ACE2), and viral main protease, spike, envelope, membrane and nucleocapsid proteins. Our results reveal that the reported drugs Arbidol, Chloroquine and Remdesivir may hinder the entry and release of virions through the bindings with ACE2, spike and envelope proteins. Due to the similar binding patterns, NHC (\u03b2-d-N4-hydroxycytidine) and Triazavirin are also in prospects for clinical use. Main protease (3CLpro) is likely to be a feasible target of drug design. The screening results to target 3CL-pro reveal that Mitoguazone, Metformin, Biguanide Hydrochloride, Gallic acid, Caffeic acid, Sulfaguanidine and Acetylcysteine seem be possible inhibitors and have potential application in the clinical therapy of COVID-19.", "doc_id": "dog7i13o"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2.", "abstract": "The SARS-CoV-2 virus is more transmissible than previous coronaviruses and causes a more serious illness than influenza. The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. Using a naive llama single-domain antibody library and PCR-based maturation, we have produced two closely related nanobodies, H11-D4 and H11-H4, that bind RBD (KD of 39 and 12 nM, respectively) and block its interaction with ACE2. Single-particle cryo-EM revealed that both nanobodies bind to all three RBDs in the spike trimer. Crystal structures of each nanobody-RBD complex revealed how both nanobodies recognize the same epitope, which partly overlaps with the ACE2 binding surface, explaining the blocking of the RBD-ACE2 interaction. Nanobody-Fc fusions showed neutralizing activity against SARS-CoV-2 (4-6 nM for H11-H4, 18 nM for H11-D4) and additive neutralization with the SARS-CoV-1/2 antibody CR3022.", "doc_id": "47z1p8c9"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Covid-19, Coronavirus, SARS-CoV-2 and the small bowel.", "abstract": "Although SARS-CoV-2 may primarily enter the cells of the lungs, the small bowel may also be an important entry or interaction site, as the enterocytes are rich in angiotensin converting enzyme (ACE)-2 receptors. The initial gastrointestinal symptoms that appear early during the course of Covid-19 support this hypothesis. Furthermore, SARS-CoV virions are preferentially released apically and not at the basement of the airway cells. Thus, in the setting of a productive infection of conducting airway epithelia, the apically released SARS-CoV may be removed by mucociliary clearance and gain access to the GI tract via a luminal exposure. In addition, post-mortem studies of mice infected by SARS-CoV have demonstrated diffuse damage to the GI tract, with the small bowel showing signs of enterocyte desquamation, edema, small vessel dilation and lymphocyte infiltration, as well as mesenteric nodes with severe hemorrhage and necrosis. Finally, the small bowel is rich in furin, a serine protease which can separate the S-spike of the coronavirus into two \"pinchers\" (S1 and 2). The separation of the S-spike into S1 and S2 is essential for the attachment of the virion to both the ACE receptor and the cell membrane. In this special review, we describe the interaction of SARS-CoV-2 with the cell and enterocyte and its potential clinical implications.", "doc_id": "0cvh83zu"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Structural basis of a shared antibody response to SARS-CoV-2.", "abstract": "Molecular understanding of neutralizing antibody responses to SARS-CoV-2 could accelerate vaccine design and drug discovery. We analyzed 294 anti-SARS-CoV-2 antibodies and found that IGHV3-53 is the most frequently used IGHV gene for targeting the receptor-binding domain (RBD) of the spike protein. Co-crystal structures of two IGHV3-53 neutralizing antibodies with RBD, with or without Fab CR3022, at 2.33 to 3.20 \u00c5 resolution revealed that the germline-encoded residues dominate recognition of the ACE2 binding site. This binding mode limits the IGHV3-53 antibodies to short CDR H3 loops, but accommodates light-chain diversity. These IGHV3-53 antibodies show minimal affinity maturation and high potency, which is promising for vaccine design. Knowledge of these structural motifs and binding mode should facilitate design of antigens that elicit this type of neutralizing response.", "doc_id": "12o2r9zx"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Considerations around the SARS-CoV-2 Spike Protein with particular attention to COVID-19 brain infection and neurological symptoms.", "abstract": "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.", "doc_id": "2bz78yl1"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Molecular simulation of SARS-CoV-2 spike protein binding to pangolin ACE2 or human ACE2 natural variants reveals altered susceptibility to infection.", "abstract": "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.", "doc_id": "d4rekhom"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Binding of the SARS-CoV-2 Spike Protein to Glycans", "abstract": "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.", "doc_id": "6e3j0pn7"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "A graph-based approach identifies dynamic H-bond communication networks in spike protein S of SARS-CoV-2", "abstract": "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.", "doc_id": "f4z91s03"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Potent synthetic nanobodies against SARS-CoV-2 and molecular basis for neutralization", "abstract": "SARS-CoV-2, the Covid-19 causative virus, adheres to human cells through binding of its envelope Spike protein to the receptor ACE2. The Spike receptor-binding domain (S-RBD) mediates this key event and thus is a primary target for therapeutic neutralizing antibodies to mask the ACE2-interacting interface. Here, we generated 99 synthetic nanobodies (sybodies) using ribosome and phage display. The best sybody MR3 binds the RBD with KD of 1.0 nM and neutralizes SARS-CoV-2 pseudovirus with IC50 of 0.40 \u03bcg mL-1. Crystal structures of two sybody-RBD complexes reveal a common neutralizing mechanism through which the RBD-ACE2 interaction is competitively inhibited by sybodies. The structures allowed the rational design of a mutant with higher affinity and improved neutralization efficiency by \u223c24-folds, lowering the IC50 from 12.32 to 0.50 \u03bcg mL-1. Further, the structures explain the selectivity of sybodies between SARS-CoV strains. Our work presents an alternative approach to generate neutralizers against newly emerged viruses. One sentence summary Structural and biochemical studies revealed the molecular basis for the neutralization mechanism of in vitro-selected and rationally designed nanobody neutralizers for SARS-CoV-2 pseudovirus.", "doc_id": "88wfcc3y"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Computational methods to develop potential neutralizing antibody Fab region against SARS-CoV-2 as therapeutic and diagnostic tool", "abstract": "SARS-CoV-2, a global pandemic originated from Wuhan city of China in the month of December 2019. There is an urgency to identify potential antibodies to neutralize the virus and also as a diagnostic tool candidate. At present palliative treatments using existing antiviral drugs are under trails to treat SARS-CoV-2.Whole Genome sequence of Wuhan market sample of SARS-CoV-2 was obtained from NCBI Gene ID MN908947.3.Spike protein sequence PDB ID 6VSB obtained from RCSB database. Spike protein sequence had shown top V gene match with IGLV1-44*01, IGLV1-47*02 and has VL type chain. Whole Genome sequence had shown top V gene match with IGHV1-38-4*01 and has VH type chain. VD chain had shown link to allele HLA-A0206 80%, HLA-A0217 80%, HLA-A2301 75%, HLA-A0203 75%, HLA-A0202 70% and HLA-A0201 55% of binding levels. Some conserved regions of spike protein had shown strong binding affinity with HLA-A-0*201, HLA-A24, HLA-B-5701 and HLA-B-5703 alpha chains. Synthetic Fab construct BCR type antibody IgG (CR5840) had shown Polyspecific binding activity with spike glycoprotein when compared with available Anti-SARS antibody CR3022.Thus we propose CR5840 Fab constructed antibody as potential neutralizing antibody for SARS-CoV-2. Based on germline analysis we also propose cytotoxic T lymphocyte epitope peptide selective system as effective tool for the development of SARS-CoV-2 vaccine.", "doc_id": "2jrichn5"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM", "abstract": "The recent outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid international spread pose a global health emergency. The trimeric spike (S) glycoprotein interacts with its receptor human ACE2 to mediate viral entry into host-cells. Here we present cryo-EM structures of an uncharacterized tightly closed SARS-CoV-2 S-trimer and the ACE2-bound-S-trimer at 2.7-\u00c5 and 3.8-\u00c5-resolution, respectively. The tightly closed S-trimer with inactivated fusion peptide may represent the ground prefusion state. ACE2 binding to the up receptor-binding domain (RBD) within S-trimer triggers continuous swing-motions of ACE2-RBD, resulting in conformational dynamics of S1 subunits. Noteworthy, SARS-CoV-2 S-trimer appears much more sensitive to ACE2-receptor than SARS-CoV S-trimer in terms of receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and residue Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2, and provided structural basis of the spike D614G-mutation induced enhanced infectivity. Our findings offer a thorough picture on the mechanism of ACE2-induced conformational transitions of S-trimer from ground prefusion state towards postfusion state, thereby providing important information for development of vaccines and therapeutics aimed to block receptor binding.", "doc_id": "4y37676n"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Extracellular vesicles containing ACE2 efficiently prevent infection by SARS-CoV-2 Spike protein-containing virus", "abstract": "SARS-CoV-2 entry is mediated by binding of the spike protein (S) to the surface receptor ACE2 and subsequent priming by TMPRRS2 allowing membrane fusion. Here, we produced extracellular vesicles (EVs) exposing ACE2 and demonstrate that ACE2-EVs are efficient decoys for SARS-CoV-2 S protein-containing lentivirus. Reduction of infectivity positively correlates with the level of ACE2, is 500 to 1500 times more efficient than with soluble ACE2 and further enhanced by the inclusion of TMPRSS2.", "doc_id": "4dadwwtc"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "A potent neutralizing human antibody reveals the N-terminal domain of the Spike protein of SARS-CoV-2 as a site of vulnerability", "abstract": "The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global public health threat. Most research on therapeutics against SARS-CoV-2 focused on the receptor binding domain (RBD) of the Spike (S) protein, whereas the vulnerable epitopes and functional mechanism of non-RBD regions are poorly understood. Here we isolated and characterized monoclonal antibodies (mAbs) derived from convalescent COVID-19 patients. An mAb targeting the N-terminal domain (NTD) of the SARS-CoV-2 S protein, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2, although it does not block the interaction between angiotensin-converting enzyme 2 (ACE2) receptor and S protein. The cryo-EM structure of the SARS-CoV-2 S protein in complex with 4A8 has been determined to an overall resolution of 3.1 Angstrom and local resolution of 3.4 Angstrom for the 4A8-NTD interface, revealing detailed interactions between the NTD and 4A8. Our functional and structural characterizations discover a new vulnerable epitope of the S protein and identify promising neutralizing mAbs as potential clinical therapy for COVID-19.", "doc_id": "b3l4sy1u"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "In silico detection of SARS-CoV-2 specific B-cell epitopes and validation in ELISA for serological diagnosis of COVID-19", "abstract": "Rapid generation of diagnostics is paramount to understand epidemiology and to control the spread of emerging infectious diseases such as COVID-19. Computational methods to predict serodiagnostic epitopes that are specific for the pathogen could help accelerate the development of new diagnostics. A systematic survey of 27 SARS-CoV-2 proteins was conducted to assess whether existing B-cell epitope prediction methods, combined with comprehensive mining of sequence databases and structural data, could predict whether a particular protein would be suitable for serodiagnosis. Nine of the predictions were validated with recombinant SARS-CoV-2 proteins in the ELISA format using plasma and sera from patients with SARS-CoV-2 infection, and a further 11 predictions were compared to the recent literature. Results appeared to be in agreement with 12 of the predictions, in disagreement with 3, while a further 5 were deemed inconclusive. We showed that two of our top five candidates, the N-terminal fragment of the nucleoprotein and the receptor-binding domain of the spike protein, have the highest sensitivity and specificity and signal-to-noise ratio for detecting COVID-19 sera/plasma by ELISA. Mixing the two antigens together for coating ELISA plates led to a sensitivity of 94% (N=80 samples from persons with RT-PCR confirmed SARS-CoV2 infection), and a specificity of 97.2% (N=106 control samples).", "doc_id": "90a9rhsh"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Understanding the B and T cells epitopes of spike protein of severe respiratory syndrome coronavirus-2: A computational way to predict the immunogens", "abstract": "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.", "doc_id": "ch004jxy"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "De novo design of high-affinity antibody variable regions (Fv) against the SARS-CoV-2 spike protein", "abstract": "The emergence of SARS-CoV-2 is responsible for the pandemic of respiratory disease known as COVID-19, which emerged in the city of Wuhan, Hubei province, China in late 2019. Both vaccines and targeted therapeutics for treatment of this disease are currently lacking. Viral entry requires binding of the viral spike receptor binding domain (RBD) with the human angiotensin converting enzyme (hACE2). In an earlier paper1, we report on the specific residue interactions underpinning this event. Here we report on the de novo computational design of high affinity antibody variable regions through the recombination of VDJ genes targeting the most solvent-exposed hACE2-binding residues of the SARS-CoV-2 spike protein using the software tool OptMAVEn-2.02. Subsequently, we carry out computational affinity maturation of the designed prototype variable regions through point mutations for improved binding with the target epitope. Immunogenicity was restricted by preferring designs that match sequences from a 9-mer library of \u201chuman antibodies\u201d based on H-score (human string content, HSC)3. We generated 106 different designs and report in detail on the top five that trade-off the greatest affinity for the spike RBD epitope (quantified using the Rosetta binding energies) with low H-scores. By grafting the designed Heavy (VH) and Light (VL) chain variable regions onto a human framework (Fc), high-affinity and potentially neutralizing full-length monoclonal antibodies (mAb) can be constructed. Having a potent antibody that can recognize the viral spike protein with high affinity would be enabling for both the design of sensitive SARS-CoV-2 detection devices and for their deployment as therapeutic antibodies.", "doc_id": "crz52oo8"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Unfractionated heparin potently inhibits the binding of SARS-CoV-2 spike protein to a human cell line", "abstract": "The SARS-CoV-2 spike protein is known to bind to the receptor, ACE2, on the surface of target cells. The spike protein is processed by membrane proteases, including TMPRSS2, and is either internalised or fuses directly with the cell, leading to infection. We identified a human cell line that expresses both ACE2 and TMPRSS2, the RT4 urinary bladder transitional carcinoma, and used it to develop a proxy assay for viral interactions with host cells. A tagged recombinant form of the spike protein, containing both the S1 and S2 domains, binds strongly to RT4 cells as determined by flow cytometry. Binding is temperature dependent and increases sharply at 37\u00b0C, suggesting that processing of the spike protein is likely to be important in the interaction. As the spike protein has previously been shown to bind heparin, a soluble glycosaminoglycan, we used a flow cytometry assay to determine the effect of heparin on spike protein binding to RT4 cells. Unfractionated heparin inhibited spike protein binding with an IC50 value of <0.05U/ml whereas two low molecular weight heparins were much less effective. This suggests that heparin, particularly unfractionated forms, could be considered to reduce clinical manifestations of COVID-19 by inhibiting continuing viral infection. Despite the sensitivity to heparin, we found no evidence that host cell glycosaminoglycans such as heparan and chondroitin sulphates play a major role in spike protein attachment.", "doc_id": "3w5fvbts"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "AI334 and AQ806 antibodies recognize the spike S protein from SARS-CoV-2 by ELISA", "abstract": "We tested 10 recombinant antibodies directed against the spike S protein from SARS-CoV-1. Among them, antibodies AI334 and AQ806 detect by ELISA the spike S protein from SARS-CoV-2.", "doc_id": "5xm7cwjz"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Structures of potent and convergent neutralizing antibodies bound to the SARS-CoV-2 spike unveil a unique epitope responsible for exceptional potency", "abstract": "Understanding the mechanism of neutralizing antibodies (NAbs) against SARS-CoV-2 is critical for effective vaccines and therapeutics development. We recently reported an exceptionally potent NAb, BD-368-2, and revealed the existence of VH3-53/VH3-66 convergent NAbs in COVID-19. Here we report the 3.5-\u00c5 cryo-EM structure of BD-368-2\u2019s Fabs in complex with a mutation-induced prefusion-state-stabilized spike trimer. Unlike VH3-53/VH3-66 NAbs, BD-368-2 fully blocks ACE2 binding by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their \u201cup\u201d and \u201cdown\u201d positions. BD-368-2 also triggers fusogenic-like structural rearrangements of the spike trimer, which could impede viral entry. Moreover, BD-368-2 completely avoids the common epitope of VH3-53/VH3-66 NAbs, evidenced by multiple crystal structures of their Fabs in tripartite complexes with RBD, suggesting a new way of pairing potent NAbs to prevent neutralization escape. Together, these results rationalize a unique epitope that leads to exceptional neutralization potency, and provide guidance for NAb therapeutics and vaccine designs against SARS-CoV-2.", "doc_id": "60gscdyu"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Structure of the nCoV trimeric spike", "abstract": "", "doc_id": "5yke4jkv"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Local computational methods to improve the interpretability and analysis of cryo-EM maps", "abstract": "Cryo-electron microscopy (cryo-EM) maps usually show heterogeneous distributions of B-factors and electron density occupancies and are typically B-factor sharpened to improve their contrast and interpretability at high-resolutions. However, \u2018over-sharpening\u2019 due to the application of a single global B-factor can distort processed maps causing connected densities to appear broken and disconnected. This issue limits the interpretability of cryo-EM maps, i.e. ab initio modelling. In this work, we propose 1) approaches to enhance high-resolution features of cryo-EM maps, while preventing map distortions and 2) methods to obtain local B-factors and electron density occupancy maps. These algorithms have as common link the use of the spiral phase transformation and are called LocSpiral, LocBSharpen, LocBFactor and LocOccupancy. Our results, which include improved maps of recent SARS-CoV-2 structures, show that our methods can improve the interpretability and analysis of obtained reconstructions.", "doc_id": "4kslllaq"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Prefusion spike protein stabilization through computational mutagenesis", "abstract": "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\u2019 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.", "doc_id": "86hv27vh"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Genetic variants in TMPRSS2 and Structure of SARS-CoV-2 spike glycoprotein and TMPRSS2 complex", "abstract": "SARS-CoV-2, a highly transmittable pathogen has infected over 3.8 million people around the globe. The spike glycoprotein of SARS-CoV-2 engages host ACE2 for adhesion, TMPRSS2 for activation and entry. With the aid of whole-exome sequencing, we report a variant rs12329760 in TMPRSS2 gene and its mutant V160M, which might impede viral entry. Furthermore, we identified TMPRSS2 cleavage sites in S2 domain of spike glycoprotein and report the structure of TMPRSS2 in complex with spike glycoprotein. We also report the structures of protease inhibitors in complex with TMPRSS2, which could hamper the interaction with spike protein. These findings advance our understanding on the role of TMPRSS2 and in the development of potential therapeutics.", "doc_id": "alrbutoy"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Scientists have turned the structure of the coronavirus into music", "abstract": "You\u2019ve probably seen dozens of images of the novel coronavirus\u2014now responsible for 1 million infections and tens of thousands of deaths Now, scientists have come up with a way for you to hear it: by translating the structure of its famous spike protein into music", "doc_id": "4qy726j1"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "SARS-CoV-2 Encodes a PPxY Late Domain Motif that is Known to Enhance Budding and Spread in Enveloped RNA Viruses", "abstract": "Currently, the global COVID-19 (Coronavirus Disease-2019) pandemic is affecting the health and/or socioeconomic life of almost each people in the world. Finding vaccines and therapeutics is urgent but without forgetting to elucidate the molecular mechanisms that allow some viruses to become dangerous for humans. Here, analysis of all proteins of SARS-CoV-2 revealed a unique PPxY Late (L) domain motif 25PPAY28 in spike protein inside hot disordered loop predicted subject to phosphorylation and binding. It was demonstrated in enveloped RNA viruses that PPxY motif recruits Nedd4 E3 ubiquitin ligases and ultimately the ESCRT complex to enhance virus budding and release that means a high viral load, hence facilitating new infections. Note that PPxY motif is not present in proteins of SARS-CoV. This suggests that PPxY motif by its role in enhancing the viral load could explain why SARS-CoV-2 is more contagious than SARS-CoV. Of course, after the experimental verifications showing that PPxY motif plays the same role as reported for other enveloped RNA viruses, it could become an interesting target for the development of novel host-oriented antivirals therapeutics for preventing S protein to recruit Nedd4 E3 ubiquitin ligases partners.", "doc_id": "50d92kjk"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping", "abstract": "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.", "doc_id": "e20gtx0z"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Dual nature of human ACE2 glycosylation in binding to SARS-CoV-2 spike", "abstract": "Binding of the spike protein of SARS-CoV-2 to the human angiotensin converting enzyme 2 (ACE2) receptor triggers translocation of the virus into cells. Both the ACE2 receptor and the spike protein are heavily glycosylated, including at sites near their binding interface. We built fully glycosylated models of the ACE2 receptor bound to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Using atomistic molecular dynamics (MD) simulations, we found that the glycosylation of the human ACE2 receptor contributes substantially to the binding of the virus. Interestingly, the glycans at two glycosylation sites, N90 and N322, have opposite effects on spike protein binding. The glycan at the N90 site partly covers the binding interface of the spike RBD. Therefore, this glycan can interfere with the binding of the spike protein and protect against docking of the virus to the cell. By contrast, the glycan at the N322 site interacts tightly with the RBD of the ACE2-bound spike protein and strengthens the complex. Remarkably, the N322 glycan binds into a conserved region of the spike protein identified previously as a cryptic epitope for a neutralizing antibody. By mapping the glycan binding sites, our MD simulations aid in the targeted development of neutralizing antibodies and SARS-CoV-2 fusion inhibitors.", "doc_id": "cvqgtpbw"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Structural modeling of 2019-novel coronavirus (nCoV) spike protein reveals a proteolytically-sensitive activation loop as a distinguishing feature compared to SARS-CoV and related SARS-like coronaviruses.", "abstract": "The 2019 novel coronavirus (2019-nCoV) is currently causing a widespread outbreak centered on Hubei province, China and is a major public health concern. Taxonomically 2019-nCoV is closely related to SARS-CoV and SARS-related bat coronaviruses, and it appears to share a common receptor with SARS-CoV (ACE-2). Here, we perform structural modeling of the 2019-nCoV spike glycoprotein. Our data provide support for the similar receptor utilization between 2019-nCoV and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains, which we predict to be proteolytically-sensitive. We suggest this loop confers fusion activation and entry properties more in line with MERS-CoV and other coronaviruses, and that the presence of this structural loop in 2019-nCoV may affect virus stability and transmission.", "doc_id": "88iu8n5h"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Receptor-binding domain of SARS-Cov spike protein: soluble expression in E. coli, purification and functional characterization.", "abstract": "AIM Spike protein of coronavirus is responsible for virus binding, fusion and entry, and is a major inducer of neutralizing antibodies. This paper was to find a soluble and functional recombinant receptor-binding domain of severe acute respiratory syndrome-associated coronavirus (SARS-Cov), and to analyze its receptor binding ability. METHODS Three fusion tags (glutathione S-transferase, GST; thioredoxin, Trx; maltose-binding protein, MBP), which preferably contributes to increasing solubility and to facilitating the proper folding of heteroprotein, were used to acquire the soluble and functional expression of RBD protein in Escherichia coli (BL21(DE3) and Rosetta-gamiB(DE3) strains). The receptor binding ability of the purified soluble RBD protein was then detected by ELISA and flow cytometry assay. RESULTS RBD of SARS-Cov spike protein was expressed as inclusion body when fused as TrxA tag form in both BL21 (DE3) and Rosetta-gamiB (DE3) under many different cultures and induction conditions. And there was no visible expression band on SDS-PAGE when RBD was expressed as MBP tagged form. Only GST tagged RBD was soluble expressed in BL21(DE3), and the protein was purified by AKTA Prime Chromatography system. The ELISA data showed that GST/RBD antigen had positive reaction with anti-RBD mouse monoclonal antibody 1A5. Further flow cytometry assay demonstrated the high efficiency of RBD's binding ability to ACE2 (angiotensin-converting enzyme 2) positive Vero E6 cell. And ACE2 was proved as a cellular receptor that meditated an initial-affinity interaction with SARS-Cov spike protein. The geometrical mean of GST and GST/RBD binding to Vero E6 cells were 77.08 and 352.73 respectively. CONCLUSION In this paper, we get sufficient soluble N terminal GST tagged RBD protein expressed in E.coli BL21(DE3); data from ELISA and flow cytometry assay demonstrate that the recombinant protein is functional and binding to ACE2 positive Vero E6 cell efficiently. And the recombinant RBD derived from E.coli can be used to developing subunit vaccine to block S protein binding with receptor and to neutralizing SARS-Cov infection.", "doc_id": "2y5pzp8l"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "In silico design of antiviral peptides targeting the spike protein of SARS-CoV-2", "abstract": "An outbreak caused by 2019 novel coronavirus (2019-nCoV) was first identified in Wuhan City, Hubei Province, China. The new virus was later named SARS-CoV-2. The virus has affected tens of thousands of patients in the world. The infection of SARS-CoV-2 causes severe pneumonia and even death. It is urgently needed to find a therapeutic method to treat patients with SARS-CoV-2 infection. Studies showed that the surface spike (S) protein is essential for the coronavirus binding and entry of host cells. The heptad repeats 1 and 2 (HR1 and HR2) in the S protein play a decisive role in the fusion of the viral membrane with the host cell membrane. We predicted the HR1 and HR2 regions in S protein by sequence alignment. We simulated a computational model of HR1/2 regions and the fusion core. The binding energy of HR1 and HR2 of the fusion core was -33.4 kcal/mol. We then designed antivirus peptides by molecular dynamics simulation of the fusion core. The binding energy of HR2-based antiviral peptide to HR1 was -43.0 kcal/mol, which was stronger than the natural stage of the fusion core, suggesting that the predicted antiviral peptide can competitively bind with HR1 to prevent forming of the fusion core. The antiviral peptides can prevent SARS-CoV-2 membrane fusion and can potentially be used for the prevention and treatment of infections.", "doc_id": "acps8jj1"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Is SARS-CoV-2 originated from laboratory? A rebuttal to the claim of formation via laboratory recombination", "abstract": "", "doc_id": "csnwhn5g"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "A spike with which to beat COVID-19?", "abstract": "", "doc_id": "esitu0s6"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Role of the GTNGTKR motif in the N-terminal receptor-binding domain of the SARS-CoV-2 spike protein", "abstract": "The 2019 novel coronavirus disease (COVID-19) that emerged in China has been declared as public health emergency of international concern by the World Health Organization and the causative pathogen was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, we analyzed the structural characteristics of the N-terminal domain of the S1 subunit (S1-NTD) of the SARS-CoV-2 spike protein in comparison to the SARS-CoV in particular, and to other viruses presenting similar characteristic in general. Given the severity and the wide and rapid spread of the SARS-CoV-2 infection, it is very likely that the virus recognizes other receptors/co-receptors besides the ACE2. The NTD of the SARS-CoV-2 contains a receptor-binding motif different from that of SARS-CoV, with some insertions that could confer to the new coronavirus new receptor binding abilities. In particular, motifs similar to the insertion 72GTNGTKR78 have been found in structural proteins of other viruses; and these motifs were located in putative regions involved in recognizing protein and sugar receptors, suggesting therefore that similar binding abilities could be displayed by the SARS-CoV-2 S1-NTD. Moreover, concerning the origin of these NTD insertions, our findings point towards an evolutionary acquisition rather than the hypothesis of an engineered virus.", "doc_id": "39giu15x"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Targeting the SARS-CoV-2 spike glycoprotein prefusion conformation: virtual screening and molecular dynamics simulations applied to the identification of potential fusion inhibitors", "abstract": "The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a renewed interest in studying the role of the spike S glycoprotein in regulating coronavirus infections in the natural host. Taking advantage of the cryo-electron microscopy structure of SARS-CoV-2 S trimer in the prefusion conformation, we performed a virtual screening simulation with the aim to identify novel molecules that could be used as fusion inhibitors. The spike glycoprotein structure has been completed using modeling techniques and its inner cavity, needful for the postfusion transition of the trimer, has been scanned for the identification of strongly interacting available drugs. Finally, the stability of the protein-drug top complexes has been tested using classical molecular dynamics simulations. The free energy of interaction of the molecules to the spike protein has been evaluated through the MM/GBSA method and per-residue decomposition analysis. Results have been critically discussed considering previous scientific knowledge concerning the selected compounds and sequence alignments have been carried out to evaluate the spike glycoprotein similarity among the betacoronavirus family members. Finally, a cocktail of drugs that may be used as SARS-CoV-2 fusion inhibitors has been suggested.", "doc_id": "d4yidznm"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses", "abstract": "Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here, we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells, and confirm that human ACE2 is the receptor for the recently emerging SARS-CoV-2.", "doc_id": "36e0n1ee"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Understanding the B and T cell epitopes of spike protein of severe acute respiratory syndrome coronavirus-2: A computational way to predict the immunogens", "abstract": "The 2019 novel severe acute 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 the spike (S) glycoprotein of SARS-CoV-2 by its interactions with the human leukocyte antigen alleles. We identified 24 peptide stretches on the SARS-CoV-2 S protein that are well conserved among the reported strains. The S protein structure further validated the presence of predicted peptides on the surface, of which 20 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. Also, identified T-cell epitopes might be considered for incorporation in vaccine designs.", "doc_id": "f2pj1w4m"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane", "abstract": "This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane. First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite. Then, using the recently determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI. These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE. We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations. All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.", "doc_id": "641crxte"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Developing a Fully-glycosylated Full-length SARS-CoV-2 Spike Protein Model in a Viral Membrane", "abstract": "This technical study describes all-atom modeling and simulation of a fully-glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane. First, starting from PDB:6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite. Then, using the recently-determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI. These fully-glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE. We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations. All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19), so researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.", "doc_id": "9pyubizz"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2", "abstract": "Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome-coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo-electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B0AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection.", "doc_id": "86sipee4"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Identification of 22 N-glycosites on spike glycoprotein of SARS-CoV-2 and accessible surface glycopeptide motifs: implications for vaccination and antibody therapeutics", "abstract": "Coronaviruses hijack human enzymes to assemble the sugar coat on their spike glycoproteins. The mechanisms by which human antibodies may recognize the antigenic viral peptide epitopes hidden by the sugar coat are unknown. Glycosylation by insect cells differs from the native form produced in human cells, but insect cell-derived influenza vaccines have been approved by the US Food and Drug Administration. In this study, we analyzed recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein secreted from BTI-Tn-5B1-4 insect cells, by trypsin and chymotrypsin digestion followed by mass spectrometry analysis. We acquired tandem mass spectrometry (MS/MS) spectrums for glycopeptides of all 22 predicted N-glycosylated sites. We further analyzed the surface accessibility of spike proteins according to cryogenic electron microscopy and homolog-modeled structures, and available antibodies that bind to SARS-CoV-1. All 22 N-glycosylated sites of SARS-CoV-2 are modified by high-mannose N-glycans. MS/MS fragmentation clearly established the glycopeptide identities. Electron densities of glycans cover most of the spike receptor-binding domain of SARS-CoV-2, except YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ, similar to a region FSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQ in SARS-CoV-1. Other surface-exposed domains include those located on central helix, connecting region, heptad repeats, and N-terminal domain. Because the majority of antibody paratopes bind to the peptide portion with or without sugar modification, we propose a snake-catching model for predicted paratopes: a minimal length of peptide is first clamped by a paratope, and sugar modifications close to the peptide either strengthen or do not hinder the binding.", "doc_id": "0i5dcbzz"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Antibody signature induced by SARS-CoV-2 spike protein immunogens in rabbits", "abstract": "Multiple vaccine candidates against SARS-CoV-2 based on viral spike protein are under development. However, there is limited information on the quality of antibody responses generated with these vaccine modalities. To better understand antibody responses induced by spike protein-based vaccines, we performed a qualitative study by immunizing rabbits with various SARS-CoV-2 spike protein antigens: S ectodomain (S1+S2; amino acids 16 to 1213), which lacks the cytoplasmic and transmembrane domains (CT-TM), the S1 domain (amino acids 16 to 685), the receptor binding domain (RBD) (amino acids 319 to 541), and the S2 domain (amino acids 686 to 1213, lacking the RBD, as control). Resulting antibody quality and function were analyzed by enzyme-linked immunosorbent assay (ELISA), RBD competition assay, surface plasmon resonance (SPR) against different spike proteins in native conformation, and neutralization assays. All three antigens (S1+S2 ectodomain, S1 domain, and RBD), but not S2, generated strong neutralizing antibodies against SARS-CoV-2. Vaccination-induced antibody repertoire was analyzed by SARS-CoV-2 spike genome fragment phage display libraries (SARS-CoV-2 GFPDL), which identified immunodominant epitopes in the S1, S1-RBD, and S2 domains. Furthermore, these analyses demonstrated that the RBD immunogen elicited a higher antibody titer with five-fold higher affinity antibodies to native spike antigens compared with other spike antigens, and antibody affinity correlated strongly with neutralization titers. These findings may help guide rational vaccine design and facilitate development and evaluation of effective therapeutics and vaccines against COVID-19 disease.", "doc_id": "ff8846vf"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation", "abstract": "The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.", "doc_id": "2b5hue2r"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Structural and simulation analysis of hotspot residues interactions of SARS-CoV 2 with human ACE2 receptor", "abstract": "The novel corona virus disease 2019 (SARS-CoV 2) pandemic outbreak was alarming. The binding of SARS-CoV (CoV) spike protein (S-Protein) Receptor Binding Domain (RBD) to Angiotensin converting enzyme 2 (ACE2) receptor initiates the entry of corona virus into the host cells leading to the infection. However, considering the mutations reported in the SARS-CoV 2 (nCoV), the structural changes and the binding interactions of the S-protein RBD of nCoV were not clear. The present study was designed to elucidate the structural changes, hot spot binding residues and their interactions between the nCoV S-protein RBD and ACE2 receptor through computational approaches. Based on the sequence alignment, a total of 58 residues were found mutated in nCoV S-protein RBD. These mutations led to the structural changes in the nCoV S-protein RBD 3d structure with 4 helices, 10 sheets and intermittent loops. The nCoV RBD was found binding to ACE2 receptor with 11 hydrogen bonds and 1 salt bridge. The major hot spot amino acids involved in the binding identified by interaction analysis after simulations includes Glu 35, Tyr 83, Asp 38, Lys 31, Glu 37, His 34 amino acid residues of ACE2 receptor and Gln 493, Gln 498, Asn 487, Tyr 505 and Lys 417 residues in nCoV S-protein RBD. Based on the hydrogen bonding, RMSD and RMSF, total and potential energies, the nCoV was found binding to ACE2 receptor with higher stability and rigidity. Concluding, the hotspots information will be useful in designing blockers for the nCoV spike protein RBD. [Formula: see text]Communicated by Ramaswamy H. Sarma.", "doc_id": "4x4ecdhn"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Mining of epitopes on spike protein of SARS-CoV-2 from COVID-19 patients", "abstract": "", "doc_id": "40wjyq8h"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells", "abstract": "The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here, we report the rapid identification of SARS-CoV-2-neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. From 8,558 antigen-binding IgG1+ clonotypes, 14 potent neutralizing antibodies were identified, with the most potent one, BD-368-2, exhibiting an IC50 of 1.2 and 15 ng/mL against pseudotyped and authentic SARS-CoV-2, respectively. BD-368-2 also displayed strong therapeutic and prophylactic efficacy in SARS-CoV-2-infected hACE2-transgenic mice. Additionally, the 3.8 \u00c5 cryo-EM structure of a neutralizing antibody in complex with the spike-ectodomain trimer revealed the antibody's epitope overlaps with the ACE2 binding site. Moreover, we demonstrated that SARS-CoV-2-neutralizing antibodies could be directly selected based on similarities of their predicted CDR3H structures to those of SARS-CoV-neutralizing antibodies. Altogether, we showed that human neutralizing antibodies could be efficiently discovered by high-throughput single B cell sequencing in response to pandemic infectious diseases.", "doc_id": "4cgp5hr3"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity? Insights from All-Atom Simulations", "abstract": "The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic is setting the global health crisis of our time, causing a devastating societal and economic burden. An idiosyncratic trait of coronaviruses is the presence of spike glycoproteins on the viral envelope, which mediate the virus binding to specific host receptor, enabling its entry into the human cells. In spite of the high sequence identity of SARS-CoV-2 with its closely related SARS-CoV emerged in 2002, the atomic-level determinants underlining the molecular recognition of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor and, thus, the rapid virus spread into human body, remain unresolved. Here, multi-microsecond-long molecular dynamics simulations enabled us to unprecedentedly dissect the key molecular traits liable of the higher affinity/specificity of SARS-CoV-2 toward ACE2 as compared to SARS-CoV. This supplies a minute per-residue contact map underlining its stunningly high infectivity. Harnessing this knowledge is pivotal for urgently developing effective medical countermeasures to face the ongoing global health crisis.", "doc_id": "6z4kx0y9"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Comparing the Binding Interactions in the Receptor Binding Domains of SARS-CoV-2 and SARS-CoV", "abstract": "SARS-CoV-2, since emerging in Wuhan, China, has been a major concern because of its high infection rate and has left more than six million infected people around the world. Many studies endeavored to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV, in order to find solutions to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV spike (S) protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the S proteins of SARS-CoV and SARS-CoV-2 to the ACE2. Our results show that the protein surface of the ACE2 at the receptor binding domain (RBD) exhibits negative electrostatic potential, while a positive potential is observed for the S proteins of SARS-CoV/SARS-CoV-2. In addition, the binding energies at the interface are slightly higher for SARS-CoV-2 because of enhanced electrostatic interactions. The major contributions to the electrostatic binding energies result from the salt bridges forming between R426 and ACE-2-E329 in the case of SARS-CoV and K417 and ACE2-D30 in the SARS-CoV-2. In addition, our results indicate that the enhancement in the binding energy is not due to a single mutant but rather because of the sophisticated structural changes induced by all these mutations together. This finding suggests that it is implausible for the SARS-CoV-2 to be a lab-engineered virus.", "doc_id": "ai7q035z"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "The MERS-CoV Receptor DPP4 as a Candidate Binding Target of the SARS-CoV-2 Spike", "abstract": "The ongoing outbreak of the novel coronavirus pneumonia COVID-19 has caused great number of cases and deaths, but our understanding about the pathogen SARS-CoV-2 remains largely unclear. The attachment of the virus with the cell-surface receptor and a cofactor is the first step for the infection. Here, bioinformatics approaches combining human-virus protein interaction prediction and protein docking based on crystal structures have revealed the high affinity between human dipeptidylpeptidase 4 (DPP4) and the spike (S) receptor-binding domain of SARS-CoV-2. Intriguingly, the crucial binding residues of DPP4 are identical to those that are bound to the MERS-CoV-S. Moreover, E484 insertion and adjacent substitutions should be most essential for this DPP4-binding ability acquirement of SARS-CoV-2-S compared with SARS-CoV-S. This potential utilization of DPP4 as a binding target for SARS-CoV-2 may offer novel insight into the viral pathogenesis and help the surveillance and therapeutics strategy for meeting the challenge of COVID-19.", "doc_id": "dxikgdmn"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody", "abstract": "The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. These results suggest that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.", "doc_id": "2jif4hqb"} {"topic_name": "SARS-CoV-2 spike structure", "topic_id": "36", "title": "Design of engineered surfaces for prospective detection of Sars-CoV-2 using quartz crystal microbalance based techniques", "abstract": "INTRODUCTION: Rapid transmission of the severe acute respiratory syndrome coronavirus 2 has affected the whole world and forced it to a halt (lockdown). A fast and label free detection method for the novel coronavirus needs to be developed along with the existing enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR) based methods. AREAS COVERED: In this report, biophysical aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein are outlined based on its recent reported electron microscopy structure. Protein binding sites are analyzed theoretically, which consisted of hydrophobic and positive charged amino acid residues. Different strategies to form mixed self-assembled monolayers (SAMs) of hydrophobic (CH3) and negatively charged (COOH) groups are discussed to be used for the specific and strong interactions with spike protein. Bio-interfacial interactions between the spike protein and device (sensor) surface and its implications towards designing suitable engineered surfaces are summarized. EXPERT OPINION: Implementation of the engineered surfaces in quartz crystal microbalance (QCM) based detection techniques for the diagnosis of the novel coronavirus from oral swab samples is highlighted. The proposed strategy can be explored for the label free and real time detection with sensitivity up to ng level. These engineered surfaces can be reused after desorption.", "doc_id": "2ezuf5ce"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Metagenomic Analysis of Fever, Thrombocytopenia and Leukopenia Syndrome (FTLS) in Henan Province, China: Discovery of a New Bunyavirus", "abstract": "Since 2007, many cases of fever, thrombocytopenia and leukopenia syndrome (FTLS) have emerged in Henan Province, China. Patient reports of tick bites suggested that infection could contribute to FTLS. Many tick-transmitted microbial pathogens were tested for by PCR/RT-PCR and/or indirect immunofluorescence assay (IFA). However, only 8% (24/285) of samples collected from 2007 to 2010 tested positive for human granulocytic anaplasmosis (HGA), suggesting that other pathogens could be involved. Here, we used an unbiased metagenomic approach to screen and survey for microbes possibly associated with FTLS. BLASTx analysis of deduced protein sequences revealed that a novel bunyavirus (36% identity to Tehran virus, accession: HQ412604) was present only in sera from FTLS patients. A phylogenetic analysis further showed that, although closely related to Uukuniemi virus of the Phlebovirus genus, this virus was distinct. The candidate virus was examined for association with FTLS among samples collected from Henan province during 2007\u20132010. RT-PCR, viral cultures, and a seroepidemiologic survey were undertaken. RT-PCR results showed that 223 of 285 (78.24%) acute-phase serum samples contained viral RNA. Of 95 patients for whom paired acute and convalescent sera were available, 73 had serologic evidence of infection, with 52 seroconversions and 21 exhibiting a 4-fold increase in antibody titer to the virus. The new virus was isolated from patient acute-phase serum samples and named Henan Fever Virus (HNF virus). Whole-genome sequencing confirmed that the virus was a novel bunyavirus with genetic similarity to known bunyaviruses, and was most closely related to the Uukuniemi virus (34%, 24%, and 29% of maximum identity, respectively, for segment L, M, S at maximum query coverage). After the release of the GenBank sequences of SFTSV, we found that they were nearly identical (>99% identity). These results show that the novel bunyavirus (HNF virus) is strongly correlated with FTLS.", "doc_id": "2p7qrgx0"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Main Routes of Entry and Genomic Diversity of SARS-CoV-2, Uganda.", "abstract": "We established rapid local viral sequencing to document the genomic diversity of severe acute respiratory syndrome coronavirus 2 entering Uganda. Virus lineages closely followed the travel origins of infected persons. Our sequence data provide an important baseline for tracking any further transmission of the virus throughout the country and region.", "doc_id": "mx1w3l0t"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "About the origin of the first two Sars-CoV-2 infections in Italy: inference not supported by appropriate sequence analysis.", "abstract": "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.", "doc_id": "4flvyqgn"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "SARS-CoV-2 Phylogenetic Analysis, Lazio Region, Italy, February-March 2020.", "abstract": "We report phylogenetic and mutational analysis of severe acute respiratory syndrome coronavirus 2 virus strains from the Lazio region of Italy and provide information about the dynamics of virus spread. Data suggest effective containment of clade V strains, but subsequently, multiple waves of clade G strains were circulating widely in Europe.", "doc_id": "c3ezmshe"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Detection of coronaviruses in Pteropus & Rousettus species of bats from different States of India.", "abstract": "Background & objectives : Bats are considered to be the natural reservoir for many viruses, of which some are potential human pathogens. In India, an association of Pteropus medius bats with the Nipah virus was reported in the past. It is suspected that the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also has its association with bats. To assess the presence of CoVs in bats, we performed identification and characterization of bat CoV (BtCoV) in P. medius and Rousettus species from representative States in India, collected during 2018 and 2019. Methods : Representative rectal swab (RS) and throat swab specimens of Pteropus and Rousettus spp. bats were screened for CoVs using a pan-CoV reverse transcription-polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. A single-step RT-PCR was performed on the RNA extracted from the bat specimens. Next-generation sequencing (NGS) was performed on a few representative bat specimens that were tested positive. Phylogenetic analysis was carried out on the partial sequences of RdRp gene sequences retrieved from both the bat species and complete viral genomes recovered from Rousettus spp. Results : Bat samples from the seven States were screened, and the RS specimens of eight Rousettus spp. and 21 Pteropus spp. were found positive for CoV RdRp gene. Among these, by Sanger sequencing, partial RdRp sequences could be retrieved from three Rousettus and eight Pteropus bat specimens. Phylogenetic analysis of the partial RdRp region demonstrated distinct subclustering of the BtCoV sequences retrieved from these Rousettus and Pteropus spp. bats. NGS led to the recovery of four sequences covering approximately 94.3 per cent of the whole genome of the BtCoVs from Rousettus bats. Three BtCoV sequences had 93.69 per cent identity to CoV BtRt-BetaCoV/GX2018. The fourth BtCoV sequence was 96.8 per cent identical to BtCoV HKU9-1. Interpretation & conclusions : This study was a step towards understanding the CoV circulation in Indian bats. Detection of potentially pathogenic CoVs in Indian bats stresses the need for enhanced screening for novel viruses in them. One Health approach with collaborative activities by the animal health and human health sectors in these surveillance activities shall be of use to public health. This would help in the development of diagnostic assays for novel viruses with outbreak potential and be useful in disease interventions. Proactive surveillance remains crucial for identifying the emerging novel viruses with epidemic potential and measures for risk mitigation.", "doc_id": "rdfch63j"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Genomic analysis of SARS-CoV-2 strains among Indians returning from Italy, Iran & China, & Italian tourists in India.", "abstract": "", "doc_id": "huffrnt8"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Dominant and rare SARS-Cov2 variants responsible for the COVID-19 pandemic in Athens, Greece.", "abstract": "SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel Coronavirus responsible for the Coronavirus Disease-2019 (COVID-19) pandemic. Since the beginning of the pandemic, the virus has spread in almost the entire world. Tracing and tracking virus international and local transmission has been an enormous challenge. Chains of infections starting from various countries worldwide seeded the outbreak of COVID-19 in Athens, capital city of Greece. Full-genome analysis of isolates from Athens' Hospitals and other healthcare providers revealed the variety of SARS-CoV-2 that initiated the pandemic before lock-down and passenger flight restrictions. The present work may serve as reference for resolving future lines of infection in the area and Europe especially after resumption of passenger flight connections to Athens and Greece during summer of 2020.", "doc_id": "0qn4c5t3"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "A genome epidemiological study of SARS-CoV-2 introduction into Japan", "abstract": "Background: After the first case of COVID-19 in Japan on 15 January 2020, multiple nationwide COVID-19 clusters were identified by the end of February. The Japanese government focused on mitigating emerging COVID-19 clusters by conducting active nationwide epidemiological surveillance. However, an increasing number of cases appeared until early April, many with unclear infection routes exhibiting no recent history of travel outside Japan. We aimed to evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences from COVID-19 cases until early April and characterise the genealogical networks to demonstrate possible routes of spread in Japan. Methods: Nasopharyngeal specimens were collected from patients and a quantitative reverse transcription polymerase chain reaction testing for SARS-CoV-2 was performed. Positive RNA samples were subjected whole genome sequencing and a haplotype network analysis was performed. Findings: Some of the primary clusters identified during January and February in Japan directly descended from Wuhan-Hu-1-related isolates in China and other distinct clusters. Clusters were almost contained until mid-March; the haplotype network analysis demonstrated that COVID-19 cases from late March through early April may have caused an additional large cluster related to the outbreak in Europe, leading to additional spread within Japan. National self-restraint during February was effective in mitigating the COVID-19 spread, but late action on stopping immigration and declaring national emergency in Japan might be involved in the later increase in cases. Interpretation: Genome surveillance suggested that at least two distinct SARS-CoV-2 introductions from China and other countries occurred. Funding: Japan Agency for Medical Research and Development.", "doc_id": "naebdelz"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Phylogenomics and phylodynamics of SARS-CoV-2 retrieved genomes from India", "abstract": "The ongoing SARS-CoV-2 pandemic is one of the biggest outbreaks after the Spanish flu of 1918. Understanding the epidemiology of viral outbreaks is the first step towards vaccine development programs. This is the first phylodynamics study attempted on of SARS-CoV-2 genomes from India to infer its current evolution in the context of an ongoing pandemic. Out of 286 retrieved SARS-CoV-2 whole genomes from India, 138 haplotypes were generated and analyzed. Median-joining network was built to investigate the relatedness of SARS-CoV-2 haplotypes in India. The BDSIR package of BEAST2 was used to calculate the reproduction number (R0) and the infectious rate of the virus. Past and current population trend was investigated using the stamp date method in coalescent Bayesian skyline plot, implemented in BEAST2 and by exponential growth prior in BEAST 1.10.4. Median-joining network reveals two distinct ancestral clusters A and B showing genetic affinities with Wuhan outbreak sample. The network also illustrates the autochthonous development of isolates in a few instances. High basic reproduction number of SARS-nCoV-2 in India points towards the phase of active community transmission. The Bayesian skyline plot revel exponential rise in the effective population size (Ne) of Indian isolates from the first week of January to the first week of April 2020. More genome sequencing and analyses of the virus will be required in coming days to monitor COVID19 after the upliftment of lock down in India.", "doc_id": "8bf5te4l"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Distribution of COVID-19 and phylogenetic tree construction of sars-CoV-2 in Indonesia", "abstract": "Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has spread quickly across the world and has been declared a pandemic. Indonesia has many COVID-19 cases, with a high mortality rate. This study aimed to describe the distribution of COVID-19 in Indonesia and constructed the SARS-CoV-2 phylogenetic tree from Indonesian isolates and those from other countries, including other CoVs to determine their relationship. The distribution data of COVID-19 in Indonesia were obtained from the COVID-19 Management Handling Unit and descriptively analyzed. SARS-CoV-2 isolates were retrieved from the GenBank\u00ae (National Center of Biotechnology Information, USA) and GISAID EpiCoV\u2122 databases and were used to construct phylogenetic trees using MEGA X software. Of the 37 provinces in Indonesia, five provinces with the highest case fatality rates were DKI Jakarta, Jawa Barat, Jawa Timur, and Banten, and the five provinces with the highest cure rate were Kepulauan Riau, Bali, Aceh, Gorontalo, and DI Yogyakarta. SARS-CoV-2 Indonesian isolates were closely related to SARS-CoV-2 isolates from other countries. The rapid and widespread distribution of SARS-CoV-2 in Indonesia was caused by the lack of compliance with territorial restrictions and dishonesty with medical personnel. These data revealed that mutations can occur during the transmission process, which can be caused by a history of travel and increased patient immunity.", "doc_id": "eg2lxopi"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Multiple SARS-CoV-2 introductions shaped the early outbreak in Central Eastern Europe: comparing Hungarian data to a worldwide sequence data-matrix", "abstract": "Severe Acute Respiratory Syndrome Coronavirus 2 is the third highly pathogenic human coronavirus in history. Since the emergence in Hubei province, China, during late 2019 the situation evolved to pandemic level. Following China, Europe was the second epicenter of the pandemic. To better comprehend the detailed founder mechanisms of the epidemic evolution in Central-Eastern Europe, particularly in Hungary, we determined the full-length SARS-CoV-2 genomes from 32 clinical samples collected from laboratory confirmed COVID-19 patients over the first month of disease in Hungary. We applied a haplotype network analysis on all available complete genomic sequences of SARS-CoV-2 from GISAID database as of the 21th of April, 2020. We performed additional phylogenetic and phylogeographic analyses to achieve the recognition of multiple and parallel introductory events into our region. Here we present a publicly available network imaging of the worldwide haplotype relations of SARS-CoV-2 sequences and conclude the founder mechanisms of the outbreak in Central-Eastern Europe.", "doc_id": "cg9pyoam"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches", "abstract": "Whole Genome Sequence of four samples from COVID-19 outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, England). The constructed phylogenetic tree indicates probable multiple independent introduction events. The success of future containment measures concernig new introductions will be highly challenging for country due to the significant proportion of BH population living abroad.", "doc_id": "tl5fm2yu"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Diagnostics and spread of SARS-CoV-2 in Western Africa: An observational laboratory-based study from Benin", "abstract": "Information on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spread in Africa is limited by fragile 2 surveillance systems and insufficient diagnostic capacity. 3 We assessed the coronavirus disease-19 (COVID-19)-related diagnostic workload in Benin, Western Africa, 4 characterized SARS-CoV-2 genomes from 12 acute cases of COVID-19, used those together with public data to 5 estimate SARS-CoV-2 transmission dynamics in a Bayesian framework, validated a widely used diagnostic dual target 6 RT-PCR kit donated to African countries, and conducted serological analyses in 68 sera from confirmed COVID-19 7 cases and from febrile patients sampled before the predicted SARS-CoV-2 introduction. 8 We found a 15-fold increase in the monthly laboratory workload due to COVID-19. Genomic surveillance showed 9 introductions of three distinct SARS-CoV-2 lineages. SARS-CoV-2 genome-based analyses yielded an R0 estimate of 10 4.4 (95% confidence interval: 2.0-7.7), suggesting intense spread of SARS-CoV-2 in Africa. RT-PCR-based tests 11 were highly sensitive but showed variation of internal controls and between diagnostic targets. Commercially available 12 SARS-CoV-2 ELISAs showed up to 25% false-positive results depending on antigen and antibody types, likely due 13 to unspecific antibody responses elicited by acute malaria according to lack of SARS-CoV-2-specific neutralizing 14 antibody responses and relatively higher parasitemia in those sera. 15 We confirm an overload of the diagnostic capacity in Benin and provide baseline information on the usability of 16 genome-based surveillance in resource-limited settings. Sero-epidemiological studies needed to assess SARS-CoV-2 17 spread may be put at stake by low specificity of tests in tropical settings globally. The increasing diagnostic challenges 18 demand continuous support of national and supranational African stakeholders.", "doc_id": "du5bdjlp"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Laboratory based surveillance of SARS-CoV-2 in Pakistan", "abstract": "COVID-19 cases are alarmingly increasing in Pakistan since May 2020. Laboratory based surveillance system has been in place since the start of the pandemic. The genomic surveillance of SARS-CoV-2 strains isolated locally has been conducted based on partial ORF1b. The sequences were classified to show the phylogenetic correlation and showed 100% homology with those detected in neighboring countries India and China. The rapid increase in cases has led to development of robust strategies to enhance the laboratory testing capacity. We are currently meeting the country requirement to diagnose the virus in the community. Nonetheless, factors like recent ease in lockdown measures has led to massive rise in number of cases in few weeks time.", "doc_id": "iz8e6cf1"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "CoronaHiT: large scale multiplexing of SARS-CoV-2 genomes using Nanopore sequencing", "abstract": "The COVID-19 pandemic has spread to almost every country in the world since it started in China in late 2019. Controlling the pandemic requires a multifaceted approach including whole genome sequencing to support public health interventions at local and national levels. One of the most widely used methods for sequencing is the ARTIC protocol, a tiling PCR approach followed by Oxford Nanopore sequencing (ONT) of up to 24 samples at a time. There is a need for a higher throughput method to reduce cost per genome. Here we present CoronaHiT, a method capable of multiplexing up to 95 small genomes on a single Nanopore flowcell, which uses transposase mediated addition of adapters and PCR based addition of symmetric barcodes. We demonstrate the method using 48 and 94 SARS-CoV-2 genomes per flowcell, amplified using the ARTIC protocol, and compare performance with Illumina and ARTIC ONT sequencing. Results demonstrate that all sequencing methods produce inaccurate genomes when the RNA extract from SARS-CoV-2 positive clinical sample has a cycle threshold (Ct) >= 32. Results from set same set of 23 samples with a broad range of Cts show that the consensus genomes have >90% coverage (GISAID criteria) for 78.2% of samples for CoronaHiT-48, 73.9% for CoronaHiT-94, 78.2% for Illumina and 73.9% for ARTIC ONT, and all have the same clustering on a maximum likelihood tree. In conclusion, we demonstrate that CoronaHiT can multiplex up to 94 SARS-CoV-2 genomes per nanopore flowcell without compromising the quality of the resulting genomes while reducing library preparation complexity and significantly reducing cost. This protocol will aid the rapid expansion of SARS-CoV-2 genome sequencing globally, to help control the pandemic.", "doc_id": "j35epl2e"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Early phylodynamics analysis of the COVID-19 epidemics in France", "abstract": "France was one of the first countries to be reached by the COVID-19 pandemics. Here, we analyse 196 SARS-Cov-2 genomes collected between Jan 24 and Mar 24 2020, and perform a phylodynamics analysis. In particular, we analyse the doubling time, reproduction number (Rt) and infection duration associated with the epidemic wave that was detected in incidence data starting from Feb 27. We show that a slowing down of the epidemic spread can be detected in Mar, which is consistent with the implementation of the national lock-down on Mar 17. The inferred distributions for the infection duration and Rt are in line with those estimated from contact tracing data. Overall, this analysis shows the potential to use sequence genomic data to inform public health decisions in an epidemic crisis context.", "doc_id": "0e1wmy41"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Introductions and early spread of SARS-CoV-2 in France", "abstract": "Following the emergence of coronavirus disease (COVID-19) in Wuhan, China in December 2019, specific COVID-19 surveillance was launched in France on January 10, 2020. Two weeks later, the first three imported cases of COVID-19 into Europe were diagnosed in France. We sequenced 97 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from samples collected between January 24 and March 24, 2020 from infected patients in France. Phylogenetic analysis identified several early independent SARS-CoV-2 introductions without local transmission, highlighting the efficacy of the measures taken to prevent virus spread from symptomatic cases. In parallel, our genomic data reveals the later predominant circulation of a major clade in many French regions, and implies local circulation of the virus in undocumented infections prior to the wave of COVID-19 cases. This study emphasizes the importance of continuous and geographically broad genomic sequencing and calls for further efforts with inclusion of asymptomatic infections.", "doc_id": "gyr8k4j2"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Comprehensive genome analysis of 6,000 USA SARS-CoV-2 isolates reveals haplotype signatures and localized transmission patterns by state and by country", "abstract": "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.", "doc_id": "ydl44zg8"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Computational search of hybrid human/ SARS-CoV-2 dsRNA reveals unique viral sequences that diverge from other coronavirus strains", "abstract": "The role of the RNAi/Dicer/Ago system to degrade RNA viruses has been elusive in mammals, which prompted authors to think that interferon (IFN) synthesis is essential in this clade relegating the RNAi defense strategy against viral infection as accessory function. We explore the theoretical possibilities that RNAi triggered by SARS-CoV-2 might degrade some host transcripts in the opposite direction although this hypothesis seems counter intuitive. SARS-CoV-2 genome was therefore computational searched for exact intra pairing within the viral RNA and also hybrid exact pairing with human transcriptome over a minimum 20 bases length. Minimal segments of 20 bases length of SARS-CoV-2 RNA were found based on the theoretical matching with existing complementary strands in the human host transcriptome. Few human genes potentially annealing with SARS-CoV-2 RNA, among them mitochondrial deubiquitinase USP30, a subunit of ubiquitin protein ligase complex FBXO21 along with two long coding RNAs were retrieved. The hypothesis that viral originated RNAi might mediate degradation of messengers of the host transcriptome was corroborated by clinical observation and phylogenetic comparative analysis indicating a strong specificity of these hybrid pairing sequences for both SARS-CoV-2 and human genomes.", "doc_id": "386bqaui"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Analyzing hCov genome sequences: Applying Machine Intelligence and beyond", "abstract": "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.", "doc_id": "0x90yubt"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Using nucleocapsid proteins to investigate the relationship between SARS-CoV-2 and closely related bat and pangolin coronaviruses", "abstract": "An initial outbreak of coronavirus disease 2019 (COVID-19) in China has resulted in a massive global pandemic causing well over 10,000,000 cases and 500,000 deaths worldwide. The virus responsible, SARS-CoV-2, has been found to possess a very close association with Bat-CoV RaTG13 and Pangolin-CoV MP789. The nucleocapsid protein can serve as a decent model for determining phylogenetic, evolutionary, and structural relationships between coronaviruses. Therefore, this study uses the nucleocapsid gene and protein to further investigate the relationship between SARS-CoV-2 and closely related bat and pangolin coronaviruses. Sequence and phylogenetic analyses have revealed the nucleocapsid gene and protein in SARS-CoV-2 are both closely related to those found in Bat-CoV RaTG13 and Pangolin-CoV MP789. Evidence of recombination was detected within the N gene, along with the presence of a double amino acid insertion found in the N-terminal region. Homology modeling for the N-Terminal Domain revealed similar structures but distinct electrostatic surfaces and topological variations in the \u03b2-hairpin that likely reflect specific adaptive functions. In respect to SARS-CoV-2, two amino acids (37S and 267A) were found to exist only in its N protein, along with an extended \u03b2-hairpin in the N-Terminal Domain. Collectively, this study strengthens the relationship among SARS-CoV-2, Bat-CoV RaTG13, and Pangolin-CoV MP789, providing additional insights into the structure and adaptive nature of the nucleocapsid protein found in these coronaviruses. Furthermore, this data will help enhance our understanding of the complete history behind SARS-CoV-2 and help assist in antiviral and vaccine development.", "doc_id": "e37ns629"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "An Analysis of SARS-CoV-2 Using ViReport", "abstract": "The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of cases and hundreds of thousands of deaths. Given the current lack of treatments or vaccines available, it may be useful to trace the evolu-tion and spread of the virus to better develop methods of preventative intervention. In this study, we analyzed over 4,000 full genome sequences of human SARS-CoV-2 using novel tool ViReport [13], an automated workflow for performing phylogenetic analyses on viral sequences and generating comprehensive molecular epidemiologi-cal reports. The complete ViReport output can be found at https://github.com/mirandajsong/ViReport-SARS-CoV-2.", "doc_id": "whmawr4q"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Spread dynamics of SARS-CoV-2 epidemic in China: a phylogenetic analysis", "abstract": "To reveal the detailed spread dynamics of SARS-CoV-2 epidemic in China, a phylogenetic analysis was performed by the Bayesian inference framework tool. 233 strains were retrieved from confirmed cases in China until March 31, 2020. The tMRCA of SARS-CoV-2 strains in China could be traced back to December 9, 2019. According to the effective population size curve reconstructed by Skyline model, this research revealed the influence of travel ban measures on the effective population size in China. Furthermore, we divided the epidemic process of SARS-CoV-2 in China into 4 stages according to the effective population size curve. With the Bayesian stochastic search variable selection method, phylogeographical reconstruction detailedly described the geographic spread behavior of SARS-CoV-2 in each stage and confirmed the importance of travel ban in blocking SARS-CoV-2 cross-regional spread. This article summarizes the influence of prevention and control measures in China, which has a positive impact on the world.", "doc_id": "ifsk0ep1"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Early Phylogenetic Estimate Of The Effective Reproduction Number Of 2019-nCoV", "abstract": "To reconstruct the evolutionary dynamics of the 2019 novel coronavirus, 52 2019\u2212nCOV genomes available on 04 February 2020 at GISAID were analysed. The two models used to estimate the reproduction number (coalescent\u2212based exponential growth and a birth\u2212death skyline method) indicated an estimated mean evolutionary rate of 7.8 x 10\u22124 subs/site/year (range 1.1x10\u22124\u221215x10\u22124). The estimated R value was 2.6 (range 2.1\u22125.1), and increased from 0.8 to 2.4 in December 2019. The estimated mean doubling time of the epidemic was between 3.6 and 4.1 days. This study proves the usefulness of phylogeny in supporting the surveillance of emerging new infections even as the epidemic is growing.", "doc_id": "chhemr7s"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "COVID-19 in Latin America: Contrasting phylodynamic inference with epidemiological surveillance.", "abstract": "Introduction: SARS-CoV-2 infection has represented the one of the largest challenges for humanity. This virus was first detected in Latin America and the Caribbean (LAC) in Brazil in February 26, 2020 and it has revealed important gaps in infectious disease surveillance that must be covered. Phylodynamic analysis is a tool that can help to monitor and adapt traditional surveillance measures in order to cover those. Therefore, this work aims to contrast data driven from epidemiologic surveillance in LAC with parameters inferred from phylodynamic analysis of reported genomes of SARS-CoV-2 across different LAC countries Methods: We obtained epidemiological data from daily reports provided by European Centre for Disease Prevention and Control up to 13th May, 2020. We estimated Effective Reproductive Number (Re) and calculated epidemic curves with exponential growth (EG) and maximum likelihood (ML) methods. SARS-CoV-2 phylodynamic in Latin-American was analyzed using sequences reported in GISAID for Central and South America up to May 13th 2020. Sequences were aligned, and ML phylogeny was constructed. Coalescent model Birth Death SIR (serial) was run, and SIR trajectories from the birth-death SIR model were plotted. Results: A total of 404,448 cases were reported up to 13th May 2020. Overall reproduction number for Latin America, estimated through the EG and ML methods, were 1.424 (IC95% 1.422 to 1.426) and 1.305 (IC95% 1.299 to 1.311) respectively. Phylodynamic analysis for Latin America showed an overall Re of 1.27 (IC95% 1.07 to 1.49). We did not find statistically significant differences between epidemiological and phylodynamic data at the cut-off time, except for Brazil. Discussion: Our results support that epidemiological and genomic surveillance are two complementary approaches. Evidence suggests that even with a low number of sequences proper estimations of Re could be performed. We suggest that countries, especially developing countries, should consider to add genomic surveillance to their systems for monitoring and adapting epidemiological surveillance of SARS-CoV-2.", "doc_id": "pfu6q0v1"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Genomic epidemiology of SARS-CoV-2 spread in Scotland highlights the role of European travel in COVID-19 emergence", "abstract": "Abstract SARS-CoV-2, the causative agent of COVID-19, emerged in Wuhan, China in December 2019 and spread rapidly throughout the world. Understanding the introductions of this new coronavirus in different settings may assist control efforts and the establishment of frameworks to support rapid response in future infectious disease outbreaks. We investigated the first four weeks of emergence of the SARS-CoV-2 virus in Scotland after the first case reported on the 1st March 2020. We obtained full genome sequences from 452 individuals with a laboratory-confirmed diagnosis of COVID-19, representing 20% of all cases until 1st April 2020 (n=2310). This permitted a genomic epidemiology approach to study the introductions and spread of the SARS-2 virus in Scotland. From combined phylogenetic and epidemiological analysis, we estimated at least 113 introductions of SARS-CoV-2 into Scotland during this period. Clusters containing multiple sequences suggestive of onward transmission occurred in 48/86 (56%). 