\ BIP! Finder for COVID-19 - Impact-based ranking

BIP! Finder for COVID-19

This version of BIP! Finder aims to ease the exploration of COVID-19-related literature by enabling ranking articles based on various impact metrics.

Last Update: 18 - 01 - 2023 (628506 entries)

Provided impact measures:
Popularity: Citation-based measure reflecting the current impact.
Influence: Citation-based measure reflecting the total impact.
Reader Attention: The current number of Mendeley readers.
Social Media Attention: The number of recent tweets related to this article.
*More details on these impact measures can be found here.
Score interpretations:
Exceptional score (in top 0.01%).
Substantial score (in top 1%).
Average score (in bottom 99%).
Score not available.
Main data sources:
CORD-19 dataset(1) (list of papers)
LitCovid hub(2) (list of papers)
PMC & PubMed (citations)
Mendeley (number of readers)
COVID-19-TweetIDs(3) (tweets)

Use:  Impact  Relevance & Impact
TitleVenueYearImpactSource
151Protecting the front line: a cross-sectional survey analysis of the occupational factors contributing to healthcare workers' infection and psychological distress during the COVID-19 pandemic in the USA  

OBJECTIVE: The COVID-19 pandemic has been associated with significant occupational stressors and challenges for front-line healthcare workers (HCWs), including COVID-19 exposure risk. Our study sought to assess factors contributing to HCW infection and psychological distress during the COVID-19 pandemic in the USA. DESIGN: We conducted a cross sectional survey of HCWs (physicians, nurses, emergency medical technicians (EMTs), non-clinical staff) during May 2020. Participants completed a 42-item survey assessing disease transmission risk (clinical role, work environment, availability of personal protective equipment) and mental health (anxiety, depression and burn-out). SETTING: The questionnaire was disseminated over various social media platforms. 3083 respondents from 48 states, the District of Columbia and US territories accessed the survey. PARTICIPANTS: Using a convenience sample of HCWs who worked during the pandemic, 3083 respondents accessed the survey and 2040 participants completed at least 80% of the survey. PRIMARY OUTCOME: Prevalence of self-reported COVID-19 infection, in addition to burn-out, depression and anxiety symptoms. RESULTS: Participants were largely from the Northeast and Southern USA, with attending physicians (31.12%), nurses (26.80%), EMTs (13.04%) with emergency medicine department (38.30%) being the most common department and specialty represented. Twenty-nine per cent of respondents met the criteria for being a probable case due to reported COVID-19 symptoms or a positive test. HCWs in the emergency department (31.64%) were more likely to contract COVID-19 compared with HCWs in the ICU (23.17%) and inpatient settings (25.53%). HCWs that contracted COVID-19 also reported higher levels of depressive symptoms (mean diff.=0.31; 95% CI 0.16 to 0.47), anxiety symptoms (mean diff.=0.34; 95% CI 0.17 to 0.52) and burn-out (mean diff.=0.54; 95% CI 0.36 to 0.71). CONCLUSION: HCWs have experienced significant physical and psychological risk while working during the COVID-19 pandemic. These findings highlight the urgent need for increased support for provider physical and mental health well-being.

BMJ Open2020       LitCov and CORD-19
152Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy  

N/A

JAMA Intern Med2020       LitCov and CORD-19
153An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus  

Passive serotherapy can confer immediate protection against microbial infection, but methods to rapidly generate human neutralizing monoclonal antibodies are not yet available. We have developed an improved method for Epstein-Barr virus transformation of human B cells. We used this method to analyze the memory repertoire of a patient who recovered from severe acute respiratory syndrome coronavirus (SARS-CoV) infection and to isolate monoclonal antibodies specific for different viral proteins, including 35 antibodies with in vitro neutralizing activity ranging from 10(−8)M to 10(−11)M. One such antibody confers protection in vivo in a mouse model of SARS-CoV infection. These results show that it is possible to interrogate the memory repertoire of immune donors to rapidly and efficiently isolate neutralizing antibodies that have been selected in the course of natural infection. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1080) contains supplementary material, which is available to authorized users.

Nat Med2004       CORD-19
154Transmission dynamics of the etiological agent of SARS in Hong Kong: impact of public health interventions  

N/A

Science2003       CORD-19
155Identification and containment of an outbreak of SARS in a community hospital  

N/A

CMAJ2003       CORD-19
156A crucial role of angiotensin-converting enzyme 2 (ACE2) in SARS coronavirus induced lung injury  

During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world(1,2,3). A new coronavirus (SARS-CoV) was identified as the SARS pathogen(4,5,6,7), which triggered severe pneumonia and acute, often lethal, lung failure(8). Moreover, among infected individuals influenza such as the Spanish flu(9,10) and the emergence of new respiratory disease viruses(11,12) have caused high lethality resulting from acute lung failure(13). In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor(14). The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1267) contains supplementary material, which is available to authorized users.

