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32519164
In December 2019, a new and highly contagious infectious disease emerged in Wuhan, China. The etiologic agent was identified as a novel coronavirus, now known as Severe Acute Syndrome Coronavirus-2 (SARS-CoV-2). Recent research has revealed that virus entry takes place upon the union of the virus S surface protein with the type I transmembrane metallo-carboxypeptidase, angiotensin converting enzyme 2 (ACE-2) identified on epithelial cells of the host respiratory tract. Virus triggers the synthesis and release of pro-inflammatory cytokines, including IL-6 and TNF-alpha and also promotes downregulation of ACE-2, which promotes a concomitant increase in levels of angiotensin II (AT-II). Both TNF-alpha and AT-II have been implicated in promoting overexpression of tissue factor (TF) in platelets and macrophages. Additionally, the generation of antiphospholipid antibodies associated with COVID-19 may also promote an increase in TF. TF may be a critical mediator associated with the development of thrombotic phenomena in COVID-19, and should be a target for future study.
[ "Treatment", "Mechanism" ]
1
32691006
A novel coronavirus disease (COVID-19), transmitted from humans to humans, has rapidly become the pandemic responsible for the current global health crisis. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is said to be of zoonotic origin. This review describes the etiology and signs and symptoms as well as the current allopathic therapy for COVID-19. Additionally, findings of previous studies on the immunomodulatory effects and antiviral activities of particular foods and herbs on influenza virus and coronaviruses have been collated, with the aim of promoting the use of dietary therapy and herbal medicine as COVID-19 preventive therapies, while specific drugs and vaccines are yet to be discovered or are still under development. The volume of existing reports is irrefutable evidence that foods and herbs possess a potential antiviral ability against SARS-CoV-2 and can prevent COVID-19. Foods and herbs could be used as dietary or complementary therapy to prevent infection and strengthen immunity, as antiviral agents for masks, as disinfectants to curb aerosol transmission, or as sanitizing agents to disinfect surfaces. However, these hypotheses need to be experimentally verified for SARS-CoV-2 and COVID-19 patients.
[ "Treatment", "Prevention" ]
2
32858315
BACKGROUND: In December 2019, the novel coronavirus (SARS-CoV-2) infection was first reported in Wuhan city, central China, which has spread rapidly. The common clinical features of patients with SARS-CoV-2 infection included fever, fatigue, and damage to the respiratory or digestive system. However, it is still unclear whether SARS-CoV-2 infection could cause damage to the central nervous system (CNS) inducing psychiatric symptoms. CASE REPORT: Herein, we present the first case of SARS-CoV-2 infection with manic-like symptoms and describe the diagnosis, clinical course, and treatment of the case, focusing on the identifications of SARS-CoV-2 in the specimen of cerebrospinal fluid (CSF). The patient developed manic-like symptoms when his vital signs recovered on illness day 17. After manic-like attack, the detection of SARS-CoV-2 specific IgG antibody in CSF was positive, while the reverse transcriptase-polymerase chain reaction (RT-PCR) on CSF for the SARS-CoV-2 was negative. The patient received Olanzapine for treatment and his mood problems concurrently improved as indicated by scores of Young Manic Rating Scale (YMRS). LIMITATION: This is a single case report only, and the RT-PCR test for SARS-CoV-2 in CSF was not performed simultaneously when SARS-CoV-2 was positive in samples of sputum and stool. CONCLUSION: This first case of COVID-19 patient with manic-like symptoms highlights the importance of evaluation of mental health status and may contribute to our understanding of potential risk of CNS impairments by SARS-CoV-2 infection.
[ "Case Report" ]
3
32985329
During the coronavirus disease 2019 (COVID-19) pandemic, there is an important risk of infection in health care workers, including oral health care workers (OHCWs), due to the characteristics of dental practice. In this retrospective study, data pertaining to the 31 OHCWs diagnosed with COVID-19 in Wuhan, Hubei Province, were retrieved and analyzed. Questionnaires were administered to the subjects over the Internet and telephone. Clinical and epidemiological characteristics and information on the use of personal protective equipment (PPE) were collected. There were 22 females and 9 males, with a median age of 39 y. Although the severity of most cases of COVID-19 (93.5%) was mild or moderate, 1 case was severe, and another case was critical, resulting in death. Fever was the main first symptom of COVID-19, followed by fatigue and myalgia. Most of the OHCWs routinely used PPE such as medical masks, gloves, caps, and work clothes while performing clinical work. N95 or KN95 masks were rarely available because of the scarcity of PPE during the outbreak. Nineteen OHCWs reported a contact history, among whom 7 worked in a fever clinic, 5 reported contact with dental patients suspected of having COVID-19, and 7 reported contact with family members with COVID-19-related symptoms at least 1 d earlier. Our findings indicated that there were few clusters of COVID-19 in dental settings. Since the outbreak, the Hospital of Stomatology, Wuhan University, has provided emergency dental treatment, and none of their staff were infected while providing dental service, which indicates that comprehensive measures such as the use of advanced PPE and environmental disinfection can prevent cross-infection in dental practice. The analysis of the procedures followed during the emergency treatments indicated that OHCWs preferred to recommend conservative treatment to patients, suggesting that attention should be paid to the psychological impact of COVID-19 on dental practitioners.
[ "Prevention" ]
4
32812051
OBJECTIVES: Sofosbuvir and daclatasvir are direct-acting antivirals highly effective against hepatitis C virus. There is some in silico and in vitro evidence that suggests these agents may also be effective against SARS-CoV-2. This trial evaluated the effectiveness of sofosbuvir in combination with daclatasvir in treating patients with COVID-19. METHODS: Patients with a positive nasopharyngeal swab for SARS-CoV-2 on RT-PCR or bilateral multi-lobar ground-glass opacity on their chest CT and signs of severe COVID-19 were included. Subjects were divided into two arms with one arm receiving ribavirin and the other receiving sofosbuvir/daclatasvir. All participants also received the recommended national standard treatment which, at that time, was lopinavir/ritonavir and single-dose hydroxychloroquine. The primary endpoint was time from starting the medication until discharge from hospital with secondary endpoints of duration of ICU stay and mortality. RESULTS: Sixty-two subjects met the inclusion criteria, with 35 enrolled in the sofosbuvir/daclatasvir arm and 27 in the ribavirin arm. The median duration of stay was 5 days for the sofosbuvir/daclatasvir group and 9 days for the ribavirin group. The mortality in the sofosbuvir/daclatasvir group was 2/35 (6%) and 9/27 (33%) for the ribavirin group. The relative risk of death for patients treated with sofosbuvir/daclatasvir was 0.17 (95% CI 0.04-0.73, P = 0.02) and the number needed to treat for benefit was 3.6 (95% CI 2.1-12.1, P < 0.01). CONCLUSIONS: Given these encouraging initial results, and the current lack of treatments proven to decrease mortality in COVID-19, further investigation in larger-scale trials seems warranted.
[ "Treatment" ]
5
32926870
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has severely affected ICUs and critical care health-care providers (HCPs) worldwide. RESEARCH QUESTION: How do regional differences and perceived lack of ICU resources affect critical care resource use and the well-being of HCPs? STUDY DESIGN AND METHODS: Between April 23 and May 7, 2020, we electronically administered a 41-question survey to interdisciplinary HCPs caring for patients critically ill with COVID-19. The survey was distributed via critical care societies, research networks, personal contacts, and social media portals. Responses were tabulated according to World Bank region. We performed multivariate log-binomial regression to assess factors associated with three main outcomes: limiting mechanical ventilation (MV), changes in CPR practices, and emotional distress and burnout. RESULTS: We included 2,700 respondents from 77 countries, including physicians (41%), nurses (40%), respiratory therapists (11%), and advanced practice providers (8%). The reported lack of ICU nurses was higher than that of intensivists (32% vs 15%). Limiting MV for patients with COVID-19 was reported by 16% of respondents, was lowest in North America (10%), and was associated with reduced ventilator availability (absolute risk reduction [ARR], 2.10; 95% CI, 1.61-2.74). Overall, 66% of respondents reported changes in CPR practices. Emotional distress or burnout was high across regions (52%, highest in North America) and associated with being female (mechanical ventilation, 1.16; 95% CI, 1.01-1.33), being a nurse (ARR, 1.31; 95% CI, 1.13-1.53), reporting a shortage of ICU nurses (ARR, 1.18; 95% CI, 1.05-1.33), reporting a shortage of powered air-purifying respirators (ARR, 1.30; 95% CI, 1.09-1.55), and experiencing poor communication from supervisors (ARR, 1.30; 95% CI, 1.16-1.46). INTERPRETATION: Our findings demonstrate variability in ICU resource availability and use worldwide. The high prevalence of provider burnout and its association with reported insufficient resources and poor communication from supervisors suggest a need for targeted interventions to support HCPs on the front lines.
[ "Prevention" ]
6
32611634
The SARS-CoV-2 (COVID-19) pandemic has rapidly moved telemedicine from discretionary to necessary. Here, we describe how the Stanford Neurology Department (1) rapidly adapted to the COVID-19 pandemic, resulting in over 1,000 video visits within 4 weeks, and (2) accelerated an existing quality improvement plan of a tiered roll out of video visits for ambulatory neurology to a full-scale roll out. Key issues we encountered and addressed were related to equipment/software, provider engagement, workflow/triage, and training. On reflection, the key drivers of our success were provider engagement and dedicated support from a physician champion, who plays a critical role understanding stakeholder needs. Before COVID-19, physician interest in telemedicine was mixed. However, in response to county and state stay-at-home orders related to COVID-19, physician engagement changed completely; all providers wanted to convert a majority of visits to video visits as quickly as possible. Rapid deployment of neurology video visits across all its subspecialties is feasible. Our experience and lessons learned can facilitate broader utilization, acceptance, and normalization of video visits for neurology patients in the present as well as the much anticipated postpandemic era.
[ "Prevention" ]
7
32207676
The novel coronavirus (COVID-19) began in China in early December 2019 and rapidly has spread to many countries around the globe, with the number of confirmed cases increasing every day. An epidemic has been recorded since February 20 in a middle province in Northern Italy (Lodi province, in the low Po Valley). The first line hospital had to redesign its logistical and departmental structure to respond to the influx of COVID-19-positive patients who needed hospitalization. Logistical and structural strategies were guided by the crisis unit, managing in 8 days from the beginning of the epidemic to prepare the hospital to be ready to welcome more than 200 COVID-19-positive patients with different ventilatory requirements, keeping clean emergency access lines, and restoring surgical interventions and deferred urgent, routine activity.
[ "Prevention" ]
8
32563601
Study objective: Most coronavirus disease 2019 (COVID-19) reports have focused on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients. However, at initial presentation, most patients' viral status is unknown. Determination of factors that predict initial and subsequent need for ICU and invasive mechanical ventilation is critical for resource planning and allocation. We describe our experience with 4,404 persons under investigation and explore predictors of ICU care and invasive mechanical ventilation at a New York COVID-19 epicenter. Methods: We conducted a retrospective cohort study of all persons under investigation and presenting to a large academic medical center emergency department (ED) in New York State with symptoms suggestive of COVID-19. The association between patient predictor variables and SARS-CoV-2 status, ICU admission, invasive mechanical ventilation, and mortality was explored with univariate and multivariate analyses. Results: Between March 12 and April 14, 2020, we treated 4,404 persons under investigation for COVID-19 infection, of whom 68% were discharged home, 29% were admitted to a regular floor, and 3% to an ICU. One thousand six hundred fifty-one of 3,369 patients tested have had SARS-CoV-2-positive results to date. Of patients with regular floor admissions, 13% were subsequently upgraded to the ICU after a median of 62 hours (interquartile range 28 to 106 hours). Fifty patients required invasive mechanical ventilation in the ED, 4 required out-of-hospital invasive mechanical ventilation, and another 167 subsequently required invasive mechanical ventilation in a median of 60 hours (interquartile range 26 to 99) hours after admission. Testing positive for SARS-CoV-2 and lower oxygen saturations were associated with need for ICU and invasive mechanical ventilation, and with death. High respiratory rates were associated with the need for ICU care. Conclusion: Persons under investigation for COVID-19 infection contribute significantly to the health care burden beyond those ruling in for SARS-CoV-2. For every 100 admitted persons under investigation, 9 will require ICU stay, invasive mechanical ventilation, or both on arrival and another 12 within 2 to 3 days of hospital admission, especially persons under investigation with lower oxygen saturations and positive SARS-CoV-2 swab results. This information should help hospitals manage the pandemic efficiently.
[ "Diagnosis", "Treatment" ]
9
32778470
STATEMENT OF PROBLEM: The novel Coronavirus Disease 2019 (COVID-19) is a global pandemic, and many countries and regions are still currently in the midst of the outbreak. This pandemic has caused prosthodontics units to suspend their clinical and educational operations in academia. PURPOSE: The purpose of this article was to review the experiences from the Department of Prosthodontics, Wuhan University School and Hospital of Stomatology (DP-WHUSHS), during the COVID-19 outbreak and the protocols DP-WHUSHS used to resume clinical activities after the outbreak. MATERIAL AND METHODS: The descriptive approach was used in this article to provide a chronological narrative of the experiences and protocols from the DP-WHUSHS during the COVID-19 outbreak and after the outbreak. RESULTS: During the COVID-19 outbreak period, clinical care was provided for patients with dental emergencies by using enhanced grade 2 or grade 3 personal protective equipment (PPE). Teledentistry was used to provide care for patients with nonemergency needs. Online webinars and lectures were conducted for the predoctoral students, residents, and dentists to minimize the interruption in their education and engage the dental community amid the pandemic. Various factors were considered before clinical activities resumed after the outbreak subsided. Additional resources were allocated for facility preparation and management and employee training. New infection control and clinical operation protocols were developed to minimize the health-care-associated infection of airborne transmission diseases. The psychological health and mental wellness of the employees were emphasized. Distance or online education is still under rapid development to provide students and dentists opportunities to advance their knowledge amid the pandemic. CONCLUSIONS: Within the limitation of this descriptive review, the following conclusions were drawn. Patient welfare and emergency needs should be considered amid the pandemic. Enhanced grade 2 or grade 3 PPE should be used during the outbreak. Multifactorial considerations for work resumption after the outbreak included facility preparation and management, training for employees, and clinical operation management. In-person psychological consultation and online mental wellness programs were available to employees to improve their mental wellness. Distance or online education was under rapid development to minimize the interruption in education for the students and to engage the dental community amid a pandemic.