42/86 (51%) clusters had no known international travel history indicating undetected introductions. The majority of viral sequences were most closely related to those circulating in other European countries, including Italy, Austria and Spain. Travel-associated introductions of SARS-CoV-2 into Scotland predated travel restrictions in the UK and other European countries. The first local transmission occurred three days after the first case. A shift from travel-associated to sustained community transmission was apparent after only 11 days. Undetected introductions occurred prior to the first known case of COVID-19. Earlier travel restrictions and quarantine measures might have resulted in fewer introductions into Scotland, thereby reducing the number of cases and the subsequent burden on health services. The high number of introductions and transmission rates were likely to have impacted on national contact tracing efforts. Our results also demonstrate that local real-time genomic epidemiology can be used to monitor transmission clusters and facilitate control efforts to restrict the spread of COVID-19.", "doc_id": "bxuwx1jj"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Genomic epidemiology reveals multiple introductions and spread of SARS-CoV-2 in the Indian state of Karnataka", "abstract": "Karnataka, a state in south India, reported its first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on March 8, 2020, more than a month after the first case was reported in India. We used a combination of contact tracing and genomic epidemiology to trace the spread of SARS-CoV-2 in the state up until May 21, 2020 (1578 cases). We obtained 47 full genomes of SARS-CoV-2 which clustered into six lineages (Pangolin lineages-A, B, B.1, B.1.1, B.4, and B.6). The lineages in Karnataka were known to be circulating in China, Southeast Asia, Iran, Europe and other parts of India and are likely to have been imported into the state both by international and domestic travel. Our sequences grouped into 12 contact clusters and 11 cases with no known contacts. We found nine of the 12 contact clusters had a single lineage of the virus, consistent with multiple introductions and most (8/12) were contained within a single district, consistent with local spread. In most of the twelve clusters, the index case (9/12) and spreaders (8/12) were symptomatic. Of the 47 sequences, 31 belonged to the B/B.6 lineage, including seven of eleven cases with no known contact, this is consistent with the ongoing transmission of this lineage in the state. Genomic epidemiology of SARS-CoV-2 in Karnataka is consistent with multiple introductions of the virus followed by local transmission in parallel with ongoing viral evolution. This is the first study from India combining genomic data with epidemiological information emphasizing the need for an integrated approach to outbreak response.", "doc_id": "mdsiv6tr"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Whole Genome Sequencing of SARS-CoV-2: Adapting Illumina Protocols for Quick and Accurate Outbreak Investigation During a Pandemic", "abstract": "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.", "doc_id": "lsqg65ez"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Comparative analysis of twelve genomes of three novel group 2c and group 2d coronaviruses reveals unique group and subgroup features.", "abstract": "Twelve complete genomes of three novel coronaviruses-bat coronavirus HKU4 (bat-CoV HKU4), bat-CoV HKU5 (putative group 2c), and bat-CoV HKU9 (putative group 2d)-were sequenced. Comparative genome analysis showed that the various open reading frames (ORFs) of the genomes of the three coronaviruses had significantly higher amino acid identities to those of other group 2 coronaviruses than group 1 and 3 coronaviruses. Phylogenetic trees constructed using chymotrypsin-like protease, RNA-dependent RNA polymerase, helicase, spike, and nucleocapsid all showed that the group 2a and 2b and putative group 2c and 2d coronaviruses are more closely related to each other than to group 1 and 3 coronaviruses. Unique genomic features distinguishing between these four subgroups, including the number of papain-like proteases, the presence or absence of hemagglutinin esterase, small ORFs between the membrane and nucleocapsid genes and ORFs (NS7a and NS7b), bulged stem-loop and pseudoknot structures downstream of the nucleocapsid gene, transcription regulatory sequence, and ribosomal recognition signal for the envelope gene, were also observed. This is the first time that NS7a and NS7b downstream of the nucleocapsid gene has been found in a group 2 coronavirus. The high Ka/Ks ratio of NS7a and NS7b in bat-CoV HKU9 implies that these two group 2d-specific genes are under high selective pressure and hence are rapidly evolving. The four subgroups of group 2 coronaviruses probably originated from a common ancestor. Further molecular epidemiological studies on coronaviruses in the bats of other countries, as well as in other animals, and complete genome sequencing will shed more light on coronavirus diversity and their evolutionary histories.", "doc_id": "ghekwo95"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Full genome sequence of the first SARS-CoV-2 detected in Mexico", "abstract": "SARS-CoV-2 was first detected in the city of Wuhan, Hubei Province, China. In this report, we describe the complete genome sequence of the first imported SARS-CoV-2, detected in a Mexican patient who had traveled to Bergamo, Italy. Phylogenetic analysis showed that this isolate belongs to subclade A2a (lineage G) and is closely related to isolates from Finland, Germany and Brazil, all of which were from patients with a history of travel to Italy. This is the first report of the complete genome sequence of this virus in Mexico.", "doc_id": "oi2cm546"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "First detection and genome sequencing of SARS-CoV-2 in an infected cat in France", "abstract": "After its first description in Wuhan (China), SARS-CoV-2 the agent of coronavirus disease 2019 (COVID-19) rapidly spread worldwide. Previous studies suggested that pets could be susceptible to SARS-CoV-2. Here, we investigated the putative infection by SARS-CoV-2 in 22 cats and 11 dogs from owners previously infected or suspected of being infected by SARS-CoV-2. For each animal, rectal, nasopharyngeal swabs and serum were taken. Swabs were submitted to RT-qPCR assays targeting 2 genes of SARS-CoV-2. All dogs were tested SARS-CoV-2 negative. One cat was tested positive by RT-qPCR on rectal swab. Nasopharyngeal swabs from this animal were tested negative. This cat showed mild respiratory and digestive signs. Serological analysis confirms the presence of antibodies against the SARS-CoV-2 in both serum samples taken 10 days apart. Genome sequence analysis revealed that the cat SARS-CoV-2 belongs to the phylogenetic clade A2a like most of the French human SARS-CoV-2. This study reports for the first time the natural infection of a cat in France (near Paris) probably through their owners. There is currently no evidence that cats can spread COVID-19 and owners should not abandon their pets or compromise their welfare.", "doc_id": "m5fcayl1"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster", "abstract": "BACKGROUND: An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. METHODS: In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. FINDINGS: From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36-66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3-6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6-10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. INTERPRETATION: Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. FUNDING: The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).", "doc_id": "gr0lzz6r"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "[Genomic analysis of a 2019-novel coronavirus (2019-nCoV) strain in the first COVID-19 patient found in Hangzhou]", "abstract": "Objective: To understand the viral genomic characteristics of a 2019-novel coronavirus (2019-nCoV) strain in the first COVID-19 patient found in Hangzhou, China. Methods: Viral RNA was extracted in throat swab and sputum sample of the patient and was performed real-time reverse transcription PCR detection and obtained viral genome by high-throughput sequencing method. Phylogenetic analysis was conducted using 29 2019-nCoV genomes and 30 \u00df-coronavirus genomes deposited in NCBI GenBank. Fifteen genomes from Wuhan were grouped by mutation sites and others were identified by Wuhan's or specific mutation sites. Results: A 29 833 bp length genome of the first 2019-nCoV strain in Hangzhou was obtained, covering full length of the coding regions of coronavirus. Phylogenetic analysis showed that the genome was closest to the genome of a bat SARS-like coronavirus strain RaTG13 with an identity of 96.11% (28 666/29 826). Among the genes between two genomes, E genes were highly conserved (99.56%), while S genes had lowest identity (92.87%). The genome sequence similarities among 29 strains from China (Hangzhou, Wuhan, and Shenzhen), Japan, USA, and Finland, were all more than 99.9%; however, some single nucleotide polymorphisms were identified in some strains. Conclusion: The genome of Hangzhou 2019-nCoV strain was very close to the genomes of strains from other cities in China and overseas collected at early epidemic phase. The 2019-nCoV genome sequencing method used in this paper provides an useful tool for monitoring variation of viral genes.", "doc_id": "yphmntoc"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Reply to S\u00e1nchez-Pacheco et al., Chookajorn, and Mavian et al.: Explaining phylogenetic network analysis of SARS-CoV-2 genomes", "abstract": "", "doc_id": "vr2d3rh3"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Potential of large \"first generation\" human-to-human transmission of 2019-nCoV", "abstract": "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.", "doc_id": "1vkz0b0o"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Genomic characterization and phylogenetic analysis of SARS-COV-2 in Italy", "abstract": "This report describes the isolation, molecular characterization, and phylogenetic analysis of the first three complete genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from three patients involved in the first outbreak of COVID-19 in Lombardy, Italy. Early molecular epidemiological tracing suggests that SARS-CoV-2 was present in Italy weeks before the first reported cases of infection.", "doc_id": "1mbn5cc5"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "SARS-CoV-2 Phylogenetic Analysis, Lazio Region, Italy, February-March 2020", "abstract": "We report phylogenetic and mutational analysis of severe acute respiratory syndrome coronavirus 2 virus strains from the Lazio region of Italy and provide information about the dynamics of virus spread. Data suggest effective containment of clade V strains, but subsequently, multiple waves of clade G strains were circulating widely in Europe.", "doc_id": "hj9hj4xh"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis", "abstract": "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.", "doc_id": "dqyjdast"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Importation and early local transmission of COVID-19 in Brazil, 2020", "abstract": "We conducted the genome sequencing and analysis of the first confirmed COVID-19 infections in Brazil. Rapid sequencing coupled with phylogenetic analyses in the context of travel history corroborate multiple independent importations from Italy and local spread during the initial stage of COVID-19 transmission in Brazil.", "doc_id": "0v1appqr"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Detection of coronaviruses in Pteropus & Rousettus species of bats from different States of India", "abstract": "Background & objectives: Bats are considered to be the natural reservoir for many viruses, of which some are potential human pathogens. In India, an association of Pteropus medius bats with the Nipah virus was reported in the past. It is suspected that the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also has its association with bats. To assess the presence of CoVs in bats, we performed identification and characterization of bat CoV (BtCoV) in P. medius and Rousettus species from representative States in India, collected during 2018 and 2019. Methods: Representative rectal swab (RS) and throat swab specimens of Pteropus and Rousettus spp. bats were screened for CoVs using a pan-CoV reverse transcription-polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. A single-step RT-PCR was performed on the RNA extracted from the bat specimens. Next-generation sequencing (NGS) was performed on a few representative bat specimens that were tested positive. Phylogenetic analysis was carried out on the partial sequences of RdRp gene sequences retrieved from both the bat species and complete viral genomes recovered from Rousettus spp. Results: Bat samples from the seven States were screened, and the RS specimens of eight Rousettus spp. and 21 Pteropus spp. were found positive for CoV RdRp gene. Among these, by Sanger sequencing, partial RdRp sequences could be retrieved from three Rousettus and eight Pteropus bat specimens. Phylogenetic analysis of the partial RdRp region demonstrated distinct subclustering of the BtCoV sequences retrieved from these Rousettus and Pteropus spp. bats. NGS led to the recovery of four sequences covering approximately 94.3 per cent of the whole genome of the BtCoVs from Rousettus bats. Three BtCoV sequences had 93.69 per cent identity to CoV BtRt-BetaCoV/GX2018. The fourth BtCoV sequence was 96.8 per cent identical to BtCoV HKU9-1. Interpretation & conclusions: This study was a step towards understanding the CoV circulation in Indian bats. Detection of potentially pathogenic CoVs in Indian bats stresses the need for enhanced screening for novel viruses in them. One Health approach with collaborative activities by the animal health and human health sectors in these surveillance activities shall be of use to public health. This would help in the development of diagnostic assays for novel viruses with outbreak potential and be useful in disease interventions. Proactive surveillance remains crucial for identifying the emerging novel viruses with epidemic potential and measures for risk mitigation.", "doc_id": "lhoks3ds"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "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", "abstract": "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.", "doc_id": "r25aqii5"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak", "abstract": "From December 2019, an outbreak of unusual pneumonia was reported in Wuhan with many cases linked to Huanan Seafood Market that sells seafood as well as live exotic animals. We investigated two patients who developed acute respiratory syndromes after independent contact history with this market. The two patients shared common clinical features including fever, cough, and multiple ground-glass opacities in the bilateral lung field with patchy infiltration. Here, we highlight the use of a low-input metagenomic next-generation sequencing (mNGS) approach on RNA extracted from bronchoalveolar lavage fluid (BALF). It rapidly identified a novel coronavirus (named 2019-nCoV according to World Health Organization announcement) which was the sole pathogens in the sample with very high abundance level (1.5% and 0.62% of total RNA sequenced). The entire viral genome is 29,881\u00e2\u0080 nt in length (GenBank MN988668 and MN988669, Sequence Read Archive database Bioproject accession PRJNA601736) and is classified into \u00df-coronavirus genus. Phylogenetic analysis indicates that 2019-nCoV is close to coronaviruses (CoVs) circulating in Rhinolophus (Horseshoe bats), such as 98.7% nucleotide identity to partial RdRp gene of bat coronavirus strain BtCoV/4991 (GenBank KP876546, 370\u00e2\u0080 nt sequence of RdRp and lack of other genome sequence) and 87.9% nucleotide identity to bat coronavirus strain bat-SL-CoVZC45 and bat-SL-CoVZXC21. Evolutionary analysis based on ORF1a/1b, S, and N genes also suggests 2019-nCoV is more likely a novel CoV independently introduced from animals to humans.", "doc_id": "o6yruxyd"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Introductions and early spread of SARS-CoV-2 in France, 24 January to 23 March 2020", "abstract": "Following SARS-CoV-2 emergence in China, a specific surveillance was implemented in France. Phylogenetic analysis of sequences retrieved through this surveillance suggests that detected initial introductions, involving non-clade G viruses, did not seed local transmission. Nevertheless, identification of clade G variants subsequently circulating in the country, with the earliest from a patient who neither travelled to risk areas nor had contact with travellers, suggests that SARS-CoV-2 might have been present before the first recorded local cases.", "doc_id": "up5dbxap"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "A new coronavirus associated with human respiratory disease in China", "abstract": "Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1-3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.", "doc_id": "6vqxx85h"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Genomic analysis of SARS-CoV-2 strains among Indians returning from Italy, Iran & China, & Italian tourists in India", "abstract": "", "doc_id": "oubeywbn"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Sampling bias and incorrect rooting make phylogenetic network tracing of SARS-COV-2 infections unreliable", "abstract": "", "doc_id": "xkwx7ct9"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Importation of SARS-CoV-2 infection leads to major COVID-19 epidemic in Taiwan", "abstract": "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.", "doc_id": "giu9j0k1"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Virus Isolation from the First Patient with SARS-CoV-2 in Korea", "abstract": "Novel coronavirus (SARS-CoV-2) is found to cause a large outbreak started from Wuhan since December 2019 in China and SARS-CoV-2 infections have been reported with epidemiological linkage to China in 25 countries until now. We isolated SARS-CoV-2 from the oropharyngeal sample obtained from the patient with the first laboratory-confirmed SARS-CoV-2 infection in Korea. Cytopathic effects of SARS-CoV-2 in the Vero cell cultures were confluent 3 days after the first blind passage of the sample. Coronavirus was confirmed with spherical particle having a fringe reminiscent of crown on transmission electron microscopy. Phylogenetic analyses of whole genome sequences showed that it clustered with other SARS-CoV-2 reported from Wuhan.", "doc_id": "s7dr7ue8"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States", "abstract": "The novel coronavirus SARS-CoV-2 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 United States, 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 effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.", "doc_id": "y3lr8obh"} {"topic_name": "SARS-CoV-2 phylogenetic analysis", "topic_id": "37", "title": "Isolation and rapid sharing of the 2019 novel coronavirus (SARS-CoV-2) from the first patient diagnosed with COVID-19 in Australia", "abstract": "OBJECTIVES: To describe the first isolation and sequencing of SARS-CoV-2 in Australia and rapid sharing of the isolate. SETTING: SARS-CoV-2 was isolated from a 58-year-old man from Wuhan, China who arrived in Melbourne on 19 January 2020 and was admitted to the Monash Medical Centre, Melbourne from the emergency department on 24 January 2020 with fever, cough, and progressive dyspnoea. MAJOR OUTCOMES: Clinical course and laboratory features of the first reported case of COVID-19 (the illness caused by SARS-CoV-2) in Australia; isolation, whole genome sequencing, imaging, and rapid sharing of virus from the patient. RESULTS: A nasopharyngeal swab and sputum collected when the patient presented to hospital were each positive for SARS-CoV-2 (reverse transcription polymerase chain reaction). Inoculation of Vero/hSLAM cells with material from the nasopharyngeal swab led to the isolation of SARS-CoV-2 virus in culture. Electron microscopy of the supernatant confirmed the presence of virus particles with morphology characteristic of viruses of the family Coronaviridae. Whole genome sequencing of the viral isolate and phylogenetic analysis indicated the isolate exhibited greater than 99.99% sequence identity with other publicly available SARS-CoV-2 genomes. Within 24 hours of isolation, the first Australian SARS-CoV-2 isolate was shared with local and overseas reference laboratories and major North American and European culture collections. CONCLUSIONS: The ability to rapidly identify, propagate, and internationally share our SARS-CoV-2 isolate is an important step in collaborative scientific efforts to deal effectively with this international public health emergency by developing better diagnostic procedures, vaccine candidates, and antiviral agents.", "doc_id": "sz24szfh"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Differential expression and regulation of major histocompatibility complex (MHC) products in neural and glial cells of the human fetal brain", "abstract": "The cells of the central nervous system (CNS) have the peculiarity of physiologically expressing very low levels of HLA molecules. In multiple sclerosis (MS), however, as in endocrine autoimmune diseases, there is a marked increase of HLA expression in the tissue (i.e. the plaques) and this is attributable not only to infiltrating cells but also to the astrocytes. To gain an insight into the regulation of HLA in the different cell types in the CNS and to compare it to that observed in the endocrine organs, we have studied the effect of the lympho/monokines interferon (IFN)-\u03b1 and -\u03b3, tumour necrosis factor (TNF)-\u03b1, and interleukin (IL)-2 and other agents on this aspect of the biology of human fetal brain cells in culture. A two-colour immunofluorescence technique which combines antibodies to diverse CNS cell markers and monoclonal antibodies (MoAbs) to the non-polymorphic region of HLA molecules was used throughout this study. In control cultures, only astrocytes expressed MHC class I, but after incubation with either IFN-\u03b3 or TNF-\u03b1 oligodendrocytes acquired class I expression. Surprisingly, astrocytes became spontaneously class II positive in culture and this was greatly enhanced by IFN-\u03b3. Other agents such as IL-2, epidermal growth factor, phorbolmyristate acetate and lectins had no effect. The expression of HLA molecules in the cells of the CNS both in basal conditions and in response to lymphokines is therefore selective and highly heterogenous, thus reflecting their intrinsic biological diversity. These findings may help to explain the features of the immunopathology of MS and also of latent viral infections of neural cells.", "doc_id": "c5snhymz"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "COVID-19 and coronaviral hepatitis: evidence of collateral damage", "abstract": "", "doc_id": "85tj6kkw"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "The spectrum of pathological findings in coronavirus disease (COVID-19) and the pathogenesis of SARS-CoV-2", "abstract": "", "doc_id": "72uvawth"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "COVID-19 as an Acute Inflammatory Disease.", "abstract": "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.", "doc_id": "70s35cip"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Mitochondria and Microbiota dysfunction in COVID-19 pathogenesis.", "abstract": "The COVID-19 pandemic caused by the coronavirus (SARS-CoV-2) has taken the world by surprise into a major crisis of overwhelming morbidity and mortality. This highly infectious disease is associated with respiratory failure unusual in other coronavirus infections. Mounting evidence link the accelerated progression of the disease in COVID-19 patients to the hyper-inflammatory state termed as the \"cytokine storm\" involving major systemic perturbations. These include iron dysregulation manifested as hyperferritinemia associated with disease severity. Iron dysregulation induces reactive oxygen species (ROS) production and promotes oxidative stress. The mitochondria are the hub of cellular oxidative homeostasis. In addition, the mitochondria may circulate \"cell-free\" in non-nucleated platelets, in extracellular vesicles and mitochondrial DNA is found in the extracellular space. The heightened inflammatory/oxidative state may lead to mitochondrial dysfunction leading to platelet damage and apoptosis. The interaction of dysfunctional platelets with coagulation cascades aggravates clotting events and thrombus formation. Furthermore, mitochondrial oxidative stress may contribute to microbiota dysbiosis, altering coagulation pathways and fueling the inflammatory/oxidative response leading to the vicious cycle of events. Here, we discuss various cellular and systemic incidents caused by SARS-CoV-2 that may critically impact intra and extracellular mitochondrial function, and contribute to the progression and severity of the disease. It is crucial to understand how these key modulators impact COVID-19 pathogenesis in the quest to identify novel therapeutic targets that may reduce fatal outcomes of the disease.", "doc_id": "15qlty1g"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "The course of Covid 19 in Inflammatory Bowel Disease: protective role of TNF antagonists Response to: Corticosteroids, but not TNF Antagonists, are Associated with Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results from an International Registry.", "abstract": "", "doc_id": "8xiuwgrm"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Coronavirus Disease 2019 (COVID-19) and Cardiac Injury.", "abstract": "", "doc_id": "64in4bei"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "COVID-19 in children and altered inflammatory responses.", "abstract": "", "doc_id": "56u94l95"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "COVID-19 and Mesenchymal Stem Cell Treatment; Mystery or Not.", "abstract": "On December 31, 2019, novel SARS-CoV2 spread from Wuhan China to more than 200 territories around world and the World Health Organization declared a COVID-19 pandemic on January 30, 2020. At this time there is no particular therapy, drug or vaccine available to deal with COVID-19. Today actual data indicates that about 17% of closed COVID-19 cases died. Health care professionals, ministry of health in countries and the public are trying to read the runes to see when the COVID-19 pandemic will be over. Although mild cases of COVID-19 can be controlled with antiviral, anti-inflammatory and immunomodulatory treatment, severe cases may need intensive care unit support and ventilation. Cytokine storms cause high inflammatory responses and pneumonia in severe cases. Mesenchymal stem cells are immunomodulatory and they have regenerative capacity. In this sense, mesenchymal stem cells may improve the patient's clinical and immunological response to COVID-19.", "doc_id": "c3h8jcoj"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19.", "abstract": "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-1\u03b2-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-1\u03b2-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.", "doc_id": "bqvn3ceq"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research.", "abstract": "Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.", "doc_id": "9b5cuyae"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Neutrophils and Neutrophil Extracellular Traps Drive Necroinflammation in COVID-19.", "abstract": "The COVID-19 pandemic is progressing worldwide with an alarming death toll. There is an urgent need for novel therapeutic strategies to combat potentially fatal complications. Distinctive clinical features of severe COVID-19 include acute respiratory distress syndrome, neutrophilia, and cytokine storm, along with severe inflammatory response syndrome or sepsis. Here, we propose the putative role of enhanced neutrophil infiltration and the release of neutrophil extracellular traps, complement activation and vascular thrombosis during necroinflammation in COVID-19. Furthermore, we discuss how neutrophilic inflammation contributes to the higher mortality of COVID-19 in patients with underlying co-morbidities such as diabetes and cardiovascular diseases. This perspective highlights neutrophils as a putative target for the immunopathologic complications of severely ill COVID-19 patients. Development of the novel therapeutic strategies targeting neutrophils may help reduce the overall disease fatality rate of COVID-19.", "doc_id": "6ri6bxfc"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Early Short Course Corticosteroids in Hospitalized Patients with COVID-19", "abstract": "Background: There is no proven antiviral or immunomodulatory therapy for COVID-19. The disease progression associated with the pro-inflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19. Methods: We conducted a single pre-test, single post-test quasi-experiment in a multi-center health system in Michigan from March 12 to March 27, 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on March 20, 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of pre- and post-corticosteroid groups were evaluated. A composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality was the primary outcome measure. All patients had at least 14 days of follow-up. Results: We analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in pre-and post-corticosteroid groups, respectively. The composite endpoint occurred at a significantly lower rate in post-corticosteroid group compared to pre-corticosteroid group (34.9% vs. 54.3%, p=0.005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was observed in the post-corticosteroid group (8 vs. 5 days, p < 0.001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (aOR: 0.45; 95% CI [0.25-0.81]). Conclusion: An early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes.", "doc_id": "0m3svdmy"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Release of potential pro-inflammatory peptides from SARS-CoV-2 spike glycoproteins in neutrophil-extracellular traps", "abstract": "COVID-2019 has progressed in around 10-15% of patients to an acute respiratory distress syndrome characterized by extensive pulmonary inflammation and elevated production of pro-inflammatory cytokines. Neutrophil activation seems to be crucial in the initiation and perpetuation of this exacerbated lung inflammation. However, the precise mechanisms by which this activation occurs remain yet elusive. To this end, this in silico study tried to identify potential proinflammatory inducing peptides (PIPs) produced by the action of the elastase released in neutrophil-extracellular traps over SARS-CoV-2 particles. We found nine potential PIPs exclusive from the SARS-CoV-2, showing homology against T cell recognition epitopes. Moreover, 78 percent of these exclusive PIPs were found produced by the enzymatic cleavage on the spike glycoproteins, suggesting that high PIP concentrations might be released following SARS-CoV-2 huge replication rate. Therefore, these PIPs might play a role in the exacerbated inflammatory response observed in some patients. Highlights Nine potential PIPs were predicted exclusive from the SARS-CoV-2. SARS-CoV-2 PIPs showed homology against T cell recognition epitopes. Most of PIPs were produced by enzymatic cleavage of the spike glycoproteins. The release of these PIPs might be related to the increased inflammatory response observed in the patients. Graphical abstract", "doc_id": "5mj7sgfl"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy", "abstract": "Importance. The analysis of lung tissues of patients with COVID-19 may help understand pathogenesis and clinical outcomes in this life-threatening respiratory illness. Objective. To determine the histological patterns in lung tissue of patients with severe COVID-19. Design and participants. Lungs tissues of 38 cases who died for COVID-19 in two hospital of Northern Italy were systematically analysed. Hematoxylin-eosin staining, immunohistochemistry for the inflammatory infiltrate and cellular components, electron microscopy were performed. Results. The features of the exudative and proliferative phases of Diffuse Alveolar Disease (DAD) were found: capillary congestion, necrosis of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia and reactive atypia, platelet-fibrin thrombi. The inflammatory infiltrate was composed by macrophages in alveolar lumens and lymphocytes mainly in the interstitium. Electron microscopy revealed viral particles within cytoplasmic vacuoles of pneumocytes. Conclusions and relevance. The predominant pattern of lung lesions in COVID-19 patients is DAD, as described for the other two coronavirus that infect humans, SARS-CoV and MERS-CoV. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequently found. The main relevant finding is the presence of platelet-fibrin thrombi in small arterial vessels; this important observation fits into the clinical context of coagulopathy which dominates in these patients and which is one of the main targets of therapy.", "doc_id": "8pkwqg5j"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Functional characterization of SARS-CoV-2 infection suggests a complex inflammatory response and metabolic alterations", "abstract": "Covid-19, caused by the SARS-CoV-2 virus, has reached the category of a worldwide pandemic. Even though intensive efforts, no effective treatments or a vaccine are available. Molecular characterization of the transcriptional response in Covid-19 patients could be helpful to identify therapeutic targets. In this study, RNAseq data from peripheral blood mononuclear cell samples from Covid-19 patients and healthy controls was analyzed from a functional point of view using probabilistic graphical models. Two networks were built: one based on genes differentially expressed between healthy and infected individuals and another one based on the 2,000 most variable genes in terms of expression in order to make a functional characterization. In the network based on differentially expressed genes, two inflammatory response nodes with different tendencies were identified, one related to cytokines and chemokines, and another one related to bacterial infections. In addition, differences in metabolism, which were studied in depth using Flux Balance Analysis, were identified. SARS-CoV2-infection caused alterations in glutamate, methionine and cysteine, and tetrahydrobiopterin metabolism. In the network based on 2,000 most variable genes, also two inflammatory nodes with different tendencies between healthy individuals and patients were identified. Similar to the other network, one was related to cytokines and chemokines. However, the other one, lower in Covid-19 patients, was related to allergic processes and self-regulation of the immune response. Also, we identified a decrease in T cell node activity and an increase in cell division node activity. In the current absence of treatments for these patients, functional characterization of the transcriptional response to SARS-CoV-2 infection could be helpful to define targetable processes. Therefore, these results may be relevant to propose new treatments. Author Summary SARS-CoV-2 infection caused Covid-19 which has reached the category of a worldwide pandemic. However, no treatments or vaccines are still available. For this reason, it is still necessary the molecular study of this disease. In this study, we reanalyzed data from peripheral blood mononuclear cells from Covid-19 patients and healthy controls using computational techniques that allow the study of differential biological processes and metabolic pathways. The results suggested a complex inflammatory response, involving genes related to response to bacterial infection and allergic processes, and alterations in metabolic pathways such as glutamate metabolism, cysteine and methionine metabolism or tetrahydrobiopterin metabolism. These processes could be used in the future as therapeutic targets in Covi-19 infection.", "doc_id": "108k7gng"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Immune-Inflammatory Parameters in COVID-19 Cases: A Systematic Review and Meta-Analysis", "abstract": "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 \u00d7 10(9)/L, lymphocyte count0 5 ng/mL, and CRP>10 mg/L were risk factors for disease progression in patients with COVID-19 (WBC count>10 \u00d7 10(9)/L: OR = 2 92, 95% CI: 1 96-4 35;lymphocyte count0 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", "doc_id": "9knsva7e"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "The biology and pathogenesis of coronaviruses.", "abstract": "", "doc_id": "8xwirqgg"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "17\u00df-Estradiol, a potential ally to alleviate SARS-CoV-2 infection", "abstract": "Considering that female sexual hormones may modulate the inflammatory response and also exhibit direct effects on the cells of the immune system, herein, we intend to discuss the sex differences and the role of estradiol in modulating the lung and systemic inflammatory response, focusing on its possible application as a treatment modality for SARS-CoV-2 patients. COVID-19 patients develop severe hypoxemia early in the course of the disease, which is silent most of the time. Small fibrinous thrombi in pulmonary arterioles and a tumefaction of endothelial were observed in the autopsies of fatal COVID-19 cases. Studies showed that the viral infection induces a vascular process in the lung, which included vasodilation and endothelial dysfunction. Further, the proportions of CD4+ T and CD8+ T lymphocytes were strongly reduced in patients with severe SARS-CoV-2 infection. Estradiol is connected with CD4+ T cell numbers and increases T-reg cell populations, affecting immune responses to infection. It is known that estradiol exerts a protective effect on endothelial function, activating the generation of nitric oxide (NO) via endothelial nitric oxide synthase. Estrogen attenuates the vasoconstrictor response to various stimuli and induces vasodilation in the pulmonary vasculature during stress situations like hypoxia. It exerts a variety of rapid actions, which are initiated after its coupling with membrane receptors, which in turn, may positively modulate vascular responses in pulmonary disease and help to maintain microvascular flow. Direct and indirect mechanisms underlying the effects of estradiol were investigated, and the results point to a possible protective effect of estradiol against COVID-19, indicating that it may be considered as an adjuvant therapeutic element for the treatment of patients affected by the novel coronavirus.", "doc_id": "4s15m2ak"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "COVID-19: Unanswered questions on immune response and pathogenesis", "abstract": "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.", "doc_id": "08ftq7hl"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "[From SARS to COVID-19: pathogens, receptor, pathogenesis and principles of the treatment]", "abstract": "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.", "doc_id": "a290vxor"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19", "abstract": "BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that has resulted in nearly 1,000,000 laboratory-confirmed cases including over 50,000 deaths. Although SARS-CoV-2 and SARS-CoV share a number of common clinical manifestations, SARS-CoV-2 appears to be highly efficient in person-to-person transmission and frequently cause asymptomatic infections. However, the underlying mechanism that confers these viral characteristics on high transmissibility and asymptomatic infection remain incompletely understood. METHODS: We comprehensively investigated the replication, cell tropism, and immune activation profile of SARS-CoV-2 infection in human lung tissues with SARS-CoV included as a comparison. RESULTS: SARS-CoV-2 infected and replicated in human lung tissues more efficiently than that of SARS-CoV. Within the 48-hour interval, SARS-CoV-2 generated 3.20 folds more infectious virus particles than that of SARS-CoV from the infected lung tissues (P<0.024). SARS-CoV-2 and SARS-CoV were similar in cell tropism, with both targeting types I and II pneumocytes, and alveolar macrophages. Importantly, despite the more efficient virus replication, SARS-CoV-2 did not significantly induce types I, II, or III interferons in the infected human lung tissues. In addition, while SARS-CoV infection upregulated the expression of 11 out of 13 (84.62%) representative pro-inflammatory cytokines/chemokines, SARS-CoV-2 infection only upregulated 5 of these 13 (38.46%) key inflammatory mediators despite replicating more efficiently. CONCLUSIONS: Our study provided the first quantitative data on the comparative replication capacity and immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung tissues. Our results provided important insights on the pathogenesis, high transmissibility, and asymptomatic infection of SARS-CoV-2.", "doc_id": "0phtilhi"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Covid-19 in Immune-Mediated Inflammatory Diseases - Case Series from New York", "abstract": "", "doc_id": "87oqu4gx"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Characteristics of inflammatory factors and lymphocyte subsets in patients with severe COVID-19", "abstract": "To investigate the inflammatory factors and lymphocyte subsets which play an important role in the course of severe coronavirus disease 2019 (COVID-19). A total of 27 patients with severe COVID-19 who were admitted to Tongji Hospital in Wuhan from 1 to 21 February 2020 were recruited to the study. The characteristics of interleukin-1\u00df (IL-1\u00df), IL-2 receptor (IL-2R), IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF)-α, C-reactive protein (CRP), serum ferritin and procalcitonin (PCT), and lymphocyte subsets of these patients were retrospectively compared before and after treatment. Before treatment, there was no significant difference in most inflammatory factors (IL-1\u00df, IL-2R, IL-6, IL-8, IL-10, CRP, and serum ferritin) between male and female patients. Levels of IL-2R, IL-6, TNF-α, and CRP decreased significantly after treatment, followed by IL-8, IL-10, and PCT. Serum ferritin was increased in all patients before treatment but did not decrease significantly after treatment. IL-1\u00df was normal in most patients before treatment. Lymphopenia was common among these patients with severe COVID-19. Analysis of lymphocyte subsets showed that CD4+ and particularly CD8+ T lymphocytes increased significantly after treatment. However, B lymphocytes and natural killer cells showed no significant changes after treatment. A pro-inflammatory response and decreased level of T lymphocytes were associated with severe COVID-19.", "doc_id": "6h0qwtnm"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Potential role of endothelial cell surface ectopic redox complexes in COVID-19 disease pathogenesis", "abstract": "The novel coronavirus infectious disease (COVID-19) has rapidly spread and poses a great challenge to researchers, both in elucidating its pathogenic mechanism and developing effective treatments. It has been recently proposed that COVID-19 is an endothelial disease. Indeed, the COVID-19 virus binds to angiotensin-converting enzyme type 2 (ACE2), which is expressed in endothelial cells. ACE2 could be implicated in the production of reactive oxygen species (ROS) caused by endothelial dysfunction due to viral damage. Consequently, oxidative stress could prime these cells to acquire a pro-thrombotic and pro-inflammatory phenotype, predisposing patients to thromboembolic and vasculitic events and to disseminated intravascular coagulopathy (DIC). This implies a pivotal role played by oxygen in the pathogenetic mechanism of COVID-19 disease, in that its availability would tune the oxidant state and consequent damage.", "doc_id": "2ilinc5k"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "A new pharmacological approach based on remdesivir aerosolized administration on SARS-CoV-2 pulmonary inflammation: A possible and rational therapeutic application", "abstract": "The new zoonotic coronavirus (SARS-CoV-2) responsible for coronavirus disease (COVID-19) is a new strain of coronavirus not previously seen in humans and which appears to come from bat species. It originated in Wuhan, Hubei Province, China, and spread rapidly throughout the world, causing over 5,569,679 global cases and 351,866 deaths in almost every country in the world, including Europe, particularly Italy. In general, based on existing data published to date, 80.9% of patients infected with the virus develop mild infection; 13.8% severe pneumonia; 4.7% respiratory failure, septic shock or multi-organ failure; 3% of these cases are fatal. Critical patients have been shown to develop acute respiratory distress syndrome (ARDS) and hospitalization in intensive care units. The average age of patients admitted to hospital is 57-79 years, with one third half with an underlying disease. Asymptomatic infections have also been described, but their frequency is not known. SARS-CoV-2 transmission is mainly airborne from one person to another via droplets. The data available so far seem to indicate that SARS-CoV-2 is capable of producing an excessive immune reaction in the host. The virus attacks type II pneumocytes in the lower bronchi through the binding of the Spike protein (S protein) to viral receptors, of which the angiotensin 2 conversion enzyme (ACE2) receptor is the most important. ACE2 receptor is widely expressed in numerous tissues, including the oropharynx and conjunctiva, but mostly distributed in ciliated bronchial epithelial cells and type II pneumocytes in the lower bronchi. The arrival of SARS-CoV-2 in the lungs causes severe primary interstitial viral pneumonia that can lead to the \"cytokine storm syndrome\", a deadly uncontrolled systemic inflammatory response triggered by the activation of interleukin 6 (IL-6), whose effect is extensive lung tissue damage and disseminated intravascular coagulation (DIC), that are life-threatening for patients with COVID-19. In the absence of a therapy of proven efficacy, current management consists of off-label or compassionate use therapies based on antivirals, antiparasitic agents in both oral and parenteral formulation, anti-inflammatory drugs, oxygen therapy and heparin support and convalescent plasma. Like most respiratory viruses can function and replicate at low temperatures (i.e. 34-35 \u00b0C) and assuming viral thermolability of SARS-CoV-2, local instillation or aerosol of antiviral (i.e. remdesivir) in humid heat vaporization (40\u00b0-41 \u00b0C) in the first phase of infection (phenotype I, before admission), both in asymptomatic but nasopharyngeal swab positive patients, together with antiseptic-antiviral oral gargles and povidone-iodine eye drops for conjunctiva (0,8-5% conjunctival congestion), would attack the virus directly through the receptors to which it binds, significantly decreasing viral replication, risk of evolution to phenotypes IV and V, reducing hospitalization and therefore death.", "doc_id": "aq938nbq"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "The case of complement activation in COVID-19 multiorgan impact", "abstract": "The novel coronavirus disease COVID-19 originates in the lungs, but it may extend to other organs, causing, in severe cases, multiorgan damage, including cardiac injury and acute kidney injury. In severe cases, the presence of kidney injury is associated with increased risk of death, highlighting the relevance of this organ as a target of SARS-CoV-2 infection. COVID-19-associated tissue injury is not primarily mediated by viral infection, but rather is a result of the inflammatory host immune response, which drives hypercytokinemia and aggressive inflammation that affect lung parenchymal cells, diminishing oxygen uptake, but also endothelial cells, resulting in endotheliitis and thrombotic events and intravascular coagulation. The complement system represents the first response of the host immune system to SARS-CoV-2 infection, but there is growing evidence that unrestrained activation of complement induced by the virus in the lungs and other organs plays a major role in acute and chronic inflammation, endothelial cell dysfunction, thrombus formation, and intravascular coagulation, and ultimately contributes to multiple organ failure and death. In this review, we discuss the relative role of the different complement activation products in the pathogenesis of COVID-19-associated tissue inflammation and thrombosis and propose the hypothesis that blockade of the terminal complement pathway may represent a potential therapeutic option for the prevention and treatment of lung and multiorgan damage.", "doc_id": "0mien60n"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19", "abstract": "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-1\u00df-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-1\u00df-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.", "doc_id": "3dpdg5ls"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Crosstalk between endoplasmic reticulum stress and anti-viral activities: A novel therapeutic target for COVID-19", "abstract": "The outbreak of COVID-19 caused by 2019-nCov/SARS-CoV-2 has become a pandemic with an urgent need for understanding the mechanisms and identifying a treatment. Viral infections including SARS-CoV are associated with increased levels of reactive oxygen species, disturbances of Ca++ caused by unfolded protein response (UPR) mediated by endoplasmic reticulum (ER) stress and is due to the exploitation of virus's own protein i.e., viroporins into the host cells. Several clinical trials are on-going including testing Remdesivir (anti-viral), Chloroquine and Hydroxychloroquine derivatives (anti-malarial drugs) etc. Unfortunately, each drug has specific limitations. Herein, we review the viral protein involvement to activate ER stress transducers (IRE-1, PERK, ATF-6) and their downstream signals; and evaluate combination therapies for COVID-19 mediated ER stress alterations. Melatonin is an immunoregulator, anti-pyretic, antioxidant, anti-inflammatory and ER stress modulator during viral infections. It enhances protective mechanisms for respiratory tract disorders. Andrographolide, isolated from Andrographis paniculata, has versatile biological activities including immunomodulation and determining SARS-CoV-2 binding site. Considering the properties of both compounds in terms of anti-inflammatory, antioxidant, anti-pyrogenic, anti-viral and ER stress modulation and computational approaches revealing andrographolide docks with the SARS-CoV2 binding site, we predict that this combination therapy may have potential utility against COVID-19.", "doc_id": "aci8ol07"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Features of COVID-19 post-infectious cytokine release syndrome in children presenting to the emergency department", "abstract": "The 2019 coronavirus disease (COVID-19) has not appeared to affect children as severely as adults. However, approximately 1 month after the COVID-19 peak in New York City in April 2020, cases of children with prolonged fevers abruptly developing inflammatory shock-like states have been reported in Western Europe and the United States. This case series describes four previously healthy children with COVID-19 infection confirmed by serologic antibody testing, but negative by nasopharyngeal RT-PCR swab, presenting to the Pediatric Emergency Department (PED) with prolonged fever (5 or more days) and abrupt onset of hemodynamic instability with elevated serologic inflammatory markers and cytokine levels (IL-6, IL-8 and TNF-α). Emergency physicians must maintain a high clinical suspicion for this COVID-19 associated post-infectious cytokine release syndrome, with features that overlap with Kawasaki Disease (KD) and Toxic Shock Syndrome (TSS) in children with recent or current COVID-19 infection, as patients can decompensate quickly.", "doc_id": "04esvfhp"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Pediatric Crohn's Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated with Infliximab", "abstract": "Coronavirus disease 2019 (COVID-19) may lead to a severe inflammatory response referred to as a cytokine storm. We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn's disease patient successfully treated with Tumor Necrosis Factor-alpha (TNF-α) blockade. The patient presented with five days of fever, an erythematous maculopapular facial rash, and abdominal pain without respiratory symptoms. SARS-CoV-2 PCR was positive. Despite inpatient treatment for COVID-19 and a perianal abscess, the patient acutely decompensated, with worsening fever, tachycardia, fluid-refractory hypotension, elevation of liver enzymes, and transformation of the rash into purpura extending from the face to the trunk, upper and lower extremities, including the palmar and plantar surfaces of the hands and feet. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-α, higher than those described in either inflammatory bowel disease (IBD) or severe COVID-19 alone. The patient was treated with infliximab for TNF-α blockade to address both moderately to severely active Crohn's disease and multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19. Within hours of infliximab treatment, fever, tachycardia and hypotension resolved. Cytokine profile improved with normalization of TNF-α, a decrease in IL-6, and IL-8 concentrations. This case supports a role for blockade of TNF-α in the treatment of COVID-19 inflammatory cascade. The role of anti-TNF agents in patients with MIS-C temporally related to COVID-19 requires further investigation.", "doc_id": "8656dp79"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools", "abstract": "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.", "doc_id": "b0u07692"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response", "abstract": "The global spread of COVID-19, caused by pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for an imminent response from medical research communities to better understand this rapidly spreading infection. Employing multiple bioinformatics and computational pipelines on transcriptome data from primary normal human bronchial epithelial cells (NHBE) during SARS-CoV-2 infection revealed activation of several mechanistic networks, including those involved in immunoglobulin G (IgG) and interferon lambda (IFNL) in host cells. Induction of acute inflammatory response and activation of tumor necrosis factor (TNF) was prominent in SARS-CoV-2 infected NHBE cells. Additionally, disease and functional analysis employing ingenuity pathway analysis (IPA) revealed activation of functional categories related to cell death, while those associated with viral infection and replication were suppressed. Several interferon (IFN) responsive gene targets (IRF9, IFIT1, IFIT2, IFIT3, IFITM1, MX1, OAS2, OAS3, IFI44 and IFI44L) were highly upregulated in SARS-CoV-2 infected NBHE cell, implying activation of antiviral IFN innate response. Gene ontology and functional annotation of differently expressed genes in patient lung tissues with COVID-19 revealed activation of antiviral response as the hallmark. Mechanistic network analysis in IPA identified 14 common activated, and 9 common suppressed networks in patient tissue, as well as in the NHBE cell model, suggesting a plausible role for these upstream regulator networks in the pathogenesis of COVID-19. Our data revealed expression of several viral proteins in vitro and in patient-derived tissue, while several host-derived long noncoding RNAs (lncRNAs) were identified. Our data highlights activation of IFN response as the main hallmark associated with SARS-CoV-2 infection in vitro and in human, and identified several differentially expressed lncRNAs during the course of infection, which could serve as disease biomarkers, while their precise role in the host response to SARS-CoV-2 remains to be investigated.", "doc_id": "7sov3zpg"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Respuesta inflamatoria en relaci\u00f3n con COVID-19 y otros fenotipos protromb\u00f3ticos./ Respuesta inflamatoria en relaci\u00f3n con COVID-19 y otros fenotipos protromb\u00f3ticos./ Inflammatory Response in Relation to COVID-19 and Other Prothrombotic Phenotypes", "abstract": "The haemostatic system acts in concert with inflammation, so that after inflammatory response various mediators activate the haemostatic system through endothelial dysfunction, platelet activation and coagulation promoting thrombosis, which is termed thromboinflammation. In this process, the inflammasome acquires special relevance; its stimulation promotes innate and adaptive immune responses. Inflammasome activation plays an important physiopathological role in several disorders with inflammatory and thrombotic phenomena. The role of thromboinflammation has become relevant in the COVID-19 pandemic, in which a cytokine storm has been described as one of the responsible mechanisms.", "doc_id": "09lw7d2p"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "COVID-19 Hyperinflammation: What about Neutrophils?", "abstract": "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.", "doc_id": "9l5ajo4q"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "[Clinical observation of 6 severe COVID-19 patients treated with plasma exchange or tocilizumab]", "abstract": "OBJECTIVE: To observe the clinical effect of plasma exchange and tocilizumab in treatment of patients with severe coronavirus disease 2019 (COVID-19). METHODS: Six patients with severe COVID-19 admitted in First Affiliated Hospital of Bengbu Medical College from January 25 to February 25, 2020. Three patients were treated with plasma exchange and three patients were treated with tocilizumab. The effect on excessive inflammatory reaction of plasma exchange and tocilizumab was observed. RESULTS: The C-reactive protein (CRP) and IL-6 levels were significantly decreased and the lymphocyte and prothrombin time were improved in 3 patients after treatment with plasma exchange; while inflammation level was not significantly decreased, and lymphocyte and prothrombin time did not improve in 3 patients treated with tocilizumab. CONCLUSIONS: For severe COVID-19 patients with strong inflammatory reaction, plasma exchange may be preferred.", "doc_id": "08xf2ye5"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Involvement of interleukin 6 in SARS-CoV-2 infection: siltuximab as a therapeutic option against COVID-19", "abstract": "The aim of the study was to explore the involvement of interleukin 6 in SARS-CoV-2 infection, and to position the drug siltuximab in the management of severe forms of COVID-19. A bibliographic search was performed in Pubmed on the immune response to the disease, and in ClinicalTrials.gov on clinical trials with interleukin 6 blockers. Interleukin 6 is involved in the cytokine cascade, which originates as a consequence of an excessive immune response secondary to viral infection, aggravating lung affectation. Blockers of this cytokine (tocilizumab, sarilumab and siltuximab) are being studied as a strategy for treating the disease. Siltuximab is a monoclonal antibody indicated in Castleman's disease that could be administered in a single dose of 11 mg/kg in severe forms of COVID-19 that have increased interleukin 6.", "doc_id": "1b1hk9nf"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients", "abstract": "BACKGROUND: The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. METHODS: Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays. FINDINGS: Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts [0\u00b76 (0\u00b76-0\u00b78)] but increases in neutrophil counts [4\u00b77 (3\u00b76-5\u00b78)] than 27 mild cases [1.1 (0\u00b78-1\u00b74); 2\u00b70 (1\u00b75-2\u00b79)]. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8+ T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-\u00ce\u00b3 levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-lymphocyte ratio (NLR) (AUC=0\u00b793) and neutrophil-to-CD8+ T cell ratio (N8R) (AUC =0\u00b794) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19. INTERPRETATION: The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R and NLR may serve as a useful prognostic factor for early identification of severe COVID-19 cases. FUNDING: The National Natural Science Foundation of China, the National Science and Technology Major Project, the Health Commission of Hubei Province, Huazhong University of Science and Technology, and the Medical Faculty of the University of Duisburg-Essen and Stiftung Universitaetsmedizin, Hospital Essen, Germany.", "doc_id": "3bffha0k"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "p38 MAPK inhibition: A promising therapeutic approach for COVID-19", "abstract": "COVID-19, caused by the SARS-CoV-2 virus, is a major source of morbidity and mortality due to its inflammatory effects in the lungs and heart. The p38 MAPK pathway plays a crucial role in the release of pro-inflammatory cytokines such as IL-6 and has been implicated in acute lung injury and myocardial dysfunction. The overwhelming inflammatory response in COVID-19 infection may be caused by disproportionately upregulated p38 activity, explained by two mechanisms. First, angiotensin-converting enzyme 2 (ACE2) activity is lost during SARS-CoV-2 viral entry. ACE2 is highly expressed in the lungs and heart and converts Angiotensin II into Angiotensin 1-7. Angiotensin II signals proinflammatory, pro-vasoconstrictive, pro-thrombotic activity through p38 MAPK activation, which is countered by Angiotensin 1-7 downregulation of p38 activity. Loss of ACE2 upon viral entry may tip the balance towards destructive p38 signaling through Angiotensin II. Second, SARS-CoV was previously shown to directly upregulate p38 activity via a viral protein, similar to other RNA respiratory viruses that may hijack p38 activity to promote replication. Given the homology between SARS-CoV and SARS-CoV-2, the latter may employ a similar mechanism. Thus, SARS-CoV-2 may induce overwhelming inflammation by directly activating p38 and downregulating a key inhibitory pathway, while simultaneously taking advantage of p38 activity to replicate. Therapeutic inhibition of p38 could therefore attenuate COVID-19 infection. Interestingly, a prior preclinical study showed protective effects of p38 inhibition in a SARS-CoV mouse model. A number of p38 inhibitors are in the clinical stage and should be considered for clinical trials in serious COVID-19 infection.", "doc_id": "12dfuqtq"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Coagulation dysfunction: A hallmark in COVID-19", "abstract": "Context: The coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coagulation dysfunction is a hallmark in patients with COVID-19. Fulminant thrombotic complications emerge as critical issues in patients with severe COVID-19. Objective: To present a review of the literature and discuss the mechanisms of COVID-19 underlying coagulation activation and the implications for anticoagulant and thrombolytic treatment in the management of COVID-19. Data Sources: We performed a systemic review of scientific papers on the topic of COVID-19, online available via the PubMed NCBI, medRxiv, and Preprints as of May 15, 2020. We also shared our experience on the management of thrombotic events in patients with COVID-19. Conclusions: COVID-19-associated coagulopathy ranges from mild laboratory alterations to disseminated intravascular coagulation (DIC) with a predominant phenotype of thrombotic/multiple organ failure. Characteristically, high D-dimer levels on admission and/or continuously increasing concentrations of D-dimer is associated with disease progression and poor overall survival. SARS-CoV-2 infection triggers the immune-hemostatic response. Drastic inflammatory responses including, but not limited to, cytokine storm, vasculopathy, and NETosis may contribute to an overwhelming activation of coagulation. Hypercoagulability and systemic thrombotic complications necessitate anticoagulant and thrombolytic interventions, which provide opportunities to prevent or reduce \"excessive\" thrombin generation, while preserving \"adaptive\" hemostasis and bring additional benefit via their anti-inflammatory effect in the setting of COVID-19.", "doc_id": "8pkvaxzs"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "An inflammatory profile correlates with decreased frequency of cytotoxic cells in COVID-19", "abstract": "Increased production of inflammatory cytokines and myeloid-derived suppressor cells occur in COVID-19 patients. These inversely correlated with perforin-expressing NK and CD3+T-cells. We observed a lower perforin+ NK cells number in intensive care unit (ICU) compared to non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.", "doc_id": "c123sdum"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "COVID-19, chronic inflammatory rheumatic disease and anti-rheumatic treatments", "abstract": "Since December 2019, the pandemic caused by coronavirus disease 2019 (COVID-19) raises a real public health problem. COVID-19 appeared in Wuhan (Hubei province) in China. Drugs that have been used in rheumatology for decades seem to be effective in this infection and are for the most part being studied. The rational use of these anti-rheumatic drugs is based on the cytokinic storm (hyperproduction of IL1, IL6, TNF α) in the body by COVID-19 in its severe form. In this review, the authors make the difference between the infectious and auto-inflammatory part of COVID-19; the disease does not seem to be a risk factor for admission to the intensive care unit for patients suffering from inflammatory rheumatism; however, the poverty of studies on this subject should be noted. The authors also review anti-rheumatic drugs while studying COVID-19 treatment.", "doc_id": "7681cbwt"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Targeting the NO-cGMP-PDE5 pathway in COVID-19 infection. The DEDALO project", "abstract": "BACKGROUND: A pandemic outbreak of COVID-19 has been sweeping the world since December. It begins as a respiratory infection that, mainly in men with diabetes or renal impairment, evolves into a systemic disease, with SARDS, progressive endothelial cell damage, abnormal clotting and impaired cardiovascular and liver function. Some clinical trials are testing biological drugs to limit the immune system dysregulation, \"cytokines storm,\" that causes the systemic complications of COVID-19. The contraindications of these drugs and their cost raise concerns over the implications of their widespread availability. OBJECTIVES: Numerous clinical and experimental studies have revealed a role for the nitric oxide (NO)-cyclic GMP-phosphodiesterase type 5 (PDE5) pathway in modulating low-grade inflammation in patients with metabolic diseases, offering cardiovascular protection. PDE5 inhibition favors an anti-inflammatory response by modulating activated T cells, reducing cytokine release, lowering fibrosis, increasing oxygen diffusion, stimulating vascular repair. PDE5 is highly expressed in the lungs, where its inhibition improves pulmonary fibrosis, a complication of severe COVID-19 disease. MATERIALS AND METHODS: We performed a systematic review of all evidence documenting any involvement of the NO-cGMP-PDE5 axis in the pathophysiology of COVID-19, presenting the ongoing clinical trials aimed at modulating this axis, including our own \"silDEnafil administration in DiAbetic and dysmetaboLic patients with COVID-19 (DEDALO trial).