Nat Med2005       CORD-19
157Self-Reported Symptoms of SARS-CoV-2 Infection in a Nonhospitalized Population in Italy: Cross-Sectional Study of the EPICOVID-19 Web-Based Survey  

BACKGROUND: Understanding the occurrence of symptoms resembling those of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large nonhospitalized population at the peak of the epidemic in Italy is of paramount importance; however, data are currently scarce. OBJECTIVE: The aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test results in nonhospitalized individuals and to estimate the occurrence of symptoms associated with coronavirus disease (COVID-19) in a larger nontested population. METHODS: EPICOVID19 is a self-administered cross-sectional voluntary web-based survey of adults throughout Italy who completed an anonymous questionnaire in the period of April 13 to 21, 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios (aORs) with 95% CIs by multiple logistic regression analysis controlling for age, sex, education, smoking habits, and number of comorbidities. Thereafter, for each symptom and for combinations of the symptoms, we calculated the sensitivity, specificity, accuracy, and areas under the curve (AUCs) in a receiver operating characteristic (ROC) analysis to estimate the occurrence of COVID-19–like infection in the nontested population. RESULTS: A total of 171,310 people responded to the survey, of whom 102,543 (59.9%) were women; mean age 47.4 years. Out of the 4785 respondents with known NPS test results, 4392 were not hospitalized. Among the 4392 nonhospitalized respondents, those with positive NPS tests (856, 19.5%) most frequently reported myalgia (527, 61.6%), olfactory and taste disorders (507, 59.2%), cough (466, 54.4%), and fever (444, 51.9%), whereas 7.7% were asymptomatic. Multiple regression analysis showed that olfactory and taste disorders (aOR 10.3, 95% CI 8.4-12.7), fever (aOR 2.5, 95% CI 2.0-3.1), myalgia (aOR 1.5, 95% CI 1.2-1.8), and cough (aOR 1.3, 95% CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95% CI 5.6-9.7) to 35.5 (95% CI 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95% CI 0.795-0.825) in classifying positive NPS test results and then was applied to the nonhospitalized and nontested sample (n=165,782). We found that 7739 to 20,103 of these 165,782 respondents (4.4% to 12.1%) had experienced symptoms suggestive of COVID-19 infection. CONCLUSIONS: Our results suggest that self-reported symptoms are reliable indicators of SARS-CoV-2 infection in a pandemic context. A nonnegligible number of symptomatic respondents (up to 12.1%) were undiagnosed and potentially contributed to the spread of the infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701

JMIR Public Health Surveill2020       LitCov and CORD-19
158Comparison of SARS-CoV-2 Spike Protein Binding to ACE2 Receptors from Human, Pets, Farm Animals and Putative Intermediate Hosts  

The emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in a pandemic. Here, we used X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptors allows the definition of residues important for binding. From the 20 amino acids in ACE2 that contact S, up to 7 can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or acquisition of N-glycosylation sites located near the S interface. Of note, pigs and dogs, which are not infected or are not effectively infected and have only a few changes in the binding site, exhibit relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with that from bat coronavirus strain RaTG13 (Bat-CoV-RaTG13) and pangolin coronavirus (Pangolin-CoV) strain hCoV-19/pangolin/Guangdong/1/2019 revealed that the latter contains only one substitution, whereas Bat-CoV-RaTG13 exhibits five. However, ACE2 of pangolin exhibits seven changes relative to human ACE2, and a similar number of substitutions is present in ACE2 of bats, raccoon dogs, and civets, suggesting that SARS-CoV-2 may not be especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-CoV-2. IMPORTANCE SARS-CoV-2 is threatening people worldwide, and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear, and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes, indicating that the species barrier might be low. Exceptions are dogs and especially pigs, which revealed relatively low ACE2 expression levels in the respiratory tract. Monitoring of animals is necessary to prevent the generation of a new coronavirus reservoir. Finally, our analysis also showed that SARS-CoV-2 may not be specifically adapted to any of its putative intermediate hosts.

J Virol2020       LitCov and CORD-19
159How do children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) experience lockdown during the COVID-19 outbreak?  