[ "Prevention" ]
10
32861461
AIM: To determine the overall rate of chest imaging findings in asymptomatic cases, describe the most common patterns found, and determine the rate of later symptom development in these initially asymptomatic cases. MATERIALS AND METHODS: The PubMed and EMBASE databases were searched until 1 May 2020, for studies examining the proportion of positive chest imaging findings in asymptomatic cases diagnosed with COVID-19 and a random-effects meta-analysis of proportions was performed. Heterogeneity was assessed using the I(2) statistic. RESULTS: Among 858 non-duplicate studies, seven studies with a total of 231 asymptomatic cases met the inclusion criteria. In the primary analysis, the pooled estimate of the overall rate of positive chest computed tomography (CT) findings among asymptomatic cases was 63% (95% confidence interval [CI]: 44-78%). Among 155/231 cases that were followed up for later symptom development, 90/155 remained asymptomatic and 65/155 developed symptoms during the study period (that ranged between seven and 30 days of follow-up). The pooled estimate of the rate of positive chest CT findings was 62% (95% CI: 38-81%) in cases that remained asymptomatic, while it was 90% (95% CI: 49-99%) in cases that developed symptoms. Among CT findings, the pooled estimate of the overall rate of ground-glass opacities (GGO) at CT alone was 71% (95% CI: 50-86%). Among other CT findings reported, 22/231 patients had GGO with consolidation, 7/231 patients had stripe shadows with or without GGO, and 8/231 patients had GGO with interlobular septal thickening. Among initially asymptomatic cases with positive CT findings, the pooled estimate of the overall rate of later symptom development was 26% (95% CI: 14-43%). CONCLUSION: In COVID-19, asymptomatic cases can have positive chest CT findings, and COVID-19 should be considered among cases with CT abnormalities even when there are no other symptoms. There is a need for close clinical monitoring of asymptomatic cases with radiographic findings as a significant percentage will develop symptoms.
[ "Diagnosis" ]
11
32960880
BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). We investigated racial and ethnic disparities in patterns of COVID-19 testing (i.e., who received testing and who tested positive) and subsequent mortality in the largest integrated healthcare system in the United States. METHODS AND FINDINGS: This retrospective cohort study included 5,834,543 individuals receiving care in the US Department of Veterans Affairs; most (91%) were men, 74% were non-Hispanic White (White), 19% were non-Hispanic Black (Black), and 7% were Hispanic. We evaluated associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for a wide range of demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence. Between February 8 and July 22, 2020, 254,595 individuals were tested for COVID-19, of whom 16,317 tested positive and 1,057 died. Black individuals were more likely to be tested (rate per 1,000 individuals: 60.0, 95% CI 59.6-60.5) than Hispanic (52.7, 95% CI 52.1-53.4) and White individuals (38.6, 95% CI 38.4-38.7). While individuals from minority backgrounds were more likely to test positive (Black versus White: odds ratio [OR] 1.93, 95% CI 1.85-2.01, p < 0.001; Hispanic versus White: OR 1.84, 95% CI 1.74-1.94, p < 0.001), 30-day mortality did not differ by race/ethnicity (Black versus White: OR 0.97, 95% CI 0.80-1.17, p = 0.74; Hispanic versus White: OR 0.99, 95% CI 0.73-1.34, p = 0.94). The disparity between Black and White individuals in testing positive for COVID-19 was stronger in the Midwest (OR 2.66, 95% CI 2.41-2.95, p < 0.001) than the West (OR 1.24, 95% CI 1.11-1.39, p < 0.001). The disparity in testing positive for COVID-19 between Hispanic and White individuals was consistent across region, calendar time, and outbreak pattern. Study limitations include underrepresentation of women and a lack of detailed information on social determinants of health. CONCLUSIONS: In this nationwide study, we found that Black and Hispanic individuals are experiencing an excess burden of SARS-CoV-2 infection not entirely explained by underlying medical conditions or where they live or receive care. There is an urgent need to proactively tailor strategies to contain and prevent further outbreaks in racial and ethnic minority communities.
[ "Diagnosis" ]
12
32648093
The outbreak of novel coronavirus disease 2019 (COVID-19) has now become a global pandemic. Coagulopathy has been reported widely in critically ill COVID-19 patients and was related to high mortality. However, the comprehensive coagulation profiles have not been examined and the underlying mechanism of the coagulopathy in COVID-19 patients is unclear. To study the coagulation profiles of routine hemostasis tests, natural anticoagulants, coagulant factors and antiphospholipid antibodies in critically ill COVID-19 patients. This single-center and cross-section study included 19 patients with COVID-19, who were admitted to intensive care unit (ICU) at Tongji hospital in Wuhan, China, from Feb 23 to Mar 3, 2020. Demographic data, laboratory parameters, treatments and clinical outcomes of the patients were collected and analyzed. The final date of follow-up was Mar 31, 2020. In this study, 12 thrombotic events occurred in 9 patients, including 4 cerebral infarctions, 7 acro-ischemia and 1 internal jugular vein thrombosis. The common abnormalities of routine coagulation tests included evelated D-Dimer level (100%), prolonged prothrombin time (73.7%) and hyperfibrinogenemia (73.7%). The median activities of natural anticoagulants including protein C, protein S and antithrombin were all below the normal range. Factor VIII activities were significantly above normal range (median value 307%, IQR 198-441) in all patients. Factor V and factor VII activities were significantly lower in near-terminal stage patients. Anti-phospholipid antibodies were present in 10 patients. Strikingly, 4 cerebral infarction events were in patients had anti-phospholipid antibodies of multiple isotypes. Sustained hypercoagulable status and thrombotic events were common in critically ill patients with COVID-19. The low activities of natural anticoagulants, elevated factor VIII level and the presence of antiphospholipid antibodies, together, may contribute to the etiopathology of coagulopathy in COVID-19 patients.
[ "Treatment", "Diagnosis" ]
13
32505805
OBJECTIVE: To describe the course over time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in French women from the beginning of the pandemic until mid-April, the risk profile of women with respiratory complications, and short-term pregnancy outcomes. METHODS: We collected a case series of pregnant women with COVID-19 in a research network of 33 French maternity units between March 1 and April 14, 2020. All cases of SARS-CoV-2 infection confirmed by a positive result on real-time reverse transcriptase polymerase chain reaction tests of a nasal sample and/or diagnosed by a computed tomography chest scan were included and analyzed. The primary outcome measures were COVID-19 requiring oxygen (oxygen therapy or noninvasive ventilation) and critical COVID-19 (requiring invasive mechanical ventilation or extracorporeal membrane oxygenation, ECMO). Demographic data, baseline comorbidities, and pregnancy outcomes were also collected. RESULTS: Active cases of COVID-19 increased exponentially during March 1-31, 2020; the numbers fell during April 1-14, after lockdown was imposed on March 17. The shape of the curve of active critical COVID-19 mirrored that of all active cases. By April 14, among the 617 pregnant women with COVID-19, 93 women (15.1 %; 95 %CI 12.3-18.1) had required oxygen therapy and 35 others (5.7 %; 95 %CI 4.0-7.8) had had a critical form of COVID-19. The severity of the disease was associated with age older than 35 years and obesity, as well as preexisting diabetes, previous preeclampsia, and gestational hypertension or preeclampsia. One woman with critical COVID-19 died (0.2 %; 95 %CI 0-0.9). Among the women who gave birth, rates of preterm birth in women with non-severe, oxygen-requiring, and critical COVID-19 were 13/123 (10.6 %), 14/29 (48.3 %), and 23/29 (79.3 %) before 37 weeks and 3/123 (2.4 %), 4/29 (13.8 %), and 14/29 (48.3 %) before 32 weeks, respectively. One neonate (0.5 %; 95 %CI 0.01-2.9) in the critical group died from prematurity. CONCLUSION: COVID-19 can be responsible for significant rates of severe acute, potentially deadly, respiratory distress syndromes. The most vulnerable pregnant women, those with comorbidities, may benefit particularly from prevention measures such as a lockdown.
[ "Prevention" ]
14
33748768
Goal: To develop a micron-scale device that can operate as an MRI-based reporter for the presence of SARS-CoV-2 virus. Methods: Iron rod microdevices were constructed via template-guided synthesis and suspended in phosphate buffered saline (PBS). Heat-inactivated SARS-CoV-2 viruses were added to the samples and imaged with low-field MRI. Results: MRI of microdevices and viruses showed decreased signal intensity at low concentrations of viruses that recovered at higher concentrations. Electron micrographs suggest that reduced MRI intensity may be due to concentration-dependent shielding of water protons from local magnetic inhomogeneities caused by the iron microdevices. Conclusions: The preliminary results presented in this letter provide justification for further studies exploring the potential diagnostic role of magnetic microdevices in assessing the presence and concentration of SARS-CoV-2 viruses.
[ "Diagnosis" ]
15
32576335
OBJECTIVES: At the end of 2019, an outbreak of novel coronavirus pneumonia, called severe acute respiratory syndrome coronavirus 1 (SARS-CoV-2), was first identified in Wuhan, Hubei Province, China. It subsequently spread throughout China and elsewhere, becoming a global health emergency. In February 2020, the World Health Organization (WHO) designated the disease coronavirus disease 2019 (COVID-19). The objective of this study was to investigate the degree of knowledge of young Italians about COVID-19 and their current attitudes toward the SARS-CoV-2 and to determine if there were prejudices emerging toward Chinese. METHODS: An online survey was conducted on February 3, 4, 5, 2020, with the collaboration of Italian website "Skuola.net". Young people had the opportunity to participate by answering an ad hoc questionnaire created to investigate knowledge and attitudes about the new coronavirus, using a link published on the homepage. RESULTS: A total of 5234 responses were received, of which 3262 were females and 1972 were males. Most of the participants showed generally moderate knowledge about COVID-19. Male students, middle school students, and those who do not attend school, should increase awareness of the disease; less than half of responders say that their attitudes toward the Chinese population has worsened in the last period. CONCLUSIONS: Global awareness of this emerging infection should be increased, due to its virulence, the significant risk of mortality, and the ability of the virus to spread very quickly within the community.
[ "Prevention" ]
16
32879108
OBJECTIVES: To evaluate curative effects of coronavirus disease 2019 (COVID-19) patients by the transfusion of other convalescent plasma. METHODS: Retrospective analysis of the clinical data of 18 patients with severe and critical COVID-19, who were hospitalized in the ICU of Xianghu Branch of the First Affiliated Hospital of Nanchang University from February 1 to March 15, 2020. Patients were subdivided into an experimental group (n=6, who had transfused the plasma) and an observation group (n=12, who had no plasma transfusion). Basic clinical data and prognosis indexes of these two groups were compared. Moreover, for the experimental group, the dynamic changes of blood oxygen saturation before and after the transfusion, the changes of lymphocyte absolute value 48 hours after the transfusion, and the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid were analyzed. RESULTS: There were no significant differences in age, gender, blood type and other basic clinical data between the two groups (all P>0.05).There were no significant differences in ventilator machine weaning time, extracorporeal membrane oxygenation (ECMO) weaning time, body temperature recovery to normal time, and hospitalization days between these two groups (all P>0.05). For the experimental group, before, during and after the convalescent plasma transfusion, the blood oxygen saturation of all 6 patients at all time (1, 6, 8, 12, 24, 36, and 48 h) was more than 90%, and there was no significant fluctuation. There were 3 patients whose absolute value of lymphocyte was increased 48 hours after the transfusion, and the remaining was decreased. There were 5 patients whose SARS-CoV-2 nucleic acid detection turned negative 48 hours after the transfusion, accounting for 83.3%. CONCLUSIONS: Transfusion of convalescent plasma will not affect outcomesof COVID-19 patients, which can neutralize SARS-CoV-2 in patients and reduce the loading capacity of SARS-CoV-2.
[ "Treatment" ]
17
32054124
The outbreak of pneumonia originating in Wuhan, China, has generated 24,500 confirmed cases, including 492 deaths, as of 5 February 2020. The virus (2019-nCoV) has spread elsewhere in China and to 24 countries, including South Korea, Thailand, Japan and USA. Fortunately, there has only been limited human-to-human transmission outside of China. Here, we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected early in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.41 (credible interval [0.27, 0.55]). However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.012 (credible interval [0, 0.099]). This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a global pandemic.
[ "Transmission", "Prevention" ]
18
32019669
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.
[ "Transmission" ]
19
32837801
Purpose of the Review: The purpose of the review is to describe the Brazilian Telemedicine University Network RUTE concerning the Special Interest Group of Children and Adolescents, the new SIG-COVID19-BR activities for continuing medical education, and to update relevant information regarding diagnosis and treatment, using digital technologies. Recent Findings: A total of 145 sessions of video and webconferences were held with the participation of 6575 health professionals, including medical students, interns, and residents. Major topics involved the healthcare of children and adolescents were combined with the emergence of a new pandemic plus the need to decrease the professional knowledge gaps in geographically distant hospitals. Summary: Telemedicine is a cost-effective tool and a bridge to decrease health disparities access for proper care and assistance for any population. RUTE is a Brazilian model of telemedicine which has a positive impact attracting the participation of health professionals, and even more so, during the Covid-19 virus pandemic outbreak.
[ "Prevention" ]
20
32815655
The outbreak of coronavirus disease 2019 (COVID-19) as a pandemic has shaken the global health system and economy by their roots. This epidemic is still spreading and showing no signs of decreasing trend. Vaccination could be the only effective and economical means to control this pandemic. A number of research institutions and pharmaceutical companies have plunged into the race of vaccine development against COVID-19 which are in various stages of development. An intriguing fact of coronavirus infections is that in every decade of the 21st century there is a new major coronavirus epidemic, namely, severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome (MERS) in 2012, and now COVID-19; and such epidemics are expected in future too. Since most of the biological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still obscure, the scientists are relying on the information available on SARS-CoV and to some extent on MERS-CoV for designing and developing COVID-19 vaccines. But there is a need of vigorous testing for immunogenicity, safety, efficacy, and level of protection conferred in the hosts. This review focuses on the challenges and prospects of vaccine development against COVID-19. It highlights seriousness, bottlenecks in vaccine development, possible vaccine candidates, different vaccine strategies, safety evaluation issues, and vaccine production processes pertaining to COVID-19 based on the knowledge acquired on SARS and MERS vaccine development in the past.
[ "Treatment" ]
21
32300796
A novel coronavirus, SARS-CoV-2, emerged in December 2019, leading within a few months to a global pandemic. COVID-19, the disease caused by this highly contagious virus, can have serious health consequences, though risks of complications are highly age-dependent. Rates of hospitalization and death are less than 0.1% in children, but increase to 10% or more in older people. Moreover, at all ages, men are more likely than women to suffer serious consequences from COVID-19. These patterns are familiar to the geroscience community. The effects of age and sex on mortality rates from COVID-19 mirror the effects of aging on almost all major causes of mortality. These similarities are explored here, and underscore the need to consider the role of basic biological mechanisms of aging on potential treatment and outcomes of COVID-19.