\" RESULTS: The reviewed evidence suggests that PDE5 inhibitors could offer a new strategy in managing COVID-19 by (i) counteracting the Ang-II-mediated downregulation of AT-1 receptor; (ii) acting on monocyte switching, thus reducing pro-inflammatory cytokines, interstitial infiltration and the vessel damage responsible for alveolar hemorrhage-necrosis; (iii) inhibiting the transition of endothelial and smooth muscle cells to mesenchymal cells in the pulmonary artery, preventing clotting and thrombotic complications. DISCUSSION AND CONCLUSION: If the ongoing trials presented herein should provide positive findings, the low cost, wide availability and temperature stability of PDE5 inhibitors could make them a major resource to combat COVID-19 in developing countries.", "doc_id": "a1wfygyy"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Managing patients with rheumatic diseases during the COVID-19 pandemic: The French Society of Rheumatology answers to most frequently asked questions up to May 2020", "abstract": "BACKGROUND: Rheumatologists must contend with COVID-19 pandemic in the management of their patients and many questions have been raised on the use of both anti-inflammatory drugs and disease-modifying anti-rheumatic drugs (DMARD). The French Society of Rheumatology (SFR) selected the most critical ones to the daily practice of a rheumatologist and a group of 10 experts from SFR and Club Rheumatism and Inflammation (CRI) boards proposed responses based on the current knowledge of May 2020. METHODS: Following the availability of the first 18 questions and statements, 1400 individuals consulted the frequently asked questions between the March 31, 2020 and April 12, 2020. As a result, 16 additional questions were forwarded to the SFR, and answered by the board. An additional round of review by email and video conference was organized, which included updates of the previous statements. The scientific relevance of 5 of the questions led to their inclusion in this document. Each response received a final assessment on a scale of 0-10 with 0 meaning no agreement whatsoever and 10 being in complete agreement. The mean values of these votes for each question are presented as the levels of agreement (LoA) at the end of each response. This document was last updated on April 17, 2020. RESULTS: Based on current scientific literature already published, in most circumstances, there is no contraindication to the initiation or continuation of anti-inflammatory drugs as well as DMARDs. If signs suggestive of infection (coronavirus or other) occur, treatments should be discontinued and resumed, if necessary, after 2 weeks without any symptoms. Only, some signals suggest that people taking an immunosuppressive dose of corticosteroid therapy are at greater risk of developing severe COVID-19. Intra-articular injections of glucocorticoids are allowed when there is no reasonable therapeutic alternative, and providing that precautions to protect the patient and the practitioner from viral contamination are adopted, included appropriate information to the patient. CONCLUSIONS: Currently available data on managing patients with rheumatic diseases during the COVID-19 pandemic are reassuring and support continuing or initiating symptomatic as well as specific treatments of these diseases, the main target of their management remaining their appropriate control, even during this pandemic.", "doc_id": "01s9vj74"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response", "abstract": "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.", "doc_id": "5f63n7ex"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Possible Cause of Inflammatory Storm and Septic Shock in Patients Diagnosed with (COVID-19)", "abstract": "The novel coronavirus (SARS-CoV-2) infection which has been known as Coronavirus diseases 2019 COVID-19 has become an endemic emergent situation by the World Health Organization. So far, no successful specific treatment has been found for this disease. As has been reported, most of non-survivor patients with COVID-19 (70%) had septic shock which was significantly higher than survived ones. Although the exact pathophysiology of septic shock in these patients is still unclear, it seems to be possible that part of it would be due to the administration of empiric antibiotics with inflammatory properties especially in the absence of bacterial infection. Herein, we have reviewed possible molecular pathways of septic shock in the patients who have received antibiotics with inflammatory properties which mainly is release of interleukin 1\u00df (IL-1\u00df), IL-6, and tumor necrosis factor α (TNF- α) through different routes. Altogether, we highly recommend clinicians to look after those antibiotics with anti-inflammatory activity for both empiric antibiotic therapy and reducing the inflammation to prevent septic shock in patients with diagnosed COVID-19.", "doc_id": "9k1fm84p"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis?", "abstract": "The coronavirus 2 (SARS-CoV-2) pandemic is viciously spreading through the continents with rapidly increasing mortality rates. Current management of COVID-19 is based on the premise that respiratory failure is the leading cause of mortality. However, mounting evidence links accelerated pathogenesis in gravely ill COVID-19 patients to a hyper-inflammatory state involving a cytokine storm. Several components of the heightened inflammatory state were addressed as therapeutic targets. Another key component of the heightened inflammatory state is hyper-ferritinemia which reportedly identifies patients with increased mortality risk. In spite of its strong association with mortality, it is not yet clear if hyper-ferritinemia in COVID-19 patients is merely a systemic marker of disease progression, or a key modulator in disease pathogenesis. Here we address implications of a possible role for hyper-ferritinemia, and altered iron homeostasis in COVID-19 pathogenesis, and potential therapeutic targets in this regard.", "doc_id": "c4uiq8jd"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Hepatic complications of COVID-19 and its treatment", "abstract": "Coronavirus disease 2019 (COVID-19) is highly contagious and has a variety of clinical manifestations, it can affect a number of other organs in addition to the lungs, and liver injury may occur. Severe acute respiratory syndrome coronavirus 2 can cause liver injury through systemic inflammatory response syndrome, cytokine storms, ischemia-reperfusion injury, side effects of treatment drugs, and underlying liver disease and can attack liver cells directly via angiotensin-converting enzyme 2. Clinical studies have found that liver injury in COVID-19 patients mainly manifests as abnormal liver biochemical indicators, but there have been no reports of liver failure caused by this disease. The number of COVID-19 patients with liver injury is increasing, and the incidence of liver injury in COVID-19 patients with severe disease are higher than in patients with mild disease. Liver injury may be a risk factor, which worsens in patients with COVID-19, and hence it is necessary to pay attention to the occurrence of liver injury in the diagnosis and treatment of COVID-19.", "doc_id": "3t0y3k45"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients", "abstract": "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.", "doc_id": "19pz3kli"} {"topic_name": "COVID inflammatory response", "topic_id": "38", "title": "Novel COronaVirus Disease 2019 (COVID-19) epidemic: What are the risks for systemic sclerosis patients?", "abstract": "", "doc_id": "0gctessh"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Weather the Cytokine Storm: A Report of Successful Management of a Colon Cancer Survivor and a Critically Ill Patient with COVID-19", "abstract": "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.", "doc_id": "a8jt6rth"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "SARS-CoV-2: A Storm is Raging.", "abstract": "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 immunologic characteristics between moderate versus 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\u03b1), lymphopenia (in CD4+ and CD8+ T cells), and decreased IFN\u03b3 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.", "doc_id": "26u77dwr"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Extracorporeal Hemoadsorption: An Option for COVID-19 Associated Cytokine Storm Syndrome.", "abstract": "", "doc_id": "1250hsl6"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Cytokine storm and the prospects for immunotherapy with COVID-19.", "abstract": "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.", "doc_id": "2skjqwis"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications.", "abstract": "In light of the outbreak of the 2019 novel coronavirus disease (COVID-19), the international scientific community has joined forces to develop effective treatment strategies. The Angiotensin-Converting Enzyme (ACE) 2, is an essential receptor for cell fusion and engulfs the SARS coronavirus infections. ACE2 plays an important physiological role, practically in all the organs and systems. Also, ACE2 exerts protective functions in various models of pathologies with acute and chronic inflammation. While ACE2 downregulation by SARS-CoV-2 spike protein leads to an overactivation of Angiotensin (Ang) II/AT1R axis and the deleterious effects of Ang II may explain the multiorgan dysfunction seen in patients. Specifically, the role of Ang II leading to the appearance of Macrophage Activation Syndrome (MAS) and the cytokine storm in COVID-19 is discussed below. In this review, we summarized the latest research progress in the strategies of treatments that mainly focus on reducing the Ang II-induced deleterious effects rather than attenuating the virus replication.", "doc_id": "8wsc49yt"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Treat 2019 novel coronavirus (COVID-19) with IL-6 inhibitor: Are we already that far?", "abstract": "The world is in the midst of the coronavirus disease 2019 (COVID-19) pandemic. Interleukin 6 (IL-6) inhibitor (tocilizumab) had been suggested for the treatment of acute respiratory distress syndrome (ARDS) patients based on the concept of \"cytokine storm\" in COVID-19. However, we still lack reliable studies to verify \"cytokine storm\" in COVID-19 pneumonia. Furthermore, IL-6 inhibitor has potential hazards of inducing infectious diseases. The efficacy of IL-6 monoclonal antibody-directed therapy remains to be fully evaluated.", "doc_id": "9lv4xw2d"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Potential for jaktinib hydrochloride to treat cytokine storms in patients with COVID-19.", "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a serious public health threat to the whole world, and the number of infected is still rising dramatically at this moment. Several studies have confirmed that cytokine storms play a critical role in causing a case to worsen from mild to severe or critical. The current treatment for cytokine storms is limited, so the international medical community is focusing on a specific and effective remedy. Jaktinib hydrochloride is a broad spectrum JAK inhibitor. It can inhibit cytokine-induced immune activation by multiple mechanisms and also slow viral proliferation by inhibiting AAK1 without causing unacceptable toxicity. Jaktinib hydrochloride has great potential for the treatment of patients with coronavirus disease 2019 (COVID-19).", "doc_id": "a1m11gx9"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Brief annotations on cytokine release syndrome and interleukin-6 therapeutic blockage in SARS-CoV-2/COVID-19.", "abstract": "", "doc_id": "4qs9hq9y"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Preventing cytokine storm syndrome in COVID-19 using \u03b1-1 adrenergic receptor antagonists.", "abstract": "Medications that target catecholamine-associated inflammation may prevent cytokine storm syndrome associated with COVID-19 and other diseases.", "doc_id": "9408n63a"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "COVID-19 and the Heart.", "abstract": "Infection with the novel coronavirus, SARS-CoV-2, produces a clinical syndrome known as COVID-19. When severe, COVID-19 is a systemic illness characterized by hyperinflammation, cytokine storm and elevations of cardiac injury biomarkers. Here we review what is known about the pathophysiology of COVID-19, its cardiovascular manifestations, and emerging therapeutic prospects. In this rapidly moving field, this review was comprehensive as of April 3, 2020.", "doc_id": "d4h49d8b"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Insights into the Use of C-Reactive Protein as a Diagnostic Index of Disease Severity in COVID-19 Infections.", "abstract": "Approximately 20% of patients infected with SARS-CoV-2 (COVID-19) develop potentially life-threatening pathologies involving hyperinflammation, cytokine storm, septic shock complications, coagulation dysfunction, and multiple organ failure. Blood levels of the prototypic acute phase reactant, C-reactive protein (CRP), which is hepatically synthesized and released in response to interleukin-6 stimulation, is markedly elevated in patients with COVID-19. Markedly high CRP levels correlate with poor prognosis for survival. Insights into CRP structure-function relationships have uncovered both pro- and anti-inflammatory isoforms that may be used to monitor the extent of tissue damage associated with COVID-19 pathologies and prognoses. Herein, rationale is given for interpretation of CRP blood levels as a simple, rapid, and cost-effective way to assess disease severity and help guide therapeutic options in COVID-19 patients.", "doc_id": "d56kci3u"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Tocilizumab in the treatment of a critical COVID-19 patient: a case report.", "abstract": "In December 2019, Coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China and the rest of the world. COVID-19 is currently a global pandemic. There are cytokine storms in severe COVID-19 patients. Interleukin-6 plays an important role in cytokine storm. Tocilizumab is a blocker of interleukin-6 receptor, which is likely to become an effective drug for patients with severe COVID-19. Here, we reported a case in which tocilizumab was effective for a critical COVID-19 patient.", "doc_id": "913pnkon"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Network pharmacological analysis and mechanism prediction of Xiaochaihu Decoction in treatment of COVID-19 with syndrome of pathogenic heat lingering in lung and obstructive cardinalate/ \u5c0f\u67f4\u80e1\u6c64\u6cbb\u7597\u65e9\u671f\u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u80ba\u708e\uff08COVID-19\uff09\u90aa\u70ed\u90c1\u80ba\u3001\u67a2\u673a\u4e0d\u5229\u8bc1\u529f\u6548\u7f51\u7edc\u5206\u6790\u4e0e\u673a\u5236\u9884\u6d4b", "abstract": "Objective: To study the efficacy network and potential mechanism of Xiaochaihu Decoction (XCHD) in the treatment of coronavirus disease 2019 (COVID-19) with syndrome of pathogenic heat lingering in the lung and obstructive cardinalat, and analyze the active ingredients of XCHD with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficacy. Methods: The correspondence between COVID-19 and XCHD was analyzed by literature consulting. Based on network pharmacology, Cytoscape 3.6.0 and other software were then used to construct XCHD efficacy network of \u201cChinese medicine prescription-active ingredient-key target\u201d for pneumonia and immune regulation, in order to confirm anti-SARS-CoV-2 active ingredients in the prescription. Some softwares were used to analyze XCHD for COVID-19 treatment in multiple aspects. Results: A total of 48 active ingredients with potential anti-SARS-CoV-2 effect in herbs were collected; 140 active ingredients in XCHD for pneumonia treatment and immune regulation were analyzed, of which 12 ingredients had direct anti-SARS-CoV-2 activity including baicalein, formononetin, quercetin, etc. The active ingredients in XCHD exerted efficacy for pneumonia treatment and immunoregulation through 95 key targets such as IL-6, NOS2, and ESR1, involving multiple pathways such as the TNF signaling pathway, IL-17 signaling pathway, and influenza A. Analysis of gene co-expression and PPI interaction analysis found that ACE2 only co-expressed with NOS2 in the above targets, and also interacted with only five targets in the PPI interaction network. It is speculated that the ACE2 target only plays an important role when SARS-CoV-2 invaded the human body, and had little effect in the treatment of pneumonia after viral infection. Conclusion: The active ingredients in XCHD play a role in treating COVID-19 by inhibiting SARS-CoV-2 activity, blocking the SARS-CoV-2 invasion pathway, inhibiting cytokine storm, and regulating immunity. It is worth noting that drugs designed for the ACE2 target can block virus invasion, but may not be effective for diseases such as alveolar inflammation, Therefore, this study also provides a multi-target and multi-directional space for XCHD for early COVID-19 treatment. In addition, when XCHD is used in the early treatment of COVID-19, we should pay attention to the precise use of drugs based on syndrome accurate identification, one is to avoid adverse reactions, the other is to avoid cytokine damage caused by re-crown disease.", "doc_id": "bxo15n0c"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "The successful use of therapeutic plasma exchange for severe COVID-19 acute respiratory distress syndrome with multiple organ failure", "abstract": "The COVID-19 pandemic has brought about an urgent need for effective treatment, while conserving vital resources such as intensive care unit beds and ventilators Antivirals, convalescent plasma, and biologics have been used with mixed results The profound \"cytokine storm\" induced endotheliopathy and microthrombotic disease in patients with COVID-19 may lead to acute respiratory distress syndrome, sepsis, and multi-organ failure We present a case of SARS-COV2 pneumonia with septic shock and multi-organ failure that demonstrated significant clinical improvement after therapeutic plasma exchange A 65-year-old female with multiple comorbidities presented with progressive dyspnea and dry cough She was found to be COVID-19 positive with pneumonia, and developed progressive hypoxemia and shock requiring vasopressors, cardioversion, and non-invasive positive pressure ventilation Given her worsening sepsis with multi-organ failure, she underwent therapeutic plasma exchange with rapid clinical improvement Her case supports the theory that plasma exchange may help abate the \"cytokine storm\" induced endotheliopathy and microthrombosis associated with COVID-19 Further studies are needed to identify markers of this pathway and the potential role of plasma exchange in these critically ill patients Copyright \u00a9 The Author(s) 2020", "doc_id": "1nkr3mwm"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Multiple expression assessments of ACE2 and TMPRSS2 SARS-CoV-2 entry molecules in the urinary tract and their associations with clinical manifestations of COVID-19", "abstract": "Background Since December 2019, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first spread quickly in Wuhan, China, then globally. From previously published evidence, ACE2 and TMPRSS2, are both pivotal entry molecules that enable cellular infection by SARS-CoV-2. Meanwhile, increased expression of pro-inflammatory cytokines, or a \u201ccytokine storm,\u201d is associated with multiple organ dysfunction syndrome that is often observed in critically ill patients. Methods We investigated the expression pattern of ACE2 and TMPRSS2 in major organs in the human body, especially under specific disease conditions. Multiple sequence alignment of ACE2 in different species was used to explain animal susceptibility. Moreover, the cell-specific expression patterns of ACE2 and cytokine receptors in the urinary tract were assessed using single-cell RNA sequencing (scRNA-seq). Additional biological relevance was determined through Gene Set Enrichment Analysis (GSEA) using an ACE2 specific signature. Results Our results revealed that ACE2 and TMPRSS2 were highly expressed in genitourinary organs. ACE2 was highly and significantly expressed in the kidney among individuals with chronic kidney diseases or diabetic nephropathy. In single cells, ACE2 was primarily enriched in gametocytes in the testis, and renal proximal tubules. The receptors for pro-inflammatory cytokines, especially IL6ST, were remarkably concentrated in endothelial cells, macrophages, and spermatogonial stem cells in the testis, and renal endothelial cells, which suggested the occurrence of alternative damaging mechanisms via autoimmune attacks. Conclusions This study provided new insights into the pathogenicity mechanisms of SARS-CoV-2 that underlie the clinical manifestations observed in the human testis and kidney. These observations might substantially facilitate the development of effective treatments for this rapidly spreading disease.", "doc_id": "b3sy5alk"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Comparative Survival Analysis of Immunomodulatory Therapy for COVID-19 'Cytokine Storm': A Retrospective Observational Cohort Study", "abstract": "Background: Cytokine storm is a marker of COVID-19 illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes. Methods: We conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 patients hospitalized between March 1, 2020 and April 15, 2020, were included. Cytokine storm was defined by inflammatory markers: ferritin >700ng/mL, C-reactive protein >30mg/dL, or lactate dehydrogenase >300U/L. Patients were subdivided into six groups -no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti-interleukin 6 (IL-6) antibody (tocilizumab) or anti-IL-1 therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality. Results: There were 3,098 patients who met inclusion criteria. The most common comorbidities were hypertension (40-56%), diabetes (32-43%) and cardiovascular disease (2-15%). Patients most frequently met criteria with high lactate dehydrogenase (74.8%) alone, or in combination, followed by ferritin (71.4%) and C-reactive protein (9.4%). More than 80% of patients had an elevated D-dimer. Patients treated with a combination of tocilizumab and corticosteroids (Hazard Ratio [HR]: 0.459, 95% Confidence Interval [CI]: 0.295-0.714; p<0.0001) or corticosteroids alone (HR: 0.696, 95% CI: 0.512-0.946; p=0.01) had improved hospital survival compared to standard of care. Corticosteroids and tocilizumab was associated with increased survival when compared to corticosteroids and anakinra (HR: 0.612, 95% CI: 0.391-0.958; p-value=0.02). Conclusions: When compared to standard of care, corticosteroid and tocilizumab used in combination, or corticosteroids alone, was associated with reduced hospital mortality for patients with COVID-19 cytokine storm.", "doc_id": "7q6z46eq"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Dual-Histamine Blockade with Cetirizine - Famotidine Reduces Pulmonary Symptoms in COVID-19 Patients", "abstract": "Background: The COVID-19 pandemic due to SARS-CoV-2 infection can produce Acute Respiratory Distress Syndrome as a result of a pulmonary cytokine storm. Antihistamines are safe and effective treatments for reducing inflammation and cytokine release. Combinations of Histamine-1 and Histamine-2 receptor antagonists have been effective in urticaria, and might reduce the histamine-mediated pulmonary cytokine storm in COVID-19. Can a combination of Histamine-1 and Histamine-2 blockers improve COVID-19 inpatient outcomes? Methods: A physician-sponsored cohort study of cetirizine and famotidine was performed in hospitalized patients with severe to critical pulmonary symptoms. Pulmonologists led the inpatient care in a single medical center of 110 high-acuity patients that were treated with cetirizine 10 mg and famotidine 20 mg b.i.d. plus standard-of-care. Results: Of all patients, including those with Do Not Resuscitate directives, receiving the dual-histamine blockade for at least 48 hours, the combination drug treatment resulted in a 16.4% rate of intubation, a 7.3% rate of intubation after a minimum of 48 hours of treatment, a 15.5% rate of inpatient mortality, and 11.0 days duration of hospitalization. The drug combination exhibited reductions in symptom progression when compared to published reports of COVID-19 patients. Concomitant medications were assessed and hydroxychloroquine was correlated with worse outcomes. Conclusions: This physician-sponsored cohort study of cetirizine and famotidine provides proof-of-concept of a new safe and effective method to reduce the progression in symptom severity, presumably by minimizing the histamine-mediated cytokine storm. Further clinical studies in COVID-19 are warranted of the repurposed off-label combination of two historically-safe histamine blockers.", "doc_id": "bwbqb1pr"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Tocilizumab in Severe COVID-19 Pneumonia and Concomitant Cytokine Release Syndrome", "abstract": "Younger patients with COVID-19 may experience an exaggerated immune response to SARS-CoV-2 infection and develop cytokine release syndrome (CRS), which may be life threatening There is no proven antiviral therapy for COVID-19 so far, but profound immunosuppression has recently been suggested as a treatment for COVID-19-associated CRS We present a case of life-threatening CRS caused by COVID-19 infection with a favourable response to immunosuppressive therapy with tocilizumab (TCZ) The rapid clinical and biochemical improvement following TCZ administration suggests that treatment with immunotherapy can be life-saving in selected patients with COVID-19-induced CRS LEARNING POINTS: Cytokine release syndrome may cause sudden and potentially life-threatening clinical deterioration in COVID-19 pneumonia, particularly in younger patients Immunosuppressive therapy may provide important additional therapeutic benefit in these patients Tocilizumab, a specific IL-6 inhibitor, led to dramatic clinical improvement in a young patient with severe COVID-19-associated cytokine release syndrome", "doc_id": "694wrmg2"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Successful recovery of severe COVID-19 with cytokine storm treating with extracorporeal blood purification", "abstract": "COVID-19 associated cytokine storm could induce ARDS rapidly and the patients would require the support of mechanic ventilation. However, the prognosis was not that optimistic. The outcome might be changed if the intervention of EBP was performed timely. We present a case of severe SARS-CoV-2 infection who recovered from cytokine storm.", "doc_id": "etbky9yk"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "SARS-CoV-2: a storm is raging", "abstract": "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-α), lymphopenia (in CD4+ and CD8+ T cells), and decreased IFN-\u00ce\u00b3 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.", "doc_id": "539d5v41"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "COVID-19: Consider IL-6 receptor antagonist for the therapy of cytokine storm syndrome in SARS-CoV-2 infected patients", "abstract": "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.", "doc_id": "4s6ibvu9"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm", "abstract": "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.", "doc_id": "8o5juhgc"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities", "abstract": "The COVID-19 pandemic is a global public health crisis, with considerable mortality and morbidity exerting pressure on health-care resources, including critical care. An excessive host inflammatory response in a subgroup of patients with severe COVID-19 might contribute to the development of acute respiratory distress syndrome (ARDS) and multiorgan failure. Timely therapeutic intervention with immunomodulation in patients with hyperinflammation could prevent disease progression to ARDS and obviate the need for invasive ventilation. Granulocyte macrophage colony-stimulating factor (GM-CSF) is an immunoregulatory cytokine with a pivotal role in initiation and perpetuation of inflammatory diseases. GM-CSF could link T-cell-driven acute pulmonary inflammation with an autocrine, self-amplifying cytokine loop leading to monocyte and macrophage activation. This axis has been targeted in cytokine storm syndromes and chronic inflammatory disorders. Here, we consider the scientific rationale for therapeutic targeting of GM-CSF in COVID-19-associated hyperinflammation. Since GM-CSF also has a key role in homoeostasis and host defence, we discuss potential risks associated with inhibition of GM-CSF in the context of viral infection and the challenges of doing clinical trials in this setting, highlighting in particular the need for a patient risk-stratification algorithm.", "doc_id": "4lcstrf1"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Understanding the COVID-19 coagulopathy spectrum", "abstract": "", "doc_id": "ecrkzgrs"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "A Putative Role of de-Mono-ADP-Ribosylation of STAT1 by the SARS-CoV-2 Nsp3 Protein in the Cytokine Storm Syndrome of COVID-19", "abstract": "As more cases of COVID-19 are studied and treated worldwide, it had become apparent that the lethal and most severe cases of pneumonia are due to an out-of-control inflammatory response to the SARS-CoV-2 virus. I explored the putative causes of this specific feature through a detailed genomic comparison with the closest SARS-CoV-2 relatives isolated from bats, as well as previous coronavirus strains responsible for the previous epidemics (SARS-CoV and MERS-CoV). The high variability region of the nsp3 protein was confirmed to exhibit the most variations between closest strains. It was then studied in the context of physiological and molecular data available in the literature. A number of convergent findings suggest de-mono-ADP-ribosylation (de-MARylation) of STAT1 by the SARS-CoV-2 nsp3 as a putative cause of the cytokine storm observed in the most severe cases of COVID-19. This may suggest new therapeutic approaches and help in designing assays to predict the virulence of naturally circulating SARS-like animal coronaviruses.", "doc_id": "5hz6vy3b"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Colchicina: una herramienta terap\u00e9utica potencial frente a COVID-19. Experiencia en 5 pacientes./ [Colchicine: a potential therapeutic tool against COVID-19. Experience of 5 patients]", "abstract": "COVID-19 is a newly emerged disease that has become a global public health challenge. Due to a lack of knowledge about the virus, a significant number of potential targets for using a particular drug have been proposed. Five cases with a clinical history of biopolymers in the gluteal region that developed iatrogenic allogenosis (IA) are presented here. The 5 cases were put under colchicine treatment for IA crisis and had non-specific symptoms (headache, cough without dyspnoea, and arthralgias) with a positive SARS-CoV-2 test. Their close contacts had mild to severe symptoms and three of them died. In the SARS-CoV-2 infection different inflammatory pathways are altered where colchicine reduces cytokine levels as well as the activation of macrophages, neutrophils, and the inflammasome. The possible mechanisms that colchicine may use to prevent acute respiratory distress syndrome (ARDS) in patients with COVID-19 infection are also reviewed in this article.", "doc_id": "c02mznhw"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Tratamiento y evoluci\u00f3n del s\u00edndrome de tormenta de citoquinas asociados a infecci\u00f3n por SARS-CoV-2 en pacientes octogenarios./ [Evolution and treatment of storm cytoquine syndrome associated to SARS-CoV-2 infection among octogenarians]", "abstract": "INTRODUCTION: Cytokine storm syndrome (CTS) is a serious complication of patients with SARS-CoV-2 infection. Treatment and evolution in octogenarians are not well defined. Our objective is to describe its clinical characteristics, the treatments and its clinical evolution. PATIENTS AND METHOD: Retrospective observational study of consecutive patients admitted in the period between March 23 and April 12, 2020 with confirmed SARS-CoV-2 infection, with pneumonia by radiological study or chest tomography, whith STC criteria and who received treatment. We classified patients as those who received only glucocorticoid (GC) pulses, or GC and tocilizumab pulses. We determined serum levels of ferritin, CRP and D-dimers. The final variable was survival. RESULTS: 21 patients, (80-88 years). The mean ferritin was 1056 microg/L (317-3,553), CRP 115.8mg/dL (22-306) and D-dimers 2.9m/L (0.45-17.5). All patients received GC pulses and in 2 cases simultaneously tocilizumab. The mean follow-up time was 13.7 days (8-21). The overall mortality was 38.1% (8/21 patients). The 2 patients who received tocilizumab died. The deceased had significantly higher levels of ferritin (1,254 vs. 925microg/L; P=.045) and CRP (197.6 vs. 76mg / dL; P=.007). At the end of the follow-up, a decrease in the biochemical parameters was observed with ferritin of 727microg/L, CRP of 27mg/dl and D-dimers of 1.18mg/L. In 13/21 patients (61.9%), the CTS was controlled without the need to add other treatments. CONCLUSIONS: STC mortality from SARS-CoV-2 is high despite treatment. A greater inflammatory response was associated with a higher mortality. Although it seems that the early use of GC pulses could control it, and the use of other treatments such as tocilizumab shouldo be, with the study design and its limitations, this conclusion cannot be stablished.", "doc_id": "6cyblw51"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Cytokine storm and the prospects for immunotherapy with COVID-19", "abstract": "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.", "doc_id": "be38b41o"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Propuesta de uso de anakinra en el distr\u00e9s respiratorio agudo secundario a COVID-19./ Propuesta de uso de anakinra en el distr\u00e9s respiratorio agudo secundario a COVID-19./ Proposal for the use of anakinra in acute respiratory distress secondary to COVID-19", "abstract": "The outcome of the SARS-CoV-2 (COVID-19) infection fundamentally affects the lung field, causing acute respiratory distress syndrome (ARDS). This process is an inflammatory picture, involving an NLRP3 inflamosome-triggered cytokine storm, the main player in alveolar destruction. IL-1 beta stands out among the cytokines that are triggered in this picture. Anakinra is a potent biological drug, capable of blocking this IL-1\u00df. We propose its use in controlling ARDS secondary to COVID-19 infection.", "doc_id": "cmfggu8f"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Dipeptidyl peptidase-4 (DPP4) inhibition in COVID-19", "abstract": "AIMS: SARS-CoV-2 causes severe respiratory syndrome (COVID-19) with high mortality due to a direct cytotoxic viral effect and a severe systemic inflammation. We are herein discussing a possible novel therapeutic tool for COVID-19. METHODS: Virus binds to the cell surface receptor ACE2; indeed, recent evidences suggested that SARS-CoV-2 may be using as co-receptor, when entering the cells, the same one used by MERS-Co-V, namely the DPP4/CD26 receptor. The aforementioned observation underlined that mechanism of cell entry is supposedly similar among different coronavirus, that the co-expression of ACE2 and DPP4/CD26 could identify those cells targeted by different human coronaviruses and that clinical complications may be similar. RESULTS: The DPP4 family/system was implicated in various physiological processes and diseases of the immune system, and DPP4/CD26 is variously expressed on epithelia and endothelia of the systemic vasculature, lung, kidney, small intestine and heart. In particular, DPP4 distribution in the human respiratory tract may facilitate the entrance of the virus into the airway tract itself and could contribute to the development of cytokine storm and immunopathology in causing fatal COVID-19 pneumonia. CONCLUSIONS: The use of DPP4 inhibitors, such as gliptins, in patients with COVID-19 with, or even without, type 2 diabetes, may offer a simple way to reduce the virus entry and replication into the airways and to hamper the sustained cytokine storm and inflammation within the lung in patients diagnosed with COVID-19 infection.", "doc_id": "7ilz0gus"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Cytokine release syndrome and the prospects for immunotherapy with COVID-19. Part 2: The role of interleukin 1", "abstract": "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.", "doc_id": "fbq8yraw"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Storm, typhoon, cyclone or hurricane in patients with COVID-19? Beware of the same storm that has a different origin", "abstract": "Some of the articles being published during the severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 pandemic highlight a link between severe forms of coronavirus disease 2019 (COVID-19) and the so-called cytokine storm, also with increased ferritin levels. However, this scenario is more complex than initially thought due to the heterogeneity of hyperinflammation. Some patients with coronavirus 2019 disease (COVID-19) develop a fully blown secondary haemophagocytic lymphohistiocytosis (sHLH), whereas others, despite a consistent release of pro-inflammatory cytokines, do not fulfil sHLH criteria but still show some features resembling the phenotype of the hyperferritinemic syndrome. Despite the final event (the cytokine storm) is shared by various conditions leading to sHLH, the aetiology, either infectious, autoimmune or neoplastic, accounts for the differences in the various phases of this process. Moreover, the evidence of a hyperinflammatory microenvironment provided the rationale to employ immunomodulating agents for therapeutic purposes in severe COVID-19. This viewpoint aims at discussing the pitfalls and issues to be considered with regard to the use of immunomodulating agents in COVID-19, such as timing of treatment based on the viral load and the extent of cytokine/ferritin overexpression. Furthermore, it encompasses recent findings in the paediatric field about a novel multisystem inflammatory disease resembling toxic shock syndrome and atypical Kawasaki disease observed in children with proven SARS-CoV2 infection. Finally, it includes arguments in favour of adding COVID-19 to the spectrum of the recently defined 'hyperferritinemic syndrome', which already includes adult-onset Still's disease, macrophage activation syndrome, septic shock and catastrophic anti-phospholipid syndrome.", "doc_id": "1untezgg"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Role of Interleukin-6 in Lung Complications in Patients With COVID-19: Therapeutic Implications", "abstract": "COVID-19 is viral respiratory infection with frequently fatal lung complications in the elderly or in people with serious comorbidities. Lung destruction appears to be associated with a cytokine storm related to an increased level of interleukin-6 (IL6). Therapeutic targeting of the interleukin-6 signaling pathway can attenuate such a cytokine storm and can be beneficial for patients with COVID-19 in danger of pulmonary failure. This article demonstrates the importance of IL6 in progression of disease and the possibility of inhibition of IL6 signaling in COVID-19 therapy.", "doc_id": "bn8qjliy"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Endothelial progenitor cells and mesenchymal stem cells to overcome vascular deterioration and cytokine storm in critical patients with COVID-19", "abstract": "", "doc_id": "81xabuei"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Tocilizumab challenge: A series of cytokine storm therapy experiences in hospitalized COVID-19 pneumonia patients", "abstract": "To recognize the period of exaggerated cytokine response in patients with coronavirus disease 2019 (COVID-19) pneumonia, and to describe the clinical outcomes of using tocilizumab as a treatment option. The data of 12 adult COVID-19 pneumonia patients who were followed in the inpatient clinics of Biruni University Medical Faculty Hospital (Istanbul, Turkey) were retrospectively analyzed. Diagnostic tests, laboratory examinations, clinical findings, and computed tomography of the thorax imaging results were evaluated. A dramatic laboratory and clinical improvement was observed in 83% (10 out of 12) of patients after tocilizumab. In 17% (2 out of 12) of our patients, short-term ventilator support was required in the intensive care unit. The longest hospital stay was 18 days. However, in the end, all of our patients were discharged home with good health. Although arterial oxygen saturations (87.58 \u00b1 3.12%) dropped in room air in the pre-tocilizumab period, post-tocilizumab they normalized in all patients (94.42 \u00b1 1%). None of them had fever after tocilizumab treatment and the levels of C-reactive protein (13.08 \u00b1 12.89) were almost within normal limits. Eosinophil values were quite low at the time of diagnosis (10 \u00b1 17.06), but increased significantly post-tocilizumab (155.33 \u00b1 192.69). There is currently no proven treatment for COVID-19 induced by novel coronavirus SARS-CoV-2. Based on our experience with twelve adult COVID-19 pneumonia patients,we can say that tocilizumab, an IL-6 inhibitor, is more beneficial in preventing the damage caused by excessive cytokine response in the body if administered at the right time and provides clinical and radiological recovery.", "doc_id": "25ezat4g"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "[Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies]", "abstract": "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.", "doc_id": "3d04p4xp"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Prevention of the cytokine storm in COVID-19", "abstract": "", "doc_id": "0q16p6qz"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic", "abstract": "Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is an acute and rapidly progressive systemic inflammatory disorder characterized by cytopenia, excessive cytokine production, and hyperferritinemia. Common clinical manifestations of HLH are acute unremitting fever, lymphadenopathy, hepatosplenomegaly, and multiorgan failure. Due to a massive cytokine release, this clinical condition is considered as a cytokine storm syndrome. HPS has primary and acquired (secondary, reactive) forms. Its primary form is mostly seen in childhood and caused by various mutations with genetic inheritance and, therefore, is called familial HLH. Secondary HLH may be caused in the presence of an underlying disorder, that is, secondary to a malignant, infectious, or autoimmune/autoinflammatory stimulus. This paper aims to review the pathogenesis and the clinical picture of HLH, and its severe complication, the cytokine storm, with a special emphasis on the developed classification criteria sets for rheumatologists, since COVID-19 infection has clinical symptoms resembling those of the common rheumatologic conditions and possibly triggers HLH. MED-LINE/Pubmed was searched from inception to April 2020, and the following terms were used for data searching: \"hemophagocytic syndrome\" OR \"macrophage activation syndrome\" OR \"hemophagocytic lymphohistiocytosis\", OR \"cytokine storm\". Finally, AND \"COVID-19\" was included in this algorithm. The selection is restricted to the past 5 years and limited numbers of earlier key references were manually selected. Only full-text manuscripts, published in an English language peer-reviewed journal were included. Manuscript selection procedure and numbers are given in Fig. 2. Briefly, the database search with the following terms of \"Hemophagocytic syndrome\" OR \"Macrophage activation syndrome\" OR \"Hemophagocytic lymphohistiocytosis\" OR \"Cytokine storm\" yielded 6744 results from inception to April 2020. The selection is restricted to the past 5 years and only limited numbers of earlier key references were selected, and this algorithm resulted in 3080 manuscripts. The addition of (AND \"COVID-19\") resulted in 115 publications of which 47 studies, together with four sections of an online book were used in the final review. No statistical method was used. HLH is triggered by genetic conditions, infections, malignancies, autoimmune-autoinflammatory diseases, and some drugs. In COVID-19 patients, secondary HLH and cytokine storm may be responsible for unexplained progressive fever, cytopenia, ARDS, neurological and renal impairment. Differentiation between the primary and secondary forms of HLH is utterly important, since primary form of HLH requires complicated treatments such as hematopoietic stem cell transplantation. Further studies addressing the performance of HScore and other recommendations in the classification of these patients is necessary.", "doc_id": "azy3uf6m"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Potential for jaktinib hydrochloride to treat cytokine storms in patients with COVID-19", "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a serious public health threat to the whole world, and the number of infected is still rising dramatically at this moment. Several studies have confirmed that cytokine storms play a critical role in causing a case to worsen from mild to severe or critical. The current treatment for cytokine storms is limited, so the international medical community is focusing on a specific and effective remedy. Jaktinib hydrochloride is a broad spectrum JAK inhibitor. It can inhibit cytokine-induced immune activation by multiple mechanisms and also slow viral proliferation by inhibiting AAK1 without causing unacceptable toxicity. Jaktinib hydrochloride has great potential for the treatment of patients with coronavirus disease 2019 (COVID-19).", "doc_id": "69884505"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Utilizing tocilizumab for the treatment of cytokine release syndrome in COVID-19", "abstract": "", "doc_id": "d6dgjxe9"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Absence of severe complications from SARS-CoV-2 infection in children with rheumatic diseases treated with biologic drugs", "abstract": "We read with interest the Editorial by Cron and Chatam (1) suggesting a cytokine storm syndrome (CSS) occurring in response to SARS-CoV-2 infection and, consequently, a possible role for targeted approaches to blocking inflammatory cytokines.", "doc_id": "3n16xkvo"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes", "abstract": "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.", "doc_id": "2b6l1c0n"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab", "abstract": "Recurrences of COVID-19 were observed in a patient with long-term usage of hydroxychloroquine, leflunomide, and glucocorticoids due to her 30-year history of rheumatoid arthritis (RA). Tocilizumab was applied and intended to target both COVID-19 and RA. However, disease of this patient aggravated after usage of tocilizumab. After the discussion of a multiple disciplinary team (MDT) including rheumatologists, antimicrobial treatments were applied to target the potential opportunistic infections (Pneumocystis jirovecii and Aspergillus fumigatus), which were authenticated several days later via high throughput sequencing. As an important cytokine in immune responses, IL-6 can be a double-edged sword: interference in the IL-6-IL-6 receptor signaling may save patients from cytokine release storm (CRS), but can also weaken the anti-infectious immunity, particularly in rheumatic patients, who may have received a long-term treatment with immunosuppressive/modulatory agents. Thus, we suggest careful considerations before and close monitoring in the administration of tocilizumab in rheumatic patients with COVID-19. Besides tocilizumab, several disease-modifying antirheumatic drugs (DMARDs) can also be applied in the treatment of COVID-19. Therefore, we also reviewed and discussed the application of these DMARDs in COVID-19 condition.", "doc_id": "c4bmlh6z"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Tocilizumab's efficacy in patients with Coronavirus Disease 2019 (COVID-19) is determined by the presence of cytokine storm", "abstract": "", "doc_id": "4fsx4r6h"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "COVID 19: a clue from innate immunity", "abstract": "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.", "doc_id": "911ozh90"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment", "abstract": "Approximately 15% of patients with coronavirus disease 2019 (COVID-19) experience severe disease, and 5% progress to critical stage that can result in rapid death. No vaccines or antiviral treatments have yet proven effective against COVID-19. Patients with severe COVID-19 experience elevated plasma levels of pro-inflammatory cytokines, which can result in cytokine storm, followed by massive immune cell infiltration into the lungs leading to alveolar damage, decreased lung function, and rapid progression to death. As many of the elevated cytokines signal through Janus kinase (JAK)1/JAK2, inhibition of these pathways with ruxolitinib has the potential to mitigate the COVID-19-associated cytokine storm and reduce mortality. This is supported by preclinical and clinical data from other diseases with hyperinflammatory states, where ruxolitinib has been shown to reduce cytokine levels and improve outcomes. The urgent need for treatments for patients with severe disease support expedited investigation of ruxolitinib for patients with COVID-19.", "doc_id": "dyq0pzcn"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19", "abstract": "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.", "doc_id": "9f6fxd94"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "Melatonin Inhibits COVID-19-induced Cytokine Storm by Reversing Aerobic Glycolysis in Immune Cells: A Mechanistic Analysis", "abstract": "", "doc_id": "6fmzx1zi"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "The COVID-19 Cytokine Storm; What We Know So Far", "abstract": "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.", "doc_id": "ete5n5pw"} {"topic_name": "COVID-19 cytokine storm", "topic_id": "39", "title": "COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression ;Journal of Antimicrobial Chemotherapy ;Oxford Academic", "abstract": "A novel coronavirus disease (COVID-19), caused by infection with SARS-CoV-2, has swept across 31 provinces in China and over 40 countries worldwide The transition from first symptoms to acute respiratory distress syndrome (ARDS) is highly likely to be due to uncontrolled cytokine release There is an urgent need to identify safe and effective drugs for treatment Chloroquine (CQ) exhibits a promising inhibitory effect However, the clinical use of CQ can cause severe side effects We propose that hydroxychloroquine (HCQ), which exhibits an antiviral effect highly similar to that of CQ, could serve as a better therapeutic approach HCQ is likely to attenuate the severe progression of COVID-19, inhibiting the cytokine storm by suppressing T cell activation It has a safer clinical profile and is suitable for those who are pregnant It is cheaper and more readily available in China We herein strongly urge that clinical trials are performed to assess the preventive effects of HCQ in both disease infection and progression", "doc_id": "42ywl8gp"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Molecular characterization of SARS-CoV-2 in the first COVID-19 cluster in France reveals an amino acid deletion in nsp2 (Asp268del)", "abstract": "", "doc_id": "4c0zwhdh"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Conserved High Free Energy Sites in Human Coronavirus Spike Glycoprotein Backbones.", "abstract": "Methods previously developed by the author are applied to uncover several sites of interest in the spike glycoproteins of all known human coronaviruses (hCoVs), including SARS-CoV-2 that causes COVID-19. The sites comprise three-dimensional neighborhoods of peptides characterized by four key properties: (1) they pinpoint regions of high free energy in the backbone whose obstruction might interrupt function; (2) by their very definition, they occur rarely in the universe of all gene-encoded proteins that could obviate host response to compounds designed for their interference; (3) they are common to all seven hCoV spikes, possibly retaining activity in light of inevitable viral mutation; and (4) they are exposed in the molecular surface of the glycoprotein. These peptides in SARS-CoV-2 are given by the triples of residues (131, 117, 134), (203, 227, 228), and (1058, 730, 731) in its spike.", "doc_id": "y42lzirq"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "An overview of the genetic variations of the SARS-CoV-2 genomes isolated in Southeast Asian countries.", "abstract": "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.", "doc_id": "zf3moii7"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "SARS-CoV-2 (COVID-19) structural and evolutionary dynamicome: Insights into functional evolution and human genomics.", "abstract": "The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged the speed at which laboratories discover the viral composition and study health outcomes. The small ~30-kb ssRNA genome of coronaviruses makes them adept at cross-species spread, but also enable a robust understanding of all the proteins the viral genome encodes. We have employed protein modeling, molecular dynamic simulations, evolutionary mapping, and 3D printing to gain a full proteome- and dynamicome-level understanding of SARS-CoV-2. We established the Viral Integrated Structural Evolution Dynamic Database (VIStEDD at prokoplab.com/vistedd) to facilitate future discoveries and educational use. Here, we highlight the use of VIStEDD for nsp6, nucleocapsid (N), and spike (S) surface glycoprotein. For both nsp6 and N, we found highly conserved surface amino acids that likely drive protein-protein interactions. In characterizing viral S protein, we developed a quantitative dynamics cross-correlation matrix to gain insights into its interactions with the angiotensin I-converting enzyme 2 (ACE2)-solute carrier family 6 member 19 (SLC6A19) dimer. Using this quantitative matrix, we elucidated 47 potential functional missense variants from genomic databases within ACE2/SLC6A19/transmembrane serine protease 2 (TMPRSS2), warranting genomic enrichment analyses in SARS-CoV-2 patients. These variants had ultralow frequency but existed in males hemizygous for ACE2. Two ACE2 noncoding variants (rs4646118 and rs143185769) present in ~9% of individuals of African descent may regulate ACE2 expression and may be associated with increased susceptibility of African Americans to SARS-CoV-2. We propose that this SARS-CoV-2 database may aid research into the ongoing pandemic.", "doc_id": "mp7ajr6s"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting.", "abstract": "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.", "doc_id": "8cex7qi4"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "SARS-CoV-2 receptor mutation in Egyptian population", "abstract": "The Coronavirus disease 2019 (COVID-19) is a respiratory tract infectious disease caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 triggers severe pneumonia leading to acute respiratory distress syndrome and death in severe cases. According to WHO reported, Egypt is among the countries with low confirmed SARS CoV2 infected symptomatic cases and death. We postulate that one of the reasons for this may be due mutations in the viral receptor. Therefore this study was conducted to confirm or reject this postulation.", "doc_id": "xirt6efg"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "International expansion of a novel SARS-CoV-2 mutant", "abstract": "Letter to the editor. There is no abstract. The summary was showed: SARS-CoV-2 has inevitably mutated during its pandemic spread to cause unpredictable effects on COVID-19 and complicate epidemic control efforts. Here we report that a novel SARS-CoV-2 mutation (ORF3a) appears to be spreading worldwide, which deserves close attention.", "doc_id": "alsiqv04"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype", "abstract": "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.", "doc_id": "fujejfwb"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "ACE2 diversity in placental mammals reveals the evolutionary strategy of SARS-CoV-2", "abstract": "The recent emergence of SARS-CoV-2 is responsible for the current pandemic of COVID-19, which uses the human membrane protein ACE2 as a gateway to host-cell infection We performed a comparative genomic analysis of 70 ACE2 placental mammal orthologues to identify variations and contribute to the understanding of evolutionary dynamics behind this successful adaptation to infect humans Our results reveal that 4% of the ACE2 sites are under positive selection, all located in the catalytic domain, suggesting possibly taxon-specific adaptations related to the ACE2 function, such as cardiovascular physiology Considering all variable sites, we selected 30 of them located at the critical ACE2 binding sites to the SARS-CoV-like viruses for analysis in more detail Our results reveal a relatively high diversity of ACE2 between placental mammal species, while showing no polymorphism within human populations, at least considering the 30 inter-species variable sites A perfect scenario for natural selection favored this opportunistic new coronavirus in its trajectory of infecting humans We suggest that SARS-CoV-2 became a specialist coronavirus for human hosts Differences in the rate of infection and mortality could be related to the innate immune responses, other unknown genetic factors, as well as non-biological factors", "doc_id": "apkbzwcc"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia.", "abstract": "The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine-tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3' end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3' end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.", "doc_id": "gs9zno1d"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Genetic Variant of SARS-CoV-2 Isolates in Indonesia: Spike Glycoprotein Gene", "abstract": "Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus and the primary causative agent of coronavirus disease 2019 (COVID-19), first occurred in China and rapidly spread worldwide The government of the Republic of Indonesia confirmed its first two cases of COVID-19 in March 2020 COVID-19 is a serious illness with no efficacious antiviral medication or approved vaccine currently available Therefore, there is a need to investigate the genome of SARS-CoV-2 In this study, we characterized SARS-CoV-2 spike glycoprotein genes from Indonesia to investigate their genetic composition and variability Overall, ten SARS-CoV-2 spike glycoprotein gene sequences retrieved from GenBank (National Center for Biotechnology Information, USA) and the GISAID EpiCoV database (Germany) were compared We analyzed nucleotide variants and amino acid changes using Molecular Evolutionary Genetics Analysis (MEGA) X and analyzed gene similarity using the LALIGN web server Interestingly, we revealed several specific mutation sites, however, there were no significant changes in the genetic composition of SARS-CoV-2 spike glycoprotein genes, when compared to the WuhanHu-1 isolate from China However, this is a preliminary study and we recommend that molecular epidemiology and surveillance programs against COVID-19 in Indonesia be improved", "doc_id": "zzxdg5zo"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Impact of emerging mutations on the dynamic properties the SARS-CoV-2 main protease: an in silico investigation", "abstract": "The new coronavirus (SARS-CoV-2) is a global threat to world health and its economy. Its main protease (Mpro), which functions as a dimer, cleaves viral precursor proteins in the process of viral maturation. It is a good candidate for drug development owing to its conservation and the absence of a human homolog. An improved understanding of the protein behaviour can accelerate the discovery of effective therapies in order to reduce mortality. 100 ns all-atom molecular dynamics simulations of 50 homology modelled mutant Mpro dimers were performed at pH 7 from filtered sequences obtained from the GISAID database. Protease dynamics were analysed using RMSD, RMSF, Rg, the averaged betweenness centrality and geometry calculations. Domains from each Mpro protomer were found to generally have independent motions, while the dimer-stabilising N-finger region was found to be flexible in most mutants. A mirrored interprotomer pocket was found to be correlated to the catalytic site using compaction dynamics, and can be a potential allosteric target. The high number of titratable amino acids of Mpro may indicate an important role of pH on enzyme dynamics, as previously reported for SARS-CoV. Independent coarse-grained Monte Carlo simulations suggest a link between rigidity/mutability and enzymatic function.", "doc_id": "b56hk7jm"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "COVID-3D: An online resource to explore the structural distribution of genetic variation in SARS-CoV-2 and its implication on therapeutic development", "abstract": "The emergence of the COVID-19 pandemic has spurred a global rush to uncover basic biological mechanisms, to inform effective vaccine and drug development. Despite viral novelty, global sequencing efforts have already identified genomic variation across isolates. To enable easy exploration and spatial visualization of the potential implications of SARS-CoV-2 mutations on infection, host immunity and drug development we have developed COVID-3D (http://biosig.unimelb.edu.au/covid3d/).", "doc_id": "6476nxy0"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Cross-neutralization antibodies against SARS-CoV-2 and RBD mutations from convalescent patient antibody libraries", "abstract": "The emergence of coronavirus disease 2019 (COVID-19) pandemic led to an urgent need to develop therapeutic interventions. Among them, neutralizing antibodies play crucial roles for preventing viral infections and contribute to resolution of infection. Here, we describe the generation of antibody libraries from 17 different COVID-19 recovered patients and screening of neutralizing antibodies to SARS-CoV-2. After 3 rounds of panning, 456 positive phage clones were obtained with high affinity to RBD (receptor binding domain). Then the positive clones were sequenced and reconstituted into whole human IgG for epitope binning assays. After that, all 19 IgG were classified into 6 different epitope groups or Bins. Although all these antibodies were shown to have ability to bind RBD, the antibodies in Bin2 have more superiority to inhibit the interaction between spike protein and angiotensin converting enzyme 2 receptor (ACE2). Most importantly, the antibodies from Bin2 can also strongly bind with mutant RBDs (W463R, R408I, N354D, V367F and N354D/D364Y) derived from SARS-CoV-2 strain with increased infectivity, suggesting the great potential of these antibodies in preventing infection of SARS-CoV-2 and its mutations. Furthermore, these neutralizing antibodies strongly restrict the binding of RBD to hACE2 overexpressed 293T cells. Consistently, these antibodies effectively neutralized pseudovirus entry into hACE2 overexpressed 293T cells. In Vero-E6 cells, these antibodies can even block the entry of live SARS-CoV-2 into cells at only 12.5 nM. These results suggest that these neutralizing human antibodies from the patient-derived antibody libraries have the potential to become therapeutic agents against SARS-CoV-2 and its mutants in this global pandemic.", "doc_id": "hbr4seeh"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Ethnically diverse mutations in PIEZO1 associate with SARS-CoV-2 positivity", "abstract": "COVID-19, caused by the SARS-CoV-2 virus, carries significant risk of mortality and has spread globally with devastating societal consequences. Endothelial infection has been identified as a feature of the disease and so there is motivation to determine the relevance of endothelial membrane mechanisms affecting viral entry and response. Here, through a study of patient data in UK Biobank released on 16 April 2020, we suggest relevance of PIEZO1, a non-selective cation channel protein that both mediates endothelial responses to mechanical force and unusually indents the cell membrane. PIEZO1 notably has roles that may also be relevant in red blood cell function, pulmonary inflammation, bacterial infection and fibrotic auto-inflammation. We provide evidence that single nucleotide polymorphisms (SNPs) in the gene encoding PIEZO1 are more common in individuals who test positive for SARS-CoV-2 regardless of pre-existing hypertension, myocardial infarction, stroke, diabetes mellitus or arthritis. Some of these SNPs are more common in African and Caribbean populations, which are groups that were recently shown to have greater susceptibility to infection. One of the SNPs is a missense mutation that results in an amino acid change in an evolutionarily conserved and previously unexplored N-terminal region PIEZO1. The data support the notion of genetic factors influencing SARS-CoV-2 infection and suggest a specific role for PIEZO1.", "doc_id": "dq1yqz0t"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "COVID-19 genomic susceptibility: Definition of ACE2 variants relevant to human infection with SARS-CoV-2 in the context of ACMG/AMP Guidance", "abstract": "BACKGROUND: Mortality remains very high and unpredictable in COVID-19, with intense public protection strategies tailored to preceived risk. Genomic studies are in process to identify differences in host susceptibility to infection by the SARS-CoV-2 virus. Open source research publications are accessible to pre-genotyped individuals. Males are more at risk from severe COVID-19. METHODS: To facilitate development of Clinical Genetics support to the public and healthcare professionals, genomic structure and variants in 213,158 exomes/genomes were integrated for ACE2 encoding the SARS-CoV-2 receptor. ACMG/AMP-based pathogenicity criteria were applied. RESULTS: Across the 19 ACE2 exons on the X chromosome, 9 of 3596 (0.25%) nucleotides were homozygous variant in females compared to 262/3596 (7.3%) hemizygous variant in males (p< 0.0001). 90% of variants were very rare, although K26R affecting a SARS-CoV-2-interacting amino acid is present in ~1/239 people. Modelling the ''COVID-resistant '' state where pathogenic alleles would be beneficial, nine null alleles met PVS1. Thirty-seven variants met PM1 based on critical location +/-PP3 based on computational modelling. Modelling a ''COVID-susceptible '' state, 31 variants in four upstream open reading frames and 5' untranslated regions could meet PM1, and may have differential effects if aminoglycoside antibiotics were prescribed for pneumonia and sepsis. CONCLUSIONS: Males are more likely to exhibit consequences from a single variant ACE2 allele. Differential allele frequencies in COVID-19 susceptible and resistant individuals are likely to emerge before variants meet ACMG/AMP criteria for actionable results in patients. Prioritising genomic regions for functional study and ACMG/AMP-structured approaches to research-based presentation of COVID-19 susceptibility variant results are encouraged.", "doc_id": "75kwsokp"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Mutation density changes in SARS-CoV-2 are related to the pandemic stage but to a lesser extent in the dominant strain with mutations in spike and RdRp", "abstract": "Since its emergence in Wuhan, China in late 2019, the origin and evolution of SARS-CoV-2 have been among the most debated issues related to COVID-19. Throughout its spread around the world, the viral genome continued acquiring new mutations and some of them became widespread. Among them, 14408 C>T and 23403 A>G mutations in RdRp and S, respectively, became dominant in Europe and the US, which led to debates regarding their effects on the mutability and transmissibility of the virus. In this study, we aimed to investigate possible differences between time-dependent variation of mutation densities (MDe) of viral strains that carry these two mutations and those that do not. Our analyses at the genome and gene level led to two important findings: First, time-dependent changes in the average MDe of circulating SARS-CoV-2 genomes showed different characteristics before and after the beginning of April, when daily new case numbers started levelling off. Second, this pattern was much delayed or even non-existent for the \u201cmutant\u201d (MT) strain that harbored both 14408 C>T and 23403 A>G mutations. Although these differences were not limited to a few hotspots, it is intriguing that the MDe increase is most evident in two critical genes, S and Orf1ab, which are also the genes that harbor the defining mutations of the MT genotype. The nature of these unexpected relationships warrant further research.", "doc_id": "fglghjy6"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Mutations can reveal how the coronavirus moves\u2014but they\u2019re easy to overinterpret", "abstract": "Immediately after Christian Drosten published a genetic sequence of the novel coronavirus online on 28 February, he took to Twitter to issue a warning As the virus has raced around the world, more than 350 genome sequences have been shared on the online platform GISAID They hold clues to how the new virus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading and evolving But because the sequences represent a tiny fraction of cases and show few telltale differences, they are easy to overinterpret, as Drosten realized A virologist at the Charit\u00e9 University Hospital in Berlin, he had sequenced the virus from a German patient infected with COVID-19 in Italy The genome looked similar to that of a virus found in a patient in Munich, the capital of Bavaria, more than 1 month earlier;both shared three mutations not seen in early sequences from China Drosten realized this could give rise to the idea that the Italian outbreak was \u201cseeded\u201d by the one in Bavaria, which state public health officials said had been quashed by tracing and quarantining all contacts of the 14 confirmed cases But he thought it was just as likely that a Chinese variant carrying the three mutations had taken independent routes to both countries The newly sequenced genome \u201cis not sufficient to claim a link between Munich and Italy,\u201d Drosten tweeted", "doc_id": "8lbznr71"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Mutational Signatures and Heterogeneous Host Response Revealed Via Large-Scale Characterization of SARS-COV-2 Genomic Diversity", "abstract": "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.", "doc_id": "7se14455"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Intra-host site-specific polymorphisms of SARS-CoV-2 is consistent across multiple samples and methodologies", "abstract": "Despite the potential relevance to clinical outcome, intra-host dynamics of SARS-CoV-2 are unclear. Here, we quantify and characterize intra-host variation in SARS-CoV-2 raw sequence data uploaded to SRA as of 14 April 2020, and compare results between two sequencing methods (amplicon and RNA-Seq). Raw fastq files were quality filtered and trimmed using Trimmomatic, mapped to the WuhanHu1 reference genome using Bowtie2, and variants called with bcftools mpileup. To ensure sufficient coverage, we only included samples with 10X coverage for >90% of the genome (n=406 samples), and only variants with a depth >=10. Derived (i.e. non-reference) alleles were found at 408 sites. The number of polymorphic sites (i.e. sites with multiple alleles) within samples ranged from 0-13, with 72% of samples (295/406) having at least one polymorphic site. Correlation between number of polymorphic sites and coverage was very low for both sequencing methods (R2 < 0.1, p < 0.05). Polymorphisms were observed >1 sample at 66 sites (range: 2-38 samples). The minor allele frequency (MAF) at each shared polymorphic site was 0.03% - 48.5%. 