OBJECTIVES: During the COVID-19 pandemic, the French government has decided a general lockdown. This unprecedented situation has raised concerns about children's and adolescent's mental health. Children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) may find this context of restrained activity particularly tricky. The objectives of our study are to gather information about the well-being and global life conditions of children and adolescents with ADHD during the COVID-19 outbreak in France. METHODS: We designed a survey including both open-ended questions and questionnaire items for parents of children and adolescents with ADHD. Parents responded to the following open-ended questions: 1) “How is your child doing since the lockdown?” 2) “How is life at home since the lockdown?” 3) “If you had a remote service provision with a mental health professional (e.g. by telephone or video technology), please share your thoughts and any suggestions with us” 4) “Please share any other items that you think are important about ADHD symptoms of your child and the lockdown situation”. This survey was posted on social media on the 6th of April and disseminated by French ADHD-parent and patient organizations. The present article reports the descriptive, qualitative and textometrical analyses of the survey. RESULTS: Between day 20 and 30 of lockdown, 538 parents responded to the survey, and we included 533 responses in the final analysis. The vast majority of responders were women 95 % (95 % CI 93,50; 97,18) with children whose mean age was 10,5 (95 % CI 7.58; 13.44). Since the lockdown, 34.71 % (95 % CI 30.70; 38.94) of children experienced a worsening in well-being, 34.33 % (95 % CI 30.34; 38.56) showed no significant changes and 30.96 % (95 % CI 27.09; 35.10) were doing better according to their parents. The thematic analysis showed that an improvement of their children's anxiety was one of the main topics addressed by parents. This improvement related to less school-related strain and flexible schedules that respected their children's rhythm. Improved self-esteem was another topic that parents linked with a lesser exposure of their children to negative feed-back. Parents repeatedly reported both inattention and hyperactivity/impulsivity. However, optimal lockdown life conditions seemed to compensate for the impact of ADHD symptoms (e.g. sufficient space at home, presence of a garden). Some parents reported worsening of general well-being in their children, and this manifested as oppositional/defiant attitudes and emotional outbursts. Parents also cited sleep problems and anxiety in this context. As regards everyday life during lock-down, at-home schooling was another major topic–parents described that their children struggled to complete school-related tasks and that teachers seemed to have forgotten about academic accommodations. The lockdown situation seems to have raised parents’ awareness of the role of inattention and ADHD symptoms in their children's learning difficulties. Due to potential selection biases, the results of our survey may not be generalizable to all children and adolescents with ADHD. The main strengths of this rapid survey-based study lies in the reactivity of the participants and the quality and diversity of their responses to the open-ended questions. CONCLUSIONS: According to their parents, most children and adolescents with ADHD experience stability or improvement of their well-being. An improvement in school-related anxiety and the flexible adjustment to the children's’ rhythms as well as parents’ increased awareness of the difficulties their children experience are among the key topics in parents’ descriptions.

Encephale2020       LitCov and CORD-19
160Analysis of adjunctive serological detection to nucleic acid test for SARS-CoV-2 infection diagnosis  

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) epidemic in China, December 2019. The clinical features and treatment of COVID-19 patients remain largely elusive. However, accurate detection is required for SARS-CoV-2 infection diagnosis. We aimed to evaluate the antibodies-based test and nucleic acid-based test for SARS-CoV-2-infected patients. METHODS: We retrospectively studied 133 patients diagnosed with SARS-CoV-2 and admitted to Renmin Hospital of Wuhan University, China, from January 23 to March 1, 2020. Demographic data, clinical records, laboratory tests, and outcomes were collected. Data were accessed by SARS-CoV-2 IgM-IgG antibody test and real-time reverse transcriptase PCR (RT-PCR) detection for SARS-CoV-2 nucleic acid in COVID-19 patients. RESULTS: Of 133 COVID-19 patients, there were 44 moderate cases, 52 severe cases, and 37 critical cases with no differences in gender and age among three subgroups. In RT-PCR detection, the positive rate was 65.9%, 71.2%, and 67.6% in moderate, severe, and critical cases, respectively. Whereas the positive rate of IgM/IgG antibody detection in patients was 79.5%/93.2%, 82.7%/100%, and 73.0%/97.3% in moderate, severe, and critical cases, respectively. Moreover, the IgM and IgG antibodies concentrations were also examined with no differences among three subgroups. CONCLUSION: The IgM-IgG antibody test exhibited a useful adjunct to RT-PCR detection, and improved the accuracy in COVID-19 diagnosis regardless of the severity of illness, which provides an effective complement to the false-negative results from a nucleic acid test for SARS-CoV-2 infection diagnosis after onsets.