[ "Mechanism" ]
22
32554697
Coronaviruses (CoVs) have repeatedly emerged from wildlife hosts and infected humans and livestock animals to cause epidemics with significant morbidity and mortality. CoVs infect various organs, including respiratory and enteric systems, as exemplified by newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The constellation of viral factors that contribute to developing enteric disease remains elusive. Here, we investigated CoV interferon antagonists for their contribution to enteric pathogenesis. Using an infectious clone of an enteric CoV, porcine epidemic diarrhea virus (icPEDV), we generated viruses with inactive versions of interferon antagonist nonstructural protein 1 (nsp1), nsp15, and nsp16 individually or combined into one virus designated icPEDV-mut4. Interferon-responsive PK1 cells were infected with these viruses and produced higher levels of interferon responses than were seen with wild-type icPEDV infection. icPEDV-mut4 elicited robust interferon responses and was severely impaired for replication in PK1 cells. To evaluate viral pathogenesis, piglets were infected with either icPEDV or icPEDV-mut4. While the icPEDV-infected piglets exhibited clinical disease, the icPEDV-mut4-infected piglets showed no clinical symptoms and exhibited normal intestinal pathology at day 2 postinfection. icPEDV-mut4 replicated in the intestinal tract, as revealed by detection of viral RNA in fecal swabs, with sequence analysis documenting genetic stability of the input strain. Importantly, icPEDV-mut4 infection elicited IgG and neutralizing antibody responses to PEDV. These results identify nsp1, nsp15, and nsp16 as virulence factors that contribute to the development of PEDV-induced diarrhea in swine. Inactivation of these CoV interferon antagonists is a rational approach for generating candidate vaccines to prevent disease and spread of enteric CoVs, including SARS-CoV-2.IMPORTANCE Emerging coronaviruses, including SARS-CoV-2 and porcine CoVs, can infect enterocytes, cause diarrhea, and be shed in the feces. New approaches are needed to understand enteric pathogenesis and to develop vaccines and therapeutics to prevent the spread of these viruses. Here, we exploited a reverse genetic system for an enteric CoV, porcine epidemic diarrhea virus (PEDV), and outline an approach of genetically inactivating highly conserved viral factors known to limit the host innate immune response to infection. Our report reveals that generating PEDV with inactive versions of three viral interferon antagonists, nonstructural proteins 1, 15, and 16, results in a highly attenuated virus that does not cause diarrhea in animals and elicits a neutralizing antibody response in virus-infected animals. This strategy may be useful for generating live attenuated vaccine candidates that prevent disease and fecal spread of enteric CoVs, including SARS-CoV-2.
[ "Mechanism", "Treatment" ]
23
32773661
We report a 20-year-old female with SARS-CoV-2 encephalitis who presented with 4 days of upper respiratory symptoms, fevers and sudden acute altered mental status. An extensive work up led to the most likely cause for the neurologic decompensation to be viewed as SARS-CoV-2 symptomology.
[ "Case Report" ]
24
32944361
Background: Obstructive sleep apnea (OSA) has a high prevalence, with an estimated 425 million adults with apnea hypopnea index (AHI) of >/=15 events/hour, and is significantly underdiagnosed. This presents a significant pain point for both the sufferers, and for healthcare systems, particularly in a post COVID-19 pandemic world. As such, it presents an opportunity for new technologies that can enable screening in both developing and developed countries. In this work, the performance of a non-contact OSA screener App that can run on both Apple and Android smartphones is presented. Methods: The subtle breathing patterns of a person in bed can be measured via a smartphone using the "Firefly" app technology platform [and underpinning software development kit (SDK)], which utilizes advanced digital signal processing (DSP) technology and artificial intelligence (AI) algorithms to identify detailed sleep stages, respiration rate, snoring, and OSA patterns. The smartphone is simply placed adjacent to the subject, such as on a bedside table, night stand or shelf, during the sleep session. The system was trained on a set of 128 overnights recorded at a sleep laboratory, where volunteers underwent simultaneous full polysomnography (PSG), and "Firefly" smartphone app analysis. A separate independent test set of 120 recordings was collected across a range of Apple iOS and Android smartphones, and withheld for performance evaluation by a different team. An operating point tuned for mid-sensitivity (i.e., balancing sensitivity and specificity) was chosen for the screener. Results: The performance on the test set is comparable to ambulatory OSA screeners, and other smartphone screening apps, with a sensitivity of 88.3% and specificity of 80.0% [with receiver operating characteristic (ROC) area under the curve (AUC) of 0.92], for a clinical threshold for the AHI of >/=15 events/hour of detected sleep time. Conclusions: The "Firefly" app based sensing technology offers the potential to significantly lower the barrier of entry to OSA screening, as no hardware (other than the user's personal smartphone) is required. Additionally, multi-night analysis is possible in the home environment, without requiring the wearing of a portable PSG or other home sleep test (HST).
[ "Prevention" ]
25
32661235
Stress proteins (SPs) including heat-shock proteins (HSPs), RNA chaperones, and ER associated stress proteins are molecular chaperones essential for cellular homeostasis. The major functions of HSPs include chaperoning misfolded or unfolded polypeptides, protecting cells from toxic stress, and presenting immune and inflammatory cytokines. Regarded as a double-edged sword, HSPs also cooperate with numerous viruses and cancer cells to promote their survival. RNA chaperones are a group of heterogeneous nuclear ribonucleoproteins (hnRNPs), which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase II. hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. Dysregulation of stress proteins is associated with many human diseases including human cancer, cardiovascular diseases, neurodegenerative diseases (e.g., Parkinson's diseases, Alzheimer disease), stroke and infectious diseases. In this review, we summarized the biologic function of stress proteins, and current progress on their mechanisms related to virus reproduction and diseases caused by virus infections. As SPs also attract a great interest as potential antiviral targets (e.g., COVID-19), we also discuss the present progress and challenges in this area of HSP-based drug development, as well as with compounds already under clinical evaluation.
[ "Treatment", "Mechanism" ]
26
32869006
Background: On 11(th) March 2020, the World Health Organization declared COVID-19 as Pandemic. The estimation of transmission dynamics in the initial days of the outbreak of any infectious disease is crucial to control its spread in a new area. The serial interval is one of the significant epidemiological measures that determine the spread of infectious disease. It is the time interval between the onset of symptoms in the primary and secondary case. Objective: The present study aimed at the qualitative and quantitative synthesis of the currently available evidence for the serial interval of COVID-19. Methodology: Data on serial intervals were extracted from 11 studies following a systematic review. A meta-analysis was performed to estimate the pooled estimate of the serial interval. The heterogeneity and bias in the included studies were tested by various statistical measures and tests, including I(2) statistic, Cochran's Q test, Egger's test, and Beggs's test. Result: The pooled estimate for the serial interval was 5.40 (5.19, 5.61) and 5.19 (4.37, 6.02) days by the fixed and random effects model, respectively. The heterogeneity between the studies was found to be 89.9% by I(2) statistic. There is no potential bias introduced in the meta-analysis due to small study effects. Conclusion: The present review provides sufficient evidence for the estimate of serial interval of COVID-19, which can help in understanding the epidemiology and transmission of the disease. The information on serial interval can be useful in developing various policies regarding contact tracing and monitoring community transmission of COVID-19.
[ "Transmission", "Epidemic Forecasting", "Prevention" ]
27
32651238
Analytical sensitivity for SARS-CoV-2 detection is a key performance metric for the evaluation of viral detection assays. We determined analytical limits of detection for seven SARS-CoV-2 assays using serial dilutions of pooled patient material quantified with droplet digital PCR. Limits of detection ranged from </=10 to 74 copies/ml for commercial high-throughput laboratory analyzers (Roche Cobas, Abbott m2000, and Hologic Panther Fusion) and 167 to 511 copies/ml for sample-to-answer (DiaSorin Simplexa, GenMark ePlex) and point-of-care instruments (Abbott ID NOW). The CDC assay yielded limits of detection ranging from 85 to 499 copies/ml, depending on the extraction method and thermocycler used. These results can help to inform the assay choice for testing approaches to manage the current COVID-19 outbreak.
[ "Diagnosis" ]
28
33002914
The recent novel severe acute respiratory syndrome coronavirus 2 infection resulted in a coronavirus disease 2019 pandemic that significantly strained healthcare systems globally. The early wave of patients in Singapore with severe pneumonia requiring intensive care units are gradually being referred for post-critical illness management with our inpatient medical rehabilitation unit. There is growing information regarding the actual rehabilitation process for patients severely affected by coronavirus disease 2019. This case report shares experiences and challenges faced during rehabilitation of severe coronavirus disease 2019 pneumonia and post-intensive care syndrome. It also describes the post-discharge rehabilitation program in a setting of strict nationwide safe distancing and stay-home policies.
[ "Case Report" ]
29
32950981
Since the outbreak of coronavirus disease 2019 (COVID-19), there has been a debate whether pregnant women are at a specific risk for COVID-19 and whether it might be vertically transmittable through the placenta. We present a series of five placentas of SARS coronavirus 2 (SARS-CoV-2)-positive women who had been diagnosed with mild symptoms of COVID-19 or had been asymptomatic before birth. We provide a detailed histopathologic description of morphological changes accompanied by an analysis of presence of SARS-CoV-2 in the placental tissue. All placentas were term deliveries (40th and 41st gestational weeks). One SARS-CoV-2-positive patient presented with cough and dyspnoea. This placenta showed prominent lymphohistiocytic villitis and intervillositis and signs of maternal and foetal malperfusion. Viral RNA was present in both placenta tissue and the umbilical cord and could be visualized by in situ hybridization in the decidua. SARS-CoV-2 tests were negative at the time of delivery of 3/5 women, and their placentas did not show increased inflammatory infiltrates. Signs of maternal and/or foetal malperfusion were present in 100% and 40% of cases, respectively. There was no transplacental transmission to the infants. In our cohort, we can document different time points regarding SARS-CoV-2 infection. In acute COVID-19, prominent lymphohistiocytic villitis may occur and might potentially be attributable to SARS-CoV-2 infection of the placenta. Furthermore, there are histopathological signs of maternal and foetal malperfusion, which might have a relationship to an altered coagulative or microangiopathic state induced by SARS-CoV-2, yet this cannot be proven considering a plethora of confounding factors.
[ "Case Report" ]
30
33002740
BACKGROUND: The effectual immune response is crucial to defeat viral infections. However, exuberant immune response with features of macrophage activation syndrome (MAS) lead detrimental consequences in COVID-19 patients. Interleukin (IL)-18 is one of the leading cytokines in MAS which has not been studied in COVID-19. OBJECTIVE: To investigate the association of IL-18 with the other inflammatory markers and disease severity in COVID-19 for predicting disease prognosis. METHODS: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled into the study. Data on demographic and clinical characteristics, and laboratory values of CRP, ferritin, d-dimer and procalcitonin were measured on admission. Patients were followed up prospectively with a standardized approach until hospital discharge or death. Individuals were classified as asymptomatic, mild and severe pneumonia according to their clinical, laboratory and radiological characteristics. Worse outcome was defined as requirement of intensive care unit (ICU) admission or death. Blood samples were collected at enrollment and serum levels of IL-6 and IL-18 were determined by ELISA. Association between IL-18 and other inflammatory markers and prognosis were analyzed. RESULTS: There were 58 COVID-19 patients (50% male) with a median age of 43 (min 22-max 81) years. Twenty age and sex matched healthy subjects were served as control group. The study population was divided into three groups according to disease severity: asymptomatic (n = 20), mild pneumonia group (n = 27) and a severe group (n = 11). During follow up nine (15.5%) patients required ICU admission and three of them were died eventually. Serum IL-18 were correlated with other inflammatory markers and biochemical markers of organ injury; creatinine, liver enzymes and troponin. Serum IL-18 levels were remarkably higher in COVID-19 patients compared to healthy subjects with being highest in severe pneumonia group (p < 0.001). IL-18 serum concentrations were almost four-fold higher in patients with worse outcome compared to good outcome (p < 0.001). Serum IL-18 above the cut off value of 576 pg/mL on admission was associated with 11.7 fold increased risk of ICU admission. CONCLUSIONS: The serum concentrations of IL-18 correlate with other inflammatory markers and reflect disease severity. Results of the present study shed light on role of IL-18 on COVID-19 pathogenesis and might provide an evidence for the clinical trials on IL-18 antagonists for the treatment of severe COVID-19 patients.
[ "Treatment", "Diagnosis" ]
31
33019514
Background and objectives: the emergency department (ED) is frequently identified by patients as a possible solution for all healthcare problems, leading to a high rate of misuse of the ED, possibly causing overcrowding. The coronavirus disease 2019 (COVID-19) pandemic started in China; it then spread throughout Italy, with the first cases confirmed in Lombardy, Italy, in February 2020. This has totally changed the type of patients referred to EDs. The aim of this study was to analyze the reduction of ED admissions at a Second level urban teaching (Fondazione Policlinico Universitario Agostino Gemelli IRCCS) during the COVID-19 pandemic. Materials and Methods: in this retrospective observational cross-sectional study, we reviewed and compared clinical records of all the patients consecutively admitted to our ED over a 40-day period (21 February -31 March) in the last three years (2018-2019-2020). Mean age, sex, triage urgency level, day/night admission, main presentation symptom, and final diagnosis, according to different medical specialties, hospitalization, and discharge rate, were analyzed. Results: we analyzed 16,281 patient clinical records. The overall reduction in ED admissions in 2020 was 37.6% compared to 2019. In 2020, we observed an increase in triage urgency levels for ED admissions (the main presentation symptom was a fever). We noticed a significant drop in admissions for cardio-thoracic, gastroenterological, urological, otolaryngologic/ophthalmologic, and traumatological diseases. Acute neurological conditions registered only a slight, but significant, reduction. Oncology admissions were stable. Admissions for infectious diseases were 30% in 2020, compared to 5% and 6% in 2018 and 2019, respectively. In 2020, the hospitalization rate increased to 42.9% compared to 27.7%, and 26.4% in previous years. Conclusions: the drastic reduction of ED admissions during the pandemic may be associated with fear of the virus, suggesting that patients with serious illnesses did not go to the emergency room. Moreover, there was possible misuse of the ED in the previous year. In particular, worrisome data emerged regarding a drop in cardiology and neurology admissions. Those patients postponed medical attention, possibly with fatal consequences, just for fear of exposure to COVID-19, leading to unnecessary morbidity and mortality.