33/66 sites occurred in ORF1a1b, and 37/66 changes were non-synonymous. At 10/66 sites, derived alleles were found in samples sequenced using both methods. Polymorphic amplicon samples were found at 10/10 positions, while polymorphic RNA-Seq samples were found at 7/10 positions. In conclusion, our results suggest that intra-host variation is prevalent among clinical samples. While mutations resulting from amplification and/or sequencing errors cannot be excluded, the observation of shared polymorphic sites with high MAF across multiple samples and sequencing methods is consistent with true underlying variation. Further investigation into intra-host evolutionary dynamics, particularly with longitudinal sampling, is critical for broader understanding of disease progression.", "doc_id": "zugrtvyo"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Anti-frameshifting ligand active against SARS coronavirus-2 is resistant to natural mutations of the frameshift-stimulatory pseudoknot", "abstract": "The coronavirus SARS-CoV-2 causing the COVID-19 pandemic uses \u22121 programmed ribosomal frameshifting (\u22121 PRF) to control the expression levels of key viral proteins. Because modulating \u22121 PRF can attenuate viral propagation, ligands binding to the viral RNA pseudoknot that stimulates \u22121 PRF may prove useful as therapeutics. Mutations in the pseudoknot have been observed over the course of the pandemic, but how they affect \u22121 PRF and the activity of inhibitors is unknown. Cataloguing natural mutations in all parts of the SARS-CoV-2 pseudoknot, we studied a panel of 6 mutations in key structural regions. Most mutations left the \u22121 PRF efficiency unchanged, even when base-pairing was disrupted, but one led to a remarkable three-fold decrease, suggesting that SARS-CoV-2 propagation may be less sensitive to modulation of \u22121 PRF efficiency than some other viruses. Examining the effects of one of the few small-molecule ligands known to suppress \u22121 PRF significantly in SARS-CoV, we found that it did so by similar amounts in all SARS-CoV-2 mutants tested, regardless of the basal \u22121 PRF efficiency, indicating that the activity of anti-frameshifting ligands can be resistant to natural pseudoknot mutations. These results have important implications for therapeutic strategies targeting SARS-CoV-2 through modulation of \u22121 PRF.", "doc_id": "iinpkixn"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Pervasive RNA secondary structure in the genomes of SARS-CoV-2 and other coronaviruses \u2013 an endeavour to understand its biological purpose", "abstract": "The ultimate outcome of the COVID-19 pandemic is unknown and is dependent on a complex interplay of its pathogenicity, transmissibility and population immunity. In the current study, SARS coronavirus 2 (SARS-CoV-2) was investigated for the presence of large scale internal RNA base pairing in its genome. This property, termed genome scale ordered RNA structure (GORS) has been previously associated with host persistence in other positive-strand RNA viruses, potentially through its shielding effect on viral RNA recognition in the cell. Genomes of SARS-CoV-2 were remarkably structured, with minimum folding energy differences (MFEDs) of 15%, substantially greater than previously examined viruses such as HCV (MFED 7-9%). High MFED values were shared with all coronavirus genomes analysed created by several hundred consecutive energetically favoured stem-loops throughout the genome. In contrast to replication-association RNA structure, GORS was poorly conserved in the positions and identities of base pairing with other sarbecoviruses \u2013 even similarly positioned stem-loops in SARS-CoV-2 and SARS-CoV rarely shared homologous pairings, indicative of more rapid evolutionary change in RNA structure than in the underlying coding sequences. Sites predicted to be base-paired in SARS-CoV-2 showed substantially less sequence diversity than unpaired sites, suggesting that disruption of RNA structure by mutation imposes a fitness cost on the virus which is potentially restrictive to its longer evolution. Although functionally uncharacterised, GORS in SARS-CoV-2 and other coronaviruses represent important elements in their cellular interactions that may contribute to their persistence and transmissibility.", "doc_id": "3iy2lp8q"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Discovery of a 382-nt deletion during the early evolution of SARS-CoV-2", "abstract": "To date, the SARS-CoV-2 genome has been considered genetically more stable than SARS-CoV or MERS-CoV. Here we report a 382-nt deletion covering almost the entire open reading frame 8 (ORF8) of SARS-CoV-2 obtained from eight hospitalized patients in Singapore. The deletion also removes the ORF8 transcription-regulatory sequence (TRS), which in turn enhances the downstream transcription of the N gene. We also found that viruses with the deletion have been circulating for at least four weeks. During the SARS-CoV outbreak in 2003, a number of genetic variants were observed in the human population [1], and similar variation has since been observed across SARS-related CoVs in humans and bats. Overwhelmingly these viruses had mutations or deletions in ORF8, that have been associated with reduced replicative fitness of the virus [2]. This is also consistent with the observation that towards the end of the outbreak sequences obtained from human SARS cases possessed an ORF8 deletion that may be associated with host adaptation [1]. We therefore hypothesise that the major deletion revealed in this study may lead to an attenuated phenotype of SARS-CoV-2.", "doc_id": "v5v9bjgs"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "SARS-CoV-2 and ORF3a: Non-Synonymous Mutations and Polyproline Regions", "abstract": "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.", "doc_id": "tylwbnpl"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Variation of 2019 novel coronavirus complete genomes recorded in the 1stmonth of outbreak: Implication for mutation", "abstract": "", "doc_id": "mgc1n9lr"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Translation-associated mutational U-pressure in the first ORF of SARS-CoV-2 and other coronaviruses", "abstract": "Within four months of the ongoing COVID-19 pandemic caused by SARS-CoV-2, more than 250 nucleotide mutations have been detected in the ORF1 of the virus isolated from different parts of the globe. These observations open up an obvious question about the rate and direction of mutational pressure for further vaccine and therapeutics designing. In this study, we did a comparative analysis of ORF1a and ORF1b by using the first isolate (Wuhan strain) as the parent sequence. We observed that most of the nucleotide mutations are C to U transitions. The rate of synonymous C to U transitions is significantly higher than the rate of nonsynonymous ones, indicating negative selection on amino acid substitutions. Further, trends in nucleotide usage bias have been investigated in 49 coronaviruses species. A strong bias in nucleotide usage in fourfold degenerated sites towards uracil residues is seen in ORF1 of all the studied coronaviruses. A more substantial mutational U pressure is observed in ORF1a than in ORF1b owing to the translation of ORF1ab via programmed ribosomal frameshifting. Unlike other nucleotide mutations, mutational U pressure caused by cytosine deamination, mostly occurring in the RNA-plus strand, cannot be corrected by the proof-reading machinery of coronaviruses. The knowledge generated on the direction of mutational pressure during translation of viral RNA-plus strands has implications for vaccine and nucleoside analogue development for treating covid-19 and other coronavirus infections.", "doc_id": "ug8xh52p"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Evidence for strong mutation bias towards, and selection against, T/U content in SARS-CoV2: implications for attenuated vaccine design", "abstract": "Large-scale re-engineering of synonymous sites is a promising strategy to generate attenuated viruses for vaccines. Attenuation typically relies on de-optimisation of codon pairs and maximization of CpG dinculeotide frequencies. So as to formulate evolutionarily-informed attenuation strategies, that aim to force nucleotide usage against the estimated direction favoured by selection, here we examine available whole-genome sequences of SARS-CoV2 to infer patterns of mutation and selection on synonymous sites. Analysis of mutational profiles indicates a strong mutation bias towards T with concomitant selection against T. Accounting for dinucleotide effects reinforces this conclusion, observed TT content being a quarter of that expected under neutrality. A significantly different mutational profile at CDS sites that are not 4-fold degenerate is consistent with contemporaneous selection against T mutations more widely. Although selection against CpG dinucleotides is expected to drive synonymous site G+C content below mutational equilibrium, observed G+C content is slightly above equilibrium, possibly because of selection for higher expression. Consistent with gene-specific selection against CpG dinucleotides, we observe systematic differences of CpG content between SARS-CoV2 genes. We propose an evolutionarily informed gene-bespoke approach to attenuation that, unusually, seeks to increase usage of the already most common synonymous codons. Comparable analysis of H1N1 and Ebola finds that GC3 deviated from neutral equilibrium is not a universal feature, cautioning against generalization of results.", "doc_id": "w8ylmbey"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "SARS-CoV-2 mutations altering regulatory properties: deciphering host\u2019s and virus\u2019s perspectives", "abstract": "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\u2019s and virus\u2019s perspective by analyzing the host miRNA binding and virus\u2019s 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.", "doc_id": "6f1y5hhv"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Two mutations P/L and Y/C in SARS-CoV-2 helicase domain exist together and influence helicase RNA binding", "abstract": "RNA helicases play pivotal role in RNA replication by catalysing the unwinding of complex RNA duplex structures into single strands in ATP/NTP dependent manner. SARS coronavirus 2 (SARS-CoV-2) is a single stranded positive sense RNA virus belonging to the family Coronaviridae. The viral RNA encodes non structural protein Nsp13 or the viral helicase protein that helps the viral RNA dependent RNA polymerase (RdRp) to execute RNA replication by unwinding the RNA duplexes. In this study we identified a novel mutation at position 541of the helicase where the tyrosine (Y) got substituted with cytosine (C). We found that Y541C is a destabilizing mutation increasing the molecular flexibility and leading to decreased affinity of helicase binding with RNA. Earlier we had reported a mutation P504L in the helicase protein for which had not performed RNA binding study. Here we report that P504L mutation leads to increased affinity of helicase RNA interaction. So, both these mutations have opposite effects on RNA binding. Moreover, we found a significant fraction of isolate population where both P504L and Y541C mutations were co-existing.", "doc_id": "bx7k42rn"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "SARS-CoV2 envelope protein: Non-synonymous mutations and its consequences", "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.", "doc_id": "phl6ibbv"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Conserved High Free Energy Sites in Human Coronavirus Spike Glycoprotein Backbones", "abstract": "Methods previously developed by the author are applied to uncover several sites of interest in the spike glycoproteins of all known human coronaviruses (hCoVs), including SARS-CoV-2 that causes COVID-19. The sites comprise three-dimensional neighborhoods of peptides characterized by four key properties: (1) they pinpoint regions of high free energy in the backbone whose obstruction might interrupt function; (2) by their very definition, they occur rarely in the universe of all gene-encoded proteins that could obviate host response to compounds designed for their interference; (3) they are common to all known hCoV spikes, possibly retaining activity in light of inevitable viral mutation; and (4) they are exposed in the molecular surface of the glycoprotein. These peptides in SARS-CoV-2 are given by the triples of residues (131, 117, 134), (203, 227, 228), and (1058, 730, 731) in its spike.", "doc_id": "8ha8qv5o"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "An overview of the genetic variations of the SARS-CoV-2 genomes isolated in Southeast Asian countries", "abstract": "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.", "doc_id": "ewpfxpw2"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Comparison five primer sets from different genome region of covid-1for detection of virus infection by conventional rt-pcr", "abstract": "Background and Objectives: The new beta-coronavirus, which caused Severe Acute Respiratory Coronavirus-2 Syndrome (SARS-CoV-2), a major respiratory outbreak in Wuhan, China in December 2019, is now prevalent in many countries around the world Identifying PCR-based viruses is a well-known and relatively stable protocol Unfortunately, the high mutation rates may lead to widespread changes in viral nucleic acid sequences, and so using specific primers for PCR can be recom-mended In this study, we evaluated the power of a conventional RT-PCR to detect SARS-CoV-2 RNA among the five set primer sets Materials and Methods: The five genomic regions of the Coronavirus SARS-2 virus including Nucleocapsids (N), Enve-lope (E), RNA depended RNA Polymerase (RdRp), ORF1ab and Spike (S) were selected for primer designing A conventional RT-PCR was performed to compare sensitivity, specificity and other analytical characteristics of primers designed against two Real Time PCR commercial kits Results: The result of the comparative analysis showed that the ORF1ab, N and RdRp primers had a sensitivity, specificity and positive predictive value higher than other primers A significant difference in the analytical sensitivity between the studied primer sets in RT-PCR kits was observed Conclusion: In this study, the ORF1ab, Nucleocapsid and RdRp regions have the best primers for identifying the SARS-CoV-2 RNA between different genes that have been suggested", "doc_id": "9c449ygv"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Ratcheting down the virulence of SARS-CoV-2 in the COVID-19 pandemic", "abstract": "", "doc_id": "vxdpx9h8"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Overwhelming mutations or SNPs of SARS-CoV-2: A point of caution", "abstract": "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.", "doc_id": "j8sg5n5g"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Identification of nsp1 gene as the target of SARS-CoV-2 real-time RT-PCR using nanopore whole-genome sequencing", "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic. Accurate detection of SARS-CoV-2 using molecular assays is critical for patient management and the control of the COVID-19 pandemic. However, there is an increasing number of SARS-CoV-2 viruses with mutations at the primer or probe binding sites, and these mutations may affect the sensitivity of currently available real-time reverse transcription-polymerase chain reaction (RT-PCR) assays targeting the nucleocapsid (N), envelope (E), and open reading frame 1a or 1b genes. Using sequence-independent single-primer amplification and nanopore whole-genome sequencing, we have found that the nonstructural protein 1 (nsp1) gene, located at the 5' end of the SARS-CoV-2 genome, was highly expressed in the nasopharyngeal or saliva specimens of 9 COVID-19 patients of different clinical severity. Based on this finding, we have developed a novel nsp1 real-time RT-PCR assay. The primers and probes are highly specific for SARS-CoV-2. Validation with 101 clinical specimens showed that our nsp1 RT-PCR assay has a sensitivity of 93.1% (95% confidence interval [CI]: 86.2%-97.2%), which was similar to those of N and E gene RT-PCR assays. The diagnostic specificity was 100% (95% CI: 92.9%-100%). The addition of nsp1 for multitarget detection of SARS-CoV-2 can avoid false-negative results due to mutations at the primers/probes binding sites of currently available RT-PCR assays.", "doc_id": "9gjv37dh"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Genetic Analysis Tracks SARS-CoV-2 Mutations in Human Hosts", "abstract": "", "doc_id": "ltzk9tku"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Epidemiological, clinical, and virological characteristics of 465 hospitalized cases of coronavirus disease 2019 (COVID-19) from Zhejiang province in China", "abstract": "BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease (COVID-19) have spread throughout China. Previous studies predominantly focused on its place of origin, Wuhan, causing over estimation of the disease severity due to selection bias. We analyzed 465 confirmed cases in Zhejiang province to determine the epidemiological, clinical, and virological characteristics of COVID-19. METHODS: Epidemiological, demographic, clinical, laboratory, and management data from qRT-PCR confirmed COVID-19 patients from January 17, 2020, to January 31, 2020, were collected, followed by multivariate logistic regression analysis for independent predictors of severe/critical-type COVID-19 and bioinformatic analysis for features of SARS-CoV-2 from Zhejiang province. RESULTS: Among 465 COVID-19 patients, median age was 45 years, while hypertension, diabetes, and chronic liver disease were the most common comorbidities. History of exposure to the epidemic area was present in 170 (36.56%) and 185 (39.78%) patients were clustered in 77 families. Severe/critical-type of COVID-19 developed in 49 (10.54%) patients. Fever and cough were the most common symptoms, while diarrhea/vomiting was reported in 58 (12.47%) patients. Multivariate analysis revealed eight risk factors for severe/critical COVID-19. Glucocorticoids and antibiotics were administered to 60 (12.90%) and 218(46.88%) patients, respectively. Bioinformatics showed four single amino acid mutations and one amino acid position loss in SARS-CoV-2 from Zhejiang province, with more similarity to humans than to viruses. CONCLUSIONS: SARS-CoV-2 showed virological mutations and more human transmission in Zhejiang province, indicating considerable epidemiological and clinical changes. Caution in glucocorticoid and antibiotics use is advisable.", "doc_id": "uiy0hrrg"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Mutations can reveal how the coronavirus moves\u2014but they\u2019re easy to overinterpret ;Science ;AAAS", "abstract": "mmediately after Christian Drosten published a genetic sequence of the novel coronavirus online on 28 February, he took to Twitter to issue a warning As the virus has raced around the world, more than 350 genome sequences have been shared on the online platform GISAID They hold clues to how the new virus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading and evolving But because the sequences represent a tiny fraction of cases and show few telltale differences, they are easy to overinterpret, as Drosten realized A virologist at the Charit\u00e9 University Hospital in Berlin, he had sequenced the virus from a German patient infected with COVID-19 in Italy The genome looked similar to that of a virus found in a patient in Munich, the capital of Bavaria, more than 1 month earlier;both shared three mutations not seen in early sequences from China Drosten realized this could give rise to the idea that the Italian outbreak was \u201cseeded\u201d by the one in Bavaria, which state public health officials said had been quashed by tracing and quarantining all contacts of the 14 confirmed cases But he thought it was just as likely that a Chinese variant carrying the three mutations had taken independent routes to both countries The newly sequenced genome \u201cis not sufficient to claim a link between Munich and Italy,\u201d Drosten tweeted", "doc_id": "wk63bmgn"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Rampant C\u00e2\u0086\u0092U Hypermutation in the Genomes of SARS-CoV-2 and Other Coronaviruses: Causes and Consequences for Their Short- and Long-Term Evolutionary Trajectories", "abstract": "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 \u00d7 10-4 substitutions/site/year. Almost one-half of sequence changes were C\u00e2\u0086\u0092U transitions, with an 8-fold base frequency normalized directional asymmetry between C\u00e2\u0086\u0092U and U\u00e2\u0086\u0092C 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\u00e2\u0086\u0092U 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 \u00e2\u0089\u00ab A > G \u00e2\u0089\u00ab C) and low G+C contents may represent long-term effects of prolonged C\u00e2\u0086\u0092U 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\u00e2\u0086\u0092U 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.", "doc_id": "14pgap3r"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "International Expansion of a Novel SARS-CoV-2 Mutant", "abstract": "", "doc_id": "licudrm0"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting", "abstract": "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.", "doc_id": "eri92ki6"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "A comprehensive analysis of genome composition and codon usage patterns of emerging coronaviruses", "abstract": "An outbreak of atypical pneumonia caused by a novel Betacoronavirus (\u00dfCoV), named SARS-CoV-2 has been declared a public health emergency of international concern by the World Health Organization. In order to gain insight into the emergence, evolution and adaptation of SARS-CoV-2 viruses, a comprehensive analysis of genome composition and codon usage of \u00dfCoV circulating in China was performed. A biased nucleotide composition was found for SARS-CoV-2 genome. This bias in genomic composition is reflected in its codon and amino acid usage patterns. The overall codon usage in SARS-CoV-2 is similar among themselves and slightly biased. Most of the highly frequent codons are A- and U-ending, which strongly suggests that mutational bias is the main force shaping codon usage in this virus. Significant differences in relative synonymous codon usage frequencies among SARS-CoV-2 and human cells were found. These differences are due to codon usage preferences.", "doc_id": "3r66vrv0"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Evidence for mutations in SARS-CoV-2 Italian isolates potentially affecting virus transmission", "abstract": "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.", "doc_id": "4z6wcmxq"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate", "abstract": "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.", "doc_id": "273ppceg"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Tracing New Clinical Manifestations in Patients with COVID-19 in Chile and Its Potential Relationship with the SARS-CoV-2 Divergence", "abstract": "Purpose of Review: In this review, we discuss the current implications of the changing genomic epidemiology of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), etiological agent of the Coronavirus Disease 2019 (COVID-19) and its potential relationship with the change of clinical manifestations in patients with confirmed infection. Recent Findings: Over the course of the current pandemic, the virus has been found more diverse in new countries. Simultaneously, also new clinical manifestations are observed, particularly more prominent gastrointestinal and neurological findings. Summary: SARS-CoV-2/COVID-19 is changing not only its epidemiology, but also its genomic diversity and clinical manifestations, both aspects coupled, needs to be considered in the study of this ongoing pandemic.", "doc_id": "b1cruunn"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2", "abstract": "The COVID-19 outbreak has become a global health risk, and understanding the response of the host to the SARS-CoV-2 virus will help to combat the disease. RNA editing by host deaminases is an innate restriction process to counter virus infection, but it is not yet known whether this process operates against coronaviruses. Here, we analyze RNA sequences from bronchoalveolar lavage fluids obtained from coronavirus-infected patients. We identify nucleotide changes that may be signatures of RNA editing: adenosine-to-inosine changes from ADAR deaminases and cytosine-to-uracil changes from APOBEC deaminases. Mutational analysis of genomes from different strains of Coronaviridae from human hosts reveals mutational patterns consistent with those observed in the transcriptomic data. However, the reduced ADAR signature in these data raises the possibility that ADARs might be more effective than APOBECs in restricting viral propagation. Our results thus suggest that both APOBECs and ADARs are involved in coronavirus genome editing, a process that may shape the fate of both virus and patient.", "doc_id": "40i8ot5h"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy", "abstract": "A new coronavirus (CoV) caused a pandemic named COVID-19, which has become a global health care emergency in the present time. The virus is referred to as SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) and has a genome similar (\u00e2\u0088\u00bc82%) to that of the previously known SARS-CoV (SARS coronavirus). An attractive therapeutic target for CoVs is the main protease (Mpro) or 3-chymotrypsin-like cysteine protease (3CLpro), as this enzyme plays a key role in polyprotein processing and is active in a dimeric form. Further, Mpro is highly conserved among various CoVs, and a mutation in Mpro is often lethal to the virus. Thus, drugs targeting the Mpro enzyme significantly reduce the risk of mutation-mediated drug resistance and display broad-spectrum antiviral activity. The combinatorial design of peptide-based inhibitors targeting the dimerization of SARS-CoV Mpro represents a potential therapeutic strategy. In this regard, we have compiled the literature reports highlighting the effect of mutations and N-terminal deletion of residues of SARS-CoV Mpro on its dimerization and, thus, catalytic activity. We believe that the present review will stimulate research in this less explored yet quite significant area. The effect of the COVID-19 epidemic and the possibility of future CoV outbreaks strongly emphasize the urgent need for the design and development of potent antiviral agents against CoV infections.", "doc_id": "8bzu2gn0"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Implications of altered replication fidelity on the evolution and pathogenesis of coronaviruses", "abstract": "RNA virus evolution results from viral replication fidelity and mutational robustness in combination with selection. Recent studies have confirmed the impact of increased fidelity on RNA virus replication and pathogenesis; however, the impact of decreased fidelity is less defined. Coronaviruses have the largest RNA genomes, and encode an exoribonuclease activity that is required for high-fidelity replication. Genetically stable exoribonuclease mutants will allow direct testing of viral mutational tolerance to RNA mutagens and other selective pressures. Recent studies support the hypothesis that coronavirus replication fidelity may result from a multi-protein complex, suggesting multiple pathways to disrupt or alter virus fidelity and diversity, and attenuate pathogenesis.", "doc_id": "ac38yvcn"} {"topic_name": "coronavirus mutations", "topic_id": "40", "title": "Genetic variability of human angiotensin\u2010converting enzyme 2 (hACE2) among various ethnic populations", "abstract": "BACKGROUND: There appears to be large regional variation for susceptibility, severity, and mortality for COVID\u201019 infections. Numerous potential factors could explain the wide variability in the number of infections and death among the countries. We examined genetic differences in the human angiotensin\u2010converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARS\u2010CoV\u20102. At present, there is a paucity of data regarding the differences for ACE2 polymorphisms and expression levels between ethnicities. METHODS: We compared the allele frequency of mutations between European and East Asians. Molecular dynamic simulation were performed to investigate the influences of significant mutant on protein structure. The binding free energies were calculated between S protein and hACE2. We also examined hACE2 gene expression in eight global populations from HapMap3. RESULTS: Four missense mutations showed significant minor allele frequency difference between Asians and Caucasians. Molecular dynamic demonstrated that two of these variants (K26R and I468V) may affect binding characteristics between S protein of the virus and hACE2 receptor. We also noted marginal differences in gene expression for some populations in HapMap3 as compared to the Chinese population. CONCLUSION: Our studies reveal subtle changes in the genetics of hACE2 between human populations, but the magnitude of the difference was small and the significance is not clear in the absence of further in vitro and functional studies.", "doc_id": "48opcqzs"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Scarce resource allocation scores threaten to exacerbate racial disparities in healthcare.", "abstract": "", "doc_id": "1uupbap4"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "COVID-19 and Racial/Ethnic Disparities.", "abstract": "", "doc_id": "el6qel8s"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "The outbreak that was always here: Racial trauma in the context of COVID-19 and implications for mental health providers.", "abstract": "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).", "doc_id": "fzaso4xm"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Equitable Care for Critically Ill Patients from Culturally Diverse Communities in the COVID-19 Pandemic.", "abstract": "", "doc_id": "8rmk2142"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Commentary: Addressing Inequities in the Era of COVID-19: The Pandemic and the Urgent Need for Critical Race Theory.", "abstract": "", "doc_id": "bpjzoxjj"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "COVID-19 Pandemic: Exacerbating Racial/Ethnic Disparities in Long-Term Services and Supports.", "abstract": "What services are available and where racial and ethnic minorities receive long-term services and supports (LTSS) have resulted in a lower quality of care and life for racial/ethnic minority users. These disparities are only likely to worsen during the COVID-19 pandemic, as the pandemic has disproportionately affected racial and ethnic minority communities both in the rate of infection and virus-related mortality. By examining these disparities in the context of the pandemic, we bring to light the challenges and issues faced in LTSS by minority communities with regard to this virus as well as the disparities in LTSS that have always existed.", "doc_id": "fxtmdpds"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Seizing the Moment: Policy Advocacy to End Mass Incarceration in the Time of COVID-19.", "abstract": "The mass human and economic casualties wrought by the COVID-19 pandemic laid bare the deep inequities at the base of the disproportionate losses and suffering experienced by diverse U.S. populations. But the urgency and enormity of unmet needs requiring bold policy action also provided a unique opportunity to learn from and partner with community-based organizations that often are at the frontlines of such work. Following a review of Kingdon's model of the policy-making process, we illustrate how a partnership in a large California county navigated the streams in the policy-making process and used the window of opportunity provided by the pandemic to address a major public health problem: the incarceration of over 2 million people, disproportionately African American and Latinx, in overcrowded, unsafe jails, prisons, and detention centers. We highlight tactics and strategies used, challenges faced, and implications for health educators as policy advocates during and beyond the pandemic.", "doc_id": "fe1v252b"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Social Vulnerability and Racial Inequality in COVID-19 Deaths in Chicago.", "abstract": "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.", "doc_id": "gn8uwuca"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Acknowledging and Addressing COVID-19 Health Disparities in the American South.", "abstract": "", "doc_id": "b6jaza1w"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "The Disproportionate Impact of COVID-19 on Racial and Ethnic Minorities in the United States.", "abstract": "", "doc_id": "i6a26q3j"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "COVID-19 and African Americans.", "abstract": "", "doc_id": "fs983x5g"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Racial Disparities in COVID-19 Deaths Reveal Harsh Truths About Structural Inequality in America.", "abstract": "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.", "doc_id": "a2kjjsq1"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Social Workers Must Address Intersecting Vulnerabilities among Noninstitutionalized, Black, Latinx, and Older Adults of Color during the COVID-19 Pandemic.", "abstract": "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.", "doc_id": "ivjt0eml"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "COVID-19 and the need to prioritize health equity and social determinants of health.", "abstract": "", "doc_id": "ege96sfz"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "COVID-19\u2013Associated Collapsing Focal Segmental Glomerulosclerosis: A Report of 2 Cases", "abstract": "Collapsing glomerulopathy is an aggressive form of focal segmental glomerulosclerosis with diverse etiologies The presence of APOL1 high risk genotype is a major risk factor for collapsing glomerulopathy in African Americans Coronavirus disease 2019 (COVID-19) is an emerging pandemic with predominant respiratory manifestations However, kidney involvement is being frequently noted and is associated with higher mortality Currently kidney pathology data in COVID-19 are scant and mostly come from postmortem findings We report two African American patients who developed acute kidney injury and proteinuria in temporal association with COVID-19 Kidney biopsies showed collapsing glomerulopathy, endothelial tubuloreticular inclusions, and acute tubular injury, without evidence by electron microscopy or SARS-CoV-2 ISH of viral infection of kidney cells Both patients had APOL1 high risk genotype We propose that collapsing glomerulopathy represents a novel manifestation of COVID-19 especially in people of African descent with APOL1 risk alleles", "doc_id": "952w7vx5"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Blacks/African Americans are 5 Times More Likely to Develop COVID-19: Spatial Modeling of New York City ZIP Code-level Testing Results", "abstract": "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.", "doc_id": "crqvdk4k"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Outcomes and Cardiovascular Comorbidities in a Predominantly African-American Population with COVID-19", "abstract": "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.", "doc_id": "4f6h7agt"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Impact of COVID-19 on 2020 US life expectancy for the Black and Latino populations", "abstract": "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.", "doc_id": "bjvg2ivr"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "COVID-19 in-patient hospital mortality by ethnicity", "abstract": "There is debate about the extent to which COVID-19 affects ethnic groups differently We explored if there was variation in hospital mortality in patients with COVID Mortality rates in 1,276 inpatients in Bradford with test results for COVID-19 were analysed by ethnic group The age-adjusted risk of dying from COVID-19 was slightly lower in South Asian compared to White British patients (RR =0 87, 95% CI: 0 41 to 1 84)", "doc_id": "c8ya6f9v"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Disproportionate COVID-19 Related Mortality Amongst African Americans in Four Southern States in the United States", "abstract": "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", "doc_id": "8yvu9xhw"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Covid-19 and Inequity: A comparative spatial analysis of New York City and Chicago hot spots", "abstract": "There have been numerous reports that the impact of the ongoing COVID-19 epidemic has disproportionately impacted traditionally vulnerable communities, including well-researched social determinants of health, such as racial and ethnic minorities, migrants, and the economically challenged. The goal of this ecological cross-sectional study is to examine the demographic and economic nature of spatial hot and cold spots of SARS-CoV-2 rates in New York City and Chicago as of April 13, 2020. In both cities, cold spots (clusters of low SARS-CoV-2 rate ZIP code tabulation areas) demonstrated typical protective factors associated with the social determinants of health and the ability to social distance. These neighborhoods tended to be wealthier, have higher educational attainment, higher proportions of non-Hispanic white residents, and more workers in managerial occupations. Hot spots (clusters of high SARS-CoV-2 rate ZIP code tabulation areas) also had similarities, such as lower rates of college graduates and higher proportions of people of color. It also appears to be larger households (more people per household), rather than overall population density, that may to be a more strongly associated with hot spots. Findings suggest important differences between the cities' hot spots as well. They can be generalized by describing the NYC hot spots as working-class and middle-income communities, perhaps indicative of service workers and other occupations (including those classified as \"essential services\" during the pandemic) that may not require a college degree but pay wages above poverty levels. Chicago's hot spot neighborhoods, on the other hand, are among the city's most vulnerable, low-income neighborhoods with extremely high rates of poverty, unemployment, and non-Hispanic Black residents.", "doc_id": "0xqxledk"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "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", "abstract": "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.", "doc_id": "ix2cbs4j"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Stay-at-Home Orders, African American Population, Poverty and State-level Covid-19 Infections: Are there associations?", "abstract": "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.", "doc_id": "csujgaae"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "A case-control and cohort study to determine the relationship between ethnic background and severe COVID-19", "abstract": "Background. People of minority ethnic background may be disproportionately affected by severe COVID-19 for reasons that are unclear. We sought to examine the relationship between ethnic background and (1) hospital admission for severe COVID-19; (2) in-hospital mortality. Methods. We conducted a case-control study of 872 inner city adult residents admitted to hospital with confirmed COVID-19 (cases) and 3,488 matched controls randomly sampled from a primary healthcare database comprising 344,083 people resident in the same region. To examine in-hospital mortality, we conducted a cohort study of 1827 adults consecutively admitted with COVID-19. Data collected included hospital admission for COVID-19, demographics, comorbidities, in-hospital mortality. The primary exposure variable was self-defined ethnicity. Results. The 872 cases comprised 48.1% Black, 33.7% White, 12.6% Mixed/Other and 5.6% Asian patients. In conditional logistic regression analyses, Black and Mixed/Other ethnicity were associated with higher admission risk than white (OR 3.12 [95% CI 2.63-3.71] and 2.97 [2.30- 3.85] respectively). Adjustment for comorbidities and deprivation modestly attenuated the association (OR 2.28 [1.87-2.79] for Black, 2.66 [2.01-3.52] for Mixed/Other). Asian ethnicity was not associated with higher admission risk (OR 1.20 [0.86-1.66]). In the cohort study of 1827 patients, 455 (28.9%) died over a median (IQR) of 8 (4-16) days. Age and male sex, but not Black (adjusted HR 0.84 [0.63-1.11]) or Mixed/Other ethnicity (adjusted HR 0.69 [0.43-1.10]), were associated with in-hospital mortality. Asian ethnicity was associated with higher in-hospital mortality (adjusted HR 1.54 [0.98-2.41]). Conclusions. Black and Mixed ethnicity are independently associated with greater admission risk with COVID-19 and may be risk factors for development of severe disease. Comorbidities and socioeconomic factors only partly account for this and additional ethnicity-related factors may play a large role. The impact of COVID-19 may be different in Asians.", "doc_id": "gadui4r7"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Comorbidities and Disparities in Outcomes of COVID-19 Among African American and White Patients", "abstract": "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.", "doc_id": "cuo7qdkj"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Updated estimates of comorbidities associated with risk for COVID-19 complications based on US data", "abstract": "We updated previous estimates (wwwnc.cdc.gov/eid/article/26/8/20-0679_article) of adults with any underlying condition increasing risk of complications from COVID-19 using recent US hospitalization data instead of mortality data from China. This substitutes obesity for cancer in the definition and increased the percentage of adults reporting more than 1 condition to 56.0% (95% CI 55.7-56.4). When controlled for all measures listed, factors increasing odds of reporting any of the underlying conditions include being male, older, African American, American Indian, household income <$25,000, < high school education, underinsurance, living in the South or Midwest (vs. West), plus the risk factors of ever smoking, sedentary lifestyle, and inadequate fruit and vegetable consumption. Population-attributable risk for the listed risk factors was 13.0%, 12.6%, and 15.0% respectively. Results have potential implications for policies based on risk-stratification of the population and for improvement of risk status through lifestyle change. National support for a health promotion campaign would be timely.", "doc_id": "1dkkwt7h"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Prevalence of regular physical activity among adults--United States, 2001 and 2005.", "abstract": "Regular physical activity is associated with decreased risk for obesity, heart disease, hypertension, diabetes, certain cancers, and premature mortality. CDC and the American College of Sports Medicine recommend that adults engage in at least 30 minutes of moderate physical activity on most days and preferably on all days. Healthy People 2010 objectives include increasing the proportion of adults who engage regularly in moderate or vigorous activity to at least 50% (objective 22-2). In addition, reducing racial and ethnic health disparities, including disparities in physical activity, is an overarching national goal. To examine changes in the prevalence of regular, leisure-time, physical activity from 2001 to 2005, CDC analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS). This report summarizes the results of that analysis, which indicated that, from 2001 to 2005, the prevalence of regular physical activity increased 8.6% among women overall (from 43.0% to 46.7%) and 3.5% among men (from 48.0% to 49.7%). In addition, the prevalence of regular physical activity increased 15.0% (from 31.4% to 36.1%) among non-Hispanic black women and 12.4% (from 40.3% to 45.3%) among non-Hispanic black men, slightly narrowing previous racial disparities when compared with increases of 7.8% (from 46.0% to 49.6%) for white women and 3.4% (from 50.6% to 52.3%) for white men, respectively. CDC, state and local public health agencies, and other public health partners should continue to implement evidence-based, culturally appropriate initiatives to further increase physical-activity levels among all adults, with special focus on eliminating racial/ethnic disparities.", "doc_id": "26f514ay"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Disparities in Coronavirus 2019 Reported Incidence, Knowledge, and Behavior Among US Adults", "abstract": "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\u00e2\u0080\u00af000, 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.", "doc_id": "hhaq25w8"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "For us, COVID-19 is personal", "abstract": "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.", "doc_id": "2djys8ky"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "African American children are at higher risk of COVID-19 infection", "abstract": "", "doc_id": "flis1rey"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Taking a Closer Look at COVID-19, Health Inequities, and Racism", "abstract": "", "doc_id": "d7d1um8g"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "COVID-19 and the Widening Gap in Health Inequity", "abstract": "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.", "doc_id": "3omm8wkv"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Genetic susceptibility for COVID-19-associated sudden cardiac death in African Americans", "abstract": "", "doc_id": "h139jyk8"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Coronavirus disease 19 in minority populations of Newark, New Jersey", "abstract": "BACKGROUND: The purpose of this study is to report the clinical features and outcomes of Black/African American (AA) and Latino Hispanic patients with Coronavirus disease 2019 (COVID-19) hospitalized in an inter-city hospital in the state of New Jersey. METHODS: This is a retrospective cohort study of AA and Latino Hispanic patients with COVID-19 admitted to a 665-bed quaternary care, teaching hospital located in Newark, New Jersey. The study included patients who had completed hospitalization between March 10, 2020, and April 10, 2020. We reviewed demographics, socioeconomic variables and incidence of in-hospital mortality and morbidity. Logistic regression was used to identify predictor of in-hospital death. RESULTS: Out of 416 patients, 251 (60%) had completed hospitalization as of April 10, 2020. The incidence of In-hospital mortality was 38.6% (n = 97). Most common symptoms at initial presentation were dyspnea 39% (n = 162) followed by cough 38%(n = 156) and fever 34% (n = 143). Patients were in the highest quartile for population's density, number of housing units and disproportionately fell into the lowest median income quartile for the state of New Jersey. The incidence of septic shock, acute kidney injury (AKI) requiring hemodialysis and admission to an intensive care unit (ICU) was 24% (n = 59), 21% (n = 52), 33% (n = 82) respectively. Independent predictors of in-hospital mortality were older age, lower serum Hemoglobin < 10 mg/dl, elevated serum Ferritin and Creatinine phosphokinase levels > 1200 U/L and > 1000 U/L. CONCLUSIONS: Findings from an inter-city hospital's experience with COVID-19 among underserved minority populations showed that, more than one of every three patients were at risk for in-hospital death or morbidity. Older age and elevated inflammatory markers at presentation were associated with in-hospital death.", "doc_id": "g7cqx652"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Coronavirus Disease among Persons with Sickle Cell Disease, United States, March 20-May 21, 2020", "abstract": "Sickle cell disease (SCD) disproportionately affects Black or African American persons in the United States and can cause multisystem organ damage and reduced lifespan. Among 178 persons with SCD in the United States who were reported to an SCD-coronavirus disease case registry, 122 (69%) were hospitalized and 13 (7%) died.", "doc_id": "3ayfmpzx"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Policy Recommendations to Address High Risk of COVID-19 Among Immigrants", "abstract": "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).", "doc_id": "71rhjy74"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Covid-19: Black people and other minorities are hardest hit in US", "abstract": "", "doc_id": "hpzykj2r"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Historical Insights on Coronavirus Disease 2019 (COVID-19), the 1918 Influenza Pandemic, and Racial Disparities: Illuminating a Path Forward", "abstract": "The coronavirus disease 2019 (COVID-19) pandemic is exacting a disproportionate toll on ethnic minority communities and magnifying existing disparities in health care access and treatment. To understand this crisis, physicians and public health researchers have searched history for insights, especially from a great outbreak approximately a century ago: the 1918 influenza pandemic. However, of the accounts examining the 1918 influenza pandemic and COVID-19, only a notable few discuss race. Yet, a rich, broader scholarship on race and epidemic disease as a \"sampling device for social analysis\" exists. This commentary examines the historical arc of the 1918 influenza pandemic, focusing on black Americans and showing the complex and sometimes surprising ways it operated, triggering particular responses both within a minority community and in wider racial, sociopolitical, and public health structures. This analysis reveals that critical structural inequities and health care gaps have historically contributed to and continue to compound disparate health outcomes among communities of color. Shifting from this context to the present, this article frames a discussion of racial health disparities through a resilience approach rather than a deficit approach and offers a blueprint for approaching the COVID-19 crisis and its afterlives through the lens of health equity.", "doc_id": "6l0pqp6l"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Racial Capitalism within Public Health: How Occupational Settings Drive COVID-19 Disparities", "abstract": "Epidemiology of the U.S. COVID-19 outbreak focuses on individuals' biology and behaviors, despite centrality of occupational environments in the viral spread. This demonstrates collusion between epidemiology and racial capitalism because it obscures structural influences, absolving industries of responsibility for worker safety. In an empirical example, we analyze economic implications of race-based metrics widely used in occupational epidemiology. In the U.S., White adults have better average lung function and worse hearing than Black adults. Both impaired lung function and hearing are criteria for Worker's compensation, which is ultimately paid by industry. Compensation for respiratory injury is determined using a race-specific algorithm. For hearing, there is no race adjustment. Selective use of race-specific algorithms for workers' compensation reduces industries' liability for worker health, illustrating racial capitalism operating within public health. Widespread and unexamined belief in inherent physiological inferiority of Black Americans perpetuates systems that limit industry payouts for workplace injuries. We see a parallel in the epidemiology of COVID-19 disparities. We tell stories of industries implicated in the outbreak and review how they exemplify racial capitalism. We call on public health professionals to: critically evaluate who is served and neglected by data analysis; and center structural determinants of health in etiological evaluation.", "doc_id": "betyinap"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "The fire this time: The stress of racism, inflammation and COVID-19", "abstract": "", "doc_id": "1mzddq5v"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "COVID-19 and Racial/Ethnic Disparities", "abstract": "", "doc_id": "fpzdoza9"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Black-White Risk Differentials in COVID-19 (SARS-COV2) Transmission, Mortality and Case Fatality in the United States: Translational Epidemiologic Perspective and Challenges", "abstract": "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.", "doc_id": "9cy1jrw9"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "A culturally specific mental health and spirituality approach for African Americans facing the COVID-19 pandemic", "abstract": "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).", "doc_id": "5c6nwrdo"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "COVID 19: Surgery & the question of race", "abstract": "", "doc_id": "13ii2xq5"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Racial and Ethnic Digital Divides in Posting COVID-19 Content on Social Media Among US Adults: Secondary Survey Analysis", "abstract": "BACKGROUND: Public health surveillance experts are leveraging user-generated content on social media to track the spread and effects of COVID-19. However, racial and ethnic digital divides, which are disparities among people who have internet access and post on social media, can bias inferences. This bias is particularly problematic in the context of the COVID-19 pandemic because due to structural inequalities, members of racial and ethnic minority groups are disproportionately vulnerable to contracting the virus and to the deleterious economic and social effects from mitigation efforts. Further, important demographic intersections with race and ethnicity, such as gender and age, are rarely investigated in work characterizing social media users; however, they reflect additional axes of inequality shaping differential exposure to COVID-19 and its effects. OBJECTIVE: The aim of this study was to characterize how the race and ethnicity of US adults are associated with their odds of posting COVID-19 content on social media and how gender and age modify these odds. METHODS: We performed a secondary analysis of a survey conducted by the Pew Research Center from March 19 to 24, 2020, using a national probability sample (N=10,510). Respondents were recruited from an online panel, where panelists without an internet-enabled device were given one to keep at no cost. The binary dependent variable was responses to an item asking whether respondents \"used social media to share or post information about the coronavirus.\" We used survey-weighted logistic regressions to estimate the odds of responding in the affirmative based on the race and ethnicity of respondents (white, black, Latino, other race/ethnicity), adjusted for covariates measuring sociodemographic background and COVID-19 experiences. We examined how gender (female, male) and age (18 to 30 years, 31 to 50 years, 51 to 64 years, and 65 years and older) intersected with race and ethnicity by estimating interactions. RESULTS: Respondents who identified as black (odds ratio [OR] 1.29, 95% CI 1.02-1.64; P=.03), Latino (OR 1.66, 95% CI 1.36-2.04; P<.001), or other races/ethnicities (OR 1.33, 95% CI 1.02-1.72; P=.03) had higher odds than respondents who identified as white of reporting that they posted COVID-19 content on social media. Women had higher odds of posting than men regardless of race and ethnicity (OR 1.58, 95% CI 1.39-1.80; P<.001). Among men, respondents who identified as black, Latino, or members of other races/ethnicities were significantly more likely to post than respondents who identified as white. Older adults (65 years or older) had significantly lower odds (OR 0.73, 95% CI 0.57-0.94; P=.01) of posting compared to younger adults (18-29 years), particularly among those identifying as other races/ethnicities. Latino respondents were the most likely to report posting across all age groups. CONCLUSIONS: In the United States, members of racial and ethnic minority groups are most likely to contribute to COVID-19 content on social media, particularly among groups traditionally less likely to use social media (older adults and men). The next step is to ensure that data collection procedures capture this diversity by encompassing a breadth of search criteria and social media platforms.", "doc_id": "d6hfczkq"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "This Time Must Be Different: Disparities During the COVID-19 Pandemic", "abstract": "", "doc_id": "20h60yj2"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Differential occupational risk for COVID-19 and other infection exposure according to race and ethnicity", "abstract": "BACKGROUND: There are racial and ethnic disparities in the risk of contracting COVID-19. This study sought to assess how occupational segregation according to race and ethnicity may contribute to the risk of COVID-19. METHODS: Data about employment in 2019 by industry and occupation and race and ethnicity were obtained from the Bureau of Labor Statistics Current Population Survey. This data was combined with information about industries according to whether they were likely or possibly essential during the COVID-19 pandemic and the frequency of exposure to infections and close proximity to others by occupation. The percentage of workers employed in essential industries and occupations with a high risk of infection and close proximity to others by race and ethnicity was calculated. RESULTS: People of color were more likely to be employed in essential industries and in occupations with more exposure to infections and close proximity to others. Black workers in particular faced an elevated risk for all of these factors. CONCLUSION: Occupational segregation into high-risk industries and occupations likely contributes to differential risk with respect to COVID-19. Providing adequate projection to workers may help to reduce these disparities.", "doc_id": "8ffds4yc"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Evidence mounts on the disproportionate effect of COVID-19 on ethnic minorities", "abstract": "", "doc_id": "agpqjkko"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Social and psychological consequences of the COVID-19 pandemic in African-American communities: Lessons from Michigan", "abstract": "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).", "doc_id": "423uero3"} {"topic_name": "COVID-19 in African-Americans", "topic_id": "41", "title": "Ethnic and racial disparities in COVID-19-related deaths: counting the trees, hiding the forest", "abstract": "", "doc_id": "8kl82e6g"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005\u20132016 NHANES", "abstract": "A well-functioning immune system is essential for human health and well-being. Micronutrients such as vitamins A, C, D, E, and zinc have several functions throughout the immune system, yet inadequate nutrient intakes are pervasive in the US population. A large body of research shows that nutrient inadequacies can impair immune function and weaken the immune response. Here, we present a new analysis of micronutrient usual intake estimates based on nationally representative data in 26,282 adults (>19 years) from the 2005\u20132016 National Health and Nutrition Examination Surveys (NHANES). Overall, the prevalence of inadequacy (% of population below estimated average requirement [EAR]) in four out of five key immune nutrients is substantial. Specifically, 45% of the U.S. population had a prevalence of inadequacy for vitamin A, 46% for vitamin C, 95% for vitamin D, 84% for vitamin E, and 15% for zinc. Dietary supplements can help address nutrient inadequacy for these immune-support nutrients, demonstrated by a lower prevalence of individuals below the EAR. Given the long-term presence and widening of nutrient gaps in the U.S.\u2014specifically in critical nutrients that support immune health\u2014public health measures should adopt guidelines to ensure an adequate intake of these micronutrients. Future research is needed to better understand the interactions and complexities of multiple nutrient shortfalls on immune health and assess and identify optimal levels of intake in at-risk populations.", "doc_id": "bd10ce5d"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Vitamin D Supplementation: A Potential Approach for Coronavirus/COVID-19 Therapeutics?", "abstract": "", "doc_id": "56p8jlua"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "The link between Vitamin D and Covid-19: distinguishing facts from fiction.", "abstract": "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.", "doc_id": "n2ku9n0d"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Nutrients in prevention, treatment, and management of viral infections; special focus on Coronavirus.", "abstract": "BACKGROUND The coronavirus disease 2019 (COVID-19) is a pandemic caused by coronavirus with mild to severe respiratory symptoms. This paper aimed to investigate the effect of nutrients on the immune system and their possible roles in the prevention, treatment, and management of COVID-19 in adults. METHODS This Systematic review was designed based on the guideline of the Preferred Reporting for Systematic Reviews (PRISMA). The articles that focussed on nutrition, immune system, viral infection, and coronaviruses were collected by searching databases for both published papers and accepted manuscripts from 1990 to 2020. Irrelevant papers and articles without English abstract were excluded from the review process. RESULTS Some nutrients are actively involved in the proper functioning and strengthening of the human immune system against viral infections including dietary protein, omega-3 fatty acids, vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and selenium. Few studies were done on the effect of dietary components on prevention of COVID-19, but supplementation with these nutrients may be effective in improving the health status of patients with viral infections. CONCLUSION Following a balanced diet and supplementation with proper nutrients may play a vital role in prevention, treatment, and management of COVID-19. However, further clinical trials are needed to confirm these findings and presenting the strong recommendations against this pandemic.", "doc_id": "478wbtfb"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank.", "abstract": "BACKGROUND We examined whether the greater severity of coronavirus disease 2019 (COVID-19) amongst men and Black, Asian and Minority Ethnic (BAME) individuals is explained by cardiometabolic, socio-economic or behavioural factors. METHODS We studied 4510 UK Biobank participants tested for COVID-19 (positive, n = 1326). Multivariate logistic regression models including age, sex and ethnicity were used to test whether addition of (1) cardiometabolic factors [diabetes, hypertension, high cholesterol, prior myocardial infarction, smoking and body mass index (BMI)]; (2) 25(OH)-vitamin D; (3) poor diet; (4) Townsend deprivation score; (5) housing (home type, overcrowding) or (6) behavioural factors (sociability, risk taking) attenuated sex/ethnicity associations with COVID-19 status. RESULTS There was over-representation of men and BAME ethnicities in the COVID-19 positive group. BAME individuals had, on average, poorer cardiometabolic profile, lower 25(OH)-vitamin D, greater material deprivation, and were more likely to live in larger households and in flats/apartments. Male sex, BAME ethnicity, higher BMI, higher Townsend deprivation score and household overcrowding were independently associated with significantly greater odds of COVID-19. The pattern of association was consistent for men and women; cardiometabolic, socio-demographic and behavioural factors did not attenuate sex/ethnicity associations. CONCLUSIONS In this study, sex and ethnicity differential pattern of COVID-19 was not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels or socio-economic factors. Factors which underlie ethnic differences in COVID-19 may not be easily captured, and so investigation of alternative biological and genetic susceptibilities as well as more comprehensive assessment of the complex economic, social and behavioural differences should be prioritised.", "doc_id": "85tgrqab"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "[Vitamin D and coronavirus: a new field of use?]", "abstract": "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.", "doc_id": "34f1ie66"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Revisiting vitamin D and home-based exercises for patients with sleep apnea facing the COVID-19 quarantine.", "abstract": "", "doc_id": "ogqi5jwv"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "SARS-CoV-2 & Covid-19: Key-Roles of the 'Renin-Angiotensin' System / Vitamin D Impacting Drug and Vaccine Developments.", "abstract": "", "doc_id": "4kxo6fbn"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Covid-19: Public health agencies review whether vitamin D supplements could reduce risk.", "abstract": "", "doc_id": "c393bp1g"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Synergistic effect of Vitamin D and Remdesivir can fight COVID-19.", "abstract": "", "doc_id": "ke5hxd8o"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Evidence does not support vitamin D for reducing respiratory infections, reviews conclude.", "abstract": "", "doc_id": "aye5nop1"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Letter: ACE2, Rho kinase inhibition and the potential role of vitamin D against COVID-19.", "abstract": "", "doc_id": "cvzwj7v9"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Vitamin A and micronutrient deficiencies post-bariatric surgery: aetiology, complications and management in a complex multiparous pregnancy.", "abstract": "Adequate vitamin A is essential for healthy pregnancy, but high levels may be teratogenic. We present a patient who underwent bariatric surgery, prior to child bearing, and suffered maternal and foetal complications during eleven pregnancies, possibly associated with vitamin A deficiency, amongst multiple micronutrient deficiencies and risk factors including smoking and obesity. Maternal complications included visual disturbance, night blindness and recurrent infections. Recurrent foetal pulmonary hypoplasia and microphthalmia led to foetal and neonatal loss, not previously described in the medical literature. Current guidance on vitamin A deficiency in pregnancy is focused on developing countries where aetiology of vitamin A deficiency is different to that of women in developed countries. We describe nutritional management of the micronutritient deficiencies, focusing on vitamin A, during her last pregnancy. The need for specific antenatal nutritional guidance for pregnant women post-bariatric surgery is becoming more urgent as more mothers and offspring will be affected.", "doc_id": "5den4c7m"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Can Composite Nutritional Supplement Based on the Current Guidelines Prevent Vitamin and Mineral Deficiency After Weight Loss Surgery?", "abstract": "BACKGROUND Nutritional deficiencies occur after weight loss surgery. Despite knowledge of nutritional risk, there is little uniformity of postoperative vitamin and mineral supplementation. The objective of this study was to evaluate a composite supplement based on the clinical practice guidelines proposed in 2008 regarding vitamin and mineral supplementation after Roux-en-Y gastric bypass. The composite included iron (Fe) and calcium as well. METHODS A retrospective chart review of 309 patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) was evaluated for the development of deficiencies in iron and vitamins A, B1, B12, and D. Patients were instructed to take a custom vitamin and mineral supplement that was based on society-approved guidelines. The clinical practice guidelines were modified to include 1600 international units (IU) of vitamin D3 instead of the recommended 800 IU. RESULTS The compliant patients' deficiency rates were significantly lower than those of the noncompliant patients for iron (p = 0.001), vitamin A (p = 0.01), vitamin B12 (p \u2248 0.02), and vitamin D (p < 0.0001). Women's menstrual status did not significantly influence the development of iron deficiency. CONCLUSIONS Use of a composite based on guidelines proposed by the AACE, TOS, and the ASMBS appears to be effective for preventing iron and vitamins A, B1, B12, and D deficiencies in the LRYGB patients during the first postoperative year. Separation of calcium and Fe does not need to be mandatory. Even with simplification, compliance is far from universal.", "doc_id": "3q2jju2u"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Phototherapy and vitamin D: the importance in COVID-19 era.", "abstract": "", "doc_id": "8twhzb8c"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Association between low vitamin D and COVID-19: don't forget the vitamin D binding protein.", "abstract": "", "doc_id": "ma7cgcvm"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition?", "abstract": "BACKGROUND In December 2019, the viral pandemic of respiratory illness caused by COVID-19 began sweeping its way across the globe. Several aspects of this infectious disease mimic metabolic events shown to occur during latent subclinical magnesium deficiency. Hypomagnesemia is a relatively common clinical occurrence that often goes unrecognized since magnesium levels are rarely monitored in the clinical setting. Magnesium is the second most abundant intracellular cation after potassium. It is involved in >600 enzymatic reactions in the body, including those contributing to the exaggerated immune and inflammatory responses exhibited by COVID-19 patients. METHODS A summary of experimental findings and knowledge of the biochemical role magnesium may play in the pathogenesis of COVID-19 is presented in this perspective. The National Academy of Medicine's Standards for Systematic Reviews were independently employed to identify clinical and prospective cohort studies assessing the relationship of magnesium with interleukin-6, a prominent drug target for treating COVID-19. RESULTS Clinical recommendations are given for prevention and treatment of COVID-19. Constant monitoring of ionized magnesium status with subsequent repletion, when appropriate, may be an effective strategy to influence disease contraction and progression. The peer-reviewed literature supports that several aspects of magnesium nutrition warrant clinical consideration. Mechanisms include its \"calcium-channel blocking\" effects that lead to downstream suppression of nuclear factor-K\u03b2, interleukin-6, c-reactive protein, and other related endocrine disrupters; its role in regulating renal potassium loss; and its ability to activate and enhance the functionality of vitamin D, among others. CONCLUSION As the world awaits an effective vaccine, nutrition plays an important and safe role in helping mitigate patient morbidity and mortality. Our group is working with the Academy of Nutrition and Dietetics to collect patient-level data from intensive care units across the United States to better understand nutrition care practices that lead to better outcomes.", "doc_id": "l76bqsn0"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Reviews of Science for Science Librarians: Vitamins and Trace Elements that May Be Preventive or Ameliorating in This Age of Contagion", "abstract": "Prompted by COVID-19, many laypersons now seek information on nutritional support to ward off or help shorten the effects of serious infectious diseases, and are attracted to practices and substances that lack a serious scientific basis. This paper scanned peer-reviewed medical literature to prove a concept: That diets or supplements rich in some vitamins or minerals may indeed be important in managing threats to health caused by a variety of infectious diseases in the past and compares these findings to the current recommendations of the Academy of Nutrition and Dietetics and to research by Zhang and Liu, two China-based pioneers in countering COVID-19. Vitamins A, D, and zinc, are common to both groups and are well supported in the literature. Vitamin C is also a common denominator but has a mixed record of efficacy in dealing with prior infectious outbreaks. Iron has support and do some other vitamins and trace elements. Health science librarians should emphasize that while experts can disagree on particular micronutrients they tend to agree that decisions on protective or curative supplements or diets or should have some basis in fact.", "doc_id": "5uo2bxiv"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Spurious Correlation? A review of the relationship between Vitamin D and Covid-19 infection and mortality", "abstract": "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.", "doc_id": "hevwcofh"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Short Communication: Vitamin D and COVID-19 infection and mortality in UK Biobank", "abstract": "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.", "doc_id": "npk92gra"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Vitamin D and Inflammation: Potential Implications for Severity of Covid-19.", "abstract": "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.", "doc_id": "jvyr7pq4"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Vitamin D, Covid-19 and Children.", "abstract": "", "doc_id": "gwf79fj6"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Optimisation of Vitamin D Status for Enhanced Immuno-protection Against Covid-19.", "abstract": "", "doc_id": "9mh3ix4m"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Vitamin D and Covid-19: A Note of Caution.", "abstract": "", "doc_id": "4tvj9ugd"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "COVID-19 and vitamin D deficiency, a fatal combination?", "abstract": "", "doc_id": "2mpajrhf"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Covid-19, Cocooning and Vitamin D Intake Requirements.", "abstract": "", "doc_id": "78tqcf66"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Commentary: Myths and facts on vitamin D amidst the COVID-19 pandemic", "abstract": "", "doc_id": "6c08q80z"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Letter: low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity", "abstract": "", "doc_id": "0pfi3huo"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "COVID-19 and vitamin D-Is there a link and an opportunity for intervention?", "abstract": "", "doc_id": "0ngg5pef"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Adjustments in analyses of vitamin D status, allowing for vitamin D determinants, for Covid-19 risks", "abstract": "", "doc_id": "ayuk1ubq"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Vitamin d deficiency and ards after sars-cov-2 infection", "abstract": "", "doc_id": "i4hb58r2"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "What is the role of supplementation with ascorbic acid, zinc, vitamin D, or N-acetylcysteine for prevention or treatment of COVID-19?", "abstract": "Several agents intended to supplement dietary intake or endogenous molecules may have a theoretical role in preventing or treating COVID-19. Because of their potential to influence immune response, ascorbic acid (vitamin C), zinc, vitamin D, and N-acetylcysteine have been hypothesized to be useful for prevention or treatment of COVID-19. The authors outline the biologic plausibility, applicable clinical data, and potential role of each of these agents.", "doc_id": "ezpj225f"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Letter: Covid-19, and vitamin D", "abstract": "", "doc_id": "780skv92"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Vitamin D and inflammation: Potential implications for severity of Covid-19", "abstract": "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 \u2018sunny\u2019 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", "doc_id": "lo6u1buy"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "'Scientific Strabismus' or two related pandemics: coronavirus disease and vitamin D deficiency", "abstract": "The WHO has announced the novel coronavirus disease (COVID-19) outbreak to be a global pandemic. The distribution of community outbreaks shows seasonal patterns along certain latitude, temperature and humidity, that is, similar to the behaviour of seasonal viral respiratory tract infections. COVID-19 displays significant spread in northern mid-latitude countries with an average temperature of 5\u00ad11\u00b0C and low humidity. Vitamin D deficiency has also been described as pandemic, especially in Europe. Regardless of age, ethnicity and latitude, recent data showed that 40 % of Europeans are vitamin D deficient (25-hydroxyvitamin D (25(OH)D) levels <50 nmol/l), and 13 % are severely deficient (25(OH)D < 30 nmol/l). A quadratic relationship was found between the prevalences of vitamin D deficiency in most commonly affected countries by COVID-19 and the latitudes. Vitamin D deficiency is more common in the subtropical and mid-latitude countries than the tropical and high-latitude countries. The most commonly affected countries with severe vitamin D deficiency are from the subtropical (Saudi Arabia 46 %; Qatar 46 %; Iran 33\u00b74 %; Chile 26\u00b74 %) and mid-latitude (France 27\u00b73 %; Portugal 21\u00b72 %; Austria 19\u00b73 %) regions. Severe vitamin D deficiency was found to be nearly 0 % in some high-latitude countries (e.g. Norway, Finland, Sweden, Denmark and Netherlands). Accordingly, we would like to call attention to the possible association between severe vitamin D deficiency and mortality pertaining to COVID-19. Given its rare side effects and relatively wide safety, prophylactic vitamin D supplementation and/or food fortification might reasonably serve as a very convenient adjuvant therapy for these two worldwide public health problems alike.", "doc_id": "lj4mq31p"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "La vitamina D \u00e8 efficace contro la CoViD-19?", "abstract": "", "doc_id": "g228oxz2"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "COVID-19 transmission risk factors", "abstract": "We analyze risk factors correlated with the initial transmission growth rate of the COVID-19 pandemic. The number of cases follows an early exponential expansion; we chose as a starting point in each country the first day with 30 cases and used 12 days. We looked for linear correlations of the exponents with other variables, using 126 countries. We find a positive correlation with high C.L. with the following variables, with respective $p$-value: low Temperature ($4\\cdot10^{-7}$), high ratio of old vs.~working-age people ($3\\cdot10^{-6}$), life expectancy ($8\\cdot10^{-6}$), number of international tourists ($1\\cdot10^{-5}$), earlier epidemic starting date ($2\\cdot10^{-5}$), high level of contact in greeting habits ($6 \\cdot 10^{-5}$), lung cancer ($6 \\cdot 10^{-5}$), obesity in males ($1 \\cdot 10^{-4}$), urbanization ($2\\cdot10^{-4}$), cancer prevalence ($3 \\cdot 10^{-4}$), alcohol consumption ($0.0019$), daily smoking prevalence ($0.0036$), UV index ($0.004$, smaller sample, 73 countries), low Vitamin D levels ($p$-value $0.002-0.006$, smaller sample, $\\sim 50$ countries). There is highly significant correlation also with blood type: positive correlation with RH- ($2\\cdot10^{-5}$) and A+ ($2\\cdot10^{-3}$), negative correlation with B+ ($2\\cdot10^{-4}$). We also find positive correlation with moderate C.L. ($p$-value of $0.02\\sim0.03$) with: CO$_2$ emissions, type-1 diabetes, low vaccination coverage for Tuberculosis (BCG). Several such variables are correlated with each other and so they likely have common interpretations. We also analyzed the possible existence of a bias: countries with low GDP-per capita, typically located in warm regions, might have less intense testing and we discuss correlation with the above variables.", "doc_id": "ei059aee"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Nutrients in prevention, treatment, and management of viral infections; special focus on Coronavirus", "abstract": "BACKGROUND: The coronavirus disease 2019 (COVID-19) is a pandemic caused by coronavirus with mild to severe respiratory symptoms. This paper aimed to investigate the effect of nutrients on the immune system and their possible roles in the prevention, treatment, and management of COVID-19 in adults. METHODS: This Systematic review was designed based on the guideline of the Preferred Reporting for Systematic Reviews (PRISMA). The articles that focussed on nutrition, immune system, viral infection, and coronaviruses were collected by searching databases for both published papers and accepted manuscripts from 1990 to 2020. Irrelevant papers and articles without English abstract were excluded from the review process. RESULTS: Some nutrients are actively involved in the proper functioning and strengthening of the human immune system against viral infections including dietary protein, omega-3 fatty acids, vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and selenium. Few studies were done on the effect of dietary components on prevention of COVID-19, but supplementation with these nutrients may be effective in improving the health status of patients with viral infections. CONCLUSION: Following a balanced diet and supplementation with proper nutrients may play a vital role in prevention, treatment, and management of COVID-19. However, further clinical trials are needed to confirm these findings and presenting the strong recommendations against this pandemic.", "doc_id": "jk0ysuy4"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "COVID-19 Fatalities, Latitude, Sunlight, and Vitamin D", "abstract": "BACKGROUND: Since Vitamin D is known to be vital in regulating the immune system, and sunlight UV radiation exposure on the skin produces Vitamin D and UV intensity is highest nearest the equator, a study was done to examine the correlation between the latitude and COVID-19 fatality rates for countries. METHODS: Eighty-eight countries were selected based on their likelihood of providing reliable data. Using death rates/million for each country from the \"worldometer\" web site, a correlation analysis was done between death rates and a country's latitude. RESULTS: A highly significant, positive correlation was found between lower death rates and a country's proximity to the equator (Pearson r\u00e2\u0080\u00af=\u00e2\u0080\u00af.40 p<.0001, two-tailed t-test). The R squared of .16 means that 16% of the variation in death rates among nations is accounted for by the latitude of the country. Evidence is presented suggesting a direct correlation between sunlight exposure and reduced mortality. DISCUSSION: This study is the first to document a statistically significant correlation between a country's latitude and its COVID-19 mortality and is consistent with other research regarding latitude, Vitamin D deficiency, and COVID-19 fatalities. Limitations of this study are noted. CONCLUSION: Further research is needed to confirm the correlation between latitude and COVID-19 fatalities, and to determine the optimum amounts of safe sunlight exposure and/or vitamin D oral supplementation to reduce COVID-19 fatalities in populations that are at high risk for vitamin D deficiency.", "doc_id": "jy45c2pk"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Vitamin D and Coronavirus", "abstract": "", "doc_id": "1wfv63mh"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Effects of Micronutrients or Conditional Amino Acids on COVID-19-Related Outcomes: An Evidence Analysis Center Scoping Review", "abstract": "Recent narrative reviews have described the potential efficacy of providing individuals infected with coronavirus disease 2019 (COVID-19) with additional micronutrients to reduce disease severity. Although there are compelling reasons why providing additional micronutrients or conditional amino acids may affect COVID-19-related outcomes, evidence is lacking. The objective of this scoping review is to explore and describe the literature examining the effect of providing additional micronutrients or conditional amino acids (glutamine, arginine) in adults with conditions or infections similar to COVID-19 infection on COVID-19-related health outcomes. A literature search of the MEDLINE database and hand search of Cochrane Database of systematic reviews retrieved 1,423 unique studies, and 8 studies were included in this scoping review. Four studies examined a target population with ventilator-related pneumonia and acute respiratory distress syndrome, and the other 4 studies included patients who were at risk for ventilator-associated pneumonia. Interventions included intravenous ascorbic acid, intramuscular cholecalciferol, enteral and intramuscular vitamin E, enteral zinc sulfate, and oral and parenteral glutamine. In 6 of the 8 included studies, baseline status of the nutrient of interest was not reported and, thus, it is uncertain how outcomes may vary in the context of nutrient deficiency or insufficiency compared with sufficiency. In the absence of direct evidence examining efficacy of providing additional micronutrients or conditional amino acids to standard care, registered dietitian nutritionists must rely on clinical expertise and indirect evidence to guide medical nutrition therapy for patients infected with COVID-19.", "doc_id": "998n5g4p"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Viramina D e coronavirus: un nuovo campo di impiego?