Int Immunopharmacol2020       LitCov and CORD-19
161Prevalence and Risk Factors Associated With Self-reported Psychological Distress Among Children and Adolescents During the COVID-19 Pandemic in China  

IMPORTANCE: Schools have been suspended nationwide in 188 countries, and classes have shifted to home-based distance learning models to control the spread of the coronavirus disease 2019 (COVID-19) pandemic. Additional information is needed to determine mental health status among school-aged children and adolescents during this public health crisis and the risk factors associated with psychological distress during the pandemic. OBJECTIVE: To assess self-reported psychological distress among school-aged children and adolescents associated with the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study using data from a survey on the mental health of school-aged children and adolescents in Guangdong province, China, conducted by using a stratified cluster random sampling method between March 8 to 30, 2020. To estimate outcomes associated with location of districts, only data from students with internet protocol addresses and current addresses in Guangdong were included. Data were analyzed from April 5 to July 20, 2020. EXPOSURE: Home-based distance learning during the COVID-19 pandemic. MAIN OUTCOME AND MEASURES: The main outcome was self-reported psychological distress, measured using the total score on the 12-item General Health Questionnaire of 3 or greater. Multivariate logistic regression was used to analyze risk factors associated with mental health status. Odds ratios (ORs) were used to analyze the associations of factors with psychological distress. RESULTS: Among 1 310 600 students who completed the survey, 1 199 320 students (mean [SD] age, 12.04 [3.01] years; 619 144 [51.6%] boys) were included in the final analysis. A total of 126 355 students (10.5%) self-reported psychological distress. Compared with students in primary school, high school students had increased risk of psychological distress (OR, 1.19 [95% CI, 1.15-1.23]). Compared with students who wore a face mask frequently, students who never wore a face mask had increased risk of psychological distress (OR, 2.59 [95% CI, 2.41-2.79]). Additionally, students who spent less than 0.5 hours exercising had increased odds of self-reported psychological distress compared with students who spent more than 1 hour exercising (OR, 1.64 [95% CI, 1.61-1.67]). CONCLUSIONS AND RELEVANCE: These findings suggest that the prevalence of self-reported psychological distress among students during the COVID-19 pandemic was relatively high. Frequency of wearing a face mask and time spent exercising were factors associated with mental health. Therefore, it may be necessary for governments, schools, and families to pay attention to the mental health of school-aged children and adolescents during the COVID-19 pandemic and take corresponding countermeasures to reduce the impact of the COVID-19 pandemic on students’ mental health.

JAMA Netw Open2021       LitCov and CORD-19
162Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China  

Intensive Care Med2020       LitCov and CORD-19
163Efficacy of hydroxychloroquine for post-exposure prophylaxis to prevent SARS-CoV-2 infection among adults exposed to coronavirus disease: a structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: Primary Objective • To test the efficacy of Hydroxychloroquine (HCQ) (400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days, to complete 14 days) to prevent incident SARS-CoV-2 infection, compared to ascorbic acid among contacts of persons with SARS-CoV-2 infection Secondary objectives • To determine the safety and tolerability of HCQ as SARS-CoV-2 Post-exposure Prophylaxis (PEP) in adults • To test the efficacy of HCQ (400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days, to complete 14 days) to prevent incident SARS-CoV-2 infection 2 weeks after completing therapy, compared to ascorbic acid among contacts of persons with SARS-CoV-2 infection • To test the efficacy of HCQ to shorten the duration of SARS-CoV-2 shedding among those with SARS-CoV-2 infection in the HCQ PEP group • To test the efficacy of HCQ to prevent incident COVID-19 TRIAL DESIGN: This is a randomized, multi-center, placebo-equivalent (ascorbic acid) controlled, blinded study of HCQ PEP for the prevention of SARS-CoV-2 infection in adults exposed to the virus. PARTICIPANTS: This study will enroll up to 2000 asymptomatic adults 18 to 80 years of age (inclusive) at baseline who are close contacts of persons with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 or clinically suspected COVID-19 and a pending SARS-CoV-2 PCR test. This multisite trial will be conducted at seven sites in Seattle (UW), Los Angeles (UCLA), New Orleans (Tulane), Baltimore (UMB), New York City (NYU), Syracuse (SUNY-Upstate), and Boston (BMC). Inclusion criteria 1. Men or women 18 to 80 years of age inclusive, at the time of signing the informed consent. 2. Willing and able to provide informed consent. 3. Had a close contact of a person (index) with known PCR-confirmed SARS-CoV-2 infection or index who is currently being assessed for COVID-19. a. Household contact (i.e., residing with the index case in the 14 days prior to index diagnosis or prolonged exposure within a residence/vehicle/enclosed space without maintaining social distance). b. Medical staff, first responders, or other care persons who cared for the index case without personal protection (mask and gloves): 4. Less than 4 days since last exposure (close contact with a person with SARS-CoV-2 infection) to the index case; 5. Access to device and internet for Telehealth visits; 6. Not planning to take HCQ in addition to the study medication. Exclusion criteria 1. Known hypersensitivity to HCQ or other 4-aminoquinoline compounds. 2. Currently hospitalized. 3. Symptomatic with subjective fever, cough, or shortness of breath. 4. Current medications exclude concomitant use of HCQ. 5. Concomitant use of other anti-malarial treatment or chemoprophylaxis, including chloroquine, mefloquine, artemether, or lumefantrine. 6. History of retinopathy of any etiology. 7. Psoriasis. 8. Porphyria. 9. Known bone marrow disorders with significant neutropenia (polymorphonuclear leukocytes <1500) or thrombocytopenia (<100 K). 10. Concomitant use of digoxin, cyclosporin, cimetidine, amiodarone, or tamoxifen. 11. Known moderate or severe liver disease. 12. Known long QT syndrome. 13. Severe renal impairment. 14. Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of the study drugs or planned use during the study period. INTERVENTION AND COMPARATOR: Households will be randomized 1:1 (at the level of household), with close contact participants receiving one of the following therapies: •HCQ 400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days •Placebo-like control (ascorbic acid) 500 mg orally daily for 3 days then 250 mg orally daily for 11 days MAIN OUTCOMES: The primary outcome of the study is the incidence of SARS-CoV-2 infection through day 14 among participants who are SARS-CoV-2 negative at baseline by randomization group. RANDOMISATION: Participants will be randomized in a 1:1 ratio to HCQ or ascorbic acid at the level of the household (all eligible participants in 1 household will receive the same intervention). The randomization code and resulting allocation list will be generated and maintained by the Study Statistician. The list will be blocked and stratified by site and contact type (household versus healthcare worker). BLINDING (MASKING): This is a blinded study. HCQ and ascorbic acid will appear similar, and taste will be partially masked as HCQ can be bitter and ascorbic acid will be sour. The participants will be blinded to their randomization group once assigned. Study team members, apart from the Study Pharmacist and the unblinded statistical staff, will be blinded. Laboratory staff are blinded to the group allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size for the study is N=2 000 participants randomized 1:1 to either HCZ (n=1 000) and ascorbic acid (n=1 000). TRIAL STATUS: Protocol version: 1.2 05 April 2020 Recruitment is ongoing, started March 31 and anticipated end date is September 30, 2020. TRIAL REGISTRATION: ClinicalTrials.gov, Protocol Registry Number: NCT04328961 Date of registration: April 1, 2020, retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19
164Real Asymptomatic SARS-CoV-2 Infection Might Be Rare: Importance of Careful Interviews and Follow-up  