[ "Prevention" ]
32
32863676
The prime of COVID-19 forced institutions and hospitals to convert operating rooms into intensive care units. Now as the disease prevalence drops and plateaus in several countries, elective surgeries are being slowly resuming. Such that asymptomatic carriers too would approach hospitals for surgical needs. Coronaviruses are understood to transmit both by droplets and aerosols. Orthopaedic surgery requires regular use of high-speed instruments like power drills, oscillating saws and burrs. Several medical procedures are known to create aerosols thereby exposing the surgeon to contract the virus. Adequate know-how and protective means are mandatory to safeguard the surgical team from inevitable exposure.
[ "Prevention" ]
33
32405515
Understanding the COVID-19 pandemic is a multidisciplinary effort that requires a significant number of variables. This dataset comprises (i) sociodemographic characteristics, compiled from 35 datasets obtained at UN Data; (ii) mobility metrics that can assist the analysis of social distancing, from Google Community Mobility Reports and; (iii) daily counts of cases and deaths by COVID-19, from the European Centre for Disease Prevention and Control and the Johns Hopkins University Center for Systems Science and Engineering. This unified dataset ranges from February 15, 2020 to May 7, 2020, a total of 83 days, and is provided as a collection of time series for 131 countries with 192 variables. The pipeline to preprocess and generate the dataset, along with the dataset itself, are versioned with the Data Version Control tool (DVC) and are thus easily reproducible.
[ "Prevention" ]
34
32693665
The novel coronavirus SARS-CoV-2 after emerging in China has caused a global pandemic that is risking the lives of millions. COVID-19 has spread across the world at a very rapid rate raising concerns of capacity limitations and lack of unified responses at the global level, particularly from the world's most developed countries. The spread of further infection has been curtailed by lockdown and mass social distancing that has been enforced in most parts of the world. There are no clinical data yet suggesting that any available candidate vaccine will be effective for COVID-19 which will be a critical need for eventually preventing this disease. Extensive research is underway with some success in identification of monoclonal antibodies from COVID-19 recovered patients, which may inform on vaccine development. The clinical evaluations of COVID-19 vaccines need to follow standardized protocols that are essential for safeguarding humans. In absence of a vaccine or a widely available effective therapy, quarantine and other preventive measures are essential in curtailing the risk of pandemic spread.
[ "Treatment" ]
35
32900341
The COVID-19 pandemic continues to wreak havoc worldwide due to the lack of risk assessment, rapid spreading ability, and propensity to precipitate severe disease in comorbid conditions. In an attempt to fulfill the demand for prophylactic and treatment measures to intercept the ongoing outbreak, the drug development process is facing several obstacles and renaissance in clinical trials, including vaccines, antivirals, immunomodulators, plasma therapy, and traditional medicines. This review outlines the overview of SARS-CoV-2 infection, significant recent findings, and ongoing clinical trials concerning current and future therapeutic interventions for the management of advancing pandemic of the century.
[ "Treatment" ]
36
32962771
OBJECTIVE: The seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) IgG antibody was evaluated among employees of a Veterans Affairs healthcare system to assess potential risk factors for transmission and infection. METHODS: All employees were invited to participate in a questionnaire and serological survey to detect antibodies to SARS-CoV-2 as part of a facility-wide quality improvement and infection prevention initiative regardless of clinical or nonclinical duties. The initiative was conducted from June 8 to July 8, 2020. RESULTS: Of the 2,900 employees, 51% participated in the study, revealing a positive SARS-CoV-2 seroprevalence of 4.9% (72 of 1,476; 95% CI, 3.8%-6.1%). There were no statistically significant differences in the presence of antibody based on gender, age, frontline worker status, job title, performance of aerosol-generating procedures, or exposure to known patients with coronavirus infectious disease 2019 (COVID-19) within the hospital. Employees who reported exposure to a known COVID-19 case outside work had a significantly higher seroprevalence at 14.8% (23 of 155) compared to those who did not 3.7% (48 of 1,296; OR, 4.53; 95% CI, 2.67-7.68; P < .0001). Notably, 29% of seropositive employees reported no history of symptoms for SARS-CoV-2 infection. CONCLUSIONS: The seroprevalence of SARS-CoV-2 among employees was not significantly different among those who provided direct patient care and those who did not, suggesting that facility-wide infection control measures were effective. Employees who reported direct personal contact with COVID-19-positive persons outside work were more likely to have SARS-CoV-2 antibodies. Employee exposure to SARS-CoV-2 outside work may introduce infection into hospitals.
[ "Prevention", "Diagnosis" ]
37
32991675
QUALITY ISSUE: The emergence of COVID-19 highlights the necessity of rapidly identifying and isolating potentially infected individuals. Evaluating this preparedness requires an assessment of the full clinical system, from intake to isolation. INITIAL ASSESSMENT: Unannounced Standardized Patients (USPs) present a nimble, sensitive methodology for assessing this readiness. CHOICE OF SOLUTION: Pilot the Unannounced Standardized Patient methodology, which employs an actor trained to present as a standardized, incognito potentially infected patient, to assess clinical readiness for potential COVID-19 patients at an urban, community safety-net clinic. IMPLEMENTATION: The Unannounced Standardized Patient was trained to present at each team's front desk with the complaint of feeling unwell (reporting a fever of 101 degrees Fahrenheit in the past 24 hours) and exposure to a roommate recently returned from Beijing. The Unannounced Standardized Patient was trained to complete a behaviorally-anchored assessment of the care she received from the clinical system. EVALUATION: There was clear variation in care Unannounced Standardized Patients received; some frontline clerical staff followed best practices; others did not. Signage and information on disease spread prevention publicly available was inconsistent. Qualitative comments shared by the Unannounced Standardized Patients and those gathered during group debrief reinforced the experiences of the Unannounced Standardized Patients and hospital leadership. LESSONS LEARNED: Unannounced Standardized Patients revealed significant variation in care practices within a clinical system. Utilization of this assessment methodology can provide just-in-time clinical information about readiness and safety practices, particularly during emerging outbreaks. Unannounced Standardized Patients will prove especially powerful as clinicians and systems return to outpatient visits while remaining vigilant about potentially infected individuals.
[ "Prevention" ]
38
32767350
OBJECTIVE: The recent outbreak of SARS-CoV-2 infection in Italy has resulted in a sudden and massive flow of patients into emergency rooms, and a high number of hospitalizations with the need for respiratory isolation. Massive admission of patients to the Policlinico "Agostino Gemelli" Foundation of Rome, Italy, determined the need for reengineering the entire hospital. MATERIALS AND METHODS: In this article, we consider some of the structural and organizational changes that have been necessary to deal with the emergency, with particular reference to non-intensive medicine wards, and the preventive measures aimed at limiting the spread of SARS-CoV-2 infection among hospital staff and patients themselves. RESULTS: 577 staff members were subjected to molecular tests in 1-month period and 3.8% of the total were positive. 636 patients admitted to the COVID-19 pathway were included and analyzed: 45.4% were identified as SARS-CoV-2 positive. More SARS-CoV-2 negative patients were discharged in comparison to SARS-CoV-2 positive patients (59% vs. 41%, respectively). On the other hand, more SARS-CoV-2 positive patients were transferred to ICUs in comparison to SARS-CoV-2 negative patients (16% vs. 1%, respectively). Occurrence of death was similar between the two groups, 11% vs. 7%, for SARS-CoV-2 negative and positive patients, respectively. 25% of >/=80 years old SARS-CoV-2 positive patients died during the hospitalization, while death rate was lower in other age groups (5% in 70-79 years old patients and 0% in remaining age groups). CONCLUSIONS: Rapid hospital reengineering has probably had an impact on the management of patients with and without SARS-CoV-2 infection, and on in-hospital mortality rates over the reporting period.
[ "Prevention" ]
39
32247056
Specialist palliative care services (SPCS) have a vital role to play in the global coronavirus disease 2019 pandemic. Core expertise in complex symptom management, decision making in uncertainty, advocacy and education, and ensuring a compassionate response are essential, and SPCS are well positioned to take a proactive approach in crisis management planning. SPCS resource capacity is likely to be overwhelmed, and consideration needs to be given to empowering and supporting high-quality primary palliative care in all care locations. Our local SPCS have developed a Palliative Care Pandemic Pack to disseminate succinct and specific information, guidance, and resources designed to enable the rapid upskilling of nonspecialist clinicians needing to provide palliative care. It may be a useful tool for our SPCS colleagues to adapt as we face this global challenge collaboratively.
[ "Prevention" ]
40
32586336
BACKGROUND: Current outbreaks of COVID-19 are threatening the health care systems of several countries around the world. Control measures, based on isolation, contact tracing, and quarantine, can decrease and delay the burden of the ongoing epidemic. With respect to the ongoing COVID-19 epidemic, recent modeling work shows that these interventions may be inadequate to control local outbreaks, even when perfect isolation is assumed. The effect of infectiousness prior to symptom onset combined with asymptomatic infectees further complicates the use of contact tracing. We aim to study whether antivirals, which decrease the viral load and reduce infectiousness, could be integrated into control measures in order to augment the feasibility of controlling the epidemic. METHODS: Using a simulation-based model of viral transmission, we tested the efficacy of different intervention measures to control local COVID-19 outbreaks. For individuals that were identified through contact tracing, we evaluate two procedures: monitoring individuals for symptoms onset and testing of individuals. Additionally, we investigate the implementation of an antiviral compound combined with the contact tracing process. RESULTS: For an infectious disease in which asymptomatic and presymptomatic infections are plausible, an intervention measure based on contact tracing performs better when combined with testing instead of monitoring, provided that the test is able to detect infections during the incubation period. Antiviral drugs, in combination with contact tracing, quarantine, and isolation, result in a significant decrease of the final size and the peak incidence, and increase the probability that the outbreak will fade out. CONCLUSION: In all tested scenarios, the model highlights the benefits of control measures based on the testing of traced individuals. In addition, the administration of an antiviral drug, together with quarantine, isolation, and contact tracing, is shown to decrease the spread of the epidemic. This control measure could be an effective strategy to control local and re-emerging outbreaks of COVID-19.
[ "Prevention" ]
41
32450752
Efforts aimed at minimizing the spread of COVID-19 and "flattening the curve" may be affecting clinical care delivery for non-COVID-19 cases that include otolaryngologic and orbital conditions. We are witnessing changes in the manner that patients present, as well as modifications in clinical management strategies. An improved understanding of these phenomena and the contributing factors is essential for otolaryngologists to provide sound clinical care during this unprecedented pandemic.
[ "Prevention" ]
42
33023039
COVID-19, caused by SARS-CoV-2, has resulted in a global pandemic recently. With no approved vaccination or treatment, governments around the world have issued guidance to their citizens to remain at home in efforts to control the spread of the disease. The goal of controlling the spread of the virus is to prevent strain on hospitals. In this paper, we focus on how non-invasive methods are being used to detect COVID-19 and assist healthcare workers in caring for COVID-19 patients. Early detection of COVID-19 can allow for early isolation to prevent further spread. This study outlines the advantages and disadvantages and a breakdown of the methods applied in the current state-of-the-art approaches. In addition, the paper highlights some future research directions, which need to be explored further to produce innovative technologies to control this pandemic.
[ "Prevention", "Diagnosis" ]
43
32570833
Global differences in changes in the numbers of population-adjusted daily test-positive cases (NPDP) and deaths (NPDD) by COVID-19 were analyzed for 49 countries, including developed and developing countries. The changes as a proportion of national population were compared, adjusting by the beginning of test-positive cases increase (BPI) or deaths increase (BDI). Remarkable regional differences of more than 100-fold in NPDP and NPDD were observed. The trajectories of NPDD after BDI increased exponentially within 20 days in most countries. Machine learning analysis suggested that NPDD on 30 days after BDI was the highest in developed Western countries (1180 persons per hundred million), followed by countries in the Middle East (128), Latin America (97), and Asia (7). Furthermore, in Western countries with positive rates of the PCR test of less than 7.0%, the increase in NPDP was slowing-down two weeks after BPI, and subsequent NPDD was only 15% compared with those with higher positive rates, which suggested that the situation of testing might have affected the velocity of COVID-19 spread. The causes behind remarkable differences between regions possibly include genetic factors of inhabitants because distributions of the race and of the observed infection increasing rates were in good agreement globally.
[ "Prevention" ]
44
32659620
Infection by SARS-CoV-2 commonly begins in the nasopharynx, and the cytologic and molecular correlates are not characterized. Fifty-eight cytologic preps (20 oral and 38 from the nasopharynx) were obtained from ten patients and analyzed in a blinded fashion for SARS-CoV-2 spike and envelope protein by immunohistochemistry and viral RNA by in situ hybridization. qRTPCR identified three positive cases and seven controls; the three cases reported mild symptoms that resolved in 2-3 days. Blinded analyses confirmed the presence of the SARS-CoV-2 spike and envelope proteins and viral RNA in the three cases and viral absence in the seven controls. A signal for the positive cases was evident in each nasopharyngeal and none of the oral samples. Viral RNA/proteins localized exclusively to glandular cells and was present in high copy number. Blinded analysis of the cytology documented that the glandular cells infected by SARS-CoV-2 showed marked degeneration with ciliocytophthoria; viral inclusions were not evident. Co-expression analysis showed viral infected cells had increased apoptosis, marked by strong expression of activated caspase 3. Weekly serial testing of two of the cases showed persistence of productive viral infection for up to 2 weeks after symptom onset. It is concluded that the target cell of SARS-CoV-2 in the head and neck region is the glandular cell of the nasal passages, that viral infection is lytic and associated with high copy number that facilitates viral spread. The method outlines a simple, rapid test for productive SARS-CoV-2 based on immunohistochemistry or in situ hybridization of the glandular cells from the nasopharynx.
[ "Mechanism", "Diagnosis" ]
45
32600505
COVID-19 is a respiratory infection caused by SARSCoV-2, a newly identified coronavirus. The disease has quickly spread throughout the world and was declared a pandemic. Older people and those with comorbid conditions carry the highest burden of morbidity and mortality associated with COVID-19. As the most accessible health care professionals, community and ambulatory care pharmacists are well positioned to respond to this public health crisis by testing eligible patients-recently allowed by federal regulation-counseling them on treatment options for symptomatic relief, reinforcing prevention measures, and managing drug shortages. Hospital pharmacists also play an important role by assisting prescribers in selecting the best treatment regimens for patients, evaluating and securing investigational agents, developing criteria for drug use, mitigating drug shortages, and preserving personal protective equipment. In addition, long-term care pharmacists are instrumental in optimizing medication management and developing policies to reduce the risk of COVID-19 transmission among vulnerable residents.