/ [Vitamin D and coronavirus: a new field of use?]", "abstract": "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.", "doc_id": "gfyx3nz2"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Vitamin D deficiency and the COVID-19 pandemic", "abstract": "", "doc_id": "hqyungju"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Vitamin D, Covid-19 and Children", "abstract": "", "doc_id": "b4w5k7lh"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality", "abstract": "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.", "doc_id": "jak0gx9k"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "The potential long-term impact of the COVID-19 outbreak on patients with non-communicable diseases in Europe: consequences for healthy ageing", "abstract": "The early stages of the COVID-19 pandemic have focused on containing SARS-CoV-2 infection and identifying treatment strategies. While controlling this communicable disease is of utmost importance, the long-term effect on individuals with non-communicable diseases (NCD) is significant. Although certain NCDs appear to increase the severity of COVID-19 and mortality risk, SARS-CoV-2 infection in survivors with NCDs may also affect the progression of their pre-existing clinical conditions. Infection containment measures will have substantial short- and long-term consequences; social distancing and quarantine restrictions will reduce physical activity and increase other unhealthy lifestyles, thus increasing NCD risk factors and worsening clinical symptoms. Vitamin D levels might decrease and there might be a rise in mental health disorders. Many countries have made changes to routine management of NCD patients, e.g., cancelling non-urgent outpatient visits, which will have important implications for NCD management, diagnosis of new-onset NCDs, medication adherence, and NCD progression. We may have opportunities to learn from this unprecedented crisis on how to leverage healthcare technologies and improve procedures to optimize healthcare service provision. This article discusses how the COVID-19 outbreak and related infection control measures could hit the most frail individuals, worsening the condition of NCD patients, while further jeopardizing the sustainability of the healthcare systems. We suggest ways to define an integrated strategy that could involve both public institutional entities and the private sector to safeguard frail individuals and mitigate the impact of the outbreak.", "doc_id": "bcd0y9c1"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Optimisation of Vitamin D Status for Enhanced Immuno-protection Against Covid-19", "abstract": "", "doc_id": "kif5wp1r"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Considerations for Obesity, Vitamin D, and Physical Activity Amid the COVID-19 Pandemic", "abstract": "As the biomedical community races to disentangle the unknowns associated with severe acute respiratory syndrome coronavirus 2, the virus responsible for causing coronavirus disease, the link between diminished immune function and individuals with obesity raises important questions about the possibility for greater viral pathogenicity in this population. Increased adiposity may undermine the pulmonary microenvironment wherein viral pathogenesis and immune cell trafficking could contribute to a maladaptive cycle of local inflammation and secondary injury. A further challenge to those with obesity during the current pandemic may involve vitamin D deficiency or insufficiency. In the interest of personal and public health, we caution decision- and policy makers alike not to pin all hope on a proverbial \"silver bullet.\" Until further breakthroughs emerge, we should remember that modifiable lifestyle factors such as diet and physical activity should not be marginalized. Decades of empirical evidence support both as key factors promoting health and wellness.", "doc_id": "5n3ytru1"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Does vitamin D status impact mortality from SARS-CoV-2 infection?", "abstract": "", "doc_id": "9itdow8a"} {"topic_name": "Vitamin D and COVID-19", "topic_id": "42", "title": "Possible role of vitamin D in Covid-19 infection in pediatric population", "abstract": "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 \u00df-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.", "doc_id": "46aln4tk"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "COVID-19 and child and youth psychiatry", "abstract": "", "doc_id": "9tvy4cxv"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "COVID-19 pandemic and derogation to human rights", "abstract": "", "doc_id": "1dnmq8a8"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Navigating Uncertainty, Employment, and Women\u2019s Safety During COVID\u201019: Reflections of Sexual Assault Resistance Educators", "abstract": "COVID\u201019 affects women in ways unique to the impacts of structural inequalities related to gender, sexuality, disability, race, and socioeconomic status. In this article, we reflect on our own experiences of the pandemic, as feminist students, workers, and sexual assault resistance educators located in a Canadian post\u2010secondary setting. Situating ourselves within feminist responses to sexual violence prevention, as facilitators of the EAAA sexual assault resistance education program for university women, we reflect on the impacts of the COVID\u201019 pandemic on our work as EAAA facilitators in our Canadian university. We explore the theoretical possibilities that critical disability theory and queer theory present to the EAAA program, and argue that incorporating concepts from these frameworks will complement the goals of the EAAA program and improve inclusivity of queer, trans, and disabled participants. We conclude with a look into the future by anticipating the impacts of COVID\u201019 on our future work.", "doc_id": "5g14q9h8"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Impact of COVID-19 pandemic restrictions on community-dwelling caregivers and persons with dementia.", "abstract": "Restrictions related to the 2019 novel coronavirus (COVID-19) pose unique and significant challenges for community-dwelling caregivers and people with dementia, including disrupted routines, a lack of structure, decreased access to respite care, and new or worsening safety issues related to interpersonal violence and hygiene. In addition to identifying issues confronting caregivers, the authors also describe possible ways to address some of these pressing concerns. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "doc_id": "8kfb9alv"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Intimate partner violence in Greece: a study of 664 consecutive forensic clinical examinations.", "abstract": "BACKGROUND Intimate partner violence (IPV) is a well-known phenomenon, which affects mostly women. While IPV victims may attend emergency departments (EDs) seeking medical care, not all of them will make an allegation against their abusers. OBJECTIVE The aim of this study was to examine the prevalence and the characteristics of the victims, who had made an allegation about the violent incident and had been examined by a forensic pathologist for judicial purposes, and had attended EDs seeking medical care, before the forensic examination. METHODS We reviewed the archives of clinical examinations that were conducted at the Department of Forensic Medicine and Toxicology of National and Kapodistrian University of Athens during a 5-year period (2012-16). RESULTS Six hundred sixty-four clinical examinations were conducted at our Department for IPV allegations. According to our findings, women were more likely to seek medical care than men. Victims who have attended EDs were more likely to have sustained injuries located at least on the head or on the lower limbs. CONCLUSION The majority of IPV victims in the broader region of Attica (Greece) were women, usually married, and aged between 30 and 49 years old. Despite the fact that the majority of IPV incidents are not reported to police, every person who is engaged in the process of dealing with IPV victims has to be educated and adequately informed about this phenomenon, its implications and the possible ways to deal with it. Furthermore, victims need to be educated and informed adequately in waiting rooms of EDs.", "doc_id": "8v6dwgxw"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Home is not always a haven: The domestic violence crisis amid the COVID-19 pandemic.", "abstract": "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).", "doc_id": "54mxjzfc"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Domestic violence in the COVID-19 pandemic: a forensic psychiatric perspective.", "abstract": "", "doc_id": "j0w0yzbj"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "The Impact of Green Space on Violent Crime in Urban Environments: An Evidence Synthesis.", "abstract": "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.", "doc_id": "8ywevius"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Psychological interventions for common mental disorders in women experiencing intimate partner violence in low-income and middle-income countries: a systematic review and meta-analysis.", "abstract": "BACKGROUND Evidence on the effectiveness of psychological interventions for women with common mental disorders (CMDs) who also experience intimate partner violence is scarce. We aimed to test our hypothesis that exposure to intimate partner violence would reduce intervention effectiveness for CMDs in low-income and middle-income countries (LMICs). METHODS For this systematic review and meta-analysis, we searched MEDLINE, Embase, PsycINFO, Web of Knowledge, Scopus, CINAHL, LILACS, ScieELO, Cochrane, PubMed databases, trials registries, 3ie, Google Scholar, and forward and backward citations for studies published between database inception and Aug 16, 2019. All randomised controlled trials (RCTs) of psychological interventions for CMDs in LMICs which measured intimate partner violence were included, without language or date restrictions. We approached study authors to obtain unpublished aggregate subgroup data for women who did and did not report intimate partner violence. We did separate random-effects meta-analyses for anxiety, depression, post-traumatic stress disorder (PTSD), and psychological distress outcomes. Evidence from randomised controlled trials was synthesised as differences between standardised mean differences (SMDs) for change in symptoms, comparing women who did and who did not report intimate partner violence via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO, number CRD42017078611. FINDINGS Of 8122 records identified, 21 were eligible and data were available for 15 RCTs, all of which had a low to moderate risk of overall bias. Anxiety (five interventions, 728 participants) showed a greater response to intervention among women reporting intimate partner violence than among those who did not (difference in standardised mean differences [dSMD] 0\u00b731, 95% CI 0\u00b704 to 0\u00b757, I2=49\u00b74%). No differences in response to intervention were seen in women reporting intimate partner violence for PTSD (eight interventions, n=1436; dSMD 0\u00b714, 95% CI -0\u00b706 to 0\u00b733, I2=42\u00b76%), depression (12 interventions, n=2940; 0\u00b710, -0\u00b704 to 0\u00b725, I2=49\u00b73%), and psychological distress (four interventions, n=1591; 0\u00b707, -0\u00b705 to 0\u00b718, I2=0\u00b70%, p=0\u00b7681). INTERPRETATION Psychological interventions treat anxiety effectively in women with current or recent intimate partner violence exposure in LMICs when delivered by appropriately trained and supervised health-care staff, even when not tailored for this population or targeting intimate partner violence directly. Future research should investigate whether adapting evidence-based psychological interventions for CMDs to address intimate partner violence enhances their acceptability, feasibility, and effectiveness in LMICs. FUNDING UK National Institute for Health Research ASSET and King's IoPPN Clinician Investigator Scholarship.", "doc_id": "gll3lv5r"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Domestic violence during COVID-19: the GP role.", "abstract": "", "doc_id": "dwkwqz2f"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Crime in Italy at the time of the pandemic.", "abstract": "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.", "doc_id": "0jv5mnnl"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Violence against women in Italy during the COVID-19 pandemic.", "abstract": "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.", "doc_id": "4xq4otsd"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Coronavirus and interpersonal violence: A need for digital mental health resources.", "abstract": "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).", "doc_id": "0xc276mq"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "The hidden disaster of COVID-19: Intimate partner violence.", "abstract": "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).", "doc_id": "meey1l87"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Domestic violence amid COVID-19.", "abstract": "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.", "doc_id": "er50rvxw"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "I Can't Breathe - Race, Violence and COVID-19.", "abstract": "", "doc_id": "axiclq85"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Health care practitioners' responsibility to address intimate partner violence related to the COVID-19 pandemic.", "abstract": "", "doc_id": "cbv3yr77"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Amendment to the law to curb violence against doctors during the coronavirus disease 2019 crisis in India.", "abstract": "", "doc_id": "1qgibt2v"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Coronavirus and Quarantine: Catalysts of Domestic Violence.", "abstract": "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.", "doc_id": "427mkwsj"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "The intensive use of the internet by children and adolescents in the context of COVID-19 and the risks for self-inflicted violence.", "abstract": "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.", "doc_id": "me58dqhi"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Covid-19: EU states report 60% rise in emergency calls about domestic violence.", "abstract": "", "doc_id": "496v31lf"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Violence versus gratitude: Courses of recognition in caring situations.", "abstract": "Pandemic infection by COVID-19 could be changing the public image of the nursing profession in Italy. Recently, as in any western country, we were being registered with an increase in the number of violence against healthcare professionals. Nevertheless, due to pandemic in the social media, the nursing profession is remembered for competence, determination, courage, and humanity, and it is continually remercied by people, politicians, and journalists. In this paper, we will conduct a phenomenological argument that proposes both phenomena can be explained by Paul Ricoeur's courses of recognition. In cases of violence, patients and their family members reacting because they feel betrayed for a real or alleged injustice-primarily not to be listened to by health professionals. Nurses and other professionals are often unable to take the right grade of involvement for understanding patient's needs. On the other hand, during COVID-19 pandemic, patients and family members perceive the extraordinary daily work of caring, and they react thanking. The principle of the gift is implicated in both cases: the crisis of gift received or donated can be explaining violence; gratitude and thanks can be explaining by gratuitousness of care.", "doc_id": "bhosnbmj"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Twin public health emergencies: Covid-19 and domestic violence.", "abstract": "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.", "doc_id": "1h5a4bit"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "The increase in domestic violence during the social isolation: What does it reveals?/ Isolamento social e o aumento da viol\u00eancia dom\u00e9stica: O que isso nos revela?", "abstract": "The social isolation imposed by the COVID-19 pandemic brings out, in a empowered way, some worrying indicators about domestic violence and family violence against women. Organizations addressing domestic violence have already seen an increase in domestic violence due to forced coexistence, economic stress and fears about the Coronavirus. The article seeks to establish some relations between social isolation during the COVID-19 pandemic and the increase in violence against women, taking into account the context of a patriarchal society. Data, still incipient, published by the press of several countries were analyzed, as well as reports from international organizations and organizations focused on combating domestic violence. In parallel, a brief literature review with authors who discuss the social role of women in society.", "doc_id": "42o9qs47"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Children behind closed doors due to covid-19 isolation: Abuse, neglect and domestic violence/ Djeca iza zatvorenih vrata covid-19 izolacije: Zlostavljanje, zanemarivanje i nasilje u obitelji", "abstract": "Abuse and neglect of children is a public health issue at a global, European, and Croatian level, with significant rates of morbidity and mortality. Actual circumstances of a health crisis generate and aggravate a series of risk factors for child abuse and neglect at the level of the child and parent characteristics, family dy-namics and the wider social environment. Isolation and quarantine possibly leading to social exclusion, rep-resent a serious risk for child abuse and neglect, possibly also being the reason for fewer reports. This paper reviews clinical and empirical studies related to the rates of abuse and neglect of children during health and other crises in other countries. It also analyses trends of recent data of the Ministry of Interior with practical guidelines for improved child protection in this period.", "doc_id": "d9jjavx8"} {"topic_name": "violence during pandemic", "topic_id": "43", "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", "abstract": "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.", "doc_id": "c3xcmkuc"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Impact of COVID-19 Lockdown Policy on Homicide, Suicide, and Motor Vehicle Deaths in Peru", "abstract": "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.", "doc_id": "chmmxehj"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Firearm Purchasing and Firearm Violence in the First Months of the Coronavirus Pandemic in the United States", "abstract": "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.", "doc_id": "bmqt33yw"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Domestic violence and abuse, coronavirus, and the media narrative", "abstract": "Following lockdowns in countries around the world, reports emerged of a 'surge' or 'spikes' in the number of domestic violence and abuse cases It is critical to contextualise this: more men are not starting to be abusive or violent;rather, the patterns of abuse are becoming more frequent Spiking and surging make us think in terms of more one-off incidents but it is more likely that the pattern of abuse that is already there is increasing in terms of frequency and type because both parties remain together at all times Amid such a crisis, it is imperative that we continue to see the dynamics of domestic violence and abuse as both a pattern of abusive behaviours and a product of gendered social and cultural norms, rather than a reaction to a specific factor or event, such as COVID-19", "doc_id": "haps8x4u"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "COVID-19 and Intimate Partner Violence: A Call to Action.", "abstract": "The COVID-19 pandemic has escalated the risks and dangers for victims of Intimate Partner Violence (IPV). This article aims to describe the current state of IPV in Rhode Island as well as best practices for IPV screening and intervention using telehealth. We highlight the particular plight of undocumented immigrant victims of IPV and how healthcare providers can be responsive to their unique vulnerabilities and needs.", "doc_id": "bbu44tg2"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Elder Abuse in the Time of COVID-19-Increased Risks for Older Adults and Their Caregivers", "abstract": "", "doc_id": "3ba4p9bl"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Impact of COVID-19 pandemic restrictions on community-dwelling caregivers and persons with dementia", "abstract": "Restrictions related to the 2019 novel coronavirus (COVID-19) pose unique and significant challenges for community-dwelling caregivers and people with dementia, including disrupted routines, a lack of structure, decreased access to respite care, and new or worsening safety issues related to interpersonal violence and hygiene. In addition to identifying issues confronting caregivers, the authors also describe possible ways to address some of these pressing concerns. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "doc_id": "24io736v"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Can Homeopathy, a Particularly Mild Therapeutic Approach, Survive and Grow in a World of Violence?", "abstract": "This short treatise addresses a philosophical question concerning the place of homeopathy in our modern world. The question raised is whether a therapeutic system as peaceful, mild, and non-violent as homeopathy can survive and grow within a society that often displays the opposite characteristics.Much of contemporary society is more interested in fast and impressive cures, even if these may also bring side effects; whereas homeopathy can offer solutions with a personalized approach that requires long hours of case study by the homeopath to find the correct personal remedy that aims to bring about positive results, which the therapy can produce in deep chronic diseases.The conclusion drawn is that homeopathy does not readily fit within a modern and violent society that prefers quick and invasive solutions to its clinical problems.", "doc_id": "kj9xtdq4"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Surviving in place: The coronavirus domestic violence syndemic", "abstract": "", "doc_id": "037ctaef"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Association of COVID-19 With Intimate Partner Violence", "abstract": "", "doc_id": "dj2f88az"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Attacks against health-care personnel must stop, especially as the world fights COVID-19", "abstract": "", "doc_id": "h0l3dhg1"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "COVID-19 and Intimate Partner Violence: A Call to Action", "abstract": "The COVID-19 pandemic has escalated the risks and dangers for victims of Intimate Partner Violence (IPV) This article aims to describe the current state of IPV in Rhode Island as well as best practices for IPV screening and intervention using telehealth We highlight the particular plight of undocumented immigrant victims of IPV and how healthcare providers can be responsive to their unique vulnerabilities and needs", "doc_id": "cfwda1sw"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Domestic violence in the COVID-19 pandemic: a forensic psychiatric perspective", "abstract": "", "doc_id": "2oskze33"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Lockdown: more domestic accidents than COVID-19 in children", "abstract": "", "doc_id": "c1ckfou4"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Domestic Abuse during COVID-19: What about the boys?", "abstract": "", "doc_id": "1wxnuq6y"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Safety and services for survivors of intimate partner violence: A researcher-practitioner dialogue on the impact of COVID-19", "abstract": "This commentary offers a dialogue between a researcher and practitioner on the potential benefits of collaborative research to benefit survivors of intimate partner violence (IPV), a population exposed to high levels of violence and trauma. The dialogue occurred in a written, back-and-forth exchange, with the researcher and practitioner taking turns asking and responding to questions. The questions posed and answered in this commentary include: How are clients at an emergency domestic violence shelter experiencing the pandemic? How do you think a researcher or community member can help during a time like this? What should a researcher consider when engaging in collaborative research partnerships with service providers during this time? The answers offer insights into the importance of developing strong researcher-practitioner partnerships to improve services for trauma survivors during a global crisis. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "doc_id": "gqhbe860"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "COVID-19: Reducing the risk of infection might increase the risk of intimate partner violence", "abstract": "", "doc_id": "b1we9vls"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "COVID-19, domestic violence and abuse, and urgent dental and oral and maxillofacial surgery care", "abstract": "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.", "doc_id": "cf26y8t6"} {"topic_name": "violence during pandemic", "topic_id": "43", "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?", "abstract": "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).", "doc_id": "kzkorkcx"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "COVID-19 as a risk factor for obstetric violence", "abstract": "", "doc_id": "j29mia9l"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Gun violence during COVID-19 pandemic: Paradoxical trends in New York City, Chicago, Los Angeles and Baltimore", "abstract": "", "doc_id": "57k6dw89"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Violence against women in the covid-19 pandemic: we need upstream approaches to break the intergenerational cycle", "abstract": "", "doc_id": "6k956e5h"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Domestic violence during COVID-19: the GP role", "abstract": "", "doc_id": "2ik4mdls"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "The Urgent Need to Address Violence Against Health Workers During the COVID-19 Pandemic", "abstract": "", "doc_id": "fj5mkmgv"} {"topic_name": "violence during pandemic", "topic_id": "43", "title": "Rise in the incidence of abusive head trauma during the COVID-19 pandemic", "abstract": "", "doc_id": "6fd5mx31"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Interventions to prevent transmission of the common cold", "abstract": "Theoretically, there are several ways of preventing the common cold: quarantine, immunisation (or vaccination); early treatment of effected individuals; or physical barriers to reduce transmission. All these methods can be dismissed after considering the epidemiology of the common cold, apart from the last. Evidence for effectiveness for physical barriers (which include masks to reduce aerosol transmission; handwashing; and gloves and gowns) come from a variety of empirical studies. The chance of bias for these studies is variable, but we can conclude that all of these barrier methods have important potential for preventing transmission of the common cold, although some methods will not be acceptable to the community currently.", "doc_id": "019lj813"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Effectiveness of masks and respirators against respiratory infections in healthcare workers: A systematic review and meta-analysis", "abstract": "", "doc_id": "55se41f7"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "To masks, citizen!", "abstract": "", "doc_id": "xm35b1ml"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Face masks for community use: An awareness call to the differences in materials", "abstract": "See related Reply See related Reply", "doc_id": "j1ei5vqc"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Associations of Stay-at-Home Order and Face-Masking Recommendation with Trends in Daily New Cases and Deaths of Laboratory-Confirmed COVID-19 in the United States", "abstract": "BACKGROUND AND OBJECTIVES: Public health interventions have reduced coronavirus disease 2019 (COVID-19) transmission in several countries, but their impacts on COVID-19 epidemics in the USA are unclear. We examined associations of stay-at-home order (SAHO) and face-masking recommendation with COVID-19 epidemics in the USA. METHODS: In this quasi-experimental interrupted time-series study, we modeled temporal trends in daily new cases and deaths of laboratory-confirmed COVID-19 cases, and COVID-19 time-varying reproduction numbers in the USA between March 1 and April 20, 2020. In addition, we conducted simulation analyses. RESULTS: The number of residents under SAHO increased since March 19 and plateaued at 290,829,980 (88.6% of the U.S. population) on April 7. Trends in COVID-19 time-varying reproduction numbers peaked on March 23, further reduced on April 3, and fell below/around 1.0 on April 13. Early-implementation and early-lift of SAHO would reduce and increase COVID-19 epidemics, respectively. Multivariable piecewise log-linear regression revealed the states\u2019 neighboring relationship with New York was linked to COVID-19 daily new cases and deaths. There were two turning points in daily new-case trend, being March 28 (slope-changes = \u22120.09) and April 3 (slope-changes = \u22120.09), which appeared to be associated with implementation of SAHO on March 28 (affecting 48.5% of the US population in 22 states and District of Columbia), and face-masking recommendation on April 3, respectively. There were also two turning points in daily new-death trend, being April 9 (slope-changes = \u22120.06) and April 19 (slope-changes = \u22120.90). CONCLUSIONS: We identified two turning points of COVID-19 daily new cases or deaths in the USA, which seem to be linked to implementation of SAHO and the Center for Disease Control\u2019s face-masking recommendation.", "doc_id": "j1gi1cxu"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Face masks - a sustainable measure to mitigate COVID-19.", "abstract": "", "doc_id": "n18gp3wj"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Absence of in-flight transmission of SARS-CoV-2 likely due to use of face masks on board.", "abstract": "Using flights was severely affected during the COVID19 pandemic. We describe a 14 hours flight of 11 passengers and 4 crew members in which 2 positive SARS-COV-2 were on board. No new viral acquisitions found in this flight, probably due to the use of masks.", "doc_id": "vbjm87nc"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Universal Masking in the Covid-19 Era.", "abstract": "", "doc_id": "oh47zqod"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Respiratory virus shedding in exhaled breath and efficacy of face masks.", "abstract": "We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.", "doc_id": "g17lp8ch"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "COVID-19: The Need for Rational Use of Face Masks in Nigeria.", "abstract": "Because of the pandemic of COVID-19, the federal government of Nigeria has instituted a mandatory policy requiring everyone going out in public to wear face masks. Unfortunately, the Nigeria media is awash with images of misuse and abuse of face masks by the public, government officials, and healthcare workers. Medical masks are used widely in community settings amid reported scarcity within healthcare facilities. It is observed that some people wear face masks on their chin and neck, and mask wearers give no attention to covering their mouth and nose, especially when talking. Used face masks are kept with personal belongings or disposed indiscriminately in public spaces, leading to self and environmental contamination. Inappropriate use and disposal of face masks in Nigeria could promote the spread of the novel coronavirus in the country and negate the country's efforts to contain the COVID-19 pandemic. In the implementation of the universal masking policy in Nigeria, federal and state governments ought to consider local applicability, feasibility, and sustainability, as well as identify and mitigate all potential risks and unintended consequences. Also critical is the need for intensive public sensitization and education on appropriate use and disposal of face masks in the country.", "doc_id": "x5xijo8m"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Face masks in the covid-19 crisis: caveats, limits, and priorities.", "abstract": "", "doc_id": "amn0uj0i"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Efficacy of face masks depends on spatial relation between host and recipient and who is being protected.", "abstract": "", "doc_id": "njd5ygdq"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Face masks for all and all for face masks in the COVID-19 pandemic: community level production to face the global shortage and shorten the epidemic.", "abstract": "The current COVID-19 pandemic caused a global shortage of medical masks, leaving most exposed health personnel without appropriate protection.Since the beginning of the outbreak, the WHO has revised several times the recommendations on general use of facemasks. In various countries, the public was advised to wear facemasks, in order to ensure them to healthcare workers. Until recently, WHO recommended to limit the use of facemasks to symptomatic people and advised against off-standard solutions. Moreover, recommendations differ among and within countries, causing public confusion and individual initiative.There is wide consensus that universal appropriate use of masks may contribute both to contain the epidemic and to reduce the burden on national procurement, if a community production approach is followed. Especially in low-middle income countries, due to the scarce capacity of national industrial production or import, the use of masks produced at community level may become the only viable option.For the purpose ad hoc guidelines will be needed.Current knowledge and experience call for further and updated review of global and national guidelines in order to provide clear and consistent criteria to ensure the widest availability and appropriate use of facial protection, bearing in mind populations in socio-economic disadvantaged settings.", "doc_id": "krh7p1tg"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Let us not forget the mask in our attempts to stall the spread of COVID-19.", "abstract": "", "doc_id": "vkex8le2"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Effect of surgical masks worn concurrently over N95 filtering facepiece respirators: extended service life versus increased user burden.", "abstract": "Growing concern over the availability of Respiratory protective devices (eg, filtering facepiece Respirators), in the face of the probable extreme demand brought on by a pandemic influenza, has prompted the suggestion that useful life of N95 filtering facepiece Respirator can be extended by the concurrent use of a surgical mask as an outer protective barrier over the Respirator. Personal protective equipment generally places a strain on the user, and the detrimental physiological and psychological burdens normally imposed by Respirator use could be magnified by the addition of an extra layer of protection such as a surgical mask. The issue of this potentially increased burden of the concurrent use of a surgical facemask with an N95 filtering facepiece Respirator is investigated to afford users the necessary information to make informed decisions Regarding the use of this Respiratory personal protective equipment in the face of large-scale outbreaks of Respiratory pathogens.", "doc_id": "7h88y1fv"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Face masks for the public during covid-19: the more things change.", "abstract": "", "doc_id": "csh55i5g"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Covid-19: Important potential side effects of wearing face masks that we should bear in mind.", "abstract": "", "doc_id": "22xrjrsv"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Urgency and uncertainty: covid-19, face masks, and evidence informed policy.", "abstract": "", "doc_id": "gowus26i"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Downsides of face masks and possible mitigation strategies: a systematic review and meta-analysis", "abstract": "Objective To identify, appraise, and synthesise studies evaluating the downsides of wearing facemasks in any setting. We also discuss potential strategies to mitigate these downsides. Methods PubMed, Embase, CENTRAL, EuropePMC were searched (inception-18/5/2020), and clinical registries were searched via CENTRAL. We also did forward-backward citation search of the included studies. We included randomised controlled trials and observational studies comparing facemask use to any active intervention or to control. Two author pairs independently screened articles for inclusion, extracted data and assessed the quality of included studies. The primary outcomes were compliance, discomforts, harms, and adverse events of wearing facemasks. Findings We screened 5471 articles, including 37 (40 references); 11 were meta-analysed. For mask wear adherence, 47% more people wore facemasks in the facemask group compared to control; adherence was significantly higher (26%) in the surgical/medical mask group than in N95/P2 group. The largest number of studies reported on the discomfort and irritation outcome (20-studies); fewest reported on the misuse of masks, and none reported on mask contamination or risk compensation behaviour. Risk of bias was generally high for blinding of participants and personnel and low for attrition and reporting biases. Conclusion There are insufficient data to quantify all of the adverse effects that might reduce the acceptability, adherence, and effectiveness of face masks. New research on facemasks should assess and report the harms and downsides. Urgent research is also needed on methods and designs to mitigate the downsides of facemask wearing, particularly the assessment of alternatives such as face shields.", "doc_id": "ozr627rv"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "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.", "abstract": "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.", "doc_id": "ws8licyf"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Data-driven estimation of change points reveal correlation between face mask use and accelerated curtailing of the COVID-19 epidemic in Italy", "abstract": "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.", "doc_id": "papz6uoa"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "On the sensitivity of non-pharmaceutical intervention models for SARS-CoV-2 spread estimation", "abstract": "Introduction: A series of modelling reports that quantify the effect of non pharmaceutical interventions (NPIs) on the spread of the SARS-CoV-2 virus have been made available prior to external scientific peer-review. The aim of this study was to investigate the method used by the Imperial College COVID-19 Research Team (ICCRT) for estimation of NPI effects from the system theoretical viewpoint of model identifiability. Methods: An input-sensitivity analysis was performed by running the original software code of the systems model that was devised to estimate the impact of NPIs on the reproduction number of the SARS-CoV-2 infection and presented online by ICCRT in Report 13 on March 30 2020. An empirical investigation was complemented by an analysis of practical parameter identifiability, using an estimation theoretical framework. Results: Despite being simplistic with few free parameters, the system model was found to suffer from severe input sensitivities. Our analysis indicated that the model lacks practical parameter identifiability from data. The analysis also showed that this limitation is fundamental, and not something readily resolved should the model be driven with data of higher reliability. Discussion: Reports based on system models have been instrumental to policymaking during the SARS-CoV-2 pandemic. With much at stake during all phases of a pandemic, we conclude that it is crucial to thoroughly scrutinise any SARS-CoV-2 effect analysis or prediction model prior to considering its use as decision support in policymaking. The enclosed example illustrates what such a review might reveal.", "doc_id": "2zkrbjqe"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Quantifying Respiratory Airborne Particle Dispersion Control Through Improvised Reusable Masks", "abstract": "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.", "doc_id": "nt378esz"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Examining the protection efficacy of face shields against cough aerosol droplets using water sensitive papers", "abstract": "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.", "doc_id": "5b9jytph"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Modelling interventions to control COVID-19 outbreaks in a refugee camp", "abstract": "Refugee camp populations are expected to be vulnerable to COVID-19 due to overcrowding, unsanitary conditions, and inadequate medical facilities. Because there has been no COVID-19 outbreak in a refugee camp to date, the potential for nonpharmaceutical interventions to slow the spread of COVID-19 in refugee camps remains untested. We used an agent-based model to simulate COVID-19 outbreaks in the Moria refugee camp, and we studied the effects of feasible interventions. Subdividing the camp ('sectoring') \"flattened the curve,\" reducing peak infection by up to 70% and delaying peak infection by up to several months. The use of face masks coupled with efficient isolation of infected individuals reduced the overall incidence of infection and sometimes averted epidemics altogether. These interventions must be implemented quickly to be effective. Lockdowns had little effect on COVID-19 dynamics. Our findings provide an evidence base for camp managers planning intervention strategies against COVID-19 or future epidemics.", "doc_id": "5ifwxwlo"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Study of Air Curtain in Context of Individual Protection from Exposure to Coronavirus (SARS-CoV-2) Contained in Cough-Generated Fluid Particles", "abstract": "The ongoing respiratory COVID-19 pandemic has heavily impacted the social and private lives of the majority of the global population. This infection is primarily transmitted via virus-laden fluid particles (i.e., droplets and aerosols) that are formed in the respiratory tract of infected individuals and expelled from the mouth in the course of breathing, talking, coughing, and sneezing. To mitigate the risk of virus transmission, in many places of the world, the public has been asked or even obliged to use face covers. It is plausible that in the years ahead we will see the use of face masks, face shields and respirators become a normal practice in our life. However, wearing face covers is uncomfortable in some situations, like, for example, in summer heat, while staying on beaches or at hotel swimming pools, doing exercises in gyms, etc. Also, most types of face cover become contaminated with time and need to be periodically replaced or disinfected. These nuisances are caused by the fact that face covers are based on material barriers, which prevent inward and outward propagation of aerosol and droplets containing the pathogen. Applying well established gas-particle flow formalism, we study a non-material based protection barrier created by a flow of well directed down stream of air across the front of the open face. The~protection is driven by dragging virus-laden particles inside the width of the air flow and hence, as a consequence, displacing them away from their primary trajectories. The study, shows that such, potentially portable, air curtains can effectively provide both inward and outward protection and serve as an effective personal protective equipment (PPE) mitigating human to human transmission of virus infection like COVID-19.", "doc_id": "4zrwxcwv"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Filtration Efficiencies of Nanoscale Aerosol by Cloth Mask Materials Used to Slow the Spread of SARS-CoV-2", "abstract": "Filtration efficiency (FE), differential pressure (ΔP), quality factor (QF), and construction parameters were measured for 32 cloth materials (14 cotton, 1 wool, 9 synthetic, 4 synthetic blends, and 4 synthetic/cotton blends) used in cloth masks intended for protection from the SARS-CoV-2 virus (diameter 100 \u00b1 10 nm). Seven polypropylene-based fiber filter materials were also measured including surgical masks and N95 respirators. Additional measurements were performed on both multilayered and mixed-material samples of natural, synthetic, or natural-synthetic blends to mimic cloth mask construction methods. Materials were microimaged and tested against size selected NaCl aerosol with particle mobility diameters between 50 and 825 nm. Three of the top five best performing samples were woven 100% cotton with high to moderate yarn counts, and the other two were woven synthetics of moderate yarn counts. In contrast to recently published studies, samples utilizing mixed materials did not exhibit a significant difference in the measured FE when compared to the product of the individual FE for the components. The FE and ΔP increased monotonically with the number of cloth layers for a lightweight flannel, suggesting that multilayered cloth masks may offer increased protection from nanometer-sized aerosol with a maximum FE dictated by breathability (i.e., ΔP).", "doc_id": "9bqzvbmi"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Filtration Efficiencies of Nanoscale Aerosol by Cloth Mask Materials Used to Slow the Spread of SARS CoV-2", "abstract": "Filtration efficiency (FE), differential pressure (ΔP), quality factor (QF) and construction parameters were measured for 32 cloth materials (14 cotton, 1 wool, 9 synthetic, 4 synthetic blends, and 4 synthetic/cotton blends) used in cloth masks intended for protection from the SARS CoV-2 virus (diameter 100 \u00b1 10 nm). Seven polypropylene-based fiber filter materials were also measured, including surgical masks and N95 respirators. Additional measurements were performed on both multi-layered and mixed-material samples of natural, synthetic, or natural-synthetic blends to mimic cloth mask construction methods. Materials were micro-imaged and tested against size selected NaCl aerosol with particle mobility diameters between 50 nm and 825 nm. Three of the top five best performing samples were woven 100% cotton with high to moderate yarn counts and the other two were woven synthetics of moderate yarn counts. In contrast to recently published studies, samples utilizing mixed materials did not exhibit a significant difference in the measured FE when compared to the product of the individual FE for the components. The FE and ΔP increased monotonically with the number of cloth layers for a lightweight flannel, suggesting that multi-layered cloth masks may offer increased protection from nanometer-sized aerosol with a maximum FE dictated by breathability (i.e. ΔP).", "doc_id": "t2lg125x"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "The history and value of face masks", "abstract": "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.", "doc_id": "jyju71r1"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Importance of face masks for COVID-19 - a call for effective public education", "abstract": "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\".", "doc_id": "wee1133a"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Are face masks useful for limiting the spread of COVID-19?", "abstract": "", "doc_id": "kyv9lw5d"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Wearing face masks regardless of symptoms is crucial for preventing the spread of COVID-19 in hospitals", "abstract": "", "doc_id": "st7c4v9v"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Mask wearing to complement social distancing and save lives during COVID-19", "abstract": "", "doc_id": "0z3vfou2"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Respiratory virus shedding in exhaled breath and efficacy of face masks", "abstract": "We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.", "doc_id": "jvlun85u"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "COVID-19: Face masks and human-to-human transmission", "abstract": "", "doc_id": "j3ad9lj2"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Americans are told to wear cloth masks", "abstract": "", "doc_id": "4animmli"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Flexible Nanoporous Template for the Design and Development of Reusable Anti-COVID-19 Hydrophobic Face Masks", "abstract": "Since the outbreak of the severe respiratory disease caused by the novel coronavirus (COVID-19), the use of face masks has become ubiquitous worldwide to control the rapid spread of this pandemic. As a result, the world is currently facing a face mask shortage, and some countries have placed limits on the number of masks that can be bought by each person. Although the surgical grade N95 mask provides the highest level of protection currently available, its filtration efficiency for sub-300 nm particles is around 85% due to its wider pore size (\u00e2\u0088\u00bc300 nm). Because the COVID-19 virus shows a diameter of around 65-125 nm, there is a need for developing more efficient masks. To overcome these issues, we demonstrate the development of a flexible, nanoporous membrane to achieve a reusable N95 mask with a replaceable membrane and enhanced filtration efficiency. We first developed a flexible nanoporous Si-based template on a silicon-on-insulator wafer using KOH etching and then used the template as a hard mask during a reactive ion etching process to transfer the patterns onto a flexible and lightweight (<0.12 g) polymeric membrane. Pores with sizes down to 5 nm were achieved with a narrow distribution. Theoretical calculations show that airflow rates above 85 L/min are possible through the mask, which confirms its breathability over a wide range of pore sizes, densities, membrane thicknesses, and pressure drops. Finally, the membrane is intrinsically hydrophobic, which contributes to antifouling and self-cleaning as a result of droplets rolling and sliding on the inclined mask area.", "doc_id": "iynumlk0"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "COVID-19: The Need for Rational Use of Face Masks in Nigeria", "abstract": "Because of the pandemic of COVID-19, the federal government of Nigeria has instituted a mandatory policy requiring everyone going out in public to wear face masks. Unfortunately, the Nigeria media is awash with images of misuse and abuse of face masks by the public, government officials, and healthcare workers. Medical masks are used widely in community settings amid reported scarcity within healthcare facilities. It is observed that some people wear face masks on their chin and neck, and mask wearers give no attention to covering their mouth and nose, especially when talking. Used face masks are kept with personal belongings or disposed indiscriminately in public spaces, leading to self and environmental contamination. Inappropriate use and disposal of face masks in Nigeria could promote the spread of the novel coronavirus in the country and negate the country's efforts to contain the COVID-19 pandemic. In the implementation of the universal masking policy in Nigeria, federal and state governments ought to consider local applicability, feasibility, and sustainability, as well as identify and mitigate all potential risks and unintended consequences. Also critical is the need for intensive public sensitization and education on appropriate use and disposal of face masks in the country.", "doc_id": "1lugzjbv"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Wearing masks and the fight against the novel coronavirus (COVID-19)", "abstract": "", "doc_id": "s65ffpf1"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "A reality check on the use of face masks during the COVID-19 outbreak in Hong Kong", "abstract": "", "doc_id": "056hmnru"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Universal masking for COVID-19: evidence, ethics and recommendations", "abstract": "", "doc_id": "plw522ux"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Community Use Of Face Masks And COVID-19: Evidence From A Natural Experiment Of State Mandates In The US", "abstract": "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.].", "doc_id": "h2ahzau7"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Face masks in the covid-19 crisis: caveats, limits, and priorities", "abstract": "", "doc_id": "g5jd0rmr"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "The use of facemasks may not lead to an increase in hand-face contact", "abstract": "Advocacy of the use of facemasks by the public as a measure against the spread of COVID-19 is controversial, with some healthcare professionals arguing that the use of a face mask may increase the rate at which people touch their faces, due to readjusting the mask. We assessed the facial touching behaviour of bus passengers in China before and after the outbreak of COVID-19 and found that wearing a face mask does not increase the number of hand-face contacts and is likely, therefore, to have a positive beneficial effect on suppressing the spread of COVID-19 within populations when used in conjunction with social distancing measures.", "doc_id": "gaujhk7z"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "The role of masks and respirator protection against SARS-CoV-2", "abstract": "", "doc_id": "a0c914om"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Practice and technique of using face mask amongst adults in the community: a cross-sectional descriptive study", "abstract": "BACKGROUND: The proper use of face mask comprises the correct practice and wearing technique and is important in preventing the spread of respiratory infections. Previous studies have addressed only the aspect of practice and failed to provide a detailed account of face mask usage amongst community-based populations. This study examined the practice and technique of using face mask amongst adults. METHODS: A cross-sectional descriptive design was adopted. A quota sample of 1500 adults was recruited in Hong Kong during a nonepidemic state between January and February 2017. The participants' practice of using face mask in five given situations was assessed using a questionnaire. Their technique in using face mask, including 12 steps, was assessed using an observation checklist. Statistical tests were used to compare the differences in practice and technique amongst adults of different gender and age groups. RESULTS: Findings revealed that the performance of the participants in both categories was unsatisfactory. In terms of practice, less than one-fifth of the participants reported that they always wore face mask when taking care of family members with fever (14.7%) or respiratory infections (19.5%). Male adults and those aged 55-64 reported low frequency in using face mask during required situations. In terms of technique, none of the participants performed all the required steps in using face mask correctly. More than 90% of the participants did not perform hand hygiene before putting on (91.5%), taking off (97.3%), or after disposing (91.5%) face mask. Adults aged 55 and above performed poorer than adults in the younger age groups. CONCLUSION: Compared with previous findings obtained during an epidemic, the performance of the participants during a nonepidemic state was less satisfactory. The possibility of developing fatigue after exposure to repeated epidemics was discussed. This study contributes to a comprehensive understanding of the use of face mask in a community and reveals the underperformed areas. Effort is required to enhance the proper practice of using face mask, convey the message that hand hygiene is an essential step in wearing and taking off a face mask and increase the public's general concern in the value of using face mask.", "doc_id": "1558088w"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Role of mask/respirator protection against SARS-CoV-2", "abstract": "", "doc_id": "4gdxnnj5"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Efficacy of face masks depends on spatial relation between host and recipient and who is being protected", "abstract": "", "doc_id": "idulb2bm"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "Autoclave Sterilization and Ethanol Treatment of Re-used Surgical Masks and N95 Respirators during COVID-19: Impact on their Performance and Integrity", "abstract": "BACKGROUND: An exceptionally high demand for surgical masks and N95 filtering facepiece respirators (FFRs) during the COVID-19 pandemic has considerably exceeded their supply. These disposable devices are generally not approved for routine decontamination and re-use as standard of care while this practice has widely occurred in hospitals. The US Centers for Disease Control and Prevention allowed it \"as a crisis capacity strategy.\" However, limited testing was conducted on the impact of specific decontamination methods on the performance of N95 FFRs and no data was presented for surgical masks. AIM: We evaluated common surgical masks and N95 respirators with respect to the changes in their performance and integrity resulting from autoclave sterilization and a 70% ethanol treatment; these methods are frequently utilized for re-used filtering facepieces in hospitals. METHODS: The filter collection efficiency and pressure drop were determined for unused masks and N95 FFRs, and for those subjected to the treatments in a variety of ways. The collection efficiency was measured for particles of approximately 0.037-3.2 \u00b5m to represent aerosolized single viruses, their agglomerates, bacteria and larger particles carriers. FINDINGS: The initial collection efficiency and the filter breathability may be compromised by sterilization in an autoclave and ethanol treatment. The effect depends on a protective device, particle size, breathing flow rate, type of treatment and other factors. Additionally, physical damages were observed in N95 respirators after autoclaving. CONCLUSION: Strategies advocating decontamination and re-use of filtering facepieces in hospitals should be re-assessed considering the data obtained in this study.", "doc_id": "7r8i4u0c"} {"topic_name": "impact of masks on coronavirus transmission", "topic_id": "44", "title": "A pilot study of the impact of facial skin protectants on qualitative fit testing of N95 masks", "abstract": "", "doc_id": "kdp3yx7h"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Engaging in Late-Life Mental Health Research: a Narrative Review of Challenges to Participation", "abstract": "PURPOSE OF REVIEW: This narrative review seeks to ascertain the challenges older patients face with participation in mental health clinical research studies and suggests creative strategies to minimize these obstacles. RECENT FINDINGS: Challenges to older adults\u2019 engagement in mental health research include practical, institutional, and collaboration-related barriers applicable to all clinical trials as well as more personal, cultural, and age-related patient barriers specific to geriatric mental health research. Universal research challenges include (1) institutional barriers of lack of funding and researchers, inter-researcher conflict, and sampling bias; (2) collaboration-related barriers involving miscommunication and clinician concerns; and (3) practical patient barriers such as scheduling issues, financial constraints, and transportation difficulties. Challenges unique to geriatric mental health research include (1) personal barriers such as no perceived need for treatment, prior negative experience, and mistrust of mental health research; (2) cultural barriers involving stigma and lack of bilingual or culturally matched staff; and (3) chronic medical issues and concerns about capacity. SUMMARY: Proposed solutions to these barriers include increased programmatic focus on and funding of geriatric psychiatry research grants, meeting with clinical staff to clarify study protocols and eligibility criteria, and offering transportation for participants. To minimize stigma and mistrust of psychiatric research, studies should devise community outreach efforts, employ culturally competent bilingual staff, and provide patient and family education about the study and general information about promoting mental health.", "doc_id": "0wi340kp"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Impact of SARS-CoV-2 (Coronavirus) Pandemic on Public Mental Health", "abstract": "", "doc_id": "2ltfs6f6"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Editorial Perspective: COVID\u201019 pandemic\u2010related psychopathology in children and adolescents with mental illness", "abstract": "The coronavirus disease (COVID\u201019) pandemic is likely to have negative health consequences way beyond those caused by the virus per se \u2013 including significant psychological distress. Children and adolescents who already live with a mental illness may be particularly vulnerable to the distress associated with the pandemic \u2013 due to, for example, fear of the virus as well as the significant societal changes launched to minimize spread of the virus (social distancing and quarantine). In this editorial perspective, we (a) provide data on COVID\u201019 pandemic\u2010related psychopathology in children and adolescents from a large psychiatric treatment setting in Denmark, (b) give advice on how the likely harmful effects of the COVID\u201019 pandemic on the mental health of children and adolescents may be minimized, and (c) propose six lines of research into pandemic\u2010related psychopathology with emphasis on children and adolescents. Finally, we underline the necessity of politicians, health authorities, and funding bodies supporting these research initiatives here and now.", "doc_id": "21bghq0n"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "The COVID-19 pandemic in Australia: Lessons learnt.", "abstract": "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).", "doc_id": "3w4g6z5o"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "A population mental health perspective on the impact of COVID-19.", "abstract": "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).", "doc_id": "4q1j6g44"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "The effect of the COVID-19 pandemic on healthcare workers' mental health.", "abstract": "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.", "doc_id": "436hvwtr"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "[The Impact of the COVID-19 Pandemic on Mental Health].", "abstract": "", "doc_id": "1m5juaqg"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "The mental turmoil of hospital nurses in the COVID-19 pandemic.", "abstract": "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).", "doc_id": "1nqa3egs"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "The immediate impact of the 2019 novel coronavirus (COVID-19) outbreak on subjective sleep status.", "abstract": "BACKGROUND An outbreak of the 2019 novel coronavirus (COVID-19) has been ongoing in China since January 2020. The threat of infection affects the work and life of most of the population and may also damage sleep. This study aims to examine the subjective sleep status and mental health of the population during the peak of the COVID-19 epidemic. METHOD The data were collected through an online questionnaire with a sample of 5461 individuals in China from February 5, 2020, to February 23, 2020. Participants were divided into four groups based on their degree of threat from COVID-19: Group 1 was most closely associated with COVID-19, including inpatients diagnosed with COVID-19, first-line hospital workers and first-line management staff; Group 2 included outpatients diagnosed with COVID-19 and patients who developed a fever and visited the hospital; Group 3 included people related to Group 1 or 2, such as their colleagues, relatives, friends and rescuers; and Group 4 was the farthest removed from contact with COVID-19, covering the general public affected by COVID-19 prevention strategies. The Insomnia Severity Index (ISI), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7) and Acute Stress Disorder Scale (ASDS) were used. RESULTS Threat degree of COVID-19 (groups) had significant correlations with insomnia, depression, anxiety, and stress (p < 0.05, p < 0.01). Age, gender, and area (Hubei province or other provinces) had significant correlations with insomnia (p < 0.01). A total of 1380 (24.46%) participants were suspected of having major depression based on the PHQ-9. Additionally, 1042 (18.47%) participants were suspected of having generalized anxiety disorder based on the GAD-7. A total of 892 (15.8%) of the participants had Acute Stress Disorder (ASD) according to the ASDS. The prevalence of clinical insomnia during the outbreak was 20.05% (1131) according to the ISI. The factors of satisfaction with the current sleep pattern and how perceptible the symptoms of the current sleep pattern are to other people (p < 0.05) and the middle (difficulty staying asleep) and terminal (waking up too early) (p < 0.01) factors of the ISI were significantly different across groups. A total of 1129 (20.01%) participants spent more than one hour awake in bed. CONCLUSION The results indicated that insomnia is more severe in people who are female, young, living in the epicenter and experiencing a high degree of threat from COVID-19. As prevention and treatment efforts continue with regard to COVID-19, the general public has developed poor sleep hygiene habits, which deserve attention.", "doc_id": "0l1jubg5"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Job Insecurity and Financial Concern during the COVID-19 Pandemic are Associated with Worse Mental Health.", "abstract": "OBJECTIVE To determine whether job insecurity due to COVID-19 and financial concern were associated with worse mental health during the COVID-19 pandemic. METHOD Participants (N = 474 employed U.S. individuals) completed an online survey from April 6-12, 2020. Linear regressions were used to examine factors associated with mental health. RESULTS After accounting for demographic characteristics, health status, other COVID-19 experiences, and anxiety symptoms, greater job insecurity due to COVID-19 was related to greater depressive symptoms. Conversely, after accounting for covariates and depressive symptoms, greater financial concern was related to greater anxiety symptoms. Further, greater job insecurity was indirectly related to greater anxiety symptoms due to greater financial concern. CONCLUSIONS Findings suggest that employers should aim to reduce job insecurity and financial concern among employees during the COVID-19 pandemic to address the associated mental health consequences.", "doc_id": "4o19opfb"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Pandemic Anxiety: How Can I Help?", "abstract": "The COVID-19 pandemic has aroused a level of anxiety and uncertainty that spans demographics and diagnoses. Because the coronavirus is a novel variant, the expert scientific community presents to the public as uncertain and inconsistent in information and ways to deal with potential infection, which creates disbelief and uncertainty. The most consistent recommendation is physical distancing and self-imposed isolation to reduce the spread. However, such isolation also adds to individual and community distress. This column focuses on the neurobiological explanations for anxiety, complications to pre-existing psychiatric disorders, sub diagnostic states of stress and anxiety generally and with health care providers, and pharmacological and nonpharmacological ways of addressing this anxiety. [Journal of Psychosocial Nursing and Mental Health Services, 58(7), 7-10.].", "doc_id": "3ke51mtz"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Fear and agony of the pandemic leading to stress and mental illness: An emerging crisis in the novel coronavirus (COVID-19) outbreak.", "abstract": "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.", "doc_id": "20bgev65"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Trajectories of depression and anxiety during enforced isolation due to COVID-19: longitudinal analyses of 59,318 adults in the UK with and without diagnosed mental illness", "abstract": "Background: There is currently major concern about the impact of the global COVID-19 outbreak on mental health. A number of studies suggest that mental health deteriorated in many countries prior to enforced isolation (lockdown), but it remains unknown how mental health has changed during lockdown. Aims: This study explored trajectories of anxiety and depression over the first two months of lockdown using data from the UK, and compared the experiences of individuals with and without diagnosed mental illness. Methods: Data from 53,328 adults in the UCL COVID -19 Social Study (a well-stratified panel study weighted to population proportions collecting data weekly during the Covid-19 pandemic) were analysed from 21/03/2020-10/05/2020. Growth curve modelling was fitted accounting for socio-demographic and health covariates. Results: 24.4% of the sample had scores indicating moderate-severe anxiety, and 31.4% indicating moderate-severe depressive symptoms. Over the first two months of lockdown, there was only a slight decrease in anxiety levels amongst participants as a whole and a very small decrease in depression levels between weeks 3-6 that then increased again in weeks 7-8. Adults with pre-existing diagnoses of mental health conditions had higher levels of anxiety and depression but there was no evidence of widening inequalities in mental health experiences compared to people without existing mental illness. Conclusions: Results suggest there has been little improvement in depression and only slight improvements in anxiety since lockdown commenced in the UK. These findings suggest greater efforts need to be made to help individuals manage their mental health during the pandemic.", "doc_id": "3gxgruuo"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "How can the COVID-19 response advance global mental health?", "abstract": "", "doc_id": "14pnjakz"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "The impact of SARS-CoV-2 transmission fear and COVID-19 pandemic on the mental health of patients with primary immunodeficiency disorders, severe asthma, and other high-risk groups", "abstract": "Background: The adverse effects of COVID-19 pandemic on the mental health of high-risk group patients for morbidity and mortality and its impact on public health in the long term have not been clearly determined. Objective: To determine the level of COVID-19 related transmission fear and anxiety in healthcare workers and patients with primary immunodeficiency disorder (PID), severe asthma, and the ones with other comorbidities. Methods: The healthcare workers and patients with PID, severe asthma (all patients receiving biological agent treatment), malignancy, cardiovascular disease, hypertension (90% of patients receiving ACEI or ARB therapy), diabetes mellitus (42 % of patients receiving DPP-4 inhibitor therapy) were included in the study. A total of 560 participants, 80 individuals in each group, were provided. The hospital anxiety and depression scale ( HADS ) and Fear of illness and virus evaluation (FIVE ) scales were applied to the groups with face to face interview methods. Results: The mean age was 49.30 years and 306 (55 %) were female. The FIVE Scale and HADS-A scale scores of health care workers were significantly higher than other groups' scores (p = 0.001 and 0.006). The second-highest scores belonged to patients with PID. There was no significant difference between the groups for the HADS-D score (p=0.07). The lowest score in all scales was observed in patients with hypertension. Conclusions: This study demonstrated that in the pandemic process, patients with primary immunodeficiency, asthma patients, and other comorbid patients, especially healthcare workers, should be referred to the centers for the detection and treatment of mental health conditions.", "doc_id": "08siqoqc"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "COVID-19 pandemic and lockdown measures impact on mental health among the general population in Italy. An N=18147 web-based survey.", "abstract": "Background The psychological impact of the COronaVIrus Disease 2019 (COVID-19) outbreak and lockdown measures on the Italian population are unknown. The current study assesses rates of mental health outcomes in the Italian general population three to four weeks into lockdown measures and explores the impact of COVID-19 related potential risk factors. Methods A web-based survey spread throughout the internet between March 27th and April 6th 2020. 