BACKGROUND: There is limited information on the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) who are asymptomatic or have mild symptoms. METHODS: We performed a retrospective case series of patients with COVID-19 enrolled from February 22 to March 26, 2020. Forty cases of COVID-19 were confirmed using real-time reverse-transcription polymerase chain reaction among patients who underwent screening tests and were consecutively hospitalized at Ulsan University Hospital, Ulsan, Korea. The final follow-up date was May 19, 2020. All COVID-19 cases in Ulsan were included. Demographic and epidemiological information, comorbidities, clinical signs and symptoms, laboratory and radiologic findings, medications, treatments, outcomes, and main durations of patients with COVID-19 were compared according to supplemental oxygen requirement. RESULTS: Forty patients were included (median age, 30 years; interquartile range [IQR], 25–57 years; 58% female). Six (15%) patients required supplemental oxygen. The prevalence of asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection was 5% and that of presymptomatic infection was 13%. Cough, fever, myalgia, rhinorrhea or nasal congestion, and diarrhea were the screening criteria for diagnosing symptomatic and presymptomatic SARS-CoV-2 infections. Sputum production, chest discomfort, a large number of symptoms, abnormal procalcitonin and C-reactive protein levels, and abnormal chest X-ray or chest computed tomography findings were more common in patients requiring supplemental oxygen than in those not requiring supplemental oxygen. Overall mortality rate was 3% (1/40). Four patients (10%) were readmitted after testing positive by reverse-transcription polymerase chain reaction again. Incubation period was 5 days (IQR, 4–6 days), and the duration of viral shedding was 21 days (IQR, 14–28 days; maximum, 51 days). CONCLUSION: The prevalence of asymptomatic SARS-CoV-2 infection was 5%, which is much lower than that previously reported. This finding suggests that careful interviews and follow-ups should be performed to identify SARS-CoV-2 infections. Cough, fever, myalgia, rhinorrhea or nasal congestion, and diarrhea are adequate screening criteria for covering all symptoms of SARS-CoV-2 infection. Further evaluation is required to create representative screening criteria for COVID-19.