[ "Prevention" ]
46
32809968
Objectives We describe a standardized, scalable outpatient surveillance model for pregnant women with COVID-19 with several objectives: (1) to identify and track known, presumed, and suspected COVID-positive pregnant patients both during their acute illness and after recovery, (2) to regularly assess patient symptoms and escalate care for those with worsening disease while reducing unnecessary hospital exposure for others, (3) to educate affected patients on warning symptoms, hygiene, and quarantine recommendations, and (4) to cohort patient care, isolating stable infected patients at home and later within the same physical clinic area upon their return to prenatal care. Methods Pregnant women in an urban public hospital system with presumed or confirmed COVID-19 were added to a list in our electronic medical record as they came to the attention of providers. They received a series of phone calls based on their illness severity and were periodically assessed until deemed stable. Results A total of 83 patients were followed between March 19 and May 31, 2020. Seven (8%) were asymptomatic, 62 (75%) had mild disease, 11 (13%) had severe disease, and three (4%) had critical illness. Conclusions We encourage others to develop and utilize outpatient surveillance systems to facilitate appropriate care and to optimize maternal and fetal well-being.
[ "Prevention" ]
47
32943302
BACKGROUND: Coronavirus disease 2019 (COVID-19) playing havoc across the globe caused 585,727 deaths and 13,616,593 confirmed cases so far as per World Health Organization data released till 17th July 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) is responsible for causing this pandemic across different continents. It is not only impacting the world economy but also quarantined millions of people in their homes or hospitals. PURPOSE: At present, there is no Food and Drug Administration-approved drug or vaccine available to treat this disease. Still, people are trying various pre-existing medicines that are known to have anti-viral or anti-parasitic effects. In view of this, the present study aimed to study the binding potential of various phytochemicals present in multiple natural plant extract as a secondary metabolite to non-structural protein 15 (Nsp15) protein, a drug target known to play a crucial role in virulence of coronavirus. METHOD: Nsp15 protein was selected because it shows 89% similarity to the other SARS-CoV, which caused the earlier outbreak. The assumption is that inhibition of Nsp15 slowdowns the viral replication. Phytochemicals are selected as these are present in various plant parts (seed, flower, roots, etc.), which are used in different food cuisines in different geographical regions across the globe. The molecular docking approach was performed using two different software, i.e., Autodock, and Swissdock, to study the interaction of various phytochemicals with Nsp15 protein. Hydroxychloroquine is used as a positive control as it is used by medical professionals showing some positive effects in dealing with coronavirus. RESULTS: The present study demonstrated the binding potential of approximately 50 phytochemicals with Nsp15 and capable of inhibiting the viral replication, although in vitro and in vivo tests are required to confirm these findings. CONCLUSIONS: In conclusion, the present study successfully demonstrated the binding of phytochemicals such as sarsasapogenin, ursonic acid, curcumin, ajmalicine, novobiocin, silymarin and aranotin, piperine, gingerol, rosmarinic acid, and alpha terpinyl acetate to Nsp15 viral protein and they might play a key role in inhibiting SARS-CoV-2 replication.
[ "Treatment", "Mechanism" ]
48
32387574
Bereavement care is considered an integral component of quality end-of-life care endorsed by the palliative care movement. However, few hospitals and health care institutions offer universal bereavement care to all families of patients who die. The current coronavirus disease 2019 pandemic has highlighted this gap and created a sense of urgency, from a public health perspective, for institutions to provide support to bereaved family members. In this article, drawing on the palliative care and bereavement literature, we offer suggestions about how to incorporate palliative care tools and psychological strategies into bereavement care for families during this pandemic.
[ "Prevention" ]
49
32587063
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a severe, international shortage of N95 respirators, which are essential to protect health care providers from infection. Given the contemporary limitations of the supply chain, it is imperative to identify effective means of decontaminating, reusing, and thereby conserving N95 respirator stockpiles. To be effective, decontamination must result in sterilization of the N95 respirator without impairment of respirator filtration or user fit. Although numerous methods of N95 decontamination exist, none are universally accessible. In this work, we describe a microwave-generated steam decontamination protocol for N95 respirators for use in health care systems of all sizes, geographies, and means. Using widely available glass containers, mesh from commercial produce bags, a rubber band, and a 1,100-W commercially available microwave, we constructed an effective, standardized, and reproducible means of decontaminating N95 respirators. Employing this methodology against MS2 phage, a highly conservative surrogate for SARS-CoV-2 contamination, we report an average 6-log10 plaque-forming unit (PFU) (99.9999%) and a minimum 5-log10 PFU (99.999%) reduction after a single 3-min microwave treatment. Notably, quantified respirator fit and function were preserved, even after 20 sequential cycles of microwave steam decontamination. This method provides a valuable means of effective decontamination and reuse of N95 respirators by frontline providers facing urgent need.IMPORTANCE Due to the rapid spread of coronavirus disease 2019 (COVID-19), there is an increasing shortage of protective gear necessary to keep health care providers safe from infection. As of 9 April 2020, the CDC reported 9,282 cumulative cases of COVID-19 among U.S. health care workers (CDC COVID-19 Response Team, MMWR Morb Mortal Wkly Rep 69:477-481, 2020, https://doi.org/10.15585/mmwr.mm6915e6). N95 respirators are recommended by the CDC as the ideal method of protection from COVID-19. Although N95 respirators are traditionally single use, the shortages have necessitated the need for reuse. Effective methods of N95 decontamination that do not affect the fit or filtration ability of N95 respirators are essential. Numerous methods of N95 decontamination exist; however, none are universally accessible. In this study, we describe an effective, standardized, and reproducible means of decontaminating N95 respirators using widely available materials. The N95 decontamination method described in this work will provide a valuable resource for hospitals, health care centers, and outpatient practices that are experiencing increasing shortages of N95 respirators due to the COVID-19 pandemic.
[ "Prevention" ]
50
32352383
BACKGROUND: Since the beginning of December 2019, the coronavirus disease (COVID-19) has spread rapidly around the world, which has led to increased discussions across online platforms. These conversations have also included various conspiracies shared by social media users. Amongst them, a popular theory has linked 5G to the spread of COVID-19, leading to misinformation and the burning of 5G towers in the United Kingdom. The understanding of the drivers of fake news and quick policies oriented to isolate and rebate misinformation are keys to combating it. OBJECTIVE: The aim of this study is to develop an understanding of the drivers of the 5G COVID-19 conspiracy theory and strategies to deal with such misinformation. METHODS: This paper performs a social network analysis and content analysis of Twitter data from a 7-day period (Friday, March 27, 2020, to Saturday, April 4, 2020) in which the #5GCoronavirus hashtag was trending on Twitter in the United Kingdom. Influential users were analyzed through social network graph clusters. The size of the nodes were ranked by their betweenness centrality score, and the graph's vertices were grouped by cluster using the Clauset-Newman-Moore algorithm. The topics and web sources used were also examined. RESULTS: Social network analysis identified that the two largest network structures consisted of an isolates group and a broadcast group. The analysis also revealed that there was a lack of an authority figure who was actively combating such misinformation. Content analysis revealed that, of 233 sample tweets, 34.8% (n=81) contained views that 5G and COVID-19 were linked, 32.2% (n=75) denounced the conspiracy theory, and 33.0% (n=77) were general tweets not expressing any personal views or opinions. Thus, 65.2% (n=152) of tweets derived from nonconspiracy theory supporters, which suggests that, although the topic attracted high volume, only a handful of users genuinely believed the conspiracy. This paper also shows that fake news websites were the most popular web source shared by users; although, YouTube videos were also shared. The study also identified an account whose sole aim was to spread the conspiracy theory on Twitter. CONCLUSIONS: The combination of quick and targeted interventions oriented to delegitimize the sources of fake information is key to reducing their impact. Those users voicing their views against the conspiracy theory, link baiting, or sharing humorous tweets inadvertently raised the profile of the topic, suggesting that policymakers should insist in the efforts of isolating opinions that are based on fake news. Many social media platforms provide users with the ability to report inappropriate content, which should be used. This study is the first to analyze the 5G conspiracy theory in the context of COVID-19 on Twitter offering practical guidance to health authorities in how, in the context of a pandemic, rumors may be combated in the future.
[ "Prevention" ]
51
32867625
COVID-19 is a new respiratory illness caused by SARS-CoV-2, and has constituted a global public health emergency. Cat is susceptible to SARS-CoV-2. However, the prevalence of SARS-CoV-2 in cats remains largely unknown. Here, we investigated the infection of SARS-CoV-2 in cats during COVID-19 outbreak in Wuhan by serological detection methods. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. Fifteen sera collected after the outbreak were positive for the receptor binding domain (RBD) of SARS-CoV-2 by indirect enzyme linked immunosorbent assay (ELISA). Among them, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). In addition, we continuously monitored serum antibody dynamics of two positive cats every 10 days over 130 days. Their serum antibodies reached the peak at 10 days after first sampling, and declined to the limit of detection within 110 days. Our data demonstrated that SARS-CoV-2 has infected cats in Wuhan during the outbreak and described serum antibody dynamics in cats, providing an important reference for clinical treatment and prevention of COVID-19.
[ "Diagnosis", "Transmission", "Prevention" ]
52
33019397
BACKGROUND: There is a worldwide outbreak of coronavirus disease 2019 (COVID-19), at present, accumulative attention has been paid to COVID-19 due to its global prevalence. Acupuncture may play a beneficial role in patients who suffer from COVID-19. In China and East Asia, acupuncture has been widely used to treat diverse diseases for thousands of years, as an important method of treatment now, it plays an indispensable role in the treatment of respiratory diseases in China. This study is designed to determine the efficacy and safety of acupuncture in COVID-19. METHODS: We will search the following sources for the Randomized controlled trials (RCT): The Cochrane Library, PubMed, EMBASE, Web of Science, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure Database (CNKI), Chinese Science, and the Wanfang Database. All the above databases will be searched from the available date of inception until the latest issue. No language or publication restriction will be used. Primary outcomes will include chest CT and nucleic acid detection of respiratory samples. 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 evaluate whether acupuncture is an effective treatments for patients suffering from COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020180875.
[ "Treatment" ]
53
32347612
At present, routine dermatology practices stay mostly disrupted worldwide owing to the ongoing COVID-19 pandemic. However, dermatology services need to be resumed in future and dermatologists especially in developing countries face a mammoth task of devising plans to tackle the upcoming surge of patients while still maintaining the precautions to avoid risk of infection to health care workers and our patients. Teledermatology practice is a viable alternative and there is need of starting functioning teledermatology centers at primary health care centers and training health care workers in telemedicine. Several steps like increasing the working hours of outpatient clinics, posting dermatologists and health staffs in shifts, encouraging online registration and payment, providing time slots to patients should be taken to prevent overcrowding at outpatient departments in hospitals of developing countries like India where the usual patient turnover during summers maybe around 600 to 800 per day. Once diagnosed by the dermatologist, a subsequent meticulous use of teledermatology can limit the number of follow-up visits. To avoid student gatherings, the undergraduate and postgraduate teaching schedule should be replaced by online or virtual teaching in form of webinars and video conferencing. Above all, intense upgradation of health care infrastructure, recruitment, training of new health care staffs on mass level and huge investment in health care sector is required in all the developing countries.
[ "Prevention" ]
54
32757376
BACKGROUND: In the current situation of the COVID-19 pandemic, healthcare workers (HCWs) have to comply with hygiene conditions and use gloves more frequently and for a longer period of time than they would previously to avoid infection and prevent transmission. AIMS: We aimed to characterize the adverse skin reactions occurring after hand hygiene and glove use in HCWs in a tertiary university hospital to determine the possible causative factors and whether the use of these measures is affected. METHODS: Between April 15 and May 1, 2020, a cross-sectional survey was conducted, using online questionnaire, answered by HCWs in a tertiary university hospital. RESULTS: The increase in general hand-skin problems during the pandemic period was statistically significant (P = .004). The most common symptom was dryness. During the pandemic period, 67 (24.3%) HCWs thought that the conditions were caused by glove use, and 197 (71.4%) thought that they were due to alcohol-based hand antiseptics. The incidence of other hand-skin conditions except for vesicles was statistically higher in women than in men (P < .001). CONCLUSIONS: Increased number of hand-skin conditions during the pandemic should not be ignored, since hand hygiene and glove use are expected to increase.
[ "Prevention" ]
55
32373189
The novel coronavirus disease 2019 (COVID-19) has already evolved into a rapidly expanding pandemic. Risk factors for COVID-19, such as cardiovascular disease, chronic obstructive pulmonary disease and diabetes, are all strongly associated with smoking habits. The effects of cigarette smoking on the transmission of the virus and worsening of COVID-19 have been less addressed. Emerging data indicate that smoking history is the major determinant of worsening COVID-19 outcomes. Smoking cessation recovers airway ciliary clearance and immune function. Thus, smoking cessation awareness is strongly encouraged as a public health measure to limit the global impact of COVID-19.
[ "Prevention" ]
56
32843231
OBJECTIVE: Severely ill COVID-19 patients may end in acute respiratory distress syndrome (ARDS) and multi-organ failure. Some of them develop a systemic hyperinflammatory state produced by the massive release of inflammatory agents, known as cytokine storm syndrome (CSS). Inhibition of IL-1 by Anakinra (ANK) is a potential life-saving therapy for severe CSS cases. We propose a rationale for the use of subcutaneous ANK and review our initial experience in a small cohort of severe COVID-19 CSS patients. METHODS: Retrospective cohort study of COVID-19 patients developing ARDS (PaO2/FiO2 <300) and exhibiting signs of hyperinflammation (ferritin >1000 ng/mL and/or d-dimers > 1.5 mug/mL, plus IL-6 < 40 mg/mL) that received ANK. For comparison, a propensity score matched historical cohort of patients treated with IL-6 inhibitor Tocilizumab (TCZ) was used. Patients had previously received combinations of azithromycin, hydroxy-chloroquine, and methyl-prednisolone. Laboratory findings, respiratory function and adverse effects were monitored. Resolution of ARDS within the first 7 days of treatment was considered a favorable outcome. RESULTS: Subcutaneous ANK (100 mg every 6 h) was given to 9 COVID-19 ARDS CSS patients (77.8% males). Median age was 62 years (range, 42 to 87). A TCZ cohort of 18 patients was selected by propensity score matching and treated with intravenous single dose of 600 mg for patients weighing >75 Kg, or 400 mg if < 75 Kg. Prior to treatment, median PaO2/FiO2 ratio of the ANK and TCZ cohorts were 193 and 249, respectively (p = 0.131). After 7 days of treatment, PaO2/FiO2 ratio improved in both groups to 279 (104-335) and 331 (140-476, p = 0.099) respectively. On day 7, there was significant reduction of ferritin (p = 0.046), CRP (p = 0.043), and IL-6 (p = 0.043) levels in the ANK cohort but only of CRP (p = 0.001) in the TCZ group. Favorable outcome was achieved in 55.6% and 88.9% of the ANK and TCZ cohorts, respectively (p = 0.281). Two patients that failed to respond to TCZ improved after ANK treatment. Aminotransferase levels significantly increased between day 1 and day 7 (p = 0.004) in the TCZ group. Mortality was the same in both groups (11%). There were not any opportunistic infection in the groups nor other adverse effects attributable to treatment. CONCLUSION: Overall, 55.6% of COVID-19 ARDS CSS patients treated with ANK exhibited favorable outcome, not inferior to a TCZ treated matched cohort. ANK may be a potential alternative to TCZ for patients with elevated aminotransferases, and may be useful in non-responders to TCZ.