18147 individuals completed the questionnaire, 79.6% women. Selected outcomes were post-traumatic stress symptoms (PTSS), depression, anxiety, insomnia, perceived stress and adjustment disorder symptoms (ADS). Seemingly unrelated logistic regression analysis was performed to identify COVID-19 related risk factors. Results Respondents endorsing PTSS, depression, anxiety, insomnia, high perceived stress and adjustment disorder were 6604 (37%), 3084 (17.3%), 3700 (20.8%), 1301 (7.3%), 3895 (21.8%) and 4092 (22.9%), respectively. Being woman and younger age were associated with all of the selected outcomes. Quarantine was associated with PTSS, anxiety and ADS. Any recent COVID-related stressful life event was associated with all the selected outcomes. Discontinued working activity due to the COVID-19 was associated with all the selected outcomes, except for ADS; working more than usual was associated with PTSS, Perceived stress and ADS. Having a loved one deceased by COVID-19 was associated with PTSS, depression, perceived stress and insomnia. Conclusion We found high rates of negative mental health outcomes in the Italian general population three weeks into the COVID-19 lockdown measures and different COVID-19 related risk factors. These findings warrant further monitoring on the Italian population s mental health.", "doc_id": "4cps22s7"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Psychological Impact of COVID-19 on Pakistani University Students and How They Are Coping", "abstract": "Background: COVID-19 is spreading quickly, causing great deal of fear and unrest in the public. Methods: This web-based, cross-sectional study was conducted among students of four renowned Pakistani education institutions. Google forms were used to disseminate the online questionnaire to assess anxiety (generalized anxiety disorder 7-item scale), depression (9-item patient health questionnaire), sources of distress (14-items) and the coping strategies (Brief-COPE). Results: A total of 1134 responses (age 21.7 {+/-} 3.5 years, 70.5% females) were included. The frequency of students having moderate-severe anxiety and depression (score [\u2265] 10) were {approx} 34% and 45%, respectively. The respondents aged [\u2265] 31 years had significantly lower depression score than those below 30 years. Males had significantly less anxiety and depression scores than females. Additionally, those having a family member, friend or acquaintance infected with disease had significantly higher anxiety score. The main sources of distress were related to adverse effects of ongoing pandemic on daily life followed by the rapid disease spread. Regarding coping strategies, majority of respondents were found to have adopted religious/spiritual coping followed by acceptance. Conclusions: COVID-19 have significant adverse impact on students' mental health. The most frequent coping strategy adopted by them are religious/spiritual coping, acceptance, self-distraction and active coping. It is suggested that mental health of students should not be neglected during epidemics.", "doc_id": "10n7jr6q"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Using past and current data to estimate potential crisis service use in mental healthcare after the COVID-19 lockdown: South London and Maudsley data", "abstract": "The lockdown policy response to the COVID-19 pandemic in the UK has a potentially important impact on provision of mental healthcare with uncertain consequences over the 12 months ahead. Past activity may provide a means to predict future demand. Taking advantage of the Clinical Record Interactive Search (CRIS) data resource at the South London and Maudsley NHS Trust (SLaM; a large mental health service provider for 1.2m residents in south London), we carried out a range of descriptive analyses to inform the Trust on patient groups who might be most likely to require inpatient and home treatment team (HTT) crisis care. We considered the 12 months following UK COVID-19 lockdown policy on 16th March, drawing on comparable findings from previous years, and quantified levels of change in service delivery to those most likely to receive crisis care. For 12-month crisis days from 16th March in 2015-19, we found that most (over 80%) were accounted for by inpatient care (rather than HTT), most (around 75%) were used by patients who were current or recent Trust patients at the commencement of follow-up, and highest numbers were used by patients with a previously recorded schizophreniform disorder diagnosis. For current/recent patients on 16th March there had been substantial reductions in use of inpatient care in the following 31 days in 2020, more than previous years; changes in total non-inpatient contact numbers did not differ in 2020 compared to previous years, although there had been a marked switch from face-to-face to virtual contacts.", "doc_id": "3cwffe0i"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "The King's College London Coronavirus Health and Experiences of Colleagues at King's Study (KCL CHECK) protocol paper: a platform for study of the effects of coronavirus pandemic on staff and postgraduate students.", "abstract": "Introduction We will use an occupational sample to study the impact of COVID-19 on current staff and postgraduate research students at a large UK university. The cohort study will address some of the key questions about COVID-19 for the international community, while also providing feedback to the employer and educator. Methods and analysis Participants were recruited via email to their University email address. Administrative records were available to compare the composition of volunteer participants to underlying staff and postgraduate student populations of the University. The study comprises a baseline survey, longitudinal follow-up surveys and a viral antibody study. Baseline information was collected in April 2020 including demographics, working situation, current stresses and worries, mental health and neurological symptoms. Personal experiences of COVID-19, indirect experiences and attitudes towards the pandemic were queried, as well as satisfaction with communication and support at work. Longitudinal surveys will assess changes in COVID-19 exposure and mental health. A viral antibody detection component is being planned and will also be longitudinal in nature. Ethics and dissemination Ethical approval has been gained from KCL's Psychiatry, Nursing and Midwifery Research Ethics Committee (HR-19/20-18247). Participants were provided with information and agreed to a series of consent statements before enrolment. Data are kept on secure servers with access to personally identifiable information limited. Researchers may apply to have access to pseudonymised data. Findings will be disseminated internally to the University and participants, and externally through scientific publications.", "doc_id": "3wc2xkh1"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "FACTORS INFLUENCING MENTAL HEALTH DURING COVID-19 OUTBREAK: AN EXPLORATORY SURVEY AMONG INDIAN POPULATION", "abstract": "Purpose: Research on the impact of social distancing on mental health during epidemics is limited, especially in India. The purpose of this study is to scale the association between anxiety and socio-demographic factors during Covid19 lockdown among the general Indian population. Design/methodology/approach: A descriptive cross-sectional nationwide study was designed to enrol the general population. The inclusion criteria for this study were Indian citizens aged 15 years and above. The study was conducted from 29th March to 12th April 2020, using an online google questionnaire. The anxiety among respondents was detected and measured using a Generalised Anxiety Disorder Scale which consists of 7 questions (in English), i.e. GAD-7. Findings: Respondees were 398, and from these participants, the prevalence of anxiety was 25.4 per cent. Based on the bivariate logistic regression analysis, the predictors of anxiety were gender, religion, occupation as business/self- employed, marital status, family size, health status and sleep deprivation. Conclusion: This study reports the prevalence of anxiety among Indian population who were grounded at their homes during lockdown due to coronavirus pandemic in the country. Limitations: (1) The selection of participants through non-random sampling. (2) Because of the cross-sectional character of the study, causal conclusions cannot be drawn. Originality/Value: This paper fulfils an identified need to study the mental health status of the population under situations like lockdown, thereby helping fill a persistent gap in Indian research on this issue. Keywords: Anxiety, GAD-7, Lockdown, Coronavirus, Isolation, India", "doc_id": "006k39tj"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Mental Health Impact of COVID-19: A global study of risk and resilience factors", "abstract": "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.", "doc_id": "3qgknhmv"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Psychological Stress and Gender Differences during COVID-19 Pandemic in Chinese Population", "abstract": "Background The COVID-19 disease has been spreading for more than four months in China and been pronounced as a pandemic by the World Health Organization (WHO). As an urgent public health crisis, it has severe physical and psychological impacts on human. The related experience and mental health on individuals and society during the pandemic can be devastating and has lasting impact. Objective To investigate the psychological stress and gender difference responding to the threat of COVID-19 and relevant factors. Methods A cross-sectional population-based study using online questionnaires via a social media software, WeChat, from 20th to 27th Feb, 2020. Psychological stress was measured by visual analogue scale (VAS). The relevant factors included demographics, the epidemic and living status characteristics related to COVID-19, psychological status, the needs of psychological support services, and psychological resilience. Psychological responses to depression, anxiety were also measured. Results Total 3088 questionnaires from 32 provinces in China were collected online. The average score of psychological stress was 3.4. The risk factors related to psychological stress included: female, [\u2264]45 years old, higher education, farmer/worker/clerical and business/service, unemployed, more diseases, uncertainty local epidemic status, close contact or completed a medical observation, higher desire for knowledge about the COVID-19, the diseases, psychological, economic difficulties during the epidemic. The protect factors included: frequently contacting with colleagues, calm mood, and high psychological resilience. There were gender differences on stress, the adaption to current living/working status, the coping strategy for heating, and the psychological support service needs. Conclusion The stress, anxiety and depression were mainly related to gender, age, education, and occupation during the epidemic of COVID-19. It suggested that we should make appropriate control measures and provide different psychological supports according to different population characteristics.", "doc_id": "2c381u4v"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Association between SARS-CoV-2 infection, exposure risk and mental health among a cohort of essential retail workers in the United States", "abstract": "Objectives: To investigate SARS-CoV-2 (the virus causing COVID-19) infection and exposure risks among grocery retail workers, and to investigate their mental health state during the pandemic. Methods: This cross-sectional study was conducted in May 2020 in a single grocery retail store in Massachusetts, USA. We assessed workers personal/occupational history and perception of COVID-19 by questionnaire. The health outcomes were measured by nasopharyngeal SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) results, GAD-7 (General Anxiety Disorder-7) and PHQ-9 (Patient Health Questionnaire-9). Results: Among 104 workers tested, twenty-one (20%) had positive viral assays. Seventy-six percent positive cases were asymptomatic. After multi-variate adjustments, employees with direct customer exposure had an odds of 4.7 (95% CI 1.2 to 32.0) being tested positive for SARS-CoV-2, while smokers had an odds of 0.1 (95% CI 0.01 to 0.8) having positive assay. As to mental health, the prevalence of anxiety and depression (i.e. GAD-7 score > 4 or PHQ-9 score >4) was 24% and 8%, respectively. After adjusting for potential confounders, those able to practice social distancing consistently at work had odds of 0.2 (95% CI 0.1 to 0.7) and 0.1 (95% CI 0.01 to 0.6) screening positive for anxiety and depression, respectively. Conclusions: We found a considerable asymptomatic SARS-CoV-2 infection rate among grocery workers. Employees with direct costumer exposure were 5 times more likely to test positive for SARS-CoV-2, while cigarette smokers were 90% less likely to have positive assays. Those able to practice social distancing consistently at work had significantly lower risk of anxiety or depression.", "doc_id": "2swl8zow"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Mental health outcomes among front and second line health workers associated with the COVID-19 pandemic in Italy.", "abstract": "In this study, we report on mental health outcomes among health workers (HWs) involved with the COVID-19 pandemic in Italy. Data on mental health on 1379 HWs were collected between March 27th and March 31th 2020 using an on-line questionnaire spread throughout social networks, using a snowball technique along with sponsored social network advertisement. Key mental health outcomes were Post-Traumatic Stress Disorder symptoms (PTSD), severe depression, anxiety, insomnia and perceived stress. PTSD symptoms, severe depression, anxiety and insomnia, and high perceived stress were endorsed respectively by 681 (49.38%), 341 (24.73%), 273 (19.80%), 114 (8.27%) and 302 (21.90%) respondents. Regression analysis show that younger age, female gender, being a front-line HWs, having a colleague deceased, hospitalised or in quarantine were associated with poor mental health outcomes. This is the first report on mental health outcomes and associated risk factors among HWs associated with the COVID-19 pandemic in Italy, confirming a substantial proportion of health workers involved with the COVID-19 pandemic having mental health issues, in particular young women, first-line HWs.", "doc_id": "01d8cqn4"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "The COVID-19 pandemic in Australia: Lessons learnt", "abstract": "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).", "doc_id": "3qlmxcww"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Analyze the psychological impact of COVID-19 among the elderly population in China and make corresponding suggestions", "abstract": "", "doc_id": "20w3xh9u"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "A population mental health perspective on the impact of COVID-19", "abstract": "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).", "doc_id": "6ngsyo8o"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "[Mental health status and its influencing factors among college students during the epidemic of COVID-19]", "abstract": "OBJECTIVE: To investigate the mental health status of college students during the epidemic of COVID-19 and identify the factors influencing the mental health of the students. METHODS: Using a general questionnaire, a self-designed new coronavirus pneumonia knowledge and cognitive behavior questionnaire, the Generalized Anxiety Disorder 7 (GAD-7) and Patient Health Questionnaire 9 (PHQ-9), we conducted an internet-based questionnaire survey of 3881 college students in Guangdong Province. A multinomial-logistic regression model was used to analyze the collected data. RESULTS: The survey showed that 69.47% of the college students had a high level of awareness of COVID-19; the overall incidence of anxiety was 26.60%, and the incidences of mild, moderate and severe anxiety were 23.19%, 2.71%, and 0.70%, respectively. Depressive emotions were detected in 21.16% of the students, and the incidences of mild, moderate, and moderate-to-severe depression were 16.98%, 3.17%, and 1.01%, respectively. The results of multivariate analysis showed that an older age was associated with a higher level of awareness of COVID-19 and greater changes in future health behaviors were associated with less anxiety and depression among the students. The students currently in rural areas, of non-medical majors, and reporting half of their information concerning the epidemic being negative were more likely to have anxiety; female gender, residence in suburbs, a drinking history, and excessive negative information concerning the epidemic were all associated with the likeliness of depression. CONCLUSIONS: The college students have different levels of anxiety and depression during the epidemic. Depression and anxiety are closely related, but the factors contributing to different levels of such emotions can be different, and colleges and related departments are urged to provide precision mental health education for college students.", "doc_id": "3iknr4yx"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "The Psychological Impact of Epidemic and Pandemic Outbreaks on Healthcare Workers: Rapid Review of the Evidence", "abstract": "PURPOSE OF REVIEW: We aim to provide quantitative evidence on the psychological impact of epidemic/pandemic outbreaks (i.e., SARS, MERS, COVID-19, ebola, and influenza A) on healthcare workers (HCWs). RECENT FINDINGS: Forty-four studies are included in this review. Between 11 and 73.4% of HCWs, mainly including physicians, nurses, and auxiliary staff, reported post-traumatic stress symptoms during outbreaks, with symptoms lasting after 1-3 years in 10-40%. Depressive symptoms are reported in 27.5-50.7%, insomnia symptoms in 34-36.1%, and severe anxiety symptoms in 45%. General psychiatric symptoms during outbreaks have a range comprised between 17.3 and 75.3%; high levels of stress related to working are reported in 18.1 to 80.1%. Several individual and work-related features can be considered risk or protective factors, such as personality characteristics, the level of exposure to affected patients, and organizational support. Empirical evidence underlines the need to address the detrimental effects of epidemic/pandemic outbreaks on HCWs' mental health. Recommendations should include the assessment and promotion of coping strategies and resilience, special attention to frontline HCWs, provision of adequate protective supplies, and organization of online support services.", "doc_id": "10zzz7qe"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Covid-19 pandemic impact on mental health: a web-based cross-sectional survey on a sample of Italian general practitioners", "abstract": "BACKGROUND: Since the World Health Organization declared the new 2019 coronavirus disease (Covid-19) outbreak first a Public Health Emergency of International Concern and then a pandemic, Italy held more than 195.350 cases and 26.380 deaths. Working in the frontline with suspected Covid-19 infection patients, general practitioners (GPs) are daily under both physical and psychological pressure. Methods: A web-based cross-sectional survey was carried out on italian GPs working in Genoa (Italy), to assess the impact of Covid-19 pandemic on mental health. The survey was anonymous and a free Google Forms\u00ae software was used. RESULTS: One hundred thirty-one GPs completed the survey. Compared to GPs with absent or mild depressive symptoms (PHQ-9 < 10), GPs reporting moderate to severe depressive symptoms (N=30, 22.9%; PHQ-9 ≥ 10) reported more helplessness (96.7% vs. 79.2%, p=.025), spent more than three hours searching for COVID-19 information (43.3% vs. 19.8%, p=.024), perceived less adequate personal protective equipment (PPE) (6.7% vs. 23.8%, p=.049) and visited more COVID-19 infected patients (16.63 \u00b1 27.30 vs. 9.52 \u00b1 11.75, p=.041). Moreover, PHQ-9 ≥ 10 GPs reported a significant higher severity for both anxiety and insomnia (13.43 \u00b1 4.96 vs. 4.88 \u00b1 3.53 and 11.60 \u00b1 5.53 vs. 4.84 \u00b1 3.81, respectively; p<.001), and a worse quality of life in both mental (34.60 \u00b1 7.45 vs. 46.01 \u00b1 7.83, p<.001) and physical (43.50 \u00b1 9.37 vs. 52.94 \u00b1 4.78, p<.001) component summary. CONCLUSIONS: Our results give early insight into the urgent need to provide continuity of care for patients at the community-level, adequate PPE to GPs and a clear guidance from public health institutions. A precarious healthcare system both at a national and regional level might have triggered negative mental health outcomes in Italian GPs.", "doc_id": "18frwjak"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "When altruists cannot help: the influence of altruism on the mental health of university students during the COVID-19 pandemic", "abstract": "BACKGROUND: The positive predictive effect of altruism on physical and psychological well-being has been extensively demonstrated in previous studies, but few studies have examined the effect of altruism on negative mental health outcomes when altruists cannot perform altruistic behaviours. This study explored the influence of altruism on negative affect and mental health (anxiety and depressive symptoms) during the COVID-19 pandemic while people self-isolated at home in China. METHOD: University students were recruited to participate in a cross-sectional online survey during the outbreak of COVID-19 in China. Self-reported perceived risk, altruism, negative affect, anxiety and depressive symptoms were measured using the Self-Report Altruism Scale (SRA scale), the Positive and Negative Affect Schedule (PANAS), the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the 9-item Patient Health Questionnaire depression scale (PHQ-9). A structural equation model was used to analyse the mediating and moderating effects on mental health. RESULTS: The final sample comprised 1346 Chinese participants (Mage = 19.76 \u00b1 2.23 years, 73% female). Overall, the higher the risk the participants perceived, the more negative affect they exhibited (\u00df = 0.16, p < .001), and thus, the more anxious and depressed they felt (\u00df = 0.134, p < .001); however, this relationship between risk perception and negative affect was moderated by altruism. In contrast to previous studies, the increase in negative affect associated with the increased perceived risk was pronounced among individuals with high altruism (t = 7.68, p < .001). CONCLUSIONS: Individuals with high altruism exhibited more negative affect than those with low altruism, which indirectly increased their anxiety and depressive symptoms. These findings enrich theories of altruism and provide valuable insight into the influence of altruism on mental health during the COVID-19 outbreak.", "doc_id": "3vetg366"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Eating and exercise behaviors in eating disorders and the general population during the COVID-19 pandemic in Australia: Initial results from the COLLATE project", "abstract": "OBJECTIVE: Emerging evidence suggests that the coronavirus (COVID-19) pandemic may be negatively impacting mental health. The impact on eating and exercise behaviors is, however, currently unknown. This study aimed to identify changes in eating and exercise behaviors in an Australian sample among individuals with an eating disorder, and the general population, amidst the COVID-19 pandemic outbreak. METHOD: A total of 5,469 participants, 180 of whom self-reported an eating disorder history, completed questions relating to changes in eating and exercise behaviors since the emergence of the pandemic, as part of the COLLATE (COvid-19 and you: mentaL heaLth in AusTralia now survEy) project; a national survey launched in Australia on April 1, 2020. RESULTS: In the eating disorders group, increased restricting, binge eating, purging, and exercise behaviors were found. In the general population, both increased restricting and binge eating behaviors were reported; however, respondents reported less exercise relative to before the pandemic. DISCUSSION: The findings have important implications for providing greater monitoring and support for eating disorder patients during the COVID-19 pandemic. In addition, the mental and physical health impacts of changed eating and exercise behaviors in the general population need to be acknowledged and monitored for potential long-term consequences.", "doc_id": "1e3b1ogm"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Mental Health, Risk Factors, and Social Media Use During the COVID-19 Epidemic and Cordon Sanitaire Among the Community and Health Professionals in Wuhan, China: Cross-Sectional Survey", "abstract": "BACKGROUND: The mental health consequences of the coronavirus disease (COVID-19) pandemic, community-wide interventions, and social media use during a pandemic are unclear. The first and most draconian interventions have been implemented in Wuhan, China, and these countermeasures have been increasingly deployed by countries around the world. OBJECTIVE: The aim of this study was to examine risk factors, including the use of social media, for probable anxiety and depression in the community and among health professionals in the epicenter, Wuhan, China. METHODS: We conducted an online survey via WeChat, the most widely used social media platform in China, which was administered to 1577 community-based adults and 214 health professionals in Wuhan. Probable anxiety and probable depression were assessed by the validated Generalized Anxiety Disorder-2 (cutoff ≥3) and Patient Health Questionnaire-2 (cutoff ≥3), respectively. A multivariable logistic regression analysis was used to examine factors associated with probable anxiety and probable depression. RESULTS: Of the 1577 community-based adults, about one-fifth of respondents reported probable anxiety (n=376, 23.84%, 95% CI 21.8-26.0) and probable depression (n=303, 19.21%, 95% CI 17.3-21.2). Similarly, of the 214 health professionals, about one-fifth of surveyed health professionals reported probable anxiety (n=47, 22.0%, 95% CI 16.6-28.1) or probable depression (n=41, 19.2%, 95% CI 14.1-25.1). Around one-third of community-based adults and health professionals spent ≥2 hours daily on COVID-19 news via social media. Close contact with individuals with COVID-19 and spending ≥2 hours daily on COVID-19 news via social media were associated with probable anxiety and depression in community-based adults. Social support was associated with less probable anxiety and depression in both health professionals and community-based adults. CONCLUSIONS: The internet could be harnessed for telemedicine and restoring daily routines, yet caution is warranted toward spending excessive time searching for COVID-19 news on social media given the infodemic and emotional contagion through online social networks. Online platforms may be used to monitor the toll of the pandemic on mental health.", "doc_id": "382vn5tt"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "COVID-19 Pandemic and Impending Global Mental Health Implications", "abstract": "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.", "doc_id": "2bw8nbyb"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Impact of COVID-19 stay-at-home orders on weight-related behaviours among patients with obesity", "abstract": "How the impact of the COVID-19 stay-at-home orders is influencing physical, mental and financial health among vulnerable populations, including those with obesity is unknown. The aim of the current study was to explore the health implications of COVID-19 among a sample of adults with obesity. A retrospective medical chart review identified patients with obesity from an obesity medicine clinic and a bariatric surgery (MBS) practice. Patients completed an online survey from April 15, 2020 to May 31, 2020 to assess COVID-19 status and health behaviours during stay-at-home orders. Logistic regression models examined the impact of these orders on anxiety and depression by ethnic group. A total of 123 patients (87% female, mean age 51.2 years [SD 13.0]), mean BMI 40.2 [SD 6.7], 49.2% non-Hispanic white (NHW), 28.7% non-Hispanic black, 16.4% Hispanic, 7% other ethnicity and 33.1% completed MBS were included. Two patients tested positive for severe acute respiratory syndrome coronavirus 2 and 14.6% reported symptoms. Then, 72.8% reported increased anxiety and 83.6% increased depression since stay-at-home orders were initiated. Also 69.6% reported more difficultly in achieving weight loss goals, less exercise time (47.9%) and intensity (55.8%), increased stockpiling of food (49.6%) and stress eating (61.2%). Hispanics were less likely to report anxiety vs NHWs (adjusted odds ratios 0.16; 95% CI, 0.05-0.49; P = .009). Results here showed the COVID-19 pandemic is having a significant impact on patients with obesity regardless of infection status. These results can inform clinicians and healthcare professionals about effective strategies to minimize COVID-19 negative outcomes for this vulnerable population now and in post-COVID-19 recovery efforts.", "doc_id": "0x24l2z6"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "COVID-19 pandemic and mental health consequences: Systematic review of the current evidence", "abstract": "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.", "doc_id": "0jfwzfge"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Psychological health, sleep quality, and coping styles to stress facing the COVID-19 in Wuhan, China", "abstract": "To understand Wuhan residents' psychological reactions to the COVID-19 epidemic and offer a reference point for interventions, an online questionnaire survey was conducted. It included the Disorder 7-Item Scale (GAD-7), the Patient Health Questionnaire 9-Item Scale (PHQ-9), Athens Insomnia Scale, and Simplified Coping Style Questionnaire. Categorical data were reported as numbers and percentages. Multivariate logistic regression models were used to evaluate the association between demographic factors and anxiety, depression, sleep disorder, and passive coping style. A total of 1242 Wuhan residents investigated, 27.5% had anxiety, 29.3% had depression, 30.0% had a sleep disorder, and 29.8% had a passive response to COVID-19. Being female was the risk factor for anxiety (OR = 1.62) and sleep disorder (OR = 1.36); being married was associated with anxiety (OR = 1.75); having a monthly income between 1000 and 5000 CNY (OR = 1.44, OR = 1.83, OR = 2.61) or >5000 CNY (OR = 1.47, OR = 1.45, OR = 2.14) was a risk factor for anxiety, depression, and sleep disorder; not exercising (OR = 1.45, OR = 1.71, OR = 1. 85, OR = 1.71) was a common risk factor for anxiety, depression, sleep disorder, and passive coping style; and having a higher education level (bachelor's degree and above) (OR = 1.40) was associated with having a sleep disorder. Wuhan residents' psychological status and sleep quality were relatively poorer than they were before the COVID-19 epidemic; however, the rate of passive coping to stress was relatively higher.", "doc_id": "64v6ui6i"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "The psychological impact of preexisting mental and physical health conditions during the COVID-19 pandemic", "abstract": "The COVID-19 pandemic has substantially changed our daily lives, career trajectories, and sense of safety. Current research posits that younger adults without persisting health conditions may be at reduced risk for complications of COVID-19 infection. However, young adults are often in unstable places in their careers, education, and social lives, which may be more disrupted by policy changes than those of older adults. Thus, it is imperative to identify young adult subgroups who are at increased risk for mental health difficulties to develop targeted interventions to mitigate emotional distress. This study recruited 620 young adults, Ages 18-35 (M = 26.59; SD = 5.24), to determine whether there were differences in self-reported anxiety and depression in the weeks following the pandemic declaration by gender (male, female, or nonbinary) and health status (i.e., the absence of health conditions, the presence of either physical or mental health conditions, and the presence of both physical and mental health conditions) using a 3 \u00d7 4 analysis of variance. For both depression and anxiety, nonbinary participants reported the highest levels, followed by female participants. For health status, those with both mental and physical health conditions reported the highest anxiety and depression, followed by those with mental health conditions, physical health conditions, and no health conditions. These findings call for resources to be directed toward individuals who fall into groups reporting greater emotional distress, so that clinicians can intervene as early as possible to prevent mental health decline. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "doc_id": "2194v80f"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Influencia de la actividad f\u00edsica realizada durante el confinamiento en la pandemia del Covid-19 sobre el estado psicol\u00f3gico de adultos: un protocolo de estudio./ [Influence of physical activity during outbreak on psychological states in adults in the Covid-19 pandemic: a study protocol.]", "abstract": "This coronavirus pandemic has placed unprecedented restrictions on people's physical activity and routines. Prolonged home stays may lead to fear, panic, anxiety, and depression states, which in turn, can drive to a reduction of active lifestyles. Hence, determining the psychological response in the general population, and the influence level of home-based physical activity development could be relevant during this exceptional Covid-19 disease quarantine period. A multicenter, cross-sectional, and observational study design will be conducted in 12 Iberoamerican countries expecting to enroll 3,096 participants, through a snowball sampling technique. The study started on March 15th, 2020, and it is expected to be completed in August 2020 through online survey that will include demographic data, health status, psychological impact of the Covid-19 outbreak, mental health status, and level of physical activity. This study will be conducted following the principles established by the protocol, the Declaration of Helsinki, and the Ethical Guidelines for Clinical Research. Data from the study will be disseminated in manuscripts for submission to peer-reviewed journals as well as in abstracts for submission to relevant conferences. Trial registration number: NCT04352517, pre-results.", "doc_id": "49380xzg"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Mental Health Problems during the COVID-19 Pandemics and the Mitigation Effects of Exercise: A Longitudinal Study of College Students in China", "abstract": "(1) Background: The novel coronavirus disease 2019 (COVID-19) is a global public health emergency that has caused worldwide concern. Vast resources have been allocated to control the pandemic and treat patients. However, little attention has been paid to the adverse impact on mental health or effective mitigation strategies to improve mental health. (2) Purpose: The aim of this study was to assess the adverse impact of the COVID-19 outbreak on Chinese college students' mental health, understand the underlying mechanisms, and explore feasible mitigation strategies. (3) Methods: During the peak time of the COVID-19 outbreak in China, we conducted longitudinal surveys of sixty-six college students. Structured questionnaires collected information on demographics, physical activity, negative emotions, sleep quality, and aggressiveness level. A mixed-effect model was used to evaluate associations between variables, and the mediating effect of sleep quality was further explored. A generalized additive model was used to determine the dose-response relationships between the COVID-19 death count, physical activity, and negative emotions. (4) Results: The COVID-19 death count showed a direct negative impact on general sleep quality (\u00df = 1.37, 95% confidence interval [95% CI]: 0.55, 2.19) and reduced aggressiveness (\u00df = -6.57, 95% CI: -12.78, -0.36). In contrast, the COVID-19 death count imposed not a direct but an indirect impact on general negative emotions (indirect effect (IE) = 0.81, p = 0.012), stress (IE = 0.40, p < 0.001), and anxiety (IE = 0.27, p = 0.004) with sleep quality as a mediator. Moreover, physical activity directly alleviated general negative emotions (\u00df = -0.12, 95% CI: -0.22, -0.01), and the maximal mitigation effect occurred when weekly physical activity was about 2500 METs. (5) Conclusions: (a) The severity of the COVID-19 outbreak has an indirect effect on negative emotions by affecting sleep quality. (b) A possible mitigation strategy for improving mental health includes taking suitable amounts of daily physical activity and sleeping well.", "doc_id": "37seijbr"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Impact of COVID-19 pandemic on pre-existing mental health problems", "abstract": "", "doc_id": "43rpqe53"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Mental health burden for the public affected by the COVID-19 outbreak in China: Who will be the high-risk group?", "abstract": "In December, 2019, an outbreak of respiratory illness caused by Coronavirus disease 2019 (COVID-19) emerged in Wuhan, China and spread rapidly to other parts of China and around the world. We aimed to identify high-risk groups whose mental health conditions were vulnerable to the COVID-19 outbreak. Data were collected from 7,236 self-selected participants measured by anxiety symptoms, depressive symptoms, and sleep quality. The overall prevalence of anxiety symptoms, depressive symptoms, and poor sleep quality were 35.1%, 20.1%, and 18.2%, respectively. People aged < 35 years reported a higher prevalence of anxiety symptoms and depressive symptoms than people aged ≥ 35 years. Healthcare workers have the highest rate of poor sleep compared to other occupations. Healthcare workers/younger people who spent a high level of time (≥ 3 hours/day) had a particular higher prevalence of anxiety symptoms than in those who spent less time (< 1 hours/day and 1-2 hours/day) on the outbreak. During the COVID-19 outbreak, healthcare workers and younger people were at an especially high-risk of displaying psychological impact when they spent too much time thinking about the outbreak. Continuous monitoring of the psychological consequences for high-risk population should become routine as part of targeted interventions during times of crisis.I.", "doc_id": "0cxhxbsv"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Prevalence of and Risk Factors Associated With Mental Health Symptoms Among the General Population in China During the Coronavirus Disease 2019 Pandemic", "abstract": "Importance: People exposed to coronavirus disease 2019 (COVID-19) and a series of imperative containment measures could be psychologically stressed, yet the burden of and factors associated with mental health symptoms remain unclear. Objective: To investigate the prevalence of and risk factors associated with mental health symptoms in the general population in China during the COVID-19 pandemic. Design, Setting, and Participants: This large-sample, cross-sectional, population-based, online survey study was conducted from February 28, 2020, to March 11, 2020. It involved all 34 province-level regions in China and included participants aged 18 years and older. Data analysis was performed from March to May 2020. Main Outcomes and Measures: The prevalence of symptoms of depression, anxiety, insomnia, and acute stress among the general population in China during the COVID-19 pandemic was evaluated using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Insomnia Severity Index, and Acute Stress Disorder Scale. Logistic regression analyses were used to explore demographic and COVID-19-related risk factors. Results: Of 71\u00e2\u0080\u00af227 individuals who clicked on the survey link, 56\u00e2\u0080\u00af932 submitted the questionnaires, for a participation rate of 79.9%. After excluding the invalid questionnaires, 56\u00e2\u0080\u00af679 participants (mean [SD] age, 35.97 [8.22] years; 27\u00e2\u0080\u00af149 men [47.9%]) were included in the study; 39\u00e2\u0080\u00af468 respondents (69.6%) were aged 18 to 39 years. During the COVID-19 pandemic, the rates of mental health symptoms among the survey respondents were 27.9% (95% CI, 27.5%-28.2%) for depression, 31.6% (95% CI, 31.2%-32.0%) for anxiety, 29.2% (95% CI, 28.8%-29.6%) for insomnia, and 24.4% (95% CI, 24.0%-24.7%) for acute stress. Participants with confirmed or suspected COVID-19 and their family members or friends had a high risk for symptoms of depression (adjusted odds ratios [ORs], 3.27 [95% CI, 1.84-5.80] for patients; 1.53 [95% CI, 1.26-1.85] for family or friends), anxiety (adjusted ORs, 2.48 [95% CI, 1.43-4.31] for patients; 1.53 [95% CI, 1.27-1.84] for family or friends), insomnia (adjusted ORs, 3.06 [95% CI, 1.73-5.43] for patients; 1.62 [95% CI, 1.35-1.96] for family or friends), and acute stress (adjusted ORs, 3.50 [95% CI, 2.02-6.07] for patients; 1.77 [95% CI, 1.46-2.15] for family or friends). Moreover, people with occupational exposure risks and residents in Hubei province had increased odds of symptoms of depression (adjusted ORs, 1.96 [95% CI, 1.77-2.17] for occupational exposure; 1.42 [95% CI, 1.19-1.68] for Hubei residence), anxiety (adjusted ORs, 1.93 [95% CI, 1.75-2.13] for occupational exposure; 1.54 [95% CI, 1.30-1.82] for Hubei residence), insomnia (adjusted ORs, 1.60 [95% CI, 1.45-1.77] for occupational exposure; 1.20 [95% CI, 1.01-1.42] for Hubei residence), and acute stress (adjusted ORs, 1.98 [95% CI, 1.79-2.20] for occupational exposure; 1.49 [95% CI, 1.25-1.79] for Hubei residence). Both centralized quarantine (adjusted ORs, 1.33 [95% CI, 1.10-1.61] for depression; 1.46 [95% CI, 1.22-1.75] for anxiety; 1.63 [95% CI, 1.36-1.95] for insomnia; 1.46 [95% CI, 1.21-1.77] for acute stress) and home quarantine (adjusted ORs, 1.30 [95% CI, 1.25-1.36] for depression; 1.28 [95% CI, 1.23-1.34] for anxiety; 1.24 [95% CI, 1.19-1.30] for insomnia; 1.29 [95% CI, 1.24-1.35] for acute stress) were associated with the 4 negative mental health outcomes. Being at work was associated with lower risks of depression (adjusted OR, 0.85 [95% CI, 0.79-0.91]), anxiety (adjusted OR, 0.92 [95% CI, 0.86-0.99]), and insomnia (adjusted OR, 0.87 [95% CI, 0.81-0.94]). Conclusions and Relevance: The results of this survey indicate that mental health symptoms may have been common during the COVID-19 outbreak among the general population in China, especially among infected individuals, people with suspected infection, and people who might have contact with patients with COVID-19. Some measures, such as quarantine and delays in returning to work, were also associated with mental health among the public. These findings identify populations at risk for mental health problems during the COVID-19 pandemic and may help in implementing mental health intervention policies in other countries and regions.", "doc_id": "4lyf9ip5"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Mental health circumstances among health care workers and general public under the pandemic situation of COVID-19 (HOME-COVID-19)", "abstract": "BACKGROUND: After the spread of the coronavirus disease 2019 (COVID-19) globally, upgraded quarantine and physical distancing strategy, strict infection measures, and government's strict lockdown have been abided to confront the spread of the COVID-19 in Thailand. During the COVID-19 pandemic, concerns about the mental health and psychosocial problems among health care workers and the general population are now arising. Yet, information on mental health and psychosocial problems among health care workers and the general population have not been comprehensively reported in Thailand. As such, we conduct a cross-sectional study, a national online survey to describe the short- and long-term consequences of the COVID-19 pandemic on mental health and psychosocial problems among health care workers and the general population in Thailand. METHODS: This study is a repeated cross-sectional study, an open online voluntary national-based survey during the wave I (April 21-May 4, 2020) follow-up in the wave II (August 3-16, 2020), wave III (November 15-28, 2020), and a 1-year follow-up survey (wave IV: April 21-May 4, 2021) in Thailand. Health care workers at the hospitals and the adult general population will be invited to participate in the online survey via the SurveyMonkey that limits one-time participation per unique internet protocol address. The target sample size of at least 1182 health care workers and 1310 general populations will be required to complete the online survey for each wave of the survey. Sociodemographic characteristics and a set of measurement tools for mental and psychosocial problems for each subcohort including depression, anxiety, stress, resilient copings, neuroticism, perceived social support, wellbeing, somatic symptoms, insomnia, burnout (for healthcare workers), and public stigma toward COVID-19 infection (for the general population) will be collected. For all estimates of prevalence, we will weigh data for all wave analyses under the complex design of the survey. Subgroup analyses stratified by key characteristics will also be done to analyze the proportion differences. For the repeated cross-sectional survey, we will combine the data from the wave I to wave IV survey to analyze changes in the mental health status. We will perform multilevel logistic regression models with random intercepts to explore associations with individual-level and region-level/hospital-level predictors. We also plan to perform an ancillary systematic review and meta-analysis by incorporating data from our findings to all available evidence. RESULTS: Our findings will provide information on the short- and long-term mental health status as well as the psychosocial responses to the COVID-19 outbreak in a national sample of health care workers and the general population in Thailand. CONCLUSION: This prospective, nationally based, a repeated cross-sectional study will describe the mental health status and psychosocial problems among health care workers and the general population in Thailand during the COVID-19 pandemic. ETHICS AND DISSEMINATION: Ethical approval for the study was obtained from the Faculty of Public Health and Faculty of Pharmacy, Chiang Mai University. The findings will be disseminated through public, scientific, and professional meetings, and publications in peer-reviewed journals. THAI CLINICAL TRIALS REGISTRY (TCTR) REGISTRATION NUMBER: TCTR20200425001.", "doc_id": "40qodhns"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "COVID 19 pandemic: Mental health challenges of internal migrant workers of India", "abstract": "COVID- 19, a biomedical disease has serious physical and tremendous mental health implications as the rapidly spreading pandemic. One of the most vulnerable, but neglected, an occupational community of internal migrant workers is prone for development of psychological ill-effects due to double whammy impact of COVID-19 crisis and concomitant adverse occupational scenario. Permutations and combinations of the factors viz susceptibility for new viral infections, potential to act as vectors of transmission of infection, high prevalence of pre-existing physical health morbidities such as occupational pneumoconiosis, tuberculosis, HIV infections, pre-existing psychological morbidities, adverse psychosocial factors like absence of family support and caretaker during the crisis, their limitations to follow the rules and regulations of personal safety during the COVID 19 crisis, social exclusion, and inability to timely access the psychiatric services; all give rise to the peri-traumatic psychological distress to internal migrant workers. Superadded, is the blow of financial constraints due to loss of work, absence or suspension of occupational safety and health-related basic laws with associated occupational hazards, which make this occupational group highly vulnerable for the development of psychological illnesses. We attempt to draw the attention of mental health professionals, general medical practitioners and occupational health policymakers to the various, interrelated and interdependent predisposing and causative factors for the development of psychological ill-effects amongst internal migrant workers with the interventions needed to address it, from an occupational health perspective angle.", "doc_id": "38ru9r0t"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "The impact of the COVID-19 pandemic on the mental health of healthcare professionals", "abstract": "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.", "doc_id": "2viq4lsw"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Age differences in COVID-19 risk perceptions and mental health:Evidence from a national US survey conducted in March 2020", "abstract": "OBJECTIVES: Theories of aging posit that older adult age is associated with less negative emotions, but few studies have examined age differences at times of novel challenges. As COVID-19 spread in the United States, this study therefore aimed to examine age differences in risk perceptions, anxiety and depression. METHOD: In March 2020, a nationally representative address-based sample of 6666 US adults assessed their perceived risk of getting COVID-19, dying if getting it, getting quarantined, losing their job (if currently working), and running out of money. They completed a mental health assessment for anxiety and depression. Demographic variables and pre-crisis depression diagnosis had previously been reported. RESULTS: In regression analyses controlling for demographic variables and survey date, older adult age was associated with perceiving larger risks of dying if getting COVID-19, but with perceiving less risk of getting COVID-19, getting quarantined, or running out of money, as well as less depression and anxiety. Findings held after additionally controlling for pre-crisis reports of depression diagnosis. DISCUSSION: With the exception of perceived infection-fatality risk, US adults who were relatively older appeared to have a more optimistic outlook and better mental health during the early stages of the pandemic. Interventions may be needed to help people of all ages maintain realistic perceptions of the risks, while also managing depression and anxiety during the COVID-19 crisis. Implications for risk communication and mental health interventions are discussed.", "doc_id": "2i2nygvc"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Impact of Human Disasters and COVID-19 Pandemic on Mental Health: Potential of Digital Psychiatry", "abstract": "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.", "doc_id": "2wam1qls"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Psychological status of surgical staff during the COVID-19 outbreak", "abstract": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which appeared in early December 2019, had an atypical viral pneumonia outbreak in Wuhan, Hubei, China. And there is a high risk of global proliferation and impact. The sudden increase in confirmed cases has brought tremendous stress and anxiety to frontline surgical staff. The results showed that the anxiety and depression of surgical staff during the outbreak period were significantly higher and mental health problems appeared, so psychological interventions are essential.", "doc_id": "5klrlb4v"} {"topic_name": "coronavirus mental health impact", "topic_id": "45", "title": "Impact of COVID-19 on mental health in a Low and Middle-Income Country", "abstract": "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.", "doc_id": "5z3o57dx"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Dexamethasone to the rescue", "abstract": "", "doc_id": "yalhkgcl"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "The use of corticosteroids for COVID-19 infection", "abstract": "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.", "doc_id": "y6fvjsjl"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Dexamethasone for pulpitis", "abstract": "", "doc_id": "pfr9xk6o"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Dexamethasone in the management of covid -19.", "abstract": "", "doc_id": "6l0kb0v3"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Routine antiemetic prophylaxis with dexamethasone during COVID-19: Should oncologists reconsider?", "abstract": "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.", "doc_id": "pec5ezyy"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Dexamethasone for COVID-19? Not so fast.", "abstract": "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)].", "doc_id": "br3ahtf7"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Covid-19: Demand for dexamethasone surges as RECOVERY trial publishes preprint.", "abstract": "", "doc_id": "mtscqxzv"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Coronavirus breakthrough: dexamethasone is first drug shown to save lives.", "abstract": "", "doc_id": "3ho8117q"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "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.", "abstract": "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.", "doc_id": "ivm2d5rl"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Corticosteroid therapy for severe COVID-19 pneumonia: optimal dose and duration of administration", "abstract": "", "doc_id": "lt0mf81g"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Systemic corticosteroids show no benefit in severe and critical COVID-19 patients in Wuhan, China: A retrospective cohort study", "abstract": "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.", "doc_id": "4yjyqjpe"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "COVID-19-associated ARDS treated with DEXamethasone (CoDEX): Study design and rationale for a randomized trial.", "abstract": "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.", "doc_id": "dgy7qbl5"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Rationale for Prolonged Corticosteroid Treatment in the Acute Respiratory Distress Syndrome Caused by Coronavirus Disease 2019", "abstract": "", "doc_id": "nupi7f72"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Short-Term Dexamethasone in Sars-CoV-2 Patients.", "abstract": "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.", "doc_id": "ztd7awzv"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "A COVID-19 pandemic guideline in evidence-based medicine", "abstract": "Data sources This review article scrutinised 16 clinical studies (clinical trials and observational studies) concerning coronavirus disease of 2019 (COVID-19). Additionally, 18 guidelines about the COVID-19 were reviewed and the key points were represented in this study.Study selection The review included human trials, in-vitro studies, review articles, and credible news reports about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 complications, treatment guidelines, management strategies, and epidemiological features. There were no exclusion criteria reported in this review and the included information was in English and Chinese languages.Data extraction and synthesis A descriptive review of the literature was conducted, taking a comprehensive approach. The paper consisted of three main parts: introduction, presentation, and management. The introduction part presented basic information about the SARS-CoV-2, its evolution and transmission, and the course of disease. The presentation section introduced the signs and symptoms, diagnosis, high risk groups, and complications of COVID-19. Eventually, some evidence was presented about the prevention, medical management, and measuring responses to the treatments in the management section.Results Based on the results of this study, non-pharmaceutical interventions, including strict social isolation and distancing measures, might reduce the spread of the SARS-CoV-2 by nearly 99.3 percent (reproduction number mitigating from 406 to 2.5 in 30 days). In the supportive management section, monitoring vital signs and neonatal feeding were stated as the most important factors to consider. For symptomatic neonates, medical management and intervention were mentioned as essential. It was claimed that for adults with mild infection, the best option would be home quarantine with further medical monitoring or hospitalisation if required. The following sequence was also suggested as early supportive therapy and monitoring: intravenous fluid administration, oxygen therapy, and application of corticosteroids. Management of critical patients with critical COVID-19 included admission to intensive care unit, use of continuous positive airway pressure and bi-level positive airway pressure in certain circumstances, endotracheal intubation, invasive mechanical ventilation, extracorporeal membrane oxygenation, and fluid resuscitation and vasopressors. Additionally, this study suggested oseltamivir, iopinavir, remdesivir, chloroquine, baricitinib, ruxolitinib, and fedratinib as possible drugs to help manage COVID-19. A soaring c-reactive protein level and decreased albumin content in the blood were reported to be associated with a deteriorating status in COVID-19 patients. To keep the number of exposures to a minimum, two separate viral clearance tests taken at least 24 hours apart, were stated as necessary laboratory results before the discharge of patients with COVID-19.Conclusions The study warns about possible exponential spread of COVID-19 and proposes to adhering to tighter restrictions of social distancing. Besides the clinical guidelines presented within the study, it also encourages further up-to-date and evidence-based management guidelines for patients with COVID-19.", "doc_id": "m1gkephy"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Role of corticosteroid in the management of COVID-19: A systemic review and a Clinician's perspective", "abstract": "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.", "doc_id": "hswuwtod"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Impact of Glucocorticoid Treatment in Sars-cov-2 Infection Mortality: a Retrospective Controlled Cohort Study", "abstract": "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.", "doc_id": "5eflvvht"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "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", "abstract": "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.", "doc_id": "mapu4r1z"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines", "abstract": "The coronavirus disease (COVID-19) pandemic has led to a global struggle to cope with the sheer numbers of infected persons, many of whom require intensive care support or eventually succumb to the illness. The outbreak is managed by a combination of disease containment via public health measures and supportive care for those who are affected. To date, there is no specific anti-COVID-19 treatment. However, the urgency to identify treatments that could turn the tide has led to the emergence of several investigational drugs as potential candidates to improve outcome, especially in the severe to critically ill. While many of these adjunctive drugs are being investigated in clinical trials, professional bodies have attempted to clarify the setting where the use of these drugs may be considered as off-label or compassionate use. This review summarizes the clinical evidence of investigational adjunctive treatments used in COVID-19 patients as well as the recommendations of their use from guidelines issued by international and national organizations in healthcare.", "doc_id": "4ea77hqx"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Dexamethasone in the management of covid -19", "abstract": "", "doc_id": "7r7rzq36"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "COVID-19 infection and glucocorticoids: update from the Italian Society of Endocrinology Expert Opinion on steroid replacement in adrenal insufficiency", "abstract": "", "doc_id": "wfaqzdsa"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "The influence of corticosteroid on patients with COVID-19 infection: A meta-analysis", "abstract": "", "doc_id": "a18glafy"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Kidney transplant patients with SARS-CoV-2 infection: the brescia renal COVID task force experience", "abstract": "The outcome of kidney transplant patients with SARS-CoV-2 infection is still unclear. Here we describe the clinical characteristics, disease outcome and risk factors for ARDS and death of a cohort of 53 kidney transplant patients with COVID-19. 8/53 have been handled as outpatients due to mild disease, on average with immunosuppression reduction and the addiction of hydroxychloroquine and azithromycin; no patients required admission, developed ARDS or died. 45/53 required admission due to severe symptoms: this cohort has been managed with immunosuppression withdrawal, methylprednisolone 16 mg/day, hydroxychloroquine and antiviral drugs. Dexamethasone and tocilizumab were considered in case of ARDS. 33% of the patients developed AKI, 60% ARDS and 33% died. In this group, thrombocytopenia was associated to ARDS while lymphopenia at the baseline, higher D-dimer and lack of CRP reduction with risk of death. In the overall population, dyspnoea was associated with the risk of ARDS while age older than 60 years and dyspnoea with the risk of death with only a trend towards an increased risk of death for patients on tacrolimus. In conclusion, SARS-CoV-2 infection may have a variable outcome in renal transplant patients, with higher risk of ARDS and death in the ones requiring admission.", "doc_id": "mq4f1srs"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Drug treatment of coronavirus disease 2019 (COVID-19) in China", "abstract": "Since December 2019, the coronavirus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread throughout China as well as other countries. More than 8,700,000 confirmed COVID-19 cases have been recorded worldwide so far, with much more cases popping up overseas than those inside. As the initial epicenter in the world, China has been combating the epidemic for a relatively longer period and accumulated valuable experience in prevention and control of COVID-19. This article reviewed the clinical use, mechanism and efficacy of the clinically approved drugs recommended in the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (DTPNCP) released by National Health Commission of P.R.China, and the novel therapeutic agents now undergoing clinical trials approved by China National Medical Products Administration (NMPA) to evaluate experimental treatment for COVID-19. Reviewing the progress in drug development for the treatment against COVID-19 in China may provide insight into the epidemic control in other countries.", "doc_id": "ybc1hovk"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Dexamethasone for COVID-19? Not so fast", "abstract": "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)].", "doc_id": "6q0y3ewu"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Short-Term Dexamethasone in Sars-CoV-2 Patients", "abstract": "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", "doc_id": "fqh77aaa"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Covid-19: Demand for dexamethasone surges as RECOVERY trial publishes preprint", "abstract": "", "doc_id": "71u261na"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "A critical evaluation of glucocorticoids in the management of severe COVID-19", "abstract": "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.", "doc_id": "bhkmax7s"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Severe immune thrombocytopenic purpura in critical COVID-19", "abstract": "COVID-19 is a new disease with many undescribed clinical manifestations. We report herein a case of severe immune thrombocytopenic purpura (ITP) in a critical COVID-19 patient. A patient presented a severe episode of immune thrombocytopenia (< 10 \u00d7 109/L) 20 days after admission for a critical COVID-19. This thrombocytopenia was associated with a life-threatening bleeding. Response to first-line therapies was delayed as it took up to 13 days after initiation of intravenous immunoglobulin and high-dose dexamethasone to observe an increase in platelet count. COVID-19 may be associated with late presenting severe ITP. Such ITP may also be relatively resistant to first-line agents. Hematological manifestations of COVID-19, such as the ones associated with life-threatening bleeding, must be recognized.", "doc_id": "v6ad8ey8"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Coronavirus breakthrough: dexamethasone is first drug shown to save lives", "abstract": "", "doc_id": "9ygpm1zz"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "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", "abstract": "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.", "doc_id": "r8rd5f2j"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "A critical evaluation of glucocorticoids in the treatment of severe COVID-19", "abstract": "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\u2019 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.", "doc_id": "m2b836k8"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Pros and cons of corticosteroid therapy for COVID-19 patients", "abstract": "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.", "doc_id": "mza0oz89"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Emerging pharmacological therapies for ARDS: COVID-19 and beyond", "abstract": "ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure. Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome. Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition. The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS. We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution. We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS. Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing. The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation. Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies \u2018precision medicines.\u2019 It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS.", "doc_id": "vattsho3"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "A Spanish-translated clinical algorithm for management of suspected SARS-CoV-2 infection in pregnant women", "abstract": "", "doc_id": "nxt0ufad"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis.", "abstract": "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.", "doc_id": "fedbj460"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Initial emergency department mechanical ventilation strategies for COVID-19 hypoxemic respiratory failure and ARDS", "abstract": "INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging viral pathogen that causes the novel coronavirus disease of 2019 (COVID-19) and may result in hypoxemic respiratory failure necessitating invasive mechanical ventilation in the most severe cases. OBJECTIVE: This narrative review provides evidence-based recommendations for the treatment of COVID-19 related respiratory failure requiring invasive mechanical ventilation. DISCUSSION: In severe cases, COVID-19 leads to hypoxemic respiratory failure that may meet criteria for acute respiratory distress syndrome (ARDS). The mainstay of treatment for ARDS includes a lung protective ventilation strategy with low tidal volumes (4\u20138 mL/kg predicted body weight), adequate positive end-expiratory pressure (PEEP), and maintaining a plateau pressure of < 30 cm H(2)O. While further COVID-19 specific studies are needed, current management should focus on supportive care, preventing further lung injury from mechanical ventilation, and treating the underlying cause. CONCLUSIONS: This review provides evidence-based recommendations for the treatment of COVID-19 related respiratory failure requiring invasive mechanical ventilation.", "doc_id": "yurnv5cc"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Kidney transplant patients with SARS\u2010CoV\u20102 infection: the brescia renal COVID task force experience", "abstract": "The outcome of kidney transplant patients with SARS\u2010CoV\u20102 infection is still unclear. Here we describe the clinical characteristics, disease outcome and risk factors for ARDS and death of a cohort of 53 kidney transplant patients with COVID\u201019. 8/53 have been handled as outpatients due to mild disease, on average with immunosuppression reduction and the addiction of hydroxychloroquine and azithromycin; no patients required admission, developed ARDS or died. 45/53 required admission due to severe symptoms: this cohort has been managed with immunosuppression withdrawal, methylprednisolone 16 mg/day, hydroxychloroquine and antiviral drugs. Dexamethasone and tocilizumab were considered in case of ARDS. 33% of the patients developed AKI, 60% ARDS and 33% died. In this group, thrombocytopenia was associated to ARDS while lymphopenia at the baseline, higher D\u2010dimer and lack of CRP reduction with risk of death. In the overall population, dyspnoea was associated with the risk of ARDS while age older than 60 years and dyspnoea with the risk of death with only a trend towards an increased risk of death for patients on tacrolimus. In conclusion, SARS\u2010CoV\u20102 infection may have a variable outcome in renal transplant patients, with higher risk of ARDS and death in the ones requiring admission.", "doc_id": "esjmr1is"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Corticosteroid Administration Is Associated With Improved Outcome in Patients With Severe Acute Respiratory Syndrome Coronavirus 2-Related Acute Respiratory Distress Syndrome", "abstract": "OBJECTIVES: To compare the clinical outcome of mechanically ventilated patients with severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome, who received corticosteroid with those who did not. DESIGN: Retrospective analysis. SETTING: Intensive care setting. PATIENTS: All adult mechanically ventilated patients, who were admitted to the ICU between March 20, 2020, and May 10, 2020, for severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cohort was divided into two groups based on corticosteroid administration. The primary outcome variable was ventilator-free days at day 28. Secondary outcome variable was ICU-free days at day 30, and hospital-free days at day 30. Consecutive 61 mechanically ventilated patients with severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome were analyzed. Patient in corticosteroid group as compared with noncorticosteroid group have higher 28-day ventilator-free days (mean, 10.2; median, 7 [interquartile range, 0\u201322.3] vs mean, 4.7; median, 0 [interquartile range, 0\u201311]; p = 0.01).There was no significant difference noted in secondary outcomes (ICU-free days at day 30 and hospital-free days at day 30). CONCLUSIONS: Among mechanically ventilated severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome patients, corticosteroids use was associated with significant improvement in 28-day ventilator-free days at day 28, but no significant improvement in ICU-free days at day 30, and hospital-free days at day 30.", "doc_id": "z4k02ulw"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "COVID-19 in patients with rheumatic diseases in northern Italy: a single-centre observational and case\u2013control study", "abstract": "BACKGROUND: The highest number of COVID-19 cases in Italy have been reported in Lombardy, a region in northern Italy. We aimed to analyse the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic and musculoskeletal diseases living in a district of Lombardy with a high prevalence of COVID-19. METHODS: We did a single-centre observational study at the Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili of Brescia, Italy. We collected data from patients with rheumatic and musculoskeletal diseases enrolled in our outpatient clinic to identify confirmed or possible cases of SARS-CoV-2 infection. Data were collected through a survey that was administered via telephone or in the outpatient clinic by rheumatologists. We also did a case\u2013control study of all patients with confirmed COVID-19 pneumonia and rheumatic and musculoskeletal diseases who were admitted to the ASST Spedali Civili of Brescia during the study period. Cases were matched by age, sex, and month of hospital admission to at least two controls admitted to the same hospital for COVID-19 pneumonia during the study period. FINDINGS: Between Feb 24 and May 1, 2020, we collected data from 1525 patients with rheumatic and musculoskeletal diseases: 117 (8%) presented with symptoms that were compatible with COVID-19. 65 patients had a swab confirmation of SARS-CoV-2 infection, whereas 52 presented with a spectrum of symptoms indicative of COVID-19 but were not swab tested. Patients with confirmed COVID-19 were older than those with suspected COVID-19 (median age 68 [IQR 55\u201376] years vs 57 [49\u201367] years; p=0\u00b70010) and more likely to have arterial hypertension (33 [51%] vs 14 [27%] patients; odds ratio [OR] 2\u00b78 [95% CI 1\u00b73\u20136\u00b71]; p=0\u00b7031) and obesity (11 [17%] vs 1 [2%]; OR 11\u00b70 [1\u00b73\u201383\u00b74]; p=0\u00b70059). We found no differences in rheumatological disease or background therapy between confirmed and suspected COVID-19 cases. 47 (72%) of the 65 patients with confirmed COVID-19 developed pneumonia that required admission to hospital. 