J Korean Med Sci2020       LitCov and CORD-19
165Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy  

N/A

JAMA2020       LitCov and CORD-19
166Psychosocial factors associated with postpartum psychological distress during the Covid-19 pandemic: a cross-sectional study  

BACKGROUND: Trauma, natural and man-made catastrophic events can be predictors of postpartum psychological distress. In a public health response due to coronavirus disease 2019 outbreak, the Italian government imposed a lockdown from March 9 to May 3. This extraordinary situation may have been challenging for maternal psychological health. The aim of this study was to investigate the prevalence of depressive and post-traumatic stress symptoms in women giving birth during the Covid-19 pandemic and its associations with quarantine measures, obstetrical factors, and relational attachment style. METHODS: Women who gave birth in a high-volume obstetric/gynaecological medical centre located in an epidemic area during the Covid-19 pandemic (March 8 to June 15) were asked to complete an online survey about their childbirth experience and the perceived effect of the pandemic. The Edinburgh Postnatal Depression Scale (EPDS), the Impact of Event Scale-Revised (IES-R), and the Relationship Questionnaire (RQ) were administered to assess levels of postpartum depressive and post-traumatic stress symptoms (PTSS) and relational style of attachment, respectively. Multivariate analysis was applied to identify associations between quarantine measures, childbirth experience, attachment style, and EPDS and IES-R scores. RESULTS: The survey was completed by 163 women (response rate 60.8%). The prevalence of depressive symptoms was 44.2% (EPDS cut-off score ≥ 11) and the PTSS rate was 42.9% (IES-R cut-off score ≥ 24). Dismissive and fearful avoidant attachment styles were significantly associated with the risk of depression and PTSS, respectively. Perceived pain during birth was a risk factor for postpartum depression. Perceived support provided by healthcare staff was a protective factor against depression and PTSS. Another protective factor against PTSS was quiet on the ward due to the absence of hospital visitors. CONCLUSION: This study reports a high prevalence of postpartum depressive and PTSS in women who gave birth during the Covid-19 pandemic. Postnatal psychological distress seemed to be associated more with the prenatal experience and other individual factors than with the pandemic hospital restrictions. Early detection during pregnancy of an insecure attachment style is fundamental to provide targeted preventive and therapeutic psychological interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-020-03399-5.

BMC Pregnancy Childbirth2020       LitCov and CORD-19
167A SARS-CoV-2 protein interaction map reveals targets for drug repurposing  

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption(1,2). There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.