[ "Treatment" ]
57
32292113
The novel coronavirus disease 2019 (COVID-19) has grown to be a global public-health emergency since patients were first detected in Wuhan, China, in December 2019. As of April 9, 2020, the novel coronavirus (named as SARS-CoV-2 by the International Committee on Taxonomy of Viruses on February 11) has infected 83,251 and 1,484,811 patients in China and the world, respectively. However, we have neither confirmed effective antiviral medications nor vaccines available to deal with this emergency. In this commentary, we offer an alternative promising therapy for COVID-19, that is, mesenchymal stem cell transplantation.
[ "Treatment" ]
58
32728006
INTRODUCTION: To review published studies related to the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections with pregnancy, foetal, and neonatal outcomes during coronavirus disease 2019 (COVID-19) pandemic in a systematic manner. METHODS: A comprehensive electronic search was done through PubMed, Scopus, Medline, Cochrane database, and Google Scholar from December 01, 2019, to May 22, 2020, along with the reference list of all included studies. All cohort studies that reported on outcomes of COVID-19 during pregnancy were included. Qualitative assessment of included studies was performed using the Newcastle-Ottawa scale. RESULTS: Upon admission, most pregnant women underwent a low-dose radiation CT scan; the reports of which included unilateral/bilateral pneumonia in most patients. A marked lymphopenia was also noted in many patients with COVID-19. 513 titles were screened, and 22 studies were included, which identified 156 pregnant women with COVID-19 and 108 neonatal outcomes. The most common maternal/foetal complications included intrauterine/foetal distress (14%) and premature rupture of membranes (8%). The neonatal clinical manifestations of COVID-19 commonly included shortness of breath (6%), gastrointestinal symptoms (4%), and fever (3%). CONCLUSION: COVID-19 infection in pregnancy leads to increased risk in pregnancy complications such as preterm birth, PPROM, and may possibly lead to maternal death in rare cases. There is no evidence to support vertical transmission of SARS-CoV-2 infection to the unborn child. Due to a paucity of inconsistent data regarding the impact of COVID-19 on the newborn, caution should be undertaken to further investigate and monitor possible infection in the neonates born to COVID-19-infected mothers.
[ "Treatment", "Transmission", "Diagnosis" ]
59
32816957
Tocilizumab, a monoclonal antibody against interleukin-6, has been used to treat cytokine release syndrome (CRS) in a subset of patients with severe COVID-19 disease. Acute ulcerative bowel disease has been only rarely documented in patients treated for rheumatological conditions. The gastrointestinal side effects seen when used in the context of COVID-19 are unknown. We present a case of COVID-19 CRS in which acute terminal ileum and perforated caecal ulceration evolved after tocilizumab exposure. We raise awareness of a possible causal relationship between even a single dose of tocilizumab and gut ulceration in patients with COVID-19. Any such drug enteropathy relationship requires watchful monitoring during upcoming trials of tocilizumab in patients with COVID-19.
[ "Case Report" ]
60
32060933
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.
[ "Mechanism", "Transmission" ]
61
32905022
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 29 million people and has caused more than 900,000 deaths worldwide as of September 14, 2020. The SARS-CoV-2 human cell receptor ACE2 has recently received extensive attention for its role in SARS-CoV-2 infection. Many studies have also explored the association between ACE2 and cancer. However, a systemic investigation into associations between ACE2 and oncogenic pathways, tumor progression, and clinical outcomes in pan-cancer remains lacking. Using cancer genomics datasets from the Cancer Genome Atlas (TCGA) program, we performed computational analyses of associations between ACE2 expression and antitumor immunity, immunotherapy response, oncogenic pathways, tumor progression phenotypes, and clinical outcomes in 13 cancer cohorts. We found that ACE2 upregulation was associated with increased antitumor immune signatures and PD-L1 expression, and favorable anti-PD-1/PD-L1/CTLA-4 immunotherapy response. ACE2 expression levels inversely correlated with the activity of cell cycle, mismatch repair, TGF-beta, Wnt, VEGF, and Notch signaling pathways. Moreover, ACE2 expression levels had significant inverse correlations with tumor proliferation, stemness, and epithelial-mesenchymal transition. ACE2 upregulation was associated with favorable survival in pan-cancer and in multiple individual cancer types. These results suggest that ACE2 is a potential protective factor for cancer progression. Our data may provide potential clinical implications for treating cancer patients infected with SARS-CoV-2.
[ "Treatment", "Mechanism" ]
62
32289312
Public health emergencies have the potential to place enormous strain on health systems. The current pandemic of the novel 2019 coronavirus disease has required hospitals in numerous countries to expand their surge capacity to meet the needs of patients with critical illness. When even surge capacity is exceeded, however, principles of critical care triage may be needed as a means to allocate scarce resources, such as mechanical ventilators or key medications. The goal of a triage system is to direct limited resources towards patients most likely to benefit from them. Implementing a triage system requires careful coordination between clinicians, health systems, local and regional governments, and the public, with a goal of transparency to maintain trust. We discuss the principles of tertiary triage and methods for implementing such a system, emphasizing that these systems should serve only as a last resort. Even under triage, we must uphold our obligation to care for all patients as best possible under difficult circumstances.
[ "Prevention" ]
63
32419693
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.
[ "Prevention" ]
64
32851112
Background: Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can shed virus, thereby causing human-to-human transmission, and the viral RNA shedding is commonly used as a proxy measure for infectivity. Methods: We retrospectively reviewed confirmed cases of COVID-19 who attended the fever clinic of Wuhan Union Hospital from January 14 to February 24. In terms of the viral RNA shedding (median values) at first visit, patients were divided into a high-viral RNA shedding group and a low-viral RNA shedding group. Univariate and multivariate logistic regression analysis were performed to investigate the correlation between viral RNA shedding and clinical features. Results: A total of 918 consecutive COVID-19 patients were enrolled, and severe patients made up 26.1%. After univariate and multivariate logistic regression, advanced age (odds ratio [OR], 1.02; 95% CI, 1.01-1.03; P = .001), having severe chronic diseases (OR, 1.44; 95% CI, 1.03-2.01; P = .04), and severe illness (OR, 1.60; 95% CI, 1.12-2.28; P = .01) were independent risk factors for high viral RNA shedding. Shorter time interval from symptom onset to viral detection was a protective factor for viral RNA shedding (OR, 0.97; 95% CI, 0.94-0.99; P = .01). Compared with mild patients, severe patients have higher virus shedding over a long period of time after symptom onset (P = .01). Conclusions: Outpatients who were old, had severe illness, and had severe underlying diseases had high viral RNA shedding.
[ "Diagnosis" ]
65
32364528
We aimed to describe typical radiological features and progression of Coronavirus disease 2019 (COVID-19) patients. We reviewed the chest CT scans, laboratory findings, and clinical records of 66 COVID-19 patients who were admitted to affiliated hospitals of Nanchang university, Nanchang, China, from Jan 21 to Feb 2, 2020. CT was used to evaluate the radiological characteristics of COVID-19 patients. Only 4 patients (4/66, 6%) claimed their exposure to COVID-19 pneumonia patients. The major symptoms were fever (60/66, 91%) and cough (37/66, 56%). The predominant features of lesion were scattered (43/66, 65%), bilateral (50/66, 76%), ground-glass opacity (64/66, 97%), and air bronchogram sign (47/66, 71%). Forty-eight patients (48/66, 73%) had more than two lobes involved. Right lower lobe (58/66, 88%) and left lower lobe (49/66, 74%) were most likely invaded. Twelve patients (12/66, 18%) had at least one comorbid condition. Pleural traction (29/66, 44%), crazy paving (15/66, 23%), interlobular septal thickening (11/66, 17%), and consolidation (7/66, 11%) were also observed. The typical radiology features of COVID-19 patients are scattered ground-glass opacity in the bilateral lobes. Fever and cough are the major symptoms. Evaluating chest CT, clinical symptoms, and laboratory results could facilitate the early diagnosis of COVID-19, and judge disease progression.
[ "Diagnosis", "Treatment" ]
66
32875166
The high mortality rate from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in humans and the lack of effective therapeutic regime for its treatment necessitates the identification of new antivirals. SARS-CoV-2 relies on non-structural proteins such as Nsp13 helicase and nsp14 which are the key components of the replication-transcription complex (RTC) to complete its infectious life cycle. Therefore, targeting these essential viral proteins with small molecules will most likely to halt the disease pathogenesis. The lack of experimental structures of these proteins deters the process of structure-based identification of their specific inhibitors. In the present study, the in silico models of SARS-CoV-2 nsp13 helicase and nsp14 protein were elucidated using a comparative homology modelling approach. These in silico model structures were validated using various parameters such as Ramachandran plot, Verify 3D score, ERRAT score, knowledge-based energy and Z-score. The in silico models were further used for virtual screening of the Food and Drug Administration (FDA) approved antiviral drugs. Simeprevir (SMV), Paritaprevir (PTV) and Grazoprevir (GZR) were the common leads identified which show higher binding affinity to both nsp13 helicase and nsp14 as compared to the control inhibitors and therefore, they might be potential dual-target inhibitors. The leads also establish a network of hydrogen bonds and hydrophobic interactions with the key residues lining the active site pockets. The present findings suggest that these FDA approved antiviral drugs can be subjected to repurposing against SARS-CoV-2 infection after verifying the in silico results through in vitro and in vivo studies.
[ "Treatment", "Mechanism" ]
67
32991604
BACKGROUND: Without any pharmaceutical intervention and vaccination, the only way to combat Coronavirus Disease 2019 (COVID-19) is to slow down the spread of the disease by adopting non-pharmaceutical public health interventions (PHIs). Patient isolation, lockdown, quarantine, social distancing, changes in health care provision, and mass screening are the most common non-pharmaceutical PHIs to cope with the epidemic. However, there is neither systematic evidence on the effectiveness of non-pharmaceutical PHIs in controlling the COVID-19 nor on how these interventions work in different contexts. Therefore, in this study we will address two main objectives: 1) to assess the effectiveness of the non-pharmaceutical PHIs in controlling the spread of COVID-19 using a systematic review and meta-analyses; 2) to explore why, how, and for whom these interventions work using a realist review. MATERIALS AND METHODS: This review study has two main phases. In the first phase of this study, we will extract data from two main types of studies including quasi-experimental studies (such as quasi-randomized trials, controlled before-after studies (CBAs) and interrupted time series studies (ITSs)) and observational studies (such as cohort, case-control, and cross-sectional studies), written in the English language. We will explore effectiveness of the non-pharmaceutical PHIs targeted either suppression or mitigation strategies (or a combination of both) in controlling the COVID-19 epidemics in the community level. Effectiveness will be considered as the changes in mortality rate, incidence rate, basic reproduction number rate, morbidity rate, rates of hospitalization, rates of intensive care unit (ICU) hospitalization, and other health outcomes where possible. We will perform random-effects meta-analyses, if possible, using CMA software. In the second phase, we will conduct a realist review to find out how, why, for whom, and in what circumstances the non-pharmaceutical PHIs work. At the realist review, we will identify and explore Context-Mechanism-Outcome configurations to provide a robust explanation on the effectiveness of the interventions in different contexts using Pawson's 5-step realist review template including: "clarify scope; search for evidence; appraise primary studies and extract data; synthesize evidence and draw conclusions; and disseminate, implement and evaluate". Although the steps are presented in a linear manner, in practice, we will follow them in iterative stages to fill any potential overlap. DISCUSSION: The findings of this research will provide a crucial insight into how and in which context the non-pharmaceutical PHIs work in controlling the spread of COVID-19. Conducting a systematic review and meta-analysis in line with a realist review will allow us to draw a robust conclusion on the effects and the way in which the interventions work. Understanding the role of contextual factors in the effectiveness of non-pharmaceutical PHIs and the mechanism of this process could enable policymakers to implement appropriate policies and manage the COVID-19 epidemics more efficiently. SYSTEMATIC REVIEW REGISTRATION: CRD42020186855.
[ "Prevention" ]
68
32407853
The coronavirus disease 2019 (COVID-19) pandemic has had a profound global impact. Its rapid transmissibility has transformed healthcare delivery and forced countries to adopt strict measures to contain its spread. The vast majority of the United States cardiac surgical programs have deferred all but truly emergent/urgent operative procedures in an effort to reduce the burden on the healthcare system and to mobilize resources to combat the pandemic surge. While the number of COVID-19 cases continue to increase worldwide, the incidence of new cases has begun to decline in many North American cities. This "flattening of the curve" has prompted interest in reopening the economy, relaxing public health restrictions, and resuming nonurgent healthcare delivery. The following document provides a template whereby adult cardiac surgical programs may begin to ramp-up the care delivery in a deliberate and graded fashion as the COVID-19 pandemic burden begins to ease. "Resuscitating" the timely delivery of care is guided by three principles: (1) Collaborate to permit increased case volumes, balancing the clinical needs of patients awaiting surgical procedures with the local resources available within each healthcare system. (2) Prioritize patients awaiting elective procedures while proactively engaging all stakeholders, focusing on those with high-risk anatomy, changing/symptomatic clinical status, and, once these variables have been addressed, prioritizing by waiting times. (3) Reevaluate local conditions continuously to assess for any increase in admissions due to a recrudescence of cases, to assure adequate resources to care for patients, and to monitor in-hospital infectious transmissions to both patients and healthcare workers.