12 (10%) deaths occurred among the 117 patients with confirmed or suspected COVID-19 (ten in those with confirmed COVID-19 and two in those with suspected COVID-19). Deceased patients with confirmed COVID-19 were older than survivors (median age 78\u00b78 years [IQR 75\u00b73\u201381\u00b73] vs 65\u00b75 years [53\u00b73\u201374\u00b70]; p=0\u00b70002). We observed no differences in sex, comorbidities, or therapies between the deceased patients and survivors. The case\u2013control study comprised 26 patients with rheumatic and musculoskeletal diseases and COVID-19 pneumonia and 62 matched controls. We found no significant differences between cases and controls in duration of COVID-19 symptoms before admission, duration of stay in hospital, or the local chest X-ray scoring system. Glucocorticoids were used for severe respiratory manifestations related to lung involvement in 17 (65%) of 26 cases and tocilizumab in six (23%) of 26; thrombotic events occurred in four (15%) of 26 cases. Four (15%) of 26 cases and six (10%) of 62 controls died during the study period. INTERPRETATION: In this cohort of patients with rheumatic and musculoskeletal diseases in a geographical region with a high prevalence of COVID-19, a poor outcome from COVID-19 seems to be associated with older age and the presence of comorbidities rather than the type of rheumatic disease or the degree of pharmacological immunosuppression. FUNDING: None.", "doc_id": "k5k7hafn"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Systemic steroids in patients with COVID-19: pros and contras, an endocrinological point of view", "abstract": "", "doc_id": "zm71tjis"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Response to letter Steroids: a therapeutic option for COVID-19 pneumonia patients with end stage-stage renal disease", "abstract": "", "doc_id": "d3zai3de"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Clinical Management of Adult Coronavirus Infection Disease 2019 (COVID-19) Positive in the Setting of Low and Medium Intensity of Care: a Short Practical Review", "abstract": "Coronavirus disease 2019 (COVID-2019) is a viral infection which is rapidly spreading on a global scale and causing a severe acute respiratory syndrome that affects today about four and a half million registered cases of people around the world. The aim of this narrative review is to provide an urgent guidance for the doctors who take care of these patients. Recommendations contained in this protocol are based on limited, non-definitive, evidence and experience-based opinions about patients with low and medium intensity of care. A short guidance on the management of COVID-19 is provided for an extensive use in different hospital settings. The evidence-based knowledge of COVID-19 is rapidly evolving, and we hope that, in the near future, a definitive and most efficacious treatment will be available including a specific vaccine for SARS-CoV-2.", "doc_id": "5c6lwhno"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Adjuvant corticosteroid therapy for critically ill patients with COVID-19", "abstract": "", "doc_id": "lbx314ki"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "Role of corticosteroid in the management of COVID-19: A systemic review and a Clinician\u2019s perspective", "abstract": "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.", "doc_id": "zi86r481"} {"topic_name": "dexamethasone coronavirus", "topic_id": "46", "title": "The use of dexamethasone in the treatment of COVID-19", "abstract": "", "doc_id": "tw3luwll"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "The curious case of COVID-19 in children", "abstract": "", "doc_id": "78akrp3u"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "The intriguing features of COVID-19 in children and its impact on the pandemic", "abstract": "", "doc_id": "dtpj9bz2"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Children in Coronaviruses\u2019 Wonderland: What Clinicians Need to Know", "abstract": "Human coronaviruses (HCoVs) commonly cause mild upper-respiratory tract illnesses but can lead to more severe and diffusive diseases. A variety of signs and symptoms may be present, and infections can range in severity from the common cold and sore throat to more serious laryngeal or tracheal infections, bronchitis, and pneumonia. Among the seven coronaviruses that affect humans (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV, and the most recent coronavirus disease 2019 (COVID-19) represent potential life-threatening diseases worldwide. In adults, they may cause severe pneumonia that evolves in respiratory distress syndrome and multiorgan failure with a high mortality rate. Children appear to be less susceptible to develop severe clinical disease and present usually with mild and aspecific symptoms similar to other respiratory infections typical of childhood. However, some children, such as infants, adolescents, or those with underlying diseases may be more at-risk categories and require greater caution from clinicians. Available data on pediatric coronavirus infections are rare and scattered in the literature. The purpose of this review is to provide to clinicians a complete and updated panel useful to recognize and characterize the broad spectrum of clinical manifestations of coronavirus infections in the pediatric age.", "doc_id": "3plpi6i9"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Covid-19 in children: A brief overview after three months experience.", "abstract": "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.", "doc_id": "5gvpjxxp"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Coronavirus Disease 2019 (COVID-19) in adolescents: An update on current clinical and diagnostic characteristics.", "abstract": "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.", "doc_id": "gj5mfzxz"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Pediatric Acute Lung Injury Epidemiology and Natural History study: Incidence and outcome of the acute respiratory distress syndrome in children.", "abstract": "OBJECTIVES The incidence and outcome of the acute respiratory distress syndrome in children are not well-known, especially under current ventilatory practices. The goal of this study was to determine the incidence, etiology, and outcome of acute respiratory distress syndrome in the pediatric population in the setting of lung protective ventilation. DESIGN A 1-yr, prospective, multicenter, observational study in 12 geographical areas of Spain (serving a population of 3.77 million \u2264 15 yrs of age) covered by 21 pediatric intensive care units. SUBJECTS All consecutive pediatric patients receiving invasive mechanical ventilation and meeting American-European Consensus Criteria for acute respiratory distress syndrome. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected. A total of 146 mechanically ventilated patients fulfilled the acute respiratory distress syndrome definition, representing a incidence of 3.9/100,000 population \u2264 15 yrs of age/yr. Pneumonia and sepsis were the most common causes of acute respiratory distress syndrome. At the time of meeting acute respiratory distress syndrome criteria, mean PaO2/FIO2 was 99 mm Hg \u00b1 41 mm Hg, mean tidal volume was 7.6 mL/kg \u00b1 1.8 mL/kg predicted body weight, mean plateau pressure was 27 cm H2O \u00b1 6 cm H2O, and mean positive end-expiratory pressure was 8.9 cm \u00b1 2.9 cm H2O. Overall pediatric intensive care unit and hospital mortality were 26% (95% confidence interval 19.6-33.7) and 27.4% (95% confidence interval 20.8-35.1), respectively. At 24 hrs, after the assessment of oxygenation under standard ventilatory settings, 118 (80.8%) patients continued to meet acute respiratory distress syndrome criteria (PaO2/FIO2 104 mm Hg \u00b1 36 mm Hg; pediatric intensive care units mortality 30.5%), whereas 28 patients (19.2%) had a PaO2/FIO2 >200 mm Hg (pediatric intensive care units mortality 7.1%) (p = .014). CONCLUSIONS This is the largest study to estimate prospectively the pediatric population-based acute respiratory distress syndrome incidence and the first incidence study performed during the routine application of lung protective ventilation in children. Our findings support a lower acute respiratory distress syndrome incidence and mortality than those reported for adults. PaO2/FIO2 ratios at acute respiratory distress syndrome onset and at 24 hrs after onset were helpful in defining groups at greater risk of dying (clinical trials registered with http://www.clinicaltrials.gov; NCT 01142544).", "doc_id": "fo4235me"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "COVID-19 in Children, Pregnancy and Neonates: A Review of Epidemiologic and Clinical Features.", "abstract": "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.", "doc_id": "21fnyxw7"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Clinical and epidemiological characteristics of children with COVID-19.", "abstract": "", "doc_id": "c6zv9ik8"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Pediatric COVID-19: Systematic review of the literature.", "abstract": "OBJECTIVES There is limited data regarding the demographics and clinical features of SARS-CoV-2 infection in children. This information is especially important as pneumonia is the single leading cause of death in children worldwide. This Systematic Review aims to elucidate a better understanding of the global impact of COVID-19 on the pediatric population. METHODS A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into pediatric COVID-19 epidemiology. Specifically, Pubmed and Google Scholar databases were searched to identify any relevant article with a focus on Pediatric Covid 19, Pediatric Covid-19, Pediatric SARS-COV-2, and Pediatric Coronavirus 19. References within the included articles were reviewed. All articles that met criteria where analyzed for demographics, clinical, laboratory, radiographic, treatment and outcomes data. RESULTS Ten studies including two case series and 8 retrospective chart reviews, altogether describing a total of 2914 pediatric patients with COVID-19 were included in this systematic review. Of the patients whose data was available, 56% were male, the age range was 1 day to 17 years, 79% were reported to have no comorbidities, and of the 21% with comorbidities, the most common were asthma, immunosupression, and cardiovascular disease. Of pediatric patients that were tested and positive for an infection with SARS-CoV-2, patients were asymptomatic, 14.9% of the time. Patients presented with cough (48%), fever (47%) and sore throat/pharyngitis (28.6%), more commonly than with upper respiratory symptoms/rhinorrhea/sneezing/nasal congestion (13.7%), vomiting/nausea (7.8%) and diarrhea (10.1%). Median lab values including those for WBC, lymphocyte count and CRP, were within the reference ranges with the exception of procalcitonin levels, which were slightly elevated in children with COVID-19 (median procalcitonin levels ranged from 0.07 to 0.5 ng/mL. Computed tomography (CT) results suggest that unilateral CT imaging findings are present 36% of cases while 64% of pediatric patients with COVID-19 had bilateral findings. Of the studies with age specific hospitalization data available, 27.0% of patients hospitalized were infants under 1 year of age. Various treatment regimens including interferon, antivirals, and hydroxychloroquine therapies have been trialed on the pediatric population but there are currently no studies showing efficacy of one regimen over the other. The mortality rate of children that were hospitalized with COVID-19 was 0.0018%. CONCLUSION In contrast to adults, most infected children appear to have a milder course and have better outcomes overall. Additional care may be needed for children with comorbidities and younger children. This review also suggests that unilateral CT chest imaging findings were seen in 36.4% pediatric COVID-19 patients. This is particularly concerning as the work-up of pediatric patients with cough may warrant a bronchoscopy to evaluate for airway foreign bodies. Extra precautions need to be taken with personal protective equipment for these cases, as aerosolizing procedures may be a method of viral transmission. LEVEL OF EVIDENCE 4 (Systematic Review).", "doc_id": "4pwxplhh"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Coronavirus disease 2019 (COVID-19) in children and/or adolescents: a meta-analysis.", "abstract": "BACKGROUND To assess the overall prevalence of clinical signs, symptoms, and radiological findings in children and/or adolescents with COVID-19. METHODS We systematically researched in PubMed, Scopus and Web of Science databases observational studies describing COVID-19 in children and/or adolescents until April 11, 2020. Data regarding clinical and radiological features were extracted from eligible studies and meta-analysis was performed using random-effects modeling. RESULTS We examined 19 eligible studies for a total of 2855 children and/or adolescents with COVID-19. Approximately 47% of subjects had fever (95% confidence interval [CI] 22-72%; I2 = 98.6%), 37% cough (95%CI 15-63%; I2 = 98.6%), 4% diarrhea (95%CI 0-12%; I2 = 92.2%), 2% nasal congestion (95%CI 0-7%; I2 = 87.7%), 1% dyspnea (95%CI 0-7%; I2 = 91.5%) and 0% abdominal pain (95%CI 0-1%; I2 = 76.3%). Subjects presented mild symptoms in 79% (95%CI 65-91%; I2 = 93.5%) of cases, whereas only 4% (95%CI 1-9%; I2 = 76.4%) were critical. Among those with pneumonia on computed tomography, 26.4% (95%CI 13-41%; I2 = 80.8%) presented a unilateral involvement, 16% (95%CI 5-29%, I2 = 81.2%) had bilateral involvement and 9% (95%CI 0-24%; I2 = 88.7%) had interstitial pneumonia. CONCLUSIONS Children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. IMPACT Compared to adults, children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. This study provides new and consistence information on the clinical and radiological characteristics of COVID-19 in pediatrics. This study may help to fight COVID-19 in pediatric population.", "doc_id": "8cc26phd"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in New York City, New York.", "abstract": "Importance Descriptions of the coronavirus disease 2019 (COVID-19) experience in pediatrics will help inform clinical practices and infection prevention and control for pediatric facilities. Objective To describe the epidemiology, clinical, and laboratory features of patients with COVID-19 hospitalized at a children's hospital and to compare these parameters between patients hospitalized with and without severe disease. Design, Setting, and Participants This retrospective review of electronic medical records from a tertiary care academically affiliated children's hospital in New York City, New York, included hospitalized children and adolescents (\u226421 years) who were tested based on suspicion for COVID-19 between March 1 to April 15, 2020, and had positive results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exposures Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay. Main Outcomes and Measures Severe disease as defined by the requirement for mechanical ventilation. Results Among 50 patients, 27 (54%) were boys and 25 (50%) were Hispanic. The median days from onset of symptoms to admission was 2 days (interquartile range, 1-5 days). Most patients (40 [80%]) had fever or respiratory symptoms (32 [64%]), but 3 patients (6%) with only gastrointestinal tract presentations were identified. Obesity (11 [22%]) was the most prevalent comorbidity. Respiratory support was required for 16 patients (32%), including 9 patients (18%) who required mechanical ventilation. One patient (2%) died. None of 14 infants and 1 of 8 immunocompromised patients had severe disease. Obesity was significantly associated with mechanical ventilation in children 2 years or older (6 of 9 [67%] vs 5 of 25 [20%]; P = .03). Lymphopenia was commonly observed at admission (36 [72%]) but did not differ significantly between those with and without severe disease. Those with severe disease had significantly higher C-reactive protein (median, 8.978 mg/dL [to convert to milligrams per liter, multiply by 10] vs 0.64 mg/dL) and procalcitonin levels (median, 0.31 ng/mL vs 0.17 ng/mL) at admission (P < .001), as well as elevated peak interleukin 6, ferritin, and D-dimer levels during hospitalization. Hydroxychloroquine was administered to 15 patients (30%) but could not be completed for 3. Prolonged test positivity (maximum of 27 days) was observed in 4 patients (8%). Conclusions and Relevance In this case series study of children and adolescents hospitalized with COVID-19, the disease had diverse manifestations. Infants and immunocompromised patients were not at increased risk of severe disease. Obesity was significantly associated with disease severity. Elevated inflammatory markers were seen in those with severe disease.", "doc_id": "51e8a6lz"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Risks to children during the covid-19 pandemic: some essential epidemiology.", "abstract": "", "doc_id": "7nunexun"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Longitudinal symptom dynamics of COVID-19 infection in primary care", "abstract": "Importance: Data regarding the clinical characteristics of COVID-19 infection is rapidly accumulating. However, most studies thus far are based on hospitalized patients and lack longitudinal follow up. As the majority of COVID-19 cases are not hospitalized, prospective studies of symptoms in the population presenting to primary care are needed. Objective: To assess the longitudinal dynamic of clinical symptoms in non-hospitalized individuals prior to and throughout the diagnosis of SARS-CoV-2 infection. Design, Setting, and Participants: From 1/3/2020 to 07/06/2020, information on symptoms from either surveys or primary care visits was available for 206,377 individuals, including 2,471 who tested positive for COVID-19. Data were extracted from electronic health records (EHR) of the second largest Health Maintenance Organization in Israel, consisting of both results of PCR tests and symptoms recorded by primary care physicians, and linked longitudinal self reported symptoms. Exposures: Diagnosis of COVID-19 disease was made by PCR testing for SARS-CoV-2 from nasopharyngeal swabs. Main Outcomes and Measures: Longitudinal prevalence of clinical symptoms Results: In adults, the most prevalent symptoms recorded in EHR were cough (11.6%), fever (10.3%), and myalgia (7.7%) and the most prevalent self-reported symptoms were cough (21%), fatigue (19%) and rhinorrhea and/or nasal congestion (17%). In children, the most prevalent symptoms recorded in the EHR were fever (7%), cough (5.5%) and abdominal pain (2.4%). Emotional disturbances were documented in 15.9% of the positive adults and 4.2% of the children. Loss of taste and smell, either self-reported or documented by a physician, 3 weeks prior to testing, were the most discriminative symptoms in adults (OR =11.18 and OR=5.47 respectively). Additional symptoms included self reported confusion (OR =4.02), and fatigue (OR = 1.73) and a documentation of syncope, rhinorrhea (OR = 2.09 for both ) and fever (OR= 1.62 ) by a physician. Mean time to recovery was 23.5 +- 9.9 days. Children had a significantly shorter disease duration (21.7 +- 8.8 days, p-value=0.01). Several symptoms, including fatigue, myalgia, runny nose and shortness of breath were reported weeks after recovery. Conclusions and Relevance: As the COVID-19 pandemic progresses rapidly worldwide, obtaining accurate information on symptoms and their progression is of essence. Our study shed light on the full clinical spectrum of symptoms experienced by infected individuals in primary care, and may alert physicians for the possibility of COVID-19 infection.", "doc_id": "gg1qth9p"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Clinical features of covid-19 in children", "abstract": "In early December, pneumonia cases of unknown origin started to appear and, on the 7thof January 2020, these cases were declared to be caused by a novel beta-coronavirus according to viral genome sequencing on the 11thof February, 2020. Coronaviruses are enveloped, single strand RNA viruses that have been known to have the ability to mutate rapidly, alter tissue tropism and adjust to different epidemiological situations. As of the end of April 2020, 122,392 laboratory-confirmed cases of COVID-19 had been detected in Turkey, of whom 3,258 died. From the beginning of the COVID-19 epidemic, children seem to be less affected than adults. Therefore, there are limited data regarding the clinical features of COVID-19 in children. The majority of children with confirmed COVID-19 had a history of household contact. The most common symptoms were fever and cough. Previous data suggest that nearly half of patients are afebrile at the onset of the disease. Hospitalization and PICU admission rates for children were lower than for adults. However, PICU admission can be necessitated in children with severe disease. Infants, particularly under the age of 12 months, were more likely to develop severe disease. In children, milder and asymptomatic cases can be challenging and can play a role in transmission. In particular, clinicians should test those children who have a history of family cluster even though they are asymptomatic or present with mild symptoms.", "doc_id": "34ytd87a"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Pay attention to SARS-CoV-2 infection in children", "abstract": "", "doc_id": "9mjw60dh"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Guidelines for coronavirus disease 2019 response in children and adolescents", "abstract": "The Korean Society of Pediatric Infectious Diseases and the Korea Centers for Disease Control and Prevention issued the guidelines about coronavirus disease 2019 (COVID-19) for children and adolescents. Case definitions and management of COVID-19 in neonates, infants, children and adolescents are presented in this guideline. In addition, guidelines for caregiver management are also provided. In this review, we introduce the contents of the current guidelines for COVID-19 in children and adolescents in Korea.", "doc_id": "fwoct97q"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "COVID-19 Disease in Children: Clinical Course, Diagnosis and Treatment Overview and Literature Data Compilation", "abstract": "The novel Coronavirus is named as SARS-CoV-2 is a highly contagious infection agent compared to the previous human coronaviruses Each previous outbreak had distinctive danger The high potential of infectiousness is the primary danger of novel coronavirus While MERS-CoV infection is known to have higher mortality rate, SARS-CoV-2 has spread to many people all over the world in a concise time SARS-CoV-2 (like SARS-CoV and MERS) infects fewer children and results in milder clinical symptoms than in adults The primary pathogenesis of it is not known;the difference in children's immunities, less likelihood of exposure to the agent may be the reasons Nevertheless, along with being mostly asymptomatic, the child population is a potential source for infection spread", "doc_id": "9ppacplo"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis.", "abstract": "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.", "doc_id": "6zqp53tk"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Covid-19 in children: A brief overview after three months experience", "abstract": "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.", "doc_id": "fuhvsy2j"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Covid-19 and pregnancy", "abstract": "Guideline: Coronavirus (COVID-19) Infection in pregnancyPublished by the Royal College of Obstetricians and Gynaecologists (RCOG), with input from the Royal College of Midwives, the Royal College of Paediatrics and Child Health (RCPH), the Royal College of Anaesthetists, and the Obstetric Anaesthetists' Association.This summary is based on version 8 of the guideline, published on 17 April 2020 (https://www.rcog.org.uk/globalassets/documents/guidelines/2020-04-17-coronavirus-covid-19-infection-in-pregnancy.pdf).", "doc_id": "e16jvk6a"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Coronavirus Disease (COVID-19) in Children - What We Know So Far and What We Do Not?", "abstract": "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", "doc_id": "03vy3uaj"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Characteristics of Hospitalized Pediatric COVID-19 Cases - Chicago, Illinois, March - April 2020", "abstract": "BACKGROUND: To date, no report on COVID-19 pediatric patients in a large urban center with data on underlying comorbidities and co-infection for hospitalized cases has been published. METHODS: Case series of Chicago COVID-19 patients aged 0-17 years reported to Chicago Department of Public Health (CDPH) from 3/5/20-4/8/20. Enhanced case investigation performed. Chi-square and Wilcoxon two-sample tests to compare characteristics among hospitalized and non-hospitalized cases. RESULTS: During March 5-April 8, 2020, 6369 lab-confirmed cases of COVID-19 were reported to CDPH; 64 (1.0%) were among children 0-17 years. Ten patients (16%) were hospitalized, seven (70%) required intensive care (ICU); median length of hospitalization 4 days (range: 1-14). Reported fever and dyspnea were significantly higher in hospitalized patients compared to non-hospitalized patients (9/10 vs. 28/54, p = 0.04 and 7/10 vs. 10/54, p = 0.002, respectively). Hospitalized patients were significantly younger than non-hospitalized patients (median, 3.5 years vs. 12 years; p = 0.03) and all either had an underlying comorbidity or co-infection. Among the 34 unique households with multiple laboratory-confirmed infections, median number of laboratory-confirmed infections was 2 (range: 2-5), and 31 (91%) households had at least one COVID-19 infected adult. For 15 households with available data to assess transmission, 11 (73%) were adult-to-child, 2 (13%) child-to-child, and 2 (13%) child-to-adult. CONCLUSIONS: Enhanced case investigation of hospitalized patients revealed that underlying comorbidities and co-infection might have contributed to severe disease. Given frequency of household transmission, healthcare providers should consider alternative dispositional planning for affected families of children living with comorbidities.", "doc_id": "35lmsdhc"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Coronavirus disease (COVID-19) and neonate: What neonatologist need to know", "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About three neonates and more than 230 children cases are reported. The disease condition of the main children was mild. There is currently no evidence that SARS-CoV-2 can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID-19) is based on adult experience. Thus far, no deaths have been reported in the pediatric age group. This review describes the current understanding of COVID-19 infection in newborns and children.", "doc_id": "4qy35wdf"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "SARS-CoV-2 testing and outcomes in the first 30 days after the first case of COVID-19 at an Australian children's hospital", "abstract": "OBJECTIVE: International studies describing COVID-19 in children have shown low proportions of paediatric cases and generally a mild clinical course. We aimed to present early data on children tested for SARS-CoV-2 at a large Australian tertiary children's hospital according to the state health department guidelines, which varied over time. METHODS: We conducted a retrospective cohort study at The Royal Children's Hospital, Melbourne, Australia. It included all paediatric patients (aged 0-18 years) who presented to the ED or the Respiratory Infection Clinic (RIC) and were tested for SARS-CoV-2. The 30-day study period commenced after the first confirmed positive case was detected at the hospital on 21 March 2020, until 19 April 2020. We recorded epidemiological and clinical data. RESULTS: There were 433 patients in whom SARS-CoV-2 testing was performed in ED (331 [76%]) or RIC (102 [24%]). There were four (0.9%) who had positive SARS-CoV-2 detected, none of whom were admitted to hospital or developed severe disease. Of these SARS-CoV-2 positive patients, 1/4 (25%) had a comorbidity, which was asthma. Of the SARS-CoV-2 negative patients, 196/429 (46%) had comorbidities. Risk factors for COVID-19 were identified in 4/4 SARS-CoV-2 positive patients and 47/429 (11%) SARS-CoV-2 negative patients. CONCLUSION: Our study identified a very low rate of SARS-CoV-2 positive cases in children presenting to a tertiary ED or RIC, none of whom were admitted to hospital. A high proportion of patients who were SARS-CoV-2 negative had comorbidities.", "doc_id": "ef1qr82d"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Managing COVID-19 disease in pediatric patients", "abstract": "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.", "doc_id": "4f8v0tou"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Novel coronavirus infection (COVID-19) in children younger than one year: A systematic review of symptoms, management and outcomes", "abstract": "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.", "doc_id": "1n3t23ag"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "[Pediatric impact of COVID-19]", "abstract": "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", "doc_id": "2990fbda"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "SARS-CoV-2 infection in infants under 1 year of age in Wuhan City, China", "abstract": "BACKGROUND: The clinical characteristics and outcome of COVID-19 in children are different from those in adults. We aimed to describe the characteristics of infants under 1 year of age (excluding newborns) with COVID-19. METHODS: We retrospectively retrieved data of 36 infants with SARS-CoV-2 infection in Wuhan Children's Hospital from January 26 to March 22, 2020. Clinical features, chest imaging findings, laboratory tests results, treatments and clinical outcomes were analyzed. RESULTS: The mean age of the infected infants was 6.43 months, with a range of 2-12 months. 61.11% of the patients were males and 38.89% females. 86.11% of the infants were infected due to family clustering. Cough (77.78%) and fever (47.22%) were the most common clinical manifestations. Chest CT scan revealed 61.11% bilateral pneumonia and 36.11% unilateral pneumonia. 47.22% of the infants developed complications. Increased leucocytes, neutrophils, lymphocytes, and thrombocytes were observed in 11.11, 8.33, 36.11 and 44.44% of infants, respectively. Decreased leucocytes, neutrophils, thrombocyte and hemoglobin were observed in 8.33, 19.44, 2.78 and 36.11% of infants, respectively. Increased C-reactive protein, procalcitonin, lactate dehydrogenase, alanine aminotransferase, creatine kinase and D-dimer were observed in 19.44, 67.74, 47.22, 19.44, 22.22 and 20.69% of infants, respectively. Only one infant had a high level of creatinine. Co-infections with other respiratory pathogens were observed in 62.86% of infants. CD3 (20.69%), CD4 (68.97%), CD19 (31.03%) and Th/Ts (44.83%) were elevated; CD8 (6.9%) and CD16+CD56 (48.28%) was reduced. IL-4 (7.69%), IL-6 (19.23%), IL-10 (50%), TNF-α (11.54%) and IFN-\u00ce\u00b3 (19.23%) were elevated. Up to March 22, 97.22% of infants recovered, while a critical ill infant died. When the infant's condition deteriorates rapidly, lymphocytopenia was discovered. Meanwhile, C-reactive protein, D-dimer, alanine aminotransferase, creatine kinase, creatinine, IL-6 and IL-10 increased significantly. CONCLUSIONS: In the cohort, we discovered that lymphocytosis, elevated CD4 and IL-10, and co-infections were common in infants with COVID-19, which were different from adults with COVID-19. Most infants with COVID-19 have mild clinical symptoms and good prognosis.", "doc_id": "eghxji0p"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "[Clinical features of coronavirus disease 2019 in children aged <18 years in Jiangxi, China: an analysis of 23 cases]", "abstract": "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.", "doc_id": "4qjklght"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis", "abstract": "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.", "doc_id": "36aoqdnt"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "COVID-19 and Neonatal Respiratory Care: Current Evidence and Practical Approach", "abstract": "The novel coronavirus disease 2019 (COVID-19) pandemic has urged the development and implementation of guidelines and protocols on diagnosis, management, infection control strategies, and discharge planning. However, very little is currently known about neonatal COVID-19 and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections. Thus, many questions arise with regard to respiratory care after birth, necessary protection to health care workers (HCW) in the delivery room and neonatal intensive care unit (NICU), and safety of bag and mask ventilation, noninvasive respiratory support, deep suctioning, endotracheal intubation, and mechanical ventilation. Indeed, these questions have created tremendous confusion amongst neonatal HCW. In this manuscript, we comprehensively reviewed the current evidence regarding COVID-19 perinatal transmission, respiratory outcomes of neonates born to mothers with COVID-19 and infants with documented SARS-CoV-2 infection, and the evidence for using different respiratory support modalities and aerosol-generating procedures in this specific population. The results demonstrated that to date, neonatal COVID-19 infection is uncommon, generally acquired postnatally, and associated with favorable respiratory outcomes. The reason why infants display a milder spectrum of disease remains unclear. Nonetheless, the risk of severe or critical illness in young patients exists. Currently, the recommended respiratory approach for infants with suspected or confirmed infection is not evidence based but should include all routinely used types of support, with the addition of viral filters, proper personal protective equipment, and placement of infants in isolation rooms, ideally with negative pressure. As information is changing rapidly, clinicians should frequently watch out for updates on the subject. KEY POINTS: \u00b7 Novel coronavirus disease 2019 (COVID-19) pandemic urged development of guidelines.. \u00b7 Neonatal COVID-19 disease is uncommon.. \u00b7 Respiratory outcomes in neonates seems favorable.. \u00b7 Current neonatal respiratory care should continue.. \u00b7 Clinicians should watch frequently for updates..", "doc_id": "b50dxky4"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "[Retracted: Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen]", "abstract": "Objective: To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People's Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. Results: Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10\u00d710(9)/L. One case had white blood cell counts less than 4\u00d710(9)/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need. Conclusions: The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children's infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.", "doc_id": "a0dpwsuf"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "The role of children in the transmission of mild SARS-CoV-2 infection", "abstract": "", "doc_id": "g3jxjmzf"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "COVID-19 in children: Epidemiology, presentation, diagnosis and management", "abstract": "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.", "doc_id": "4254jznh"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "A wake-up call: COVID-19 and its impact on children's health and wellbeing", "abstract": "", "doc_id": "59l40qmg"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Novel coronavirus disease (COVID-19) in children", "abstract": "Coronavirus disease (COVID-19) was firstly reported at the end of 2019. The disease rapidly spread all around the world in a few months and was declared a worldwide pandemic by WHO in March 2020. By April 9, there were 1,436,198 confirmed COVID-19 cases in the world, nearly with 6% mortality rate. This novel infectious disease causes respiratory tract illness that may generally occur as mild upper respiratory tract disease or pneumonia. In older patients and/or patients with underlying conditions, it may result in acute respiratory distress syndrome, multi organ failure and even death. According to the current literature, children account approximately for 1%\u00ad5% of diagnosed COVID-19 cases. Generally, COVID-19 seems to be a less severe disease for children than adults. Approximately 90% of pediatric patients are diagnosed as asymptomatic, mild, or moderate disease. However, up to 6.7% of cases may be severe. Severe illness is generally seen in patients smaller than 1 year of age and patients who have underlying disesases. The epidemiological and clinical patterns of COVID-19 and treatment approaches in pediatric patients still remain unclear although many pediatric reports are published. This review aims to summarize the current epidemics, clinical presentations, diagnosis, and treatment of COVID-19 in pediatric patients.", "doc_id": "epoo8mj4"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Coronavirus disease 2019 in children: Current status", "abstract": "Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China in December 2019. The outbreak further exploded in Europe and America in mid-March 2020 to become a global health emergency. We reviewed recent published articles and on-line open messages on SARS-CoV-2-positive infants and children younger than 20 years of age. Symptoms are usually less severe in children than in adults. Twelve critically or mortally ill children were found in the published or news reports before April 6, 2020. Vertical transmission from the mother to her fetus or neonate has not been proven definitively. However, six early-onset (<7 days) and 3 late-onset neonatal SARS-CoV-2 infections were found in the literature. We also summarized the presentations and contact information of 24 SARS-CoV-2-positive children announced by the Taiwan Centers for Disease Control. Early identification and isolation, adequate management, prevention, and vaccine development are the keys to controlling the disease spread. Clinical physicians should be alert to asymptomatic children with COVID-19. Multidirectional investigations are crucial in the global fight against COVID-19.", "doc_id": "f73uff3m"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "The different clinical characteristics of corona virus disease cases between children and their families in China - the character of children with COVID-19", "abstract": "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.", "doc_id": "feqqdlof"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "COVID-19 multisystem inflammatory syndrome in three teenagers with confirmed SARS-CoV-2 infection", "abstract": "Coronavirus disease 2019 (COVID-19) is generally a relatively mild illness in children. An emerging disease entity coined as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) has been reported recently, but is very rare and only affects a very small minority of children. Here we describe the clinical presentations and outcomes of three teenagers with serologically-confirmed SARS-CoV-2 infection admitted to a pediatric intensive care unit for PIMS-TS. Although their initial presentations were very similar, their COVID-19-related disease varied in severity.", "doc_id": "dtvtvbgf"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Epidemiology and Clinical Features of Coronavirus Disease 2019 in Moroccan Children", "abstract": "OBJECTIVES: This study aims to analyze the epidemiological and clinical features of coronavirus disease 19 (COVID-19) in a Moroccan pediatric population METHODS: A retrospective study of a cohort of 74 children with RT-PCR confirmed COVID-19 We collected information on clinical and laboratory features of all children (age <18 years) admitted between 2 March, 2020 and 1 April, 2020 RESULTS: The mean (SD) age of the 74 children (40 girls) was 7 (1 5) years The mean (SD) time from illness onset to diagnosis was 2 (1) days 54 children were asymptomatic, while eight had fever, and five cases had cough Recovery was after a mean (SD) of 12 (1) days CONCLUSION: COVID-19 was mostly mild in the pediatric population in Morocco", "doc_id": "5xu73o1y"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Children with Coronavirus Disease 2019 (COVID-19): A Review of Demographic, Clinical, Laboratory and Imaging Features in 2,597 Pediatric Patients", "abstract": "An epidemic of coronavirus disease 2019 (COVID-19) has been spreading worldwide. With the rapid increase in the number of infections, children with COVID-19 appear to be rising. Most research findings 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 evaluated the demographic, clinical, laboratory and imaging features from 2,597 pediatric patients of COVID-19 that reported recently. 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 (CK-MB) was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to happen in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children, as well as to develop strategies to control the disease transmission. This article is protected by copyright. All rights reserved.", "doc_id": "fmijknz0"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "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", "abstract": "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.", "doc_id": "f1697rdp"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Lessons from COVID-19 in children: Key hypotheses to guide preventative and therapeutic strategies", "abstract": "The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), reveals a peculiar trend of milder disease and lower case fatality in children compared to adults. Consistent epidemiologic evidence of reduced severity of infection in children across different populations and countries suggests there are underlying biologic differences between children and adults that mediate differential disease pathogenesis. This presents a unique opportunity to learn about disease modifying host factors from pediatric populations. Our review summarizes the current knowledge of pediatric clinical disease, role in transmission, risks for severe disease, protective immunity, as well as novel therapies and vaccine trials for children. We then define key hypotheses and areas for future research that can use the pediatric model of disease, transmission, and immunity to develop preventive and therapeutic strategies for people of all age groups.", "doc_id": "4fwydrtj"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "SARS-CoV-2: The Path of Prevention and Control", "abstract": "The 2019 coronavirus pandemic (COVID-19) continues to expand worldwide. Although the number of cases and the death rate among children and adolescents are reported to be low compared to adults, limited data have been reported. We urgently need to find treatment and vaccine to stop the epidemic. Vaccine development is in progress, but any approved and effective vaccine for COVID-19 is at least 12 to 18 months. The World Health Organization (WHO), the Center for Disease Control and Prevention (CDC), and the Food and Agriculture Organization (FAO) have issued instructions and strategies for containing COVID-19 outbreak to the general public, physicians, travelers and injured patients to follow so that the transmission to a healthy population can be prevented. In this review, we summarize demographic data, clinical characteristics, complications and outcomes and finally prevention and control of this serious pandemic.", "doc_id": "a1p44lop"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Coronavirus Disease 2019 in Children Cared for at Texas Children's Hospital: Initial Clinical Characteristics and Outcomes", "abstract": "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.", "doc_id": "ev3fpqq0"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Spectrum of COVID-19 in Children", "abstract": "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.", "doc_id": "el6cvwtk"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "COVID-19 virus and children: What do we know?", "abstract": "", "doc_id": "1qhe325v"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Clinical characteristics of COVID-19 in children compared with adults in Shandong Province, China", "abstract": "AIMS AND BACKGROUND: The COVID-19 outbreak spread in China and is a threat to the world. We reported on the epidemiological, clinical, laboratory, and radiological characteristics of children cases to help health workers better understand and provide timely diagnosis and treatment. METHODS: Retrospectively, two research centers' case series of 67 consecutive hospitalized cases including 53 adult and 14 children cases with COVID-19 between 23 Jan 2020 and 15 Feb 2020 from Jinan and Rizhao were enrolled in this study. Epidemiological, clinical, laboratory, and radiological characteristics of children and adults were analyzed and compared. RESULTS: Most cases in children were mild (21.4%) and conventional cases (78.6%), with mild clinical signs and symptoms, and all cases were of family clusters. Fever (35.7%) and dry cough (21.4%) were described as clinical manifestations in children cases. Dry cough and phlegm were not the most common symptoms in children compared with adults (p = 0.03). In the early stages of the disease, lymphocyte counts did not significantly decline but neutrophils count did in children compared with adults (p = 0.02). There was a lower level of CRP (p = 0.00) in children compared with adults. There were 8 (57.1%) asymptomatic cases and 6 (42.9%) symptomatic cases among the 14 children cases. The age of asymptomatic patients was younger than that of symptomatic patients (p = 0.03). Even among asymptomatic patients, 5 (62.5%) cases had lung injuries including 3 (60%) cases with bilateral involvement, which was not different compared with that of symptomatic cases (p = 0.58, p = 0.74). CONCLUSIONS: The clinical symptoms of children are mild, there is substantial lung injury even among children, but that there is less clinical disease, perhaps because of a less pronounced inflammatory response, and that the occurrence of this pattern appears to inversely correlate with age.", "doc_id": "fj06xnej"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in New York City, New York", "abstract": "Importance: Descriptions of the coronavirus disease 2019 (COVID-19) experience in pediatrics will help inform clinical practices and infection prevention and control for pediatric facilities. Objective: To describe the epidemiology, clinical, and laboratory features of patients with COVID-19 hospitalized at a children's hospital and to compare these parameters between patients hospitalized with and without severe disease. Design, Setting, and Participants: This retrospective review of electronic medical records from a tertiary care academically affiliated children's hospital in New York City, New York, included hospitalized children and adolescents (≤21 years) who were tested based on suspicion for COVID-19 between March 1 to April 15, 2020, and had positive results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exposures: Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay. Main Outcomes and Measures: Severe disease as defined by the requirement for mechanical ventilation. Results: Among 50 patients, 27 (54%) were boys and 25 (50%) were Hispanic. The median days from onset of symptoms to admission was 2 days (interquartile range, 1-5 days). Most patients (40 [80%]) had fever or respiratory symptoms (32 [64%]), but 3 patients (6%) with only gastrointestinal tract presentations were identified. Obesity (11 [22%]) was the most prevalent comorbidity. Respiratory support was required for 16 patients (32%), including 9 patients (18%) who required mechanical ventilation. One patient (2%) died. None of 14 infants and 1 of 8 immunocompromised patients had severe disease. Obesity was significantly associated with mechanical ventilation in children 2 years or older (6 of 9 [67%] vs 5 of 25 [20%]; P = .03). Lymphopenia was commonly observed at admission (36 [72%]) but did not differ significantly between those with and without severe disease. Those with severe disease had significantly higher C-reactive protein (median, 8.978 mg/dL [to convert to milligrams per liter, multiply by 10] vs 0.64 mg/dL) and procalcitonin levels (median, 0.31 ng/mL vs 0.17 ng/mL) at admission (P < .001), as well as elevated peak interleukin 6, ferritin, and D-dimer levels during hospitalization. Hydroxychloroquine was administered to 15 patients (30%) but could not be completed for 3. Prolonged test positivity (maximum of 27 days) was observed in 4 patients (8%). Conclusions and Relevance: In this case series study of children and adolescents hospitalized with COVID-19, the disease had diverse manifestations. Infants and immunocompromised patients were not at increased risk of severe disease. Obesity was significantly associated with disease severity. Elevated inflammatory markers were seen in those with severe disease.", "doc_id": "63c9dt8a"} {"topic_name": "COVID-19 outcomes in children", "topic_id": "47", "title": "Neurologic and Radiographic Findings Associated With COVID-19 Infection in Children", "abstract": "Importance: Neurological manifestations have been reported in adults with coronavirus disease 2019 (COVID-19), which is caused by the highly pathogenic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective: To report the neurological manifestations of children with COVID-19. Design, Setting, and Participants: In this case-series study, patients younger than 18 years who presented with SARS-CoV-2 infection and neurological symptoms to Great Ormond Street Hospital for Children (London, UK) between March 1, 2020, and May 8, 2020, were included after infection was confirmed by either a quantitative reverse transcription-polymerase chain reaction assay by nasopharyngeal swab or a positive test result for IgG antibodies against SARS-CoV-2 in serum. Main Outcomes and Measures: Clinical and paraclinical features were retrieved from electronic patient records. Results: Of the 27 children with COVID-19 pediatric multisystem inflammatory syndrome, 4 patients (14.8%) who were previously healthy had new-onset neurological symptoms. Symptoms included encephalopathy, headaches, brainstem and cerebellar signs, muscle weakness, and reduced reflexes. All 4 patients required intensive care unit admission for the treatment of COVID-19 pediatric multisystem inflammatory syndrome. Splenium signal changes were seen in all 4 patients on magnetic resonance imaging of the brain. In the 2 patients whose cerebrospinal fluid was tested, samples were acellular, with no evidence of infection on polymerase chain reaction or culture (including negative SARS-CoV-2 polymerase chain reaction results) and negative oligoclonal band test results. In all 3 patients who underwent electroencephalography, a mild excess of slow activity was found. Tests for N-methyl-d-aspartate receptor, myelin oligodendrocyte glycoprotein, and aquaporin-4 autoantibodies had negative results in all patients. In all 3 patients who underwent nerve conduction studies and electromyography, mild myopathic and neuropathic changes were seen. Neurological improvement was seen in all patients, with 2 making a complete recovery by the end of the study. Conclusions and Relevance: In this case-series study, children with COVID-19 presented with new neurological symptoms involving both the central and peripheral nervous systems and splenial changes on imaging, in the absence of respiratory symptoms. Additional research is needed to assess the association of neurological symptoms with immune-mediated changes among children with COVID-19.", "doc_id": "7jnufpiy"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Pandemic school closures: risks and opportunities", "abstract": "", "doc_id": "ewah8x7m"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Feasibility of Social Distancing Practices in US Schools to Reduce Influenza Transmission During a Pandemic", "abstract": "Schools are socially dense environments, and school-based outbreaks often predate and fuel community-wide transmission of seasonal and pandemic influenza. While preemptive school closures can effectively reduce influenza transmission, they are disruptive and currently recommended only for pandemics. We assessed the feasibility of implementing other social distancing practices in K-12 schools as a first step in seeking an alternative to preemptive school closures. METHODS: We conducted 36 focus groups with education and public health officials across the United States. We identified and characterized themes and compared feasibility of practices by primary versus secondary school and region of the United States. RESULTS: Participants discussed 29 school practices (25 within-school practices implemented as part of the school day and 4 reduced-schedule practices that impact school hours). Participants reported that elementary schools commonly implement several within-school practices as part of routine operations such as homeroom stay, restriction of hall movement, and staggering of recess times. Because of routine implementation and limited use of individualized schedules within elementary schools, within-school practices were generally felt to be more feasible for elementary schools than secondary schools. Of reduced-schedule practices, shortening the school week and the school day was considered the most feasible; however, reduced-schedule practices were generally perceived to be less feasible than within-school practices for all grade levels. CONCLUSIONS: Our findings suggest that schools have many options to increase social distance other than closing. Future research should evaluate which of these seemingly feasible practices are effective in reducing influenza transmission in schools and surrounding communities.", "doc_id": "37821r59"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "How COVID-19 has exposed inequalities in the UK food system: The case of UK food and poverty", "abstract": "This article draws upon our perspective as academic-practitioners working in the fields of food insecurity, food systems, and inequality to comment, in the early stages of the pandemic and associated lockdown, on the empirical and ethical implications of COVID-19 for socio-economic inequalities in access to food in the UK. The COVID-19 pandemic has sharpened the profound insecurity of large segments of the UK population, an insecurity itself the product of a decade of \u2018austerity\u2019 policies. Increased unemployment, reduced hours, and enforced self-isolation for multiple vulnerable groups is likely to lead to an increase in UK food insecurity, exacerbating diet-related health inequalities. The social and economic crisis associated with the pandemic has exposed the fragility of the system of food charity which, at present, is a key response to growing poverty. A vulnerable food system, with just-in-time supply chains, has been challenged by stockpiling. Resultant food supply issues at food banks, alongside rapidly increasing demand and reduced volunteer numbers, has undermined many food charities, especially independent food banks. In the light of this analysis, we make a series of recommendations. We call for an immediate end to the five week wait for Universal Credit and cash grants for low income households. We ask central and local government to recognise that many food aid providers are already at capacity and unable to adopt additional responsibilities. The government\u2019s - significant - response to the economic crisis associated with COVID-19 has underscored a key principle: it is the government\u2019s responsibility to protect population health, to guarantee household incomes, and to safeguard the economy. Millions of households were in poverty before the pandemic, and millions more will be so unless the government continues to protect household incomes through policy change.", "doc_id": "q990hitc"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Threats and opportunities in remote learning of mathematics: implication for the return to the classroom", "abstract": "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.", "doc_id": "kj3v3fd1"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Impact of the Covid-19 Pandemic on Early Childhood Care and Education", "abstract": "", "doc_id": "516rr89e"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Returning to School: Separation Problems and Anxiety in the Age of Pandemics", "abstract": "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 \u201cnormal.\u201d 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\u2019s needs, plan ahead, provide reassurance, and depart firmly without vacillating, and we provide other tips to avoid inadvertently shaping children\u2019s 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.", "doc_id": "66c2qobr"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Covid-19: US cases soar as Trump pushes for schools to open.", "abstract": "", "doc_id": "bf7rrfqb"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Children and the COVID-19 pandemic.", "abstract": "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).", "doc_id": "4nv1kedt"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Covid-19: Delaying school reopening by two weeks would halve risks to children, says iSAGE.", "abstract": "", "doc_id": "k9kq0uir"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Covid-19: Government must plan for schools to reopen, say paediatricians.", "abstract": "", "doc_id": "9kgs0ztn"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Debate: COVID-19 and psychological well-being of children and adolescents in Italy.", "abstract": "Italy was the first country in Europe to deal with COVID-19. Measures taken by the government to contain the spread of the virus were based mainly on quarantine and social distancing, with dramatic economic, social and psychological consequences. Since March, Italian children and adolescents are facing school closures, which have caused a disruption in the daily lives of millions of young people and their families. To date, despite the slow reopening, the government has decided to maintain school closures for the entire academic year, leaving the future of young people in uncertainty. There is already some evidence that quarantine and social isolation are having negative impact on children's and adolescents' psychological well-being. Moreover, this situation will mainly affect those children and adolescents with pre-existing vulnerabilities and those suffering of mental disorders. It is imperative to keep young people's needs at the core of reconstruction plans, allowing them to return to school safely, and providing them with some strategies to heal and dealing with this stressful and potentially traumatic situation.", "doc_id": "lgf0nwgx"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Covid-19: Push to reopen schools risks new wave of infections, says Independent SAGE.", "abstract": "", "doc_id": "arzbu37s"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Covid-19: Papers justifying government's plans to reopen schools are \"inconclusive,\" say union bosses.", "abstract": "", "doc_id": "l6iqniif"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Back to school: Safe for children with underlying medical conditions.", "abstract": "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.", "doc_id": "6gn2seix"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "COVID-19 screening strategies that permit the safe re-opening of college campuses", "abstract": "Importance: The COVID-19 pandemic poses an existential threat to many US residential colleges: either they open their doors to students in September or they risk serious financial consequences. Objective: To define SARS-CoV-2 screening performance standards that would permit the safe return of students to campus for the Fall 2020 semester. Design: Decision and cost-effectiveness analysis linked to a compartmental epidemic model to evaluate campus screening using tests of varying frequency (daily-weekly), sensitivity (70%-99%), specificity (98%-99.7%), and cost ($10-$50/test). Reproductive numbers Rt = {1.5, 2.5, 3.5} defined three epidemic scenarios, with additional infections imported via exogenous shocks. We generally adhered to US government guidance for parameterization data. Participants: A hypothetical cohort of 5000 college-age, uninfected students. Main Outcome(s) and Measure(s): Cumulative tests, infections, and costs; daily isolation dormitory census; incremental cost-effectiveness; and budget impact. All measured over an 80-day, abbreviated semester. Results: With Rt = 2.5, daily screening with a 70% sensitive, 98% specific test produces 85 cumulative student infections and isolation dormitory daily census averaging 108 (88% false positives). Screening every 2 (7) days nets 135 (3662) cumulative infections and daily isolation census 66 (252) with 73% (4%) false positives. Across all scenarios, test frequency exerts more influence on outcomes than test sensitivity. Cost-effectiveness analysis selects screening every {2, 1, 7} days with a 70% sensitive test as the preferred strategy for Rt = {2.5, 3.5, 1.5}, implying a screening cost of {$470, $920, $120} per student per semester. Conclusions & Relevance: Rapid, inexpensive and frequently conducted screening (even if only 70% sensitive) would be cost-effective and produce a modest number of COVID-19 infections. While the optimal screening frequency hinges on the success of behavioral interventions to reduce the base severity of transmission (Rt), this could permit the safe return of student to campus.", "doc_id": "bk9kowhc"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Distinctive trajectories of COVID-19 epidemic by age and gender: a retrospective modeling of the epidemic in South Korea", "abstract": "Objectives: Elderly people had suffered disproportional burden of COVID-19. We hypothesized that males and females in different age groups might have different epidemic trajectories. Methods: Using publicly available data from South Korea, daily new COVID-19 cases were fitted with generalized additive models, assuming Poisson and negative binomial distributions. Epidemic dynamics by age and gender groups were explored with interactions between smoothed time terms and age and gender. Results: A negative binomial distribution fitted the daily case counts best. Interaction between the dynamic patterns of daily new cases and age groups was statistically significant (p<0.001), but not with gender group. People aged 20-39 years led the epidemic processes in the society with two peaks: one major peak around March 1 and a smaller peak around April 7, 2020. The epidemic process among people aged 60 or above was trailing behind that of younger people with smaller magnitude. After March 15, there was a consistent decline of daily new cases among elderly people, despite large fluctuations of case counts among young adults. Conclusions: Although young people drove the COVID-19 epidemic in the whole society with multiple rebounds, elderly people could still be protected from virus infection after the peak of epidemic.", "doc_id": "n6ag85ea"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Trust, threats, and consequences of the COVID-19 pandemic in Norway and Sweden: A comparative survey", "abstract": "Objectives: Norway and Sweden, two neighboring countries with similar populations, health care systems and socioeconomics, have reacted differently to the COVID-19 pandemic. Norway closed all kindergartens, schools and universities, and banned sports and cultural activities, while Sweden kept most institutions and trainings facilities open. We aimed to compare peoples' attitudes towards authorities and control measures, and effects on life in Norway and Sweden. Design: Anonymous web-based surveys for individuals age 15 or older distributed through Facebook using the snowball method. Setting: Norway and Sweden, mid-March to mid-April, 2020. Participants: Altogether, 3,508 individuals participated in the survey; 3000 in Norway and 508 in Sweden. 79% of the participants were women, 60% of the Norwegians and 47% of the Swedes were between 30-49 years, and around 45% of the participants in both countries had more than 4 years of higher education. Outcome measures: Perceived threat of the pandemic, views on infection control measures, and impact on daily life. We performed descriptive analyses of the responses and compared the two countries. Results: People had high trust in the health services in both countries, but differed in the degree of trust in their government (17% had high trust in Norway and 37% in Sweden). More Norwegians than Swedes agreed that school closure was a good measure (66% Norway and 18% in Sweden), and that countries with open schools were irresponsible (65% in Norway and 23% in Sweden). About the same amount responded that COVID-19 was a large to very large threat to the population (53% in Norway and 58% in Sweden), whereas more Norwegians than Swedes responded that the threat from repercussions of the mitigation measures were large or very large (71% in Norway and 56% in Sweden). Compliance with infection preventive measures was high and similar in the two countries (more than 98%). In Norway, 69% lived a more sedentary life during the pandemic versus 50% in Sweden; and Norwegians reported they ate more than Swedes (44% in Norway and 33% in Sweden). Conclusion: Sweden, with less restrictive measures against the COVID-19 pandemic, had a higher level of trust in the authorities, while Norwegians reported a more negative lifestyle during the pandemic. The level of trust in the health care system and self-reported compliance with preventive measures was high in both countries.", "doc_id": "jtg8x8y0"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Geospatially Referenced Demographic Agent-Based Modeling of SARS-CoV-2-Infection (COVID-19) Dynamics and Mitigation Effects in a Real-world Community", "abstract": "Re-opening societies and economies across the globe following the initial wave of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) pandemic requires scientifically-guided decision processes and policy development. Public health authorities now consider it highly likely that transmission of SARS-CoV-2 and COVID-19 will follow a pattern of seasonal circulation globally. To guide mitigation strategies and tactics in a location-specific manner, accurate simulation of prolonged or intermittent patterns of social/physical distancing is required in order to prevent healthcare systems and communities from collapsing. It is equally important to capture the stochastic appearance of individual transmission events. Traditional epidemiological/statistical models cannot make predictions in a geospatial temporal manner based on human individuals in a community. Thus, the challenge is to conduct spatio-temporal simulations of transmission chains with real-world geospatial and georeferenced information of the dynamics of the disease and the effect of different mitigation strategies such as isolation of infected individuals or location closures. Here, we present a stochastic, geospatially referenced and demography-specific agent-based model with agents representing human beings and include information on age, household composition, daily occupation and schedule, risk factors, and other relevant properties. Physical encounters between humans are modeled in a time-dependent georeferenced network of the population. The model (GERDA-1) can predict infection dynamics under normal conditions and test the effect of different mitigation scenarios such as school closures, reduced social contacts as well as closure or reopening of public/work spaces. Specifically, it also includes the fate and influence of health care workers and their access to protective gear. Key predictions so far entail: (i) the effect of specific groups on the spreading, specifically that children in school contribute substantially to distribution. (ii) the result of reopening society depends crucially on how strict the measures have been during lock-down. (iii) the outcome of reopening is a stochastic process - in the majority of cases, we must expect a second wave, in some cases not. To the best of our best knowledge, the GERDA-1 model is the first model able to predict a bimodal behavior of SARS-Cov-2 infection dynamics. Given the criticality of the global situation, informing the scientific community, decision makers and the general public seems prudent. Therefore, we here provide a pre-print of the GERDA-1 model together with a first set of predictions and analyses as work in progress.", "doc_id": "k9cpbszs"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Assessing the nationwide impact of COVID-19 mitigation policies on the transmission rate of SARS-CoV-2 in Brazil", "abstract": "COVID-19 is now identified in almost all countries in the world, with poorer regions being particularly more disadvantaged to efficiently mitigate the impacts of the pandemic. In the absence of efficient therapeutics or vaccines, control strategies are currently based on non-pharmaceutical interventions, comprising changes in population behavior and governmental interventions, among which the prohibition of mass gatherings, closure of non-essential establishments, quarantine and movement restrictions. In this work we analyzed the effects of 547 published governmental interventions, and population adherence thereof, on the dynamics of COVID-19 cases across all 27 Brazilian states, with emphasis on state capitals and remaining inland cities. A generalized SEIR model with a time-varying transmission rate (TR), that considers transmission by asymptomatic individuals, is presented. Confirmed COVID-19 cases were used to calibrate the model parameters using non-linear least squares methods. We analyze the changes on the TR and effective reproduction number as a function of both the extent of enforced measures across Brazilian states as well as population movement. The social mobility reduction index, a measure of population movement, together with the stringency index, adapted to incorporate the degree of restrictions imposed by governmental regulations, were used in conjunction to quantify and compare the effects of varying degrees of policy strictness across Brazilian states. Our results show that population adherence to social distance recommendations plays an important role for the effectiveness of interventions, and represents a major challenge to the control of COVID-19 in low- and middle-income countries.", "doc_id": "o80y5cic"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Relaxing lockdown measures in epidemic outbreaks using selective socio-economic containment with uncertainty", "abstract": "After an initial phase characterized by the introduction of timely and drastic containment measures aimed at stopping the epidemic contagion from SARS-CoV2, many governments are preparing to relax such measures in the face of a severe economic crisis caused by lockdowns. Assessing the impact of such openings in relation to the risk of a resumption of the spread of the disease is an extremely difficult problem due to the many unknowns concerning the actual number of people infected, the actual reproduction number and infection fatality rate of the disease. In this work, starting from a compartmental model with a social structure, we derive models with multiple feedback controls depending on the social activities that allow to assess the impact of a selective relaxation of the containment measures in the presence of uncertain data. Specific contact patterns in the home, work, school and other locations for all countries considered have been used. Results from different scenarios in some of the major countries where the epidemic is ongoing, including Germany, France, Italy, Spain, the United Kingdom and the United States, are presented and discussed.", "doc_id": "nrd9ajj2"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Shut and re-open: the role of schools in the spread of COVID-19 in Europe", "abstract": "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.", "doc_id": "r2x3awlw"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "An analysis of SARS-CoV-2 viral load by patient age", "abstract": "As children are under-represented in current studies aiming to analyse transmission of SARS-coronavirus 2 (SARS-CoV-2), their contribution to transmission is unclear. Viral load, as measured by RT-PCR, can inform considerations regarding transmission, especially if existing knowledge of viral load in other respiratory diseases is taken into account. RT-PCR threshold cycle data from 3303 patients who tested positive for SARS-CoV-2 (out of 77,996 persons tested in total, drawn from across Germany) were analysed to examine the relationship between patient age and estimated viral load. Two PCR systems were used. In data from the PCR system predominantly used for community and cluster screening during the early phase of the epidemic (Roche LightCycler 480 II), when such screening was frequent practice, viral loads do not differ significantly in three comparisons between young and old age groups (differences in log10 viral loads between young and old estimated from raw viral load data and a Bayesian mixture model of gamma distributions collectively range between -0.11 and -0.43). Data from a second type of PCR system (Roche cobas 6800/8800), introduced into diagnostic testing on March 16, 2020 and used during the time when household and other contact testing was reduced, show a credible but small difference in the three comparisons between young and old age groups (differences, measured as above, collectively range between -0.43 and -0.83). This small difference may be due to differential patterns of PCR instrument utilization rather than to an actual difference in viral load. Considering household transmission data on influenza, which has a similar viral load kinetic to SARS-CoV-2, the viral load differences between age groups observed in this study are likely to be of limited relevance. Combined data from both PCR instruments show that viral loads of at least 250,000 copies, a threshold we previously established for the isolation of infectious virus in cell culture at more than 5% probability, were present across the study period in 29.0% of kindergarten-aged patients 0-6 years old (n=38), 37.3% of those aged 0-19 (n=150), and in 51.4% of those aged 20 and above (n=3153). The differences in these fractions may also be due to differences in test utilization. We conclude that a considerable percentage of infected people in all age groups, including those who are pre- or mild-symptomatic, carry viral loads likely to represent infectivity. Based on these results and uncertainty about the remaining incidence, we recommend caution and careful monitoring during gradual lifting of non-pharmaceutical interventions. In particular, there is little evidence from the present study to support suggestions that children may not be as infectious as adults.", "doc_id": "apg3tmd3"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Stepping out of lockdown should start with school re-openings while maintaining distancing measures. Insights from mixing matrices and mathematical models.", "abstract": "Australia is one of a few countries which has managed to control COVID-19 epidemic before a major epidemic took place. Currently with just under 7000 cases and 100 deaths, Australia is seeing less than 20 new cases per day. This is a positive outcome, but makes estimation of current effective reproduction numbers difficult to estimate. Australia, like much of the world is poised to step out of lockdown and looking at which measures to relax first. We use age-based contact matrices, calibrated to Chinese data on reproduction numbers and difference in infectiousness and susceptibility of children to generate next generation matrices (NGMs) for Australia. These matrices have a spectral radius of 2.49, which is hence our estimated basic reproduction number for Australia. The effective reproduction number (Reff) for Australia during the April/May lockdown period is estimated by other means to be around 0.8. We simulate the impact of lockdown on the NGM by first applying observations through Google Mobility Report for Australia at 3 locations: home (increased contacts by 18%), work (reduced contacts by 34%) and other (reduced contacts by 40%), and we reduce schools to 3% reflecting attendance rates during lockdown. Applying macro-distancing to the NGM leads to a spectral radius of 1.76. We estimate that the further reduction of the reproduction number to current levels of Reff = 0.8 is achieved by a micro-distancing factor of 0.26. That is, in a given location, people are 26% as likely as usual to have an effective contact with another person. We apply both macro and micro-distancing to the NGMs to examine the impact of different exit strategies. We find that reopening schools is estimated to reduce Reff from 0.8 to 0.78. This is because increase in school contact is offset by decrease in home contact. The NGMs all estimate that adults aged 30-50 are responsible for the majority of transmission. We also find that micro-distancing is critically important to maintain Reff <1. There is considerable uncertainty in these estimates and a sensitivity and uncertainty analysis is presented.", "doc_id": "1oauxryz"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Toward sustainable learning during school suspension: Socioeconomic, occupational aspirations, and learning behavior of vietnamese students during COVID-19", "abstract": "The overspread of the novel coronavirus-SARS-CoV-2-over the globe has caused significant damage to manufacturing and service businesses, regardless of whether they are commercial, public, or not-for-profit sectors. While both the short-term and long-term impacts of most companies can be approximately measured or estimated, it is challenging to address the enduring effects of COVID-19 on teaching and learning activities. The target of this research is to investigate students' manners of studying at home during the school suspension time as a result of COVID-19. Through analyzing original survey data from 420 K6-12 students in Hanoi, Vietnam, this work demonstrates the different learning habits of students with different socioeconomic statuses and occupational aspirations during the disease's outbreak. In particular, we featured