Nature2020       LitCov and CORD-19
168Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the resulting COVID‐19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify or rule out current infection, identify people in need of care escalation, or to test for past infection and immune response. Point‐of‐care antigen and molecular tests to detect current SARS‐CoV‐2 infection have the potential to allow earlier detection and isolation of confirmed cases compared to laboratory‐based diagnostic methods, with the aim of reducing household and community transmission. OBJECTIVES: To assess the diagnostic accuracy of point‐of‐care antigen and molecular‐based tests to determine if a person presenting in the community or in primary or secondary care has current SARS‐CoV‐2 infection. SEARCH METHODS: On 25 May 2020 we undertook electronic searches in the Cochrane COVID‐19 Study Register and the COVID‐19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID‐19 publications. We did not apply any language restrictions. SELECTION CRITERIA: We included studies of people with suspected current SARS‐CoV‐2 infection, known to have, or not to have SARS‐CoV‐2 infection, or where tests were used to screen for infection. We included test accuracy studies of any design that evaluated antigen or molecular tests suitable for a point‐of‐care setting (minimal equipment, sample preparation, and biosafety requirements, with results available within two hours of sample collection). We included all reference standards to define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction (RT‐PCR) tests and established clinical diagnostic criteria). DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies and resolved any disagreements by discussion with a third review author. One review author independently extracted study characteristics, which were checked by a second review author. Two review authors independently extracted 2x2 contingency table data and assessed risk of bias and applicability of the studies using the QUADAS‐2 tool. We present sensitivity and specificity, with 95% confidence intervals (CIs), for each test using paired forest plots. We pooled data using the bivariate hierarchical model separately for antigen and molecular‐based tests, with simplifications when few studies were available. We tabulated available data by test manufacturer. MAIN RESULTS: We included 22 publications reporting on a total of 18 study cohorts with 3198 unique samples, of which 1775 had confirmed SARS‐CoV‐2 infection. Ten studies took place in North America, two in South America, four in Europe, one in China and one was conducted internationally. We identified data for eight commercial tests (four antigen and four molecular) and one in‐house antigen test. Five of the studies included were only available as preprints. We did not find any studies at low risk of bias for all quality domains and had concerns about applicability of results across all studies. We judged patient selection to be at high risk of bias in 50% of the studies because of deliberate over‐sampling of samples with confirmed COVID‐19 infection and unclear in seven out of 18 studies because of poor reporting. Sixteen (89%) studies used only a single, negative RT‐PCR to confirm the absence of COVID‐19 infection, risking missing infection. There was a lack of information on blinding of index test (n = 11), and around participant exclusions from analyses (n = 10). We did not observe differences in methodological quality between antigen and molecular test evaluations. Antigen tests Sensitivity varied considerably across studies (from 0% to 94%): the average sensitivity was 56.2% (95% CI 29.5 to 79.8%) and average specificity was 99.5% (95% CI 98.1% to 99.9%; based on 8 evaluations in 5 studies on 943 samples). Data for individual antigen tests were limited with no more than two studies for any test. Rapid molecular assays Sensitivity showed less variation compared to antigen tests (from 68% to 100%), average sensitivity was 95.2% (95% CI 86.7% to 98.3%) and specificity 98.9% (95% CI 97.3% to 99.5%) based on 13 evaluations in 11 studies of on 2255 samples. Predicted values based on a hypothetical cohort of 1000 people with suspected COVID‐19 infection (with a prevalence of 10%) result in 105 positive test results including 10 false positives (positive predictive value 90%), and 895 negative results including 5 false negatives (negative predictive value 99%). Individual tests We calculated pooled results of individual tests for ID NOW (Abbott Laboratories) (5 evaluations) and Xpert Xpress (Cepheid Inc) (6 evaluations). Summary sensitivity for the Xpert Xpress assay (99.4%, 95% CI 98.0% to 99.8%) was 22.6 (95% CI 18.8 to 26.3) percentage points higher than that of ID NOW (76.8%, (95% CI 72.9% to 80.3%), whilst the specificity of Xpert Xpress (96.8%, 95% CI 90.6% to 99.0%) was marginally lower than ID NOW (99.6%, 95% CI 98.4% to 99.9%; a difference of −2.8% (95% CI −6.4 to 0.8)) AUTHORS' CONCLUSIONS: This review identifies early‐stage evaluations of point‐of‐care tests for detecting SARS‐CoV‐2 infection, largely based on remnant laboratory samples. The findings currently have limited applicability, as we are uncertain whether tests will perform in the same way in clinical practice, and according to symptoms of COVID‐19, duration of symptoms, or in asymptomatic people. Rapid tests have the potential to be used to inform triage of RT‐PCR use, allowing earlier detection of those testing positive, but the evidence currently is not strong enough to determine how useful they are in clinical practice. Prospective and comparative evaluations of rapid tests for COVID‐19 infection in clinically relevant settings are urgently needed. Studies should recruit consecutive series of eligible participants, including both those presenting for testing due to symptoms and asymptomatic people who may have come into contact with confirmed cases. Studies should clearly describe symptomatic status and document time from symptom onset or time since exposure. Point‐of‐care tests must be conducted on samples according to manufacturer instructions for use and be conducted at the point of care. Any future research study report should conform to the Standards for Reporting of Diagnostic Accuracy (STARD) guideline.

Cochrane Database Syst Rev2020       LitCov and CORD-19
169Australia in 2030: what is our path to health for all?  

N/A

Med J Aust2021       LitCov and CORD-19
170High prevalence of SARS-CoV-2 infection among symptomatic healthcare workers in a large university tertiary hospital in São Paulo, Brazil  

BACKGROUND: Brazil became the epicenter of the COVID-19 pandemic in Latin America since May 2020, reporting the highest number of cases and deaths in the region. Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection, experiencing a significant burden from COVID-19. Identifying and understanding the clinical characteristics and risk factors associated with infection are of paramount importance to inform screening strategies and infection control practices in this scenario. The aims of this study were to investigate the prevalence and clinical characteristics of HCWs with COVID-19 symptoms. METHODS: Between March 21st and May 22nd, 2020 a cross-sectional study was performed in a tertiary university hospital in São Paulo. Prevalence of SARS-CoV-2 infection among HCWs with COVID-19 symptoms was determined by RT-PCR testing on nasopharyngeal and oropharyngeal samples. Participants were asked to complete an electronic structured questionnaire including clinical and demographic data. RESULTS: Overall, 125 (42.37%) of 295 symptomatic HCWs tested positive for SARS-CoV-2. Over the 10-week study period, positivity rates varied from 22.2% (95% CI 15.9–60.3%) in the second week to 55.9% (95% CI 43.2–68.6%) in the sixth week, reaching a plateau (38–46%) thereafter. Median (SD) age was 34.2 (9.9) years and 205 (69.5%) were female. We did not find significant differences in the prevalence of the most commonly reported underlying medical condition among healthcare workers that tested positive or negative for SARS-CoV-2 infection. After multivariable analysis, using logistic regression, anosmia (adjusted OR 4.4 95% CI 2.21–8.74) and ocular pain (adjusted OR 1.95 95% CI 1.14–3.33) were the only symptoms independently associated with positivity for SARS-CoV-2 infection. Follow-up information on clinical outcomes showed that 9 (7.2%) HCWs were hospitalized (seven were male) and 2 (1.6%) died. CONCLUSIONS: The findings of this study confirmed the high burden of SARS-CoV-2 infection among healthcare workers in the hardest hit city by the pandemic in Latin America. Anosmia and ocular pain were symptoms independently associated with COVID-19 diagnosis. In low and middle-income countries, where limited availability of tests is frequent, these findings may contribute to optimize a targeted symptom-oriented screening strategy.