[ "Prevention" ]
69
32775578
Coronavirus Disease 2019 (COVID-19) has been identified as a global pandemic by the World Health Organization (WHO). The breakout of COVID-19 in various countries and regions brings a great threat to people's life and adds an unprecedented high pressure on healthcare systems. Due to the high infectivity of COVID-19, high standard negative pressure isolation units are required to accommodate the patients with COVID-19 and protect health workers. A novel prefabricated negative pressure isolation medical unit was designed and constructed in Shenzhen, China to help to accommodate the patients with COVID-19. This article provides detailed construction cost, time and testing data for this isolation medical unit. Considering the construction happened during the lockdown in Shenzhen (and in China), the construction cost and time can provide precious and rare information as well as guidelines to construct or expand appropriate medical facilities to accommodate the patients with COVID-19.
[ "Prevention" ]
70
32979911
BACKGROUND: The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic broke out in December 2019 and is now characterized as a pandemic. Effective control of this infectious disease requires access to diagnostic techniques, for both case finding and epidemic size estimation. The molecular technique is routinely used worldwide. Although it is the "standard" case detection and management method, it has its own shortcomings. Thus, some easy-to-use rapid serological tests have been developed. METHODS: One hundred and fourteen positive RT-PCR-diagnosed patients were tested by VivaDiag Kit, a brand of rapid serological kits available in hospitals affiliated to Tehran University of Medical Sciences (TUMS), Tehran, Iran. Frozen serum specimens taken from healthy people in summer and fall 2019 were also tested as negative controls. RESULTS: Test sensitivity was 47.9% (95% confidence interval [CI]: 38.8-56.9) for IgM and 47.0% (95% CI: 38.0-56.0) for IgG. There was no difference between IgG and IgM seropositivity except in one case. Specificity was calculated as 99.0% (95% CI: 96.4-99.9) for IgM and of 100.0% (95% CI: 0.98.2-100.0) for IgG. Sensitivity was higher in men and older participants. CONCLUSION: This test can be used for epidemiological investigations, especially for the estimation of the level of infection in the community, after it is properly corrected for sensitivity and specificity. The low sensitivity could be attributed to the technical limitations of the kit or low levels of antibodies after infection. The different sensitivity in age and sex groups supports the hypothesis that different people show different immune responses to this virus.
[ "Diagnosis" ]
71
32571951
Neurotropic strains of mouse hepatitis virus (MHV), a coronavirus, cause acute and chronic demyelinating encephalomyelitis with similarities to the human disease multiple sclerosis. Here, using a lineage-tracking system, we show that some cells, primarily oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs), survive the acute MHV infection, are associated with regions of demyelination, and persist in the central nervous system (CNS) for at least 150 d. These surviving OLs express major histocompatibility complex (MHC) class I and other genes associated with an inflammatory response. Notably, the extent of inflammatory cell infiltration was variable, dependent on anatomic location within the CNS, and without obvious correlation with numbers of surviving cells. We detected more demyelination in regions with larger numbers of T cells and microglia/macrophages compared to those with fewer infiltrating cells. Conversely, in regions with less inflammation, these previously infected OLs more rapidly extended processes, consistent with normal myelinating function. Together, these results show that OLs are inducers as well as targets of the host immune response and demonstrate how a CNS infection, even after resolution, can induce prolonged inflammatory changes with CNS region-dependent impairment in remyelination.
[ "Mechanism" ]
72
32292697
Purpose: The coronavirus disease 2019 (COVID-19) reminds us of the severe acute respiratory syndrome (SARS) outbreak in 2003, and up to date, corticosteroid is commonly administrated to severe patients with COVID-19. Osteonecrosis of the femoral head (ONFH) is a common disabling complication among convalescent SARS patients who received corticosteroid therapy. In China, a considerable number of convalescent SARS patients with steroid-associated ONFH had undergone conservative treatment by traditional Chinese medicine, and this study aims to evaluate the long-term results of a spleen-invigorating Huo-Gu formula (HGF) therapy in these patients. Participants and methods: A total of 33 convalescent SARS patients (9 males and 24 females) with bilateral steroid-associated ONFH (66 hips) were enrolled in this study. All patients received oral HGF therapy for 6 months when they were confirmed the diagnosis of steroid-associated ONFH. They had been regularly followed up at an interval of 1 year. Harris hip score and medical imaging modalities, including plain radiography, computed tomography and magnetic resonance imaging, were performed to evaluate the outcomes. Results: Based on average 14 years of follow-up of HGF therapy (ranging from 6 to 16 years), 38 hips (57%) among the 66 hips developed definite osteoarthritis, and 14 hips (26%) in 53 precollapse hips (Association Research Circulation Osseous [ARCO] Stage I or II) progressed to femoral head collapse (ARCO Stage III or IV). Only five patients (also 5 hips) underwent total hip arthroplasty, and the mean hip survival time was over 15 years by the Kaplan-Meier analysis. We observed a mean Harris hip score of 63 points, which represented the reserve of 55% in pain score and 70% in physical function score. The severity of groin pain was not correlated to the severity of osteoarthritis. Conclusion: Chinese herbal HGF therapy demonstrates beneficial effects on preventing femoral head collapse, delaying total hip arthroplasty, and maintaining physical function in the treatment of steroid-associated ONFH. HGF therapy might be therefore a good alternative for the treatment of steroid-associated ONFH secondary to rheumatologic and infection diseases. Translational potential of the article: HGF therapy might be a good alternative for the treatment of steroid-associated ONFH secondary to rheumatologic and infectious diseases.
[ "Treatment" ]
73
32727067
The novel coronavirus (SARS-CoV-2) has spread globally and has been declared a pandemic by the World Health Organization. While influenza virus shows seasonality, it is unknown if COVID-19 has any weather-related affect. In this work, we analyze the patterns in local weather of all the regions affected by COVID-19 globally. Our results indicate that approximately 85% of the COVID-19 reported cases until 1 May 2020, making approximately 3 million reported cases (out of approximately 29 million tests performed) have occurred in regions with temperature between 3 and 17 degrees C and absolute humidity between 1 and 9 g/m(3). Similarly, hot and humid regions outside these ranges have only reported around 15% or approximately 0.5 million cases (out of approximately 7 million tests performed). This suggests that weather might be playing a role in COVID-19 spread across the world. However, this role could be limited in US and European cities (above 45 N), as mean temperature and absolute humidity levels do not reach these ranges even during the peak summer months. For hot and humid countries, most of them have already been experiencing temperatures >35 degrees C and absolute humidity >9 g/m(3) since the beginning of March, and therefore the effect of weather, however little it is, has already been accounted for in the COVID-19 spread in those regions, and they must take strict social distancing measures to stop the further spread of COVID-19. Our analysis showed that the effect of weather may have only resulted in comparatively slower spread of COVID-19, but not halted it. We found that cases in warm and humid countries have consistently increased, accounting for approximately 500,000 cases in regions with absolute humidity >9 g/m(3), therefore effective public health interventions must be implemented to stop the spread of COVID-19. This also means that 'summer' would not alone stop the spread of COVID-19 in any part of the world.
[ "Prevention" ]
74
32470151
The wide spectrum of symptoms observed in coronavirus disease 2019 appears to defy explanation. Apart from geographic limitation to people with prior exposure to other coronaviruses and air pollutants, inflammatory comorbidities 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 severe acute respiratory syndrome coronavirus 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.
[ "Treatment" ]
75
32527141
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.
[ "Diagnosis" ]
76
32930555
Coronavirus disease 2019 (COVID-19) has challenged us to incorporate technology into engaging, interacting with, and caring for patients, using televisits and video conferencing in ways that have previously been resisted or derided.
[ "Prevention" ]
77
32807087
BACKGROUND: During an evolving outbreak or pandemic, non-pharmaceutical interventions (NPIs) including physical distancing, isolation, and mask use may flatten the peak in communities. However, these strategies rely on community understanding and motivation to engage to ensure appropriate compliance and impact. To support current activities for COVID-19, the objectives of this narrative review was to identify the key determinants impacting on engagement. METHODS: An integrative narrative literature review focused on NPIs. We aimed to identify published peer-reviewed articles that focused on the general community (excluding healthcare workers), NPIs (including school closure, quarantine, isolation, physical distancing and hygiene behaviours), and factors/characteristics (including social, physical, psychological, capacity, motivation, economic and demographic) that impact on engagement. RESULTS: The results revealed that there are a range of demographic, social and psychological factors underpinning engagement with quarantine, school closures, and personal protective behaviours. Aside from the factors impacting on acceptance and compliance, there are several key community concerns about their use that need to be addressed including the potential for economic consequences. CONCLUSION: It is important that we acknowledge that these strategies will have an impact on an individual and the community. By understanding the barriers, we can identify what strategies need to be adopted to motivate individuals and improve community compliance. Using a behavioural framework to plan interventions based on these key barriers, will also ensure countries implement appropriate and targeted responses.
[ "Prevention" ]
78
32300516
With the emergence of the novel coronavirus disease (COVID-19) viral pandemic, there is uncertainty whether biologic agents for psoriasis may place patients at a higher risk for infection or more severe disease course. This commentary offers patient counseling recommendations based on the current available evidence. While there are currently no specific data for psoriasis biologics and COVID-19, data are presented here from phase III clinical trials of psoriasis biologics on rates of upper respiratory infection, influenza, and serious infection. Overall these data reveal that on the whole, psoriasis biologics do not show major increases in infection risk compared to placebo during the course of these trials. However, as the COVID-19 virus is a novel pathogen that is associated with mortality in a subset of patients, a cautious approach is warranted. We discuss factors that may alter the benefit-risk ratio of biologic use during this time of COVID-19 outbreak. Ultimately, treatment decisions should be made on the basis of dialogue between patient and provider, considering each patient's individualized situation. Once this pandemic has passed, it is only a matter of time before a new viral disease reignites the same issues discussed here.
[ "Treatment" ]
79
33010669
Novel coronavirus SARS-CoV-2, designated as COVID-19 by the World Health Organization (WHO) on the February 11, 2020, is one of the highly pathogenic beta-coronaviruses which infects human. Early diagnosis of COVID-19 is the most critical step to treat infection. The diagnostic tools are generally molecular methods, serology and viral culture. Recently CRISPR-based method has been investigated to diagnose and treat coronavirus infection. The emergence of 2019-nCoV during the influenza season, has led to the extensive use of antibiotics and neuraminidase enzyme inhibitors, taken orally and intravenously. Currently, antiviral inhibitors of SARS and MERS spike proteins, neuraminidase inhibitors, anti-inflammatory drugs and EK1 peptide are the available therapeutic options for SARS-CoV-2 infected individuals. In addition, Chloroquine, which was previously used for malarial and autoimmune disease, has shown efficacy in the 2019-nCoV infection treatment. In severe hypoxaemia, a combination of antibiotics, alpha-interferon, lopinavir and mechanical ventilation can effectively mitigate the symptoms. Comprehensive knowledge on the innate and adaptive immune responses, will make it possible to propose potent antiviral drugs with their effective therapeutic measures for the prevention of viral infection. This therapeutic strategy will help patients worldwide to protect themselves against severe and fatal viral infections, that potentially can evolve and develop drug resistance, and to reduce mortality rates.
[ "Treatment", "Diagnosis", "Mechanism" ]
80
32589541
Ocular complications in critical care patients are common. There has been a surge in intensive care admissions following the COVID-19 outbreak. The management of COVID-19 exposes patients to a number of specific risk factors for developing ocular complications, which include non-invasive ventilation, mechanical ventilation and prone positioning. Consequently, it is likely that there will be an increase in the number of ocular complications secondary to the management of COVID-19 patients in the intensive care unit setting, and these complications could lead to permanent visual loss and blindness. Increased awareness of eye care in the intensive care unit setting is therefore vital to help prevent visual loss and maintain quality of life for patients recovering from COVID-19.
[ "Prevention", "Treatment" ]
81
32316270
The desperate need to find drugs for COVID-19 has indicated repurposing strategies as our quickest way to obtain efficacious medicines. One of the options under investigation is the old antimalarial drug, chloroquine, and its analog, hydroxychloroquine. Developed as synthetic succedanea of cinchona alkaloids, these chiral antimalarials are currently in use as the racemate. Besides the ethical concern related to accelerated large-scale clinical trials of drugs with unproven efficacy, the known potential detrimental cardiac effects of these drugs should also be considered. In principle, the safety profile might be ameliorated by using chloroquine/hydroxychloroquine single enantiomers in place of the racemate.
[ "Treatment" ]
82
32410266
Coronavirus disease 2019 (COVID-19) has become a major global public health concern. The mortality rate for critically ill patients is up to 60%, and, thus, reducing the disease severity and case mortality is a top priority. Currently, cytokine storms are considered as the major cause of critical illness and death due to COVID-19. After a systematical review of the literature, we propose that cross-reactive antibodies associated with antibody-dependent enhancement (ADE) may actually be the cause of cytokine storms. It would be more difficult to develop vaccines for highly pathogenic human coronaviruses (CoVs) if ADE characteristics are taken into consideration. Therefore, it is urgent to find an effective way to prevent the occurrence of severe illness as severe acute respiratory syndrome CoV-2 specific drugs or vaccines are still in development. If the activation of memory B cells can be selectively inhibited in high-risk patients at an early stage of COVID-19 to reduce the production of cross-reactive antibodies against the virus, we speculate that ADE can be circumvented and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such needs and it is recommended to conduct clinical trials for mTOR inhibitors in preventing the severity of COVID-19.
[ "Treatment", "Mechanism" ]
83
32866314
The novel coronavirus disease 2019 (COVID-19) global pandemic has shifted how many patients receive outpatient care. Telehealth and remote monitoring have become more prevalent, and measurements taken in a patient's home using biometric monitoring technologies (BioMeTs) offer convenient opportunities to collect vital sign data. Healthcare providers may lack prior experience using BioMeTs in remote patient care, and, therefore, may be unfamiliar with the many versions of BioMeTs, novel data collection protocols, and context of the values collected. To make informed patient care decisions based on the biometric data collected remotely, it is important to understand the engineering solutions embedded in the products, data collection protocols, form factors (physical size and shape), data quality considerations, and availability of validation information. This article provides an overview of BioMeTs available for collecting vital signs (temperature, heart rate, blood pressure, oxygen saturation, and respiratory rate) and discusses the strengths and limitations of continuous monitoring. We provide considerations for remote data collection and sources of validation information to guide BioMeT use in the era of COVID-19 and beyond.
[ "Prevention" ]
84
32920578
Coinfection of SARS-CoV-2 and dengue virus has not been previously reported. We report a confirmed case with favourable outcome, but whether the occurrence of simultaneous infections may alter the usual clinical course of each infection is still unknown.