the differences in students' learning behaviors between private schools and public schools, as well as between students who plan to follow STEM-related careers and those who intend to engage in social science-related careers. The empirical evidence of this study can be used for the consideration of the local government to increase the sustainability of coming policies and regulations to boost students' self-efficacy, as it will affect 1.4 million students in Hanoi, as well as the larger population of nearly 10 million Vietnamese students. These results can also be the foundation for future investigations on how to elevate students' learning habits toward Sustainable Development Goal 4 (SDG4)-Quality Education-especially in fanciful situations in which the regular school operation has been disrupted, counting with limited observation and support from teachers and parents.", "doc_id": "4avkvrxo"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Career Confidential: Teacher wonders how to help students during coronavirus shutdown", "abstract": "Phyllis Fagell provides workplace advice to educators in this Kappan column. This month, a teacher wants to know how she can provide emotional support to students when the school is closed for the COVID-19 pandemic. A teachers\u2019 colleagues provide a lot of free after-school help to students, making her feel obligated to do the same, even when it interferes with her family time or when students have not been doing the work during class.", "doc_id": "n2ockn45"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Modelling Singapore COVID-19 pandemic with a SEIR multiplex network model", "abstract": "In this paper, we have implemented a large-scale agent-based model to study the outbreak of coronavirus infectious diseases (COVID-19) in Singapore, taking into account complex human interaction pattern. In particular, the concept of multiplex network is utilized to differentiate between social interactions that happen in households and workplaces. In addition, weak interactions among crowds, transient interactions within social gatherings, and dense human contact between foreign workers in dormitories are also taken into consideration. Such a categorization in terms of a multiplex of social network connections together with the Susceptible-Exposed-Infectious-Removed (SEIR) epidemic model have enabled a more precise study of the feasibility and efficacy of control measures such as social distancing, work from home, and lockdown, at different moments and stages of the pandemics.", "doc_id": "c0j2flyv"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "WHO-INTEGRATE COVID framework Version 1.0: Criteria and considerations to guide evidence-informed decision-making on non-pharmacological interventions targeting COVID-19", "abstract": "Background: Decision-making on matters of public health requires the balancing of numerous, often conflicting factors. One approach to ensure relevancy and comprehensiveness of the criteria underpinning the decision is a broad societal discourse and participatory decision-making process. However, this often was not feasible within the time constraints imposed on by the SARS-CoV-2 pandemic. While not able or intended to replace stakeholder participation, evidence-to-decision frameworks can serve as a tool to approach relevancy and comprehensiveness of the criteria considered, even if not all voices of affected stakeholders could be heard in the process. Objective: The objective of this research project was to develop a decision-making framework adapted to the challenges decision-makers face when deliberating on national and sub-national level on non-pharmacological interventions (NPIs) measures to address the global SARS-CoV-2 pandemic. Methods: We used the WHO-INTEGRATE framework Version 1.0 as a starting point. In phase I, we adapted the framework through brainstorming exercises and application to exemplary case studies. In phase II, we used the best-fit framework synthesis technique with the output of phase I serving as a priori framework. We conducted a content analysis of comprehensive strategy documents intended to guide the policy makers on the phasing out of the lockdown measures in Germany. Based on factors and criteria identified in this process, we adapted previous versions into the WHO-INTEGRATE COVID framework (WICID framework) Version 1.0. Results: Twelve comprehensive strategy documents were included in the content analysis. The revised WICID framework consists of eleven criteria, which are expanded on through 49 aspects contained within them, and the metacriterion quality of evidence. The criteria cover implications for the health of individuals and populations due to and beyond COVID-19, infringement on liberties and fundamental rights, acceptability considerations, societal, environmental, and economic implications, as well as resource and feasibility considerations. Discussion: In a third phase, the framework will be expanded through a comprehensive document analysis focusing on key-stakeholder groups across the society. The WICID framework V1.0 can be a tool to support comprehensive evidence-informed decision-making processes.", "doc_id": "n78tk8dj"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Lockdown measures in response to COVID-19 in Sub-Saharan Africa: A rapid study of nine countries", "abstract": "Lockdown measures have been introduced worldwide to contain the transmission of COVID-19. This paper defines the term lockdown and describes the design, timing and implementation of lockdown in nine countries in Sub Saharan Africa: Ghana, Nigeria, South Africa, Sierra Leone, Sudan, Tanzania, Uganda, Zambia and Zimbabwe. It also discusses the manner in which lockdown is enforced, the need to mitigate the harms of lockdown, and the association between lockdown and the reported number of COVID-19 cases and deaths. While there are some commonalities in the implementation of lockdown, a more notable finding is the variation in the design, timing and implementation of lockdown measures across the nine countries. We found that the number of reported cases is heavily dependent on the number of tests done, and that testing rates ranged from 9 to 21,261 per million population. The reported number of COVID-19 deaths per million population also varies, but is generally low when compared to countries in Europe and North America. While lockdown measures may have helped inhibit some community transmission, the pattern and nature of the epidemic remains unclear. Of concern are signs of lockdown harming health by affecting the functioning of the health system and causing social and economic harms. This paper highlights the need for inter-sectoral and trans-disciplinary research capable of providing a rigorous and holistic assessment of the harms and benefits of lockdown.", "doc_id": "m7y9wrob"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Expected impact of reopening schools after lockdown on COVID-19 epidemic in Ile-de-France", "abstract": "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.", "doc_id": "qnlf5qfd"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "What can a Pandemic Teach Us about Competency Based Medical Education?", "abstract": "Medical education is moving towards competency-based medical education (CBME) where learning and assessment are focused on predefined abilities and outcomes. While medical student and residency training have defined competencies and objectives that trainees need to achieve, training remains time -based. Students and residents graduate based on a preset length of training. The COVID -19 pandemic is disrupting educational and clinical environments and in some regions the workforce may not be adequate to respond to the needs of the community. This, therefore, presents an opportunity for the medical education community to reconsider time-based training and embrace a competency-based progression to accelerate entry into the workforce. This commentary discusses undergraduate and graduate medical education response to workforce pressures of COVID-19. On one hand, some medical schools are moving towards competency-based (early) graduation from medical school. On the other hand, residency programs have generally held to time -based completion of training. In the context of this clinical and educational disruption, there are two challenges to CBME progression of trainees. The first challenge is whether there is trust in competency-based assessment to permit time independent progression. The second involves a number of logistical issues to competency-based progression.", "doc_id": "ovef7ff1"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Prevent the resurgence of infectious disease with asymptomatic carriers", "abstract": "As many countries reached the peak of the COVID-19 outbreak, there is debate on how to reopen the economy without causing a significant resurgence. Here we show, using a microsimulation model, that how to reopen safely depends on what percentage of COVID-19 cases can be detected by testing. The higher the detection rate, the less restrictive the reopen plan needs to be. If 70% of cases can be detected, schools and businesses can reopen if 2-layer quarantine is imposed on each confirmed case. Our results suggest that increasing the detection rate is essential to prevent the resurgence of COVID-19.", "doc_id": "r2mwzzaw"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Quantifying the impact of US state non-pharmaceutical interventions on COVID-19 transmission", "abstract": "COVID-19 is an ongoing public health emergency. Without a vaccine or effective antivirals, non-pharmaceutical interventions form the foundation of current response efforts. Quantifying the efficacy of these interventions is crucial. Using mortality data and a classification guide of state level responses, we relate the intensity of interventions to statistical estimates of transmission, finding that more stringent control measures are associated with larger reductions in disease proliferation. Additionally, we observe that transmission increases with population density, but not population size. These results may help inform future response efforts.", "doc_id": "nbg1imui"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Predicting the second wave of COVID-19 in Washtenaw County, MI", "abstract": "Marissa Renardy and Denise Kirschner University of Michigan Medical School The COVID-19 pandemic has highlighted the patchwork nature of disease epidemics, with infection spread dynamics varying wildly across countries and across states within the US. These heteroge- neous patterns are also observed within individual states, with patches of concentrated outbreaks. Data is being generated daily at all of these spatial scales, and answers to questions regarded re- opening strategies are desperately needed. Mathematical modeling is useful in exactly these cases, and using modeling at a county scale may be valuable to further predict disease dynamics for the purposes of public health interventions. To explore this issue, we study and predict the spread of COVID-19 in Washtenaw County, MI, the home to University of Michigan, Eastern Michigan University, and Google, as well as serving as a sister city to Detroit, MI where there has been a serious outbreak. Here, we apply a discrete and stochastic network-based modeling framework allowing us to track every individual in the county. In this framework, we construct contact net- works based on synthetic population datasets specific for Washtenaw County that are derived from US Census datasets. We assign individuals to households, workplaces, schools, and group quarters (such as prisons). In addition, we assign casual contacts to each individual at random. Using this framework, we explicitly simulate Michigan-specific government-mandated workplace and school closures as well as social distancing measures. We also perform sensitivity analyses to identify key model parameters and mechanisms contributing to the observed disease burden in the three months following the first observed cases on COVID-19 in Michigan. We then consider several scenarios for relaxing restrictions and reopening workplaces to predict what actions would be most prudent. In particular, we consider the effects of 1) different timings for reopening, and 2) different levels of workplace vs. casual contact re-engagement. Through simulations and sensitivity analyses, we explore mechanisms driving magnitude and timing of a second wave of infections upon re-opening. This model can be adapted to other US counties using synthetic population databases and data specific to those regions.", "doc_id": "n1jmqx6m"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Effectiveness of stay-in-place-orders during COVID-19 pandemic: Evidence from US border counties.", "abstract": "Recent studies on US counties, with varying effect sizes, show that stay-in-place-orders (SIPOs) are associated with a decline in new COVID-19 cases. Our estimation approach relies on county-pairs across state-borders where one state has SIPO whereas the other state does not, controls for matched county-pair fixed effects and day of observation fixed-effects. The county-pair sample from southern, mid-western, and mountain region states (from March 1, 2020 to April 25, 2020) shows that daily COVID-19 incidence case growth rate is 1.994 percentage points lower for counties in SIPO states relative to those bordering in non-SIPO states. Specifically, we find SIPO reduced daily growth rates by 1.97, 2.14, 2.03, and 2.27 percentage points after 1 to 5 days, 6 to 10 days, 11 to 15 days, and 16 to 20 days, respectively. Our effect sizes are much smaller than in the previous studies with the caveat that states in the northeast and on the west coast could not be included in the border county-pair specification. We find limited evidence of heterogeneous effects in counties with a higher population density, percentage of black or Hispanic residents, proportion of population over 65 years, and social association rates in a county. Nor do we find evidence of meaningful differences in effects of SIPO by county Gini index, unemployment, or GDP. The results of this study could further inform policymakers in making decisions on SIPO extensions or lifting of such orders.", "doc_id": "pd6mtn11"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "SARS-CoV-2 antibody prevalence in blood in a large school community subject to a Covid-19 outbreak: a cross-sectional study", "abstract": "BACKGROUND: A SARS-CoV-2 outbreak affecting 52 people from a large school community in Santiago, Chile was identified (March 12), nine days after the first country case. We assessed the magnitude of the outbreak and the role students and staff played using a self-administered antibody detection test and survey. METHODS: The school was closed on March 13, and the entire community was placed under quarantine. We implemented a home-delivery, self-administered, IgG/IgM antibody test and survey to a classroom stratified sample of students and all staff from May 4-19. We aimed to determine overall seroprevalence rates by age group, reported symptoms, contact exposure and to explore dynamics of transmission. RESULTS: Antibody positivity rates were 9.9% (95%CI: 8.2-11.8) for 1,009 students and 16.6% (95%CI: 12.1-21.9) for 235 staff. Among students, positivity was associated with younger age (P=0.01), lower grade level (P=0.05), prior RT-PCR positivity (P=0.03), and history of contact with a confirmed case (P<0.001). Among staff, positivity was higher in teachers (P=0.01) and in those previously RT-PCR positive (P<0.001). Excluding RT-PCR positive individuals, antibody positivity was associated with fever in adults and children (P=0.02; P=0.002), abdominal pain in children (P=0.001), and chest pain in adults (P=0.02). Within antibody positive individuals, 40% of students and 18% of staff reported no symptoms (P=0.01). CONCLUSIONS: Teachers were more affected during the outbreak and younger children were at higher infection risk, likely because index case(s) were teachers and/or parents from preschool. Self-administered antibody testing, supervised remotely, proved to be a suitable and rapid tool. Our study provides useful information for school re-openings.", "doc_id": "lm29yshl"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Covid-19: US cases soar as Trump pushes for schools to open", "abstract": "", "doc_id": "7e1h4k0f"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Considering inequalities in the school closure response to COVID-19", "abstract": "", "doc_id": "0wj9k97j"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Children and the COVID-19 pandemic", "abstract": "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).", "doc_id": "17a70tu9"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "La pandemia de la COVID-19 desde la SEAP./ [The Spanish Society of Pathologists on the COVID-19 pandemic]", "abstract": "", "doc_id": "m85e3ahu"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "[Interim Guidelines for Prevention and Control of COVID-19 for Students Back to School]", "abstract": "", "doc_id": "9nq62i0d"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "COVID-19 and the re-opening of schools: a policy maker's dilemma", "abstract": "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.", "doc_id": "5eg7hf6r"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "How risk communication could have reduced controversy about school closures in Australia during the COVID-19 pandemic", "abstract": "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.", "doc_id": "pvus33s7"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Covid-19: Delaying school reopening by two weeks would halve risks to children, says iSAGE", "abstract": "", "doc_id": "f0izfja8"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Un-Muting Medical Student Education: Utilizing Telemedicine During the COVID-19 Pandemic and Beyond", "abstract": "UNSTRUCTURED: Due to the COVID-19 pandemic, medical schools have paused traditional clerkships, eliminating direct patient encounters from medical student education for the immediate future. Telemedicine offers opportunities in a variety of specialties that can augment student education during this time. The projected growth of telemedicine necessitates that students learn new skills to be effective providers. In this Viewpoint, we delineate specific telehealth opportunities that teach core competencies for patient care, while also teaching telemedicine specific skills. Schools can further augment student education through a variety of telemedicine initiatives across multiple medical fields. The explosion of telemedicine programs due to the pandemic can be a catalyst for schools to integrate telemedicine into their current curricula. The depth and variety of telemedicine opportunities allows schools to continue providing high quality medical education while maintaining social distancing policies.", "doc_id": "n1c1xl5p"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Mental health burden for Chinese middle school students affected by the COVID-19 pandemic", "abstract": "", "doc_id": "3l430xdu"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Covid-19: Government must plan for schools to reopen, say paediatricians", "abstract": "", "doc_id": "cnrx9kxy"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Somatic symptoms and concern regarding COVID-19 among Chinese college and primary school students: A cross-sectional survey", "abstract": "The rapid, ongoing and worldwide coronavirus 2019 (COVID-19) pandemic represents a global public health emergency. Our objective was to explore the impact of the COVID-19 pandemic on somatic symptoms among Chinese college and primary school students, to provide reference data pertaining to the mental health of this population in the context of a public health emergency. In February and March 2020, we explored the somatic symptoms and concerns regarding COVID-19 of 399 college and primary school students in Sichuan Province using the Somatic Self-rating Scale (SSS) and a novel questionnaire, respectively. Logistic regression analysis and non-parametric tests were used to analyze the data. The incidence of somatic symptoms among college students was 34.85 (mild, 26.26%; moderate, 8.59%). The incidence of somatic symptoms in primary school students was 2.39% (all mild). Among the entire cohort, concern regarding COVID-19 was positively correlated with the occurrence of somatic symptoms. Somatic symptoms were more likely among college students expressing greater concern regarding the threat to life and health posed by COVID-19, and the efficacy of prevention and control measures. Among primary school students, only the concern for life and health was associated with a higher likelihood of somatic symptoms. Our data indicate that governments and other relevant agencies should implement different measures to prevent and control mental health disorders diseases in primary school and college students.", "doc_id": "ne8iw9cd"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Novel coronavirus 2019 transmission risk in educational settings", "abstract": "Transmission risk of SARS-CoV-2 in schools is unknown. Our investigations especially in pre-schools could not detect SARS-CoV-2 transmission despite screening of symptomatic and asymptomatic children. The data suggests that children are not the primary drivers of SARS-CoV-2 transmission in schools and could help inform exit strategies for lifting of lockdowns.", "doc_id": "l8wu1b2q"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "Mental health effects of school closures during COVID-19", "abstract": "", "doc_id": "orc4c5lb"} {"topic_name": "school reopening coronavirus", "topic_id": "48", "title": "COVID-19-We urgently need to start developing an exit strategy", "abstract": "AIM: The purpose of this perspective is to review the options countries have to exit the draconian \"lockdowns\" in a carefully staged manner. METHODS: Experts from different countries experiencing Corona Virus Infectious Disease 2019 (COVID-19) reviewed evidence and country-specific approaches and the results of their interventions. RESULTS: Three factors are essential: 1. Reintroduction from countries with ongoing community transmission; 2. The need for extensive testing capacity and widespread community testing, and 3. An adequate supply of personal protective equipment, PPE, to protect health care workers. Discussed at length are lifting physical distancing, how to open manufacturing and construction, logistics, and the opening of higher educational institutions and schools. The use of electronic surveillance is considered. CONCLUSION: Each country should decide on the best path forward. However, we can learn from each other, and the approaches are, in reality, very similar.", "doc_id": "8je2ov11"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Deployment of convalescent plasma for the prevention and treatment of COVID-19.", "abstract": "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19), has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS-CoV-2, nor therapy for those who develop COVID-19. Immune (i.e. \"convalescent\") plasma refers to plasma that is collected from individuals, following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy to confer immediate immunity to susceptible individuals. There are numerous examples, where convalescent plasma has been used successfully as post-exposure prophylaxis and/or treatment of infectious diseases, including other outbreaks of coronaviruses (e.g., SARS-1, Middle East Respiratory Syndrome [MERS]). Convalescent plasma has also been used in the COVID-19 pandemic; limited data from China suggest clinical benefit, including radiological resolution, reduction in viral loads and improved survival. Globally, blood centers have robust infrastructure to undertake collections and construct inventories of convalescent plasma to meet the growing demand. Nonetheless, there are nuanced challenges, both regulatory and logistical, spanning donor eligibility, donor recruitment, collections and transfusion itself. Data from rigorously controlled clinical trials of convalescent plasma are also few, underscoring the need to evaluate its use objectively for a range of indications (e.g., prevention vs treatment) and patient populations (e.g., age, comorbid disease). We provide an overview of convalescent plasma, from evidence of benefit, regulatory considerations, logistical work flow and proposed clinical trials, as scale up is brought underway to mobilize this critical resource. .", "doc_id": "ew8h715h"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.", "abstract": "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.", "doc_id": "lzgwxshi"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Kinetics of viral load and antibody response in relation to COVID-19 severity.", "abstract": "The SARS-CoV-2 is the causative agent for COVID-19 pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity and neutralization antibody response in COVID-19 patients. Two groups of RT-PCR confirmed COVID-19 patients were enrolled in this study, including 12 severe patients in ICUs who needed mechanical ventilation and 11 mild patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severe patients had viral shedding in a variety of tissues for 20~40 days post onset of disease (8/12, 66.7%); while the majority of mild patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA after 10 days post-onset (9/11, 81.8%). Mild patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both severe and mild groups at 9 days post onset and remained high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in COVID-19 patients but not in MERS patients. High-levels of neutralizing antibodies were induced after about 10 days post onset in both severe and mild patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from COVID-19 patients, but not convalescent SARS and MERS patients inhibited SARS-CoV-2 entry. Anti-SARS-CoV-2 S and N IgG level exhibited moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in human after SARS-CoV-2 infection.", "doc_id": "ehe1uj7i"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Spectrum of innate and adaptive immune response to SARS CoV 2 infection across asymptomatic, mild and severe cases; a longitudinal cohort study", "abstract": "", "doc_id": "ry97bngd"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders", "abstract": "Background: To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset. Results: Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P=0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset. Conclusions: Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys and for estimating the true infection prevalence in populations.", "doc_id": "7l79ic0v"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Relative COVID-19 viral persistence and antibody kinetics", "abstract": "Importance: The COVID-19 antibody response is a critical indicator for evaluating immunity and also serves as the knowledge base for vaccine development. The picture is still not clear because of many limitations including testing tools, time of sampling, and the unclear impact of varying clinical status. In addition to these problems, antibody levels may not be equivalent to protective capacity. Objective: To define the key factor for the different patterns of COVID-19 antibody response. Design: We elucidated the antibody response with time-series throat and serum samples for viral loads and antibody levels, then used a neutralization test to evaluate protectiveness. Setting: A medical center that typically cares for patients with moderate to severe diseases. Because of the low prevalence of COVID-19 in Taiwan and local government policy, however, we also admit COVID-19 patients with mild disease or even those without symptoms for inpatient care. Participants: RT-PCR-confirmed COVID-19 patients. Results: We found that only patients with relative persistence of virus at pharynx displayed strong antibody responses that were proportional to the pharyngeal viral load. They also had proportional neutralization titers per unit of serum. Although antibody levels decreased around 2 weeks after symptom onset, the neutralization efficacy per unit antibody remained steady and even continued to increase over time. The antibody response in patients with rapid virus clearance was weak, but the neutralization efficacy per unit antibody in these patients was comparable to those with persistent presence of virus. The deceased were with higher viral load, higher level of antibody, and higher neutralization titers in the serum, but the neutralization capacity per unit antibody is relatively low. Conclusions and Relevance: Strong antibody response depends on the relative persistence of the virus, instead of the absolute virus amount. The antibody response is still weak if large amount of virus is cleared quickly. The neutralization efficacy per unit antibody is comparable between high and low antibody patterns. Strong antibody response contains more inefficient and maybe even harmful antibodies. Low antibody response is also equipped with a capable B cell pool of efficient antibodies, which may expand with next virus encounter and confer protection.", "doc_id": "nj5xe91b"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Systems-level immunomonitoring from acute to recovery phase of severe COVID-19", "abstract": "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.", "doc_id": "xwlpb3db"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Reappearance of Effector T Cells Predicts Successful Recovery from COVID-19", "abstract": "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.", "doc_id": "5lhvix51"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "IgA dominates the early neutralizing antibody response to SARS-CoV-2", "abstract": "A major dogma in immunology has it that the IgM antibody response precedes secondary memory responses built on the production of IgG, IgA and, occasionaly, IgE. Here, we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of specific, neutralizing, antibodies in serum and broncho-alveolar fluid of 145 patients with COVID-19. Surprisingly, early SARS-CoV-2-specific humoral responses were found to be typically dominated by antibodies of the IgA isotype. Peripheral expansion of IgA-plasmablasts with mucosal-homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. While the specific antibody response included IgG, IgM and IgA, the latter contributed to a much larger extent to virus neutralization, as compared to IgG. However, specific IgA serum levels notably decrease after one month of evolution. These results represent a challenging observation given the present uncertainty as to which kind of humoral response would optimally protect against re-infection, and whether vaccine regimens should consider boosting a potent, although, at least in blood, fading IgA response.", "doc_id": "ez4v8xr0"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals", "abstract": "Our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still developing. We investigated seroprevalence and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members (155 individuals; ages 5-79 years). Seropositivity for SARS-CoV-2 spike glycoprotein aligned with PCR results that confirmed previous infection. Anti-spike IgG titers remained high 60 days post-infection and did not associate with symptoms, but spike-specific IgM did associate with malaise and fever. We found limited household transmission, with children of infected individuals seldomly seropositive, highlighting professional exposure as the dominant route of infection in our cohort. We analyzed PBMCs from a subset of seropositive and seronegative adults. TLR7 agonist- activation revealed an increased population of IL-6+TNF-IL-1{beta}+ monocytes, while SARS-CoV-2 peptide stimulation elicited IL-33, IL-6, IFNa2, and IL-23 expression in seropositive individuals. IL-33 correlated with CD4+ T cell activation in PBMCs from convalescent subjects, and was likely due to T cell-mediated effects on IL-33- producing cells. IL-33 is associated with pulmonary infection and chronic diseases like asthma and COPD, but its role in COVID-19 is unknown. Analysis of published scRNAseq data of bronchoalveolar lavage fluid (BALF) from patients with mild to severe COVID-19 revealed a population of IL-33-producing cells that increases with disease. Together these findings show that IL-33 production is linked to SARS-CoV- 2 infection and warrant further investigation of IL-33 in COVID-19 pathogenesis and immunity.", "doc_id": "ns2pfiua"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Human B cell clonal expansion and convergent antibody responses to SARS-CoV-2", "abstract": "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 na\u00efve 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.", "doc_id": "bv66depf"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Neutralizing Antibodies Responses to SARS-CoV-2 in COVID-19 Inpatients and Convalescent Patients", "abstract": "Background. COVID-19 is a pandemic with no specific antiviral treatments or vaccines. The urgent needs for exploring the neutralizing antibodies from patients with different clinical characteristics are emerging. Methods. A total of 117 blood samples were collected from 70 COVID-19 inpatients and convalescent patients. The presence of neutralizing antibody was determined with a modified cytopathogenic assay based on live SARS-CoV-2. The dynamics of neutralizing antibody levels at different with different clinical characteristics were analyzed. Results. The seropositivity rate reached up to 100.0% within 20 days since onset, and remained 100.0% till day 41-53. The total GMT was 1:163.7 (95% CI, 128.5 to 208.6), and the antibody level was highest during day 31-40 since onset, and then decreased slightly. Individual differences in changes of antibody levels were observed among 8 representative convalescent patients. In multivariate GEE analysis, patients at age of 31-60 and 61-84 had a higher antibody level than those at age of 16-30 (\u03b2=1.0518, P=0.0152; \u03b2=1.3718, P=0.0020). Patients with a worse clinical classification had a higher antibody titer (\u03b2=0.4639, P=0.0227). Conclusions. The neutralizing antibodies were detected even at the early stage of disease, and a significant response showed in convalescent patients. Moreover, changes on antibody levels ware individual specific.", "doc_id": "ydov6lsi"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Clinical Characteristics of Recurrent-positive Coronavirus Disease 2019 after Curative Discharge: a retrospective analysis of 15 cases in Wuhan China", "abstract": "In China, the patients with previously negative RT-PCR results again test positive during the post-discharge isolation period. We aimed to determine the clinical characteristics of these recurrent-positive patients. We retrospectively reviewed the data of 15 recurrent-positive patients and 107 control patients with non-recurrent, moderate COVID-19 treated in Wuhan, China. Clinical data and laboratory results were comparatively analyzed. We found that recurrent-positive patients had moderate disease. The rate of recurrent-positive disease in our hospital was 1.87%. Recurrent-positive patients were significantly younger (43(35-54) years) than control patients (60(43-69) years) (P=0.011). The early LOS (length of stay in hospital before recurrence) was significantly longer in recurrent-positive patients (36(34-45) days) than in control patients (15(7-30) days) (P =0.001). The time required for the first conversion of RT-PCR results from positive to negative was significantly longer in recurrent-positive patients (14(10-17) days) than in control patients (6(3-9) days) (P =0.011). Serum COVID-19 antibody levels were significantly lower in recurrent-positive patients than in control patients (IgM: 13.69 {+/-} 4.38 vs. 68.10 {+/-} 20.85 AU/mL, P = 0.015; IgG: 78.53 {+/-} 9.30 vs. 147.85 {+/-} 13.33 AU/mL, P < 0.0001). Recurrent-positive patients were younger than control patients. The early LOS (length of stay in hospital before recurrence) was significantly longer in recurrent-positive group than that in control group. COVID-19 IgM/IgG antibody levels were significantly lower in recurrent-positive group than those in control group, which might explain why the virus RNA RT-PCR was positive after the initial clinical cure(with three times of virus RNA RT-PCR negative). The virus might not be fully eliminated because of the lower IgG level and their later replicating might result in recurrent-positive virus RNA RT-PCR.", "doc_id": "08mjfs83"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Broad phenotypic alterations and potential dysfunctions of lymphocytes in COVID-19 recovered individuals", "abstract": "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.", "doc_id": "avhxj8jk"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Clinical characteristics of rehospitalized patients with COVID-19 in China", "abstract": "This study aims to observe the clinical characteristics of recovered patients from Coronavirus Disease 2019 (COVID-19) with positive in reverse transcription-polymerase chain reaction (RT-PCR) or serum antibody. The profile, clinical symptoms, laboratory outcomes, and radiologic assessments were extracted on 11 patients, who tested positive for COVID-19 with RT-PCR or serum antibody after discharged and was admitted to Hubei No. 3 People's Hospital of Jianghan University for a second treatment in March 2020. The average interval time between the first discharge and the second admission measured 16.00 \u00b1 7.14 days, ranging from 6 to 27 days. In the second hospitalization, one patient was positive for RT-PCR and serum antibody immunoglobulin M (IgM)-immunoglobulin G (IgG), five patients were positive for both IgM and IgG but negative for RT-PCR. Three patients were positive for both RT-PCR and IgG but negative for IgM. The main symptoms were cough (54.55%), fever (27.27%), and feeble (27.27%) in the second hospitalization. Compared with the first hospitalization, there were significant decreases in gastrointestinal symptoms (5 vs 0, P = .035), elevated levels of both white blood cell count (P = .036) and lymphocyte count (P = .002), remarkedly decreases in C-reactive protein and serum amyloid A (P < .05) in the second hospitalization. Additionally, six patients' chest computed tomography (CT) exhibited notable improvements in acute exudative lesions. There could be positive results for RT-PCR analysis or serum IgM-IgG in discharged patients, even with mild clinical symptoms, however, their laboratory outcomes and chest CT images would not indicate the on-going development in those patients.", "doc_id": "evonlumf"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Seven discharged patients turning positive again for SARS-CoV-2 on quantitative RT-PCR", "abstract": "", "doc_id": "m85328ve"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "SARS-CoV-2 positivity in a discharged COVID-19 patient: a case report", "abstract": "", "doc_id": "oc7j8uu2"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Reappearance of effector T cells is associated with recovery from COVID-19", "abstract": "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 \u00ce\u00b3\u00ce\u00b4 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.", "doc_id": "871812f7"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "COVID-19 and Postinfection Immunity: Limited Evidence, Many Remaining Questions", "abstract": "", "doc_id": "6i130oxh"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Probable causes and risk factors for positive SARS-CoV-2 test in recovered patients: Evidence from Brunei Darussalam", "abstract": "Case reports of COVID-19 patients who have been discharged and subsequently report positive RT-PCR again (hereafter referred as 're-positive') do not fully describe the magnitude and significance of this issue. In order to determine the re-positive rate (proportion) and review probable causes and outcomes, we conduct a retrospective study of all 119 discharged patients in Brunei Darussalam up till April 23. Patients who were discharged are required to self-isolate at home for 14 days and undergo NP specimen collection post-discharge. Discharged patients found to be re-positive were readmitted. We reviewed the clinical and epidemiological records of all discharged patients and apply log-binomial models to obtain risk ratios for re-positive status. One in five recovered patients subsequently test positive again for SARS-CoV-2 - this risk is more than six times higher in persons aged 60 years and above. The average Ct value of re-positive patients was lower pre-discharge compared to their readmission Ct value. Out of 111 close contacts tested, none were found to be positive as a result of exposure to a re-positive patient. Our findings support prolonged but intermittent viral shedding as the probable cause for this phenomenon. We did not observe infectivity potential in these patients. This article is protected by copyright. All rights reserved.", "doc_id": "eg3pr6z0"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Rehospitalization of a Recovered Coronavirus Disease 19 (COVID-19) Child With Positive Nucleic Acid Detection", "abstract": "Since December 2019, novel coronavirus-infected pneumonia (coronavirus disease 19) occurred in Wuhan and rapidly spread throughout China and beyond. During this period, increasing of reports found that several recovered patients from different hospitals showed positive results of nucleic acid test again soon after discharge. However, little attention has been paid to recovered children. Herein, we reported a case of 8-year-old recovered child, who was rehospitalized again because of unexplained fever.", "doc_id": "zq8rv8mz"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Retest positive for SARS-CoV-2 RNA of \"recovered\" patients with COVID-19: Persistence, sampling issues, or re-infection?", "abstract": "\"Retest Positive\" for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) from \"recovered\" coronavirus disease-19 (COVID-19) has been reported and raised several important questions for this novel coronavirus and COVID-19 disease. In this commentary, we discussed several questions: (a) Can SARS-CoV-2 re-infect the individuals who recovered from COVID-19? This question is also associated with other questions: whether or not SARS-CoV-2 infection induces protective reaction or neutralized antibody? Will SARS-CoV-2 vaccines work? (b) Why could some recovered patients with COVID-19 be re-tested positive for SARS-CoV-2 RNA? (c) Are some recovered pwith atients COVID-19 with re-testing positive for SARS-CoV-2 RNA infectious? and (d) How should the COVID-19 patients with retest positive for SARS-CoV-2 be managed?", "doc_id": "5x30jj1s"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Immune response in children with COVID-19 is characterized by lower levels of T cell activation than infected adults", "abstract": "XX XXX This article is protected by copyright. All rights reserved.", "doc_id": "yva8s3md"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections", "abstract": "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.", "doc_id": "uecosx5i"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Kinetics of viral load and antibody response in relation to COVID-19 severity", "abstract": "The SARS-CoV-2 is the causative agent for COVID-19 pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity and neutralization antibody response in COVID-19 patients. Two groups of RT-PCR confirmed COVID-19 patients were enrolled in this study, including 12 severe patients in ICUs who needed mechanical ventilation and 11 mild patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severe patients had viral shedding in a variety of tissues for 20~40 days post onset of disease (8/12, 66.7%); while the majority of mild patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA after 10 days post-onset (9/11, 81.8%). Mild patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both severe and mild groups at 9 days post onset and remained high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in COVID-19 patients but not in MERS patients. High-levels of neutralizing antibodies were induced after about 10 days post onset in both severe and mild patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from COVID-19 patients, but not convalescent SARS and MERS patients inhibited SARS-CoV-2 entry. Anti-SARS-CoV-2 S and N IgG level exhibited moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in human after SARS-CoV-2 infection.", "doc_id": "vtvdk8qj"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Discharged COVID-19 Patients Testing Positive Again for SARS-CoV-2 RNA: A Minireview of Published Studies from China", "abstract": "In the ongoing COVID-19 pandemic, one potential cause of concern is that some discharged COVID-19 patients are testing positive again for SARS-CoV-2 RNA. To better understand what is happening and to provide public health policy planners and clinicians timely information, we have searched and reviewed published studies about discharged patients testing positive again for the SARS-CoV-2 RNA. Our search found 12 reports, all of which described patients in China. Our review of these reports indicates the presence of discharged patients who remain asymptomatic but test positive. However, it is unclear whether they are contagious because a positive RT-PCR test does not necessarily indicate the presence of replicating and transmissible virus. Our review suggests the need for timely, parallel testing of different samples, including for example, fecal specimens, from COVID-19 patients before and after they are discharged from hospitals. This article is protected by copyright. All rights reserved.", "doc_id": "59prqbb3"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "The treatment and follow-up of \"recurrence\" with discharged COVID-19 patients: Data from Guizhou, China", "abstract": "We reported 20 cases of discharged COVID-19 patients whose RT-PCR test results showed \"re-positive\". After finding \"re-positive \", these patients were admitted to hospital for the second time and were followed up until the end of May 2020. Methods: Record detailed treatment and follow-up process, and collect relevant data. The possible causes and potential clinical significance of this phenomenon are discussed. This article is protected by copyright. All rights reserved.", "doc_id": "4q72jj2h"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "The clinical characteristic of eight patients of COVID-19 with positive RT-PCR test after discharge", "abstract": "Corona virus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The phenomenon of positive real time reverse transcription polymerase chain reaction (RT-PCR) result of SARS-CoV-2 in recovered patients had occurred and the research about these patients was rare. In our study, we did a retrospective review of medical records from COVID-19 patients admitted to one ward of Tongji Hospital of Hua Zhong University of Science and Technology from 10 February to 13 April 2020. From 10 February to 13 April 2020, there were 108 patients of COVID-19 admitted in the one ward of Tongji Hospital. Among them, eight cases were readmission patients because the RT-PCR result of SARS-CoV-2 was positive again after discharge. On the second admission, they had no symptoms and their chest computed tomography was almost normal. Data from laboratory tests of the readmission patients showed that all eight patients had normal white blood cell count, lymphocyte count. The inflammatory factors like procalcitonin and interleukin 6 were normal. After treatment, two patients met the standard and were discharged. The other six patients were still in the hospital because their RT-PCR of SARS-CoV-2 did not get three consecutive negative results and the course of two patients had persisted more than 90 days. We still needed to be alert that these patients could infect other people as a source of infection, and we also needed to be alert that these patients become chronic virus carriers. It also aroused our concern about the discharge standard of COVID-19.", "doc_id": "nqxqljf8"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Serum antibody response in critically ill patients with COVID-19", "abstract": "", "doc_id": "tk3n9lak"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Probable causes and risk factors for positive SARS\u2010CoV\u20102 test in recovered patients: Evidence from Brunei Darussalam", "abstract": "Case reports of COVID\u201019 patients who have been discharged and subsequently report positive RT\u2010PCR again (hereafter referred as \u2018re\u2010positive\u2019) do not fully describe the magnitude and significance of this issue. In order to determine the re\u2010positive rate (proportion) and review probable causes and outcomes, we conduct a retrospective study of all 119 discharged patients in Brunei Darussalam up till April 23. Patients who were discharged are required to self\u2010isolate at home for 14 days and undergo NP specimen collection post\u2010discharge. Discharged patients found to be re\u2010positive were readmitted. We reviewed the clinical and epidemiological records of all discharged patients and apply log\u2010binomial models to obtain risk ratios for re\u2010positive status. One in five recovered patients subsequently test positive again for SARS\u2010CoV\u20102 \u2013 this risk is more than six times higher in persons aged 60 years and above. The average Ct value of re\u2010positive patients was lower pre\u2010discharge compared to their readmission Ct value. Out of 111 close contacts tested, none were found to be positive as a result of exposure to a re\u2010positive patient. Our findings support prolonged but intermittent viral shedding as the probable cause for this phenomenon. We did not observe infectivity potential in these patients. This article is protected by copyright. All rights reserved.", "doc_id": "b20pbzi4"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "The clinical characteristic of eight patients of COVID\u201019 with positive RT\u2010PCR test after discharge", "abstract": "Corona virus disease 2019 (COVID\u201019) was caused by severe acute respiratory syndrome coronavirus\u20102 (SARS\u2010CoV\u20102). The phenomenon of positive real time reverse transcription polymerase chain reaction (RT\u2010PCR) result of SARS\u2010CoV\u20102 in recovered patients had occurred and the research about these patients was rare. In our study, we did a retrospective review of medical records from COVID\u201019 patients admitted to one ward of Tongji Hospital of Hua Zhong University of Science and Technology from 10 February to 13 April 2020. From 10 February to 13 April 2020, there were 108 patients of COVID\u201019 admitted in the one ward of Tongji Hospital. Among them, eight cases were readmission patients because the RT\u2010PCR result of SARS\u2010CoV\u20102 was positive again after discharge. On the second admission, they had no symptoms and their chest computed tomography was almost normal. Data from laboratory tests of the readmission patients showed that all eight patients had normal white blood cell count, lymphocyte count. The inflammatory factors like procalcitonin and interleukin 6 were normal. After treatment, two patients met the standard and were discharged. The other six patients were still in the hospital because their RT\u2010PCR of SARS\u2010CoV\u20102 did not get three consecutive negative results and the course of two patients had persisted more than 90 days. We still needed to be alert that these patients could infect other people as a source of infection, and we also needed to be alert that these patients become chronic virus carriers. It also aroused our concern about the discharge standard of COVID\u201019.", "doc_id": "kgl3r43i"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Assessment of patients who tested positive for COVID-19 after recovery", "abstract": "", "doc_id": "15gnilwy"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "The issue of recurrently positive patients who recovered from COVID-19 according to the current discharge criteria: investigation of patients from multiple medical institutions in Wuhan, China", "abstract": "The current discharge criteria for COVID-19 require that patients have two consecutive negative results for RT-PCR detection. Here, we observed that recurrently positive RT-PCR test results in patients with three consecutive negative results (3xNegRPos, 5.4%) were significantly decreased compared with those in patients with two consecutive negative results (2xNegRPos, 20.6%); such patients reported positive RT-PCR test results within 1 to 12 days after meeting the discharge criteria. These results confirmed that many recovered patients could show a positive RT-PCR test result, and most of these patients could be identified by an additional RT-PCR test prior to discharge.", "doc_id": "jfxmqq2u"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Re-evaluation of retested nucleic acid-positive cases in recovered COVID-19 patients: Report from a designated transfer hospital in Chongqing, China", "abstract": "Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, Hubei Province, China [1], a large number of confirmed cases met the discharge criteria (one of which is two consecutive negative nucleic acid tests with an interval of at least 24 h) [2]. Previous studies have paid more attention to the epidemic situation of COVID-19 and patient diagnosis and treatment. Close attention also should be paid to the discharged patients. Surprisingly, a previous follow-up reported that some patients\u2019 nucleic acid retest results were positive again after discharge [3]. Factors impacting these follow-up test results should be further investigated. Since the first confirmed case was diagnosed in our hospital (Chongqing Emergency Medical Center, the designated transfer hospital) on February 4th, we confirmed a total of 17 cases. All patients infected with the novel coronavirus were transferred to a designated hospital in Southwest China\u2019s Chongqing by ambulance with an inbuilt negative-pressure chamber [4]. In the follow-up examination of these patients, RT-PCR tests were conducted again 3 days after discharged from the designated hospital. Four patients showed recurrence of positive results after a few days of discharge. Thus, we examined these cases herein, aiming to provide information for policy formulation and modification of discharge plans.", "doc_id": "i79b79un"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Elevated nucleoprotein-induced interferon-\u03b3 release in COVID-19 patients detected in a SARS-CoV-2 enzyme-linked immunosorbent spot assay", "abstract": "", "doc_id": "qvtvpnrr"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Recurrent pneumonia in a patient with new coronavirus infection after discharge from hospital for insufficient antibody production: a case report", "abstract": "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.", "doc_id": "73b2rcn1"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Longitudinal anti-SARS-CoV-2 antibody profile and neutralization activity of a COVID-19 patient", "abstract": "We followed\u2013up a mild COVID-19 patient for 91 days and serially monitored his serum antibodies to four SARS-CoV-2 related antigens (NP, RBD, S1 and ECD) and neutralization activities. Our data revealed a profile of serial antibody responses during the progress and a quick decline of neutralization activities after discharge.", "doc_id": "1jeh7hke"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Discharged COVID\u201019 Patients Testing Positive Again for SARS\u2010CoV\u20102 RNA: A Minireview of Published Studies from China", "abstract": "In the ongoing COVID\u201019 pandemic, one potential cause of concern is that some discharged COVID\u201019 patients are testing positive again for SARS\u2010CoV\u20102 RNA. To better understand what is happening and to provide public health policy planners and clinicians timely information, we have searched and reviewed published studies about discharged patients testing positive again for the SARS\u2010CoV\u20102 RNA. Our search found 12 reports, all of which described patients in China. Our review of these reports indicates the presence of discharged patients who remain asymptomatic but test positive. However, it is unclear whether they are contagious because a positive RT\u2010PCR test does not necessarily indicate the presence of replicating and transmissible virus. Our review suggests the need for timely, parallel testing of different samples, including for example, fecal specimens, from COVID\u201019 patients before and after they are discharged from hospitals. This article is protected by copyright. All rights reserved.", "doc_id": "snajbvr9"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Antibody responses against SARS\u2010CoV\u20102 in COVID\u201019 patients", "abstract": "The emerging coronavirus disease 2019 (COVID\u201019) caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) has become a global pandemic, and brings formidable challenges to public health, society and the economy worldwide. Currently, the antibody responses against SARS\u2010CoV\u20102 remains largely unknown. We herein estimated the longevity of specific antibodies against SARS\u2010CoV\u20102, and reported that antibodies waned over substantially in COVID\u201019 patients after recovery. This article is protected by copyright. All rights reserved.", "doc_id": "vuym41xv"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Neutralizing antibody response in mild COVID-19", "abstract": "", "doc_id": "knj0c23q"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Do you become immune once you have been infected?", "abstract": "", "doc_id": "ycv1fz03"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "The treatment and follow\u2010up of \u201crecurrence\u201d with discharged COVID\u201019 patients: Data from Guizhou, China", "abstract": "We reported 20 cases of discharged COVID\u201019 patients whose RT\u2010PCR test results showed \u201cre\u2010positive\u201d. After finding \u201cre\u2010positive \u201d, these patients were admitted to hospital for the second time and were followed up until the end of May 2020. Methods: Record detailed treatment and follow\u2010up process, and collect relevant data. The possible causes and potential clinical significance of this phenomenon are discussed. This article is protected by copyright. All rights reserved.", "doc_id": "zt6w9dri"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Functional exhaustion of antiviral lymphocytes in COVID-19 patients", "abstract": "", "doc_id": "dsuxgguf"} {"topic_name": "post-infection COVID-19 immunity", "topic_id": "49", "title": "Clinical recurrences of COVID-19 symptoms after recovery: viral relapse, reinfection or inflammatory rebound?", "abstract": "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.", "doc_id": "42t0zriz"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "Current Status of Multiple Drug Molecules, and Vaccines: An Update in SARS-CoV-2 Therapeutics", "abstract": "The coronavirus disease of 2019 (COVID-19) is a pandemic disease that has taken the lives of many around the world. It is caused by severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2). To date, the USA, Italy, Spain, France, Russia, and the UK have been hit the hardest by the virus. However, death counts are still rising. Some nations have managed to \u201cflatten\u201d the death rate via protective measures such physical distancing, quarantine measures, and therapeutic management. The structure of the SARS-CoV-2 virus comprises of S proteins, M proteins, E proteins, hemagglutinin esterases, nucleocapsid proteins, and a 30-kb RNA genome. Viral proteases cleave these polyproteins and RNA-dependent polymerases replicate the genome. Currently, there are no effective therapies against this new disease. Numerous investigators are developing novel protease inhibitors, some of which have made it into clinical trials. Researchers are also attempting to develop a vaccine. In this review paper, we discuss the latest therapeutic developments against COVID-19. [Figure: see text]", "doc_id": "y87tq9wu"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "Vaccines and Therapies in Development for SARS-CoV-2 Infections.", "abstract": "The current COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. The virus causes severe respiratory symptoms which manifest disproportionately in the elderly. Currently, there are over 6.5 million cases and 380,000 deaths reported. Given the current severity of the outbreak, there is a great need for antiviral therapies and vaccines to treat and prevent COVID-19. In this review, we provide an overview of SARS-CoV-2 and discuss the emerging therapies and vaccines that show promise in combating COVID-19. We also highlight potential viral targets that could be exploited by researchers and drug manufacturers.", "doc_id": "kf7yz3oz"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "Structural and functional conservation of the programmed -1 ribosomal frameshift signal of SARS coronavirus 2 (SARS-CoV-2).", "abstract": "About 17 years after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic, the world is currently facing the COVID-19 pandemic caused by SARS coronavirus 2 (SARS-CoV-2). According to the most optimistic projections, it will take more than a year to develop a vaccine, so the best short-term strategy may lie in identifying virus-specific targets for small molecule-based interventions. All coronaviruses utilize a molecular mechanism called programmed -1 ribosomal frameshift (-1 PRF) to control the relative expression of their proteins. Previous analyses of SARS-CoV have revealed that it employs a structurally unique three-stemmed mRNA pseudoknot that stimulates high -1 PRF rates and that it also harbors a -1 PRF attenuation element. Altering -1 PRF activity impairs virus replication, suggesting that this activity may be therapeutically targeted. Here, we comparatively analyzed the SARS-CoV and SARS-CoV-2 frameshift signals. Structural and functional analyses revealed that both elements promote similar -1 PRF rates and that silent coding mutations in the slippery sites and in all three stems of the pseudoknot strongly ablate -1 PRF activity. We noted that the upstream attenuator hairpin activity is also functionally retained in both viruses, despite differences in the primary sequence in this region. Small-angle X-ray scattering analyses indicated that the pseudoknots in SARS-CoV and SARS-CoV-2 have the same conformation. Finally, a small molecule previously shown to bind the SARS-CoV pseudoknot and inhibit -1 PRF was similarly effective against -1 PRF in SARS-CoV-2, suggesting that such frameshift inhibitors may be promising lead compounds to combat the current COVID-19 pandemic.", "doc_id": "yxiacesg"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "Quantitative measurement of activity of JAK-STAT signaling pathways in blood samples and immune cells to predict innate and adaptive cellular immune response to viral infection and accelerate vaccine development", "abstract": "The host immune response determines the clinical course of a viral infection, for example in case of COVID-19 infection. The effectiveness of vaccination also depends on the induced immune response. Currently there is no method to measure the cellular immune response in blood samples. The functional activity of cells of innate and adaptive immune system is determined by coordinated activity of signaling pathways, especially the JAK-STAT pathways. Using a previously described approach we developed mRNA-based tests to measure activity of these signaling pathways, and show that they can be used to measure in a quantitative manner the cellular innate and adaptive immune response to a viral infection or vaccine in whole blood, PBMC, and specific immune cell type samples. Pathway activity level and range in healthy individuals was established, enabling interpretation of a pathway activity score on a patient sample without the need for a reference sample. Evidence is presented that the pathway activity analysis may also be useful for in vitro vaccine development and assessment of vaccine immunogenicity. Other envisioned applications lie in development of immunomodulatory drugs and drug response prediction and monitoring. Tests are expected to be of value in the COVID-19 crisis. In addition to the described Affymetrix microarray-based pathway tests for measuring host immune response, qPCR-based versions are in development; the latter can in principle be performed within three hours in routine hospital labs.", "doc_id": "wzdgizoo"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "mRNA Vaccines: Possible Tools to Combat SARS-CoV-2", "abstract": "", "doc_id": "6emy92i5"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "LinearDesign: Efficient Algorithms for Optimized mRNA Sequence Design", "abstract": "A messenger RNA (mRNA) vaccine has emerged as a promising direction to combat the current COVID-19 pandemic. This requires an mRNA sequence that is stable and highly productive in protein expression, features which have been shown to benefit from greater mRNA secondary structure folding stability and optimal codon usage. However, sequence design remains a hard problem due to the exponentially many synonymous mRNA sequences that encode the same protein. We show that this design problem can be reduced to a classical problem in formal language theory and computational linguistics that can be solved in O(n^3) time, where n is the mRNA sequence length. This algorithm could still be too slow for large n (e.g., n = 3, 822 nucleotides for the spike protein of SARS-CoV-2), so we further developed a linear-time approximate version, LinearDesign, inspired by our recent work, LinearFold. This algorithm, LinearDesign, can compute the approximate minimum free energy mRNA sequence for this spike protein in just 11 minutes using beam size b = 1, 000, with only 0.6% loss in free energy change compared to exact search (i.e., b = +infinity, which costs 1 hour). We also develop two algorithms for incorporating the codon optimality into the design, one based on k-best parsing to find alternative sequences and one directly incorporating codon optimality into the dynamic programming. Our work provides efficient computational tools to speed up and improve mRNA vaccine development.", "doc_id": "v0m90h3n"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "Vaccines and Therapies in Development for SARS-CoV-2 Infections", "abstract": "The current COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. The virus causes severe respiratory symptoms which manifest disproportionately in the elderly. Currently, there are over 6.5 million cases and 380,000 deaths reported. Given the current severity of the outbreak, there is a great need for antiviral therapies and vaccines to treat and prevent COVID-19. In this review, we provide an overview of SARS-CoV-2 and discuss the emerging therapies and vaccines that show promise in combating COVID-19. We also highlight potential viral targets that could be exploited by researchers and drug manufacturers.", "doc_id": "u35rryzi"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "Deconvoluting Lipid Nanoparticle Structure for Messenger RNA Delivery", "abstract": "Lipid nanoparticle (LNP) packaged mRNA vaccines have been deployed against infectious diseases such as COVID-19, yet their structural features remain unclear. Cholesterol, a major constituent within LNPs, contributes to their morphology that influences gene delivery. Herein, we examine the structure of LNPs containing cholesterol derivatives using electron microscopy, differential scanning calorimetry, and membrane fluidity assays. LNPs formulated with C24 alkyl derivatives of cholesterol show a polymorphic shape and various degrees of multilamellarity and lipid partitioning, likely due to phase separation. The addition of methyl and ethyl groups to the C24 alkyl tail of the cholesterol backbone induces multilamellarity (>50% increase compared to cholesterol), while the addition of a double bond induces lipid partitioning (>90% increase compared to cholesterol). LNPs with multilamellar and faceted structures, as well as a lamellar lipid phase, showed higher gene transfection. Unraveling the structure of mRNA-LNPs can enable their rational design toward enhanced gene delivery.", "doc_id": "gidlrnu8"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "RNA to the rescue: RNA is one of the most promising targets for drug development given its wide variety of uses", "abstract": "The race for a vaccine against SARS\u2010CoV\u20102 has accelerated research on RNA\u2010based therapeutics. Beyond vaccines, RNA also shows great potential for cancer therapies.[Image: see text]", "doc_id": "xhm97wy2"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "Identification of a Noncanonical Signal for Transcription of a Novel Subgenomic mRNA of Mouse Hepatitis Virus: Implication for the Mechanism of Coronavirus RNA Transcription", "abstract": "Abstract Subgenomic RNA transcription of coronaviruses involves the interaction between the leader (or antileader) and the intergenic (IG) sequences. However, it is not clear how these two sequences interact with each other. In this report, a previously unrecognized minor species of subgenomic mRNA, termed mRNA5\u20131, was identified in cells infected with mouse hepatitis virus (MHV) strains JHM2c, JHM(2), JHM(3), A59, and MHV-1. Sequence analysis revealed that the leader-body fusion site of the mRNA is located at approximately 150 nucleotides (nt) downstream of the consensus IG sequence for mRNA 5 and did not have sequence homology with any known IG consensus sequences. To determine whether this sequence functions independently as a promoter, we cloned a 140-nt sequence (from \u224870 nt upstream to \u224870 nt downstream of the fusion site) from viral genomic RNA and placed it in front of a reporter gene in the defective-interfering (DI) RNA-chloramphenicol acetyltransferase (CAT) reporter vector. Transfection of the reporter RNA into MHV-infected cells resulted in synthesis of a CAT-specific subgenomic mRNA detected by reverse transcription-polymerase chain reaction (RT-PCR). The strength of this promoter was similar to that of the IG7 (for mRNA 7) as measured by the CAT activity. Deletion analysis showed that the sequence as few as 13 nt was sufficient to initiate mRNA transcription, while mutations within the 13-nt abolished mRNA transcription. In vitro translation study confirmed that the envelope (E) protein was translated from mRNA5\u20131, which encodes the open reading frame (ORF) 5b at its 5\u2032-end, indicating that mRNA5\u20131 is a functional message. Furthermore, when the ORF5b was replaced with the CAT gene and placed in the DI in the context of viral mini-genome, CAT was expressed not only from the first ORF of mRNA5\u20131 but also from the second and third ORF of mRNA5 and genomic DI RNA, respectively, suggesting that more than one mechanism is involved in regulation of ORF5b expression. Our findings thus support the notion that base-pairing between the leader (or antileader) and the IG is not the sole mechanism in subgenomic RNA transcription.", "doc_id": "z5uhrta5"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "Antiviral RNAi therapy: emerging approaches for hitting a moving target", "abstract": "The field of directed RNA interference (RNAi) has rapidly developed into a highly promising approach for specifically downregulating genes to alleviate disease pathology. This technology is especially well-suited to treating viral infections, and numerous examples now illustrate that a wide range of viruses can be inhibited with RNAi, both in vitro and in vivo. One principle that has arisen from this work is that antiviral RNAi therapies must be tailored to the unique life cycle of each pathogen, including the choice of delivery vehicle, route of administration, gene(s) targeted and regulation and duration of RNAi induction. Although effective strategies will be customized to each virus, all such therapies must overcome similar challenges. Importantly, treatment strategies must compensate for the inevitable fact that viral genome sequences evolve extremely rapidly, and computational and bioinformatics approaches may aid in the development of therapies that resist viral escape. Furthermore, all RNAi strategies involve the delivery of nucleic acids to target cells, and all will therefore benefit from the development of enhanced gene design and delivery technologies. Here, we review the substantial progress that has been made towards identifying effective antiviral RNAi targets and discuss strategies for translating these findings into effective clinical therapies.", "doc_id": "zvop8bxh"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "The crystal structure of nsp10-nsp16 heterodimer from SARS-CoV-2 in complex with S-adenosylmethionine", "abstract": "SARS-CoV-2 is a member of the coronaviridae family and is the etiological agent of the respiratory Coronavirus Disease 2019. The virus has spread rapidly around the world resulting in over two million cases and nearly 150,000 deaths as of April 17, 2020. Since no treatments or vaccines are available to treat COVID-19 and SARS-CoV-2, respiratory complications derived from the infections have overwhelmed healthcare systems around the world. This virus is related to SARS-CoV-1, the virus that caused the 2002-2004 outbreak of Severe Acute Respiratory Syndrome. In January 2020, the Center for Structural Genomics of Infectious Diseases implemented a structural genomics pipeline to solve the structures of proteins essential for coronavirus replication-transcription. Here we show the first structure of the SARS-CoV-2 nsp10-nsp16 2\u2019-O-methyltransferase complex with S-adenosylmethionine at a resolution of 1.80 \u00c5. This heterodimer complex is essential for capping viral mRNA transcripts for efficient translation and to evade immune surveillance.", "doc_id": "ywia2ok7"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "COVID-19 vaccine development pipeline gears up", "abstract": "", "doc_id": "yneir8ab"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "Preclinical data from SARS-CoV-2 mRNA vaccine", "abstract": "", "doc_id": "vm3oirur"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "Emerging Technologies for Use in the Study, Diagnosis, and Treatment of Patients with COVID-19", "abstract": "INTRODUCTION: The COVID-19 pandemic has caused an unprecedented health and economic worldwide crisis. Innovative solutions are imperative given limited resources and immediate need for medical supplies, healthcare support and treatments. AIM: The purpose of this review is to summarize emerging technologies being implemented in the study, diagnosis, and treatment of COVID-19. RESULTS: Key focus areas include the applications of artificial intelligence, the use of Big Data and Internet of Things, the importance of mathematical modeling for predictions, utilization of technology for community screening, the use of nanotechnology for treatment and vaccine development, the utility of telemedicine, the implementation of 3D-printing to manage new demands and the potential of robotics. CONCLUSION: The review concludes by highlighting the need for collaboration in the scientific community with open sharing of knowledge, tools, and expertise.", "doc_id": "zv4nbz9p"} {"topic_name": "mRNA vaccine coronavirus", "topic_id": "50", "title": "Preparing for Pandemics: RNA Vaccines at the Forefront", "abstract": "", "doc_id": "ozf05l65"}