[ "Case Report" ]
85
32504052
Detection of asymptomatic or subclinical novel human coronavirus SARS-CoV-2 infection is critical for understanding the overall prevalence and infection potential of COVID-19. To estimate the cumulative prevalence of SARS-CoV-2 infection in China, we evaluated the host serologic response, measured by the levels of immunoglobulins M and G in 17,368 individuals, in the city of Wuhan, the epicenter of the COVID-19 pandemic in China, and geographic regions in the country, during the period from 9 March 2020 to 10 April 2020. In our cohorts, the seropositivity in Wuhan varied between 3.2% and 3.8% in different subcohorts. Seroposivity progressively decreased in other cities as the distance to the epicenter increased. Patients who visited a hospital for maintenance hemodialysis and healthcare workers also had a higher seroprevalence of 3.3% (51 of 1,542, 2.5-4.3%, 95% confidence interval (CI)) and 1.8% (81 of 4,384, 1.5-2.3%, 95% CI), respectively. More studies are needed to determine whether these results are generalizable to other populations and geographic locations, as well as to determine at what rate seroprevalence is increasing with the progress of the COVID-19 pandemic. Serologic surveillance has the potential to provide a more faithful cumulative viral attack rate for the first season of this novel SARS-CoV-2 infection.
[ "Prevention" ]
86
33029407
The current coronavirus disease 2019 (COVID-19) pandemic is massively affecting our daily practice. Elective surgical service has been significantly altered, i.e. reduced overall service provision, special operating theatres' precautions, as well as considerations for testing patients before surgery. The process of counselling patients and obtaining their consent is a must before any surgical intervention. Several factors can affect this process particularly amid the current pandemic crisis. Only with a full understanding of all the relevant facts, including risks and available alternatives, can patients give an 'informed consent'. Therefore, we urologists need to be aware of the impact of the current COVID-19 situation on how to consent our patients. Abbreviations: COVID-19: coronavirus disease 2019; PPE: personal protective equipment.
[ "Prevention" ]
87
32844061
The purpose of a forecast, in making an estimate about the future, is to give people information to act on. In the case of a coupled human system, a change in human behavior caused by the forecast can alter the course of events that were the subject of the forecast. In this context, the forecast is an integral part of the coupled human system, with two-way feedback between forecast output and human behavior. However, forecasting programs generally do not examine how the forecast might affect the system in question. This study examines how such a coupled system works using a model of viral infection-the susceptible-infected-removed (SIR) model-when the model is used in a forecasting context. Human behavior is modified by making the contact rate responsive to other dynamics, including forecasts, of the SIR system. This modification creates two-way feedback between the forecast and the infection dynamics. Results show that a faster rate of response by a population to system dynamics or forecasts leads to a significant decline in peak infections. Responding to a forecast leads to a lower infection peak than responding to current infection levels. Inaccurate forecasts can lead to either higher or lower peak infections depending on whether the forecast under-or over-estimates the peak. The direction of inaccuracy in a forecast determines whether the outcome is better or worse for the population. While work is still needed to constrain model functional forms, forecast feedback can be an important component of epidemic dynamics that should be considered in response planning.
[ "Epidemic Forecasting", "Prevention" ]
88
32905011
The development of a massively producible vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is essential for stopping the current coronavirus disease (COVID-19) pandemic. A vaccine must stimulate effective antibody and T cell responses in vivo to induce long-term protection. Scientific researchers have been developing vaccine candidates for the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) since the outbreaks of these diseases. The prevalence of new biotechnologies such as genetic engineering has shed light on the generation of vaccines against novel viruses. In this review, we present the status of the development of coronavirus vaccines, focusing particularly on the biomimetic nanoparticle technology platform, which is likely to have a major role in future developments of personalized medicine.
[ "Treatment" ]
89
32202824
The 2019 novel coronavirus (COVID-2019) has led to a serious outbreak of often severe respiratory disease, which originated in China and has quickly become a global pandemic, with far-reaching consequences that are unprecedented in the modern era. As public health officials seek to contain the virus and mitigate the deleterious effects on worldwide population health, a related threat has emerged: global media exposure to the crisis. We review research suggesting that repeated media exposure to community crisis can lead to increased anxiety, heightened stress responses that can lead to downstream effects on health, and misplaced health-protective and help-seeking behaviors that can overburden health care facilities and tax available resources. We draw from work on previous public health crises (i.e., Ebola and H1N1 outbreaks) and other collective trauma (e.g., terrorist attacks) where media coverage of events had unintended consequences for those at relatively low risk for direct exposure, leading to potentially severe public health repercussions. We conclude with recommendations for individuals, researchers, and public health officials with respect to receiving and providing effective communications during a public health crisis. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
[ "Prevention" ]
90
32571376
Inherited heart disease represent a very heterogenous group of cardiac disorders, characterized by inherited, acquired, and often rare disorders affecting the heart muscle (cardiomyopathies) or the cardiac electrical system (ion channel disease). They are often familial diseases, and are among the leading cause of juvenile sudden death and heart failure. The aim of this paper is to give a perspective on how to run a clinical service during an epidemic or pandemic emergency and to describe the potential COVID-19 associated risks for patients affected by inherited heart diseases.
[ "Prevention" ]
91
32998369
The vitamin K-dependent factors protein S (PROS1) and growth-arrest-specific gene 6 (GAS6) and their tyrosine kinase receptors TYRO3, AXL, and MERTK, the TAM subfamily of receptor tyrosine kinases (RTK), are key regulators of inflammation and vascular response to damage. TAM signaling, which has largely studied in the immune system and in cancer, has been involved in coagulation-related pathologies. Because of these established biological functions, the GAS6-PROS1/TAM system is postulated to play an important role in SARS-CoV-2 infection and progression complications. The participation of the TAM system in vascular function and pathology has been previously reported. However, in the context of COVID-19, the role of TAMs could provide new clues in virus-host interplay with important consequences in the way that we understand this pathology. From the viral mimicry used by SARS-CoV-2 to infect cells, to the immunothrombosis that is associated with respiratory failure in COVID-19 patients, TAM signaling seems to be involved at different stages of the disease. TAM targeting is becoming an interesting biomedical strategy, which is useful for COVID-19 treatment now, but also for other viral and inflammatory diseases in the future.
[ "Treatment", "Mechanism" ]
92
33036052
The COVID-19 pandemic is a global outbreak of new onset infections with the SARS-CoV-2 virus. To date, more than 3.4 million people have been infected throughout the world. In Germany, approximately 450,000 patients suffer from inflammatory bowel disease; these patients generally require continuous expert care and support. Against the background of a rapidly accumulating knowledge base on SARS-CoV-2, 68 expert authors of the current DGVS guidelines for Crohn's disease and ulcerative colitis took part in a virtual meeting to compile up-to-date, practice-orientated recommendations aimed at improving the care of patients with IBD. These recommendations address the risk of infection, including the risk for specific patient groups, the possible course of the disease, and consequences for pharmacological and surgical therapies of the underlying disease, as well as general measures for infection prevention and adjuvant prophylactic and therapeutic options.
[ "Prevention" ]
93
32274917
The asymptomatic carrier state of COVID-19 has become a topic of concern for preventing the rebound of possible epidemic. This review describes and defines the COVID-19 asymptomatic carrier state and outlines the methods for identifying, counting and reporting of 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 the disease progression. The author presents the limited available data about the infectivity 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.
[ "Prevention", "Diagnosis" ]
94
32510050
Unidentified human remains with unknown medical history can always pose biological hazards to forensic pathologists and odontologists, including hepatitis C, HIV infection, Middle East respiratory syndrome (MERS), hemorrhagic fever viruses such as Ebola, meningitis and now Sars-Cov2. The pandemic of the new coronavirus disease (COVID-19) has reached 185 Countries with an increasing number of deaths. Forensic pathologists and odontologists may find themselves having to perform an identification autopsy to confirmed or suspected Sars-Cov2 positive deaths. By respecting the entire set of universal precautions and recommendations the highlighted risks can be minimized, and best practice in human identification should always be a priority for human rights of the dead. The following article is a summary of the recommendations for conducting dental autopsies and management of suspected COVID-19 cases.
[ "Prevention" ]
95
32563968
The objective of this document is to formalize a degraded mode management for patients with thoracic cancers in the context of the COVID-19 pandemic. The proposals are based on those of the French High Council for Public Health, on published data outside the context of COVID-19, and on a concerted analysis of the risk-benefit ratio for our patients by a panel of experts specialized on thoracic oncology under the aegis of the French-Language Society of Pulmonology (SPLF)/French-language oncology group. These proposals are evolving (10 April 2020) according to the situations encountered, which will enrich it, and are to be adapted to our institutional organisations and to the evolution of resources during the COVID-19 epidemic. Patients with symptoms and/or COVID-19+ are not discussed in this document and are managed within the framework of specific channels.
[ "Prevention" ]
96
33040480
AIMS: Patients with cardiovascular disease appear particularly susceptible to severe COVID-19 disease, but the impact of COVID-19 infection on patients with heart failure (HF) is not known. This study aimed to quantify the impact of COVID-19 infection on mortality in hospitalized patients known to have HF. METHODS AND RESULTS: We undertook a retrospective analysis of all patients admitted with a pre-existing diagnosis of HF between 1 March and 6 May 2020 to our unit. We assessed the impact of concomitant COVID-19 infection on in-hospital mortality, incidence of acute kidney injury, and myocardial injury. One hundred and thirty-four HF patients were hospitalized, 40 (29.9%) with concomitant COVID-19 infection. Those with COVID-19 infection had a significantly increased in-hospital mortality {50.0% vs. 10.6%; relative risk [RR] 4.70 [95% confidence interval (CI) 2.42-9.12], P < 0.001} and were more likely to develop acute kidney injury [45% vs. 24.5%; RR 1.84 (95% CI 1.12-3.01), P = 0.02], have evidence of myocardial injury [57.5% vs. 31.9%; RR 1.81 (95% CI 1.21-2.68), P < 0.01], and be treated for a superadded bacterial infection [55% vs. 32.5%; RR 1.67 (95% CI 1.12-2.49), P = 0.01]. CONCLUSIONS: Patients with HF admitted to hospital with concomitant COVID-19 infection have a very poor prognosis. This study highlights the need to regard patients with HF as a high-risk group to be shielded to reduce the risks of COVID-19 infection.
[ "Treatment", "Diagnosis" ]
97
32420521
Clinicians need to remember that (1) systemic inflammations can increase clozapine level; (2) clozapine, by itself, can cause inflammation, particularly during titration that is too rapid for that patient; (3) clozapine may increase the risk of infection; and (4) more specifically, clozapine may be particularly strongly associated with the risk of pneumonia. Pneumonia appears to be associated with high mortality in clozapine patients around the world. Clinicians who are alert to the risk of pneumonia in clozapine patients may significantly decrease mortality in clozapine patients. There is no data on COVID-19 infections in clozapine patients, but based on what we know about clozapine pharmacology, we can hypothesise that clozapine, possibly by impairing immunological mechanisms, may increase the risk of pneumonia in infected patients. More importantly, once fever and/or pneumonia develops, the clozapine dose should be cut in half to decrease the risk of clozapine intoxication. If there is any doubt that in spite of halving the dose there are still signs of clozapine intoxication, completely stopping clozapine may be indicated. Once the signs of inflammation and fever have disappeared, the clozapine dose can be increased to the prior dosage level.
[ "Diagnosis" ]
98
32578829
New cases of the novel coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to rise worldwide following the declaration of a pandemic by the World Health Organization (WHO). The current pandemic has completely altered the workflow of health services worldwide. However, even during this critical period, patients with other diseases, like cancer, need to be properly treated. A few reports have shown that mortality due to SARS-CoV-2 is higher in elderly patients and those with other active comorbidities, including cancer. Patients with lung cancer are at risk of pulmonary complications from COVID-19, and as such, the risk/benefit ratio of local and systemic anticancer treatment has to be considered. For each patient, several factors, including age, comorbidities, and immunosuppression, as well as the number of hospital visits for treatment, can influence this risk. The number of cases is rising exponentially in Brazil, and it is important to consider the local characteristics when approaching the pandemic. In this regard, the Brazilian Thoracic Oncology Group has developed recommendations to guide decisions in lung cancer treatment during the SARS-CoV-2 pandemic. Due to the scarcity of relevant data, discussions based on disease stage, evaluation of surgical treatment, radiotherapy techniques, systemic therapy, follow-up, and supportive care were carried out, and specific suggestions issued. All recommendations seek to reduce contagion risk by decreasing the number of medical visits and hospitalization, and in the case of immunosuppression, by adapting treatment schemes when possible. This statement should be adjusted according to the reality of each service, and can be revised as new data become available.
[ "Prevention" ]
99
32824839
The COVID-19 pandemic goes along with increased mortality from acute respiratory disease. It has been suggested that vitamin D3 supplementation might help to reduce respiratory disease mortality. We assessed the prevalence of vitamin D insufficiency and deficiency, defined by 25-hydroxyvitamin D (25(OH)D) blood levels of 30-50 and <30 nmol/L, respectively, and their association with mortality from respiratory diseases during 15 years of follow-up in a cohort of 9548 adults aged 50-75 years from Saarland, Germany. Vitamin D insufficiency and deficiency were common (44% and 15%, respectively). Compared to those with sufficient vitamin D status, participants with vitamin D insufficiency and deficiency had strongly increased respiratory mortality, with adjusted hazard ratios (95% confidence intervals) of 2.1 (1.3-3.2) and 3.0 (1.8-5.2) overall, 4.3 (1.3-14.4) and 8.5 (2.4-30.1) among women, and 1.9 (1.1-3.2) and 2.3 (1.1-4.4) among men. Overall, 41% (95% confidence interval: 20-58%) of respiratory disease mortality was statistically attributable to vitamin D insufficiency or deficiency. Vitamin D insufficiency and deficiency are common and account for a large proportion of respiratory disease mortality in older adults, supporting the hypothesis that vitamin D3 supplementation could be helpful to limit the burden of the COVID-19 pandemic, particularly among women.
[ "Prevention", "Treatment" ]

Dataset Card for BC7-LitCovid

The training and development datasets contain the publicly-available text of over 30 thousand COVID-19-related articles and their metadata (e.g., title, abstract, journal). Articles in both datasets have been manually reviewed and articles annotated by in-house models.

Citation Information

@inproceedings{chen2021overview,
  title        = {
    Overview of the BioCreative VII LitCovid Track: multi-label topic
    classification for COVID-19 literature annotation
  },
  author       = {
    Chen, Qingyu and Allot, Alexis and Leaman, Robert and Do{\u{g}}an, Rezarta
    Islamaj and Lu, Zhiyong
  },
  year         = 2021,
  booktitle    = {Proceedings of the seventh BioCreative challenge evaluation workshop}
}

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