BMC Infect Dis2020       LitCov and CORD-19
171SARS-CoV-2 pandemic and research gaps: Understanding SARS-CoV-2 interaction with the ACE2 receptor and implications for therapy  

The COVID-19 pandemic is an emerging threat to global public health. While our current understanding of COVID-19 pathogenesis is limited, a better understanding will help us develop efficacious treatment and prevention strategies for COVID-19. One potential therapeutic target is angiotensin converting enzyme 2 (ACE2). ACE2 primarily catalyzes the conversion of angiotensin I (Ang I) to a nonapeptide angiotensin or the conversion of angiotensin II (Ang II) to angiotensin 1-7 (Ang 1-7) and has direct effects on cardiac function and multiple organs via counter-regulation of the renin-angiotensin system (RAS). Significant to COVID-19, ACE2 is postulated to serve as a major entry receptor for SARS-CoV-2 in human cells, as it does for SARS-CoV. Many infected individuals develop COVID-19 with fever, cough, and shortness of breath that can progress to pneumonia. Disease progression promotes the activation of immune cells, platelets, and coagulation pathways that can lead to multiple organ failure and death. ACE2 is expressed by epithelial cells of the lungs at high level, a major target of the disease, as seen in post-mortem lung tissue of patients who died with COVID-19, which reveals diffuse alveolar damage with cellular fibromyxoid exudates bilaterally. Comparatively, ACE2 is expressed at low level by vascular endothelial cells of the heart and kidney but may also be targeted by the virus in severe COVID-19 cases. Interestingly, SARS-CoV-2 infection downregulates ACE2 expression, which may also play a critical pathogenic role in COVID-19. Importantly, targeting ACE2/Ang 1-7 axis and blocking ACE2 interaction with the S protein of SARS-CoV-2 to curtail SARS-CoV-2 infection are becoming very attractive therapeutics potential for treatment and prevention of COVID-19. Here, we will discuss the following subtopics: 1) ACE2 as a receptor of SARS-CoV-2; 2) clinical and pathological features of COVID-19; 3) role of ACE2 in the infection and pathogenesis of SARS; 4) potential pathogenic role of ACE2 in COVID-19; 5) animal models for pathological studies and therapeutics; and 6) therapeutics development for COVID-19.

Theranostics2020       LitCov and CORD-19
172A multinational, multicenter study on the psychological outcomes and associated physical symptoms amongst healthcare workers during COVID-19 outbreak  

Abstract Objective Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. Methods Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. Results Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54–5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36–3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27–7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12–4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. Conclusions Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.

Brain Behav Immun2020       LitCov and CORD-19
173Avian influenza A H5N1 infection in humans  

N/A

N Engl J Med2005       CORD-19
174Safety and efficacy assessment of allogeneic human dental pulp stem cells to treat patients with severe COVID-19: structured summary of a study protocol for a randomized controlled trial (Phase I / II)  

OBJECTIVES: To assess the safety and therapeutic effects of allogeneic human dental pulp stem cells (DPSCs) in treating severe pneumonia caused by COVID-19. TRIAL DESIGN: This is a single centre, two arm ratio 1:1, triple blinded, randomized, placebo-controlled, parallel group, clinical trial. PARTICIPANTS: 1. Adults aged 18-65 years; 2. Voluntarily participate in this clinical trial and sign the “informed consent form” or have consent from a legal representative. 3. Diagnosed with severe pneumonia of COVID-19: nucleic acid test SARS-CoV-2 positive; respiratory distress (respiratory rate > 30 times / min); hypoxia (resting oxygen saturation < 93% or arterial partial pressure of oxygen / oxygen concentration < 300 mmHg). 4. COVID-19 featured lung lesions in chest X-ray image. 1. Patients have received other experimental treatment for COVID-19 within the last 30 days; 2. Patients have severe liver condition (e.g., Child Pugh score >=C or AST> 5 times of the upper limit); 3. Patients with severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m(2)) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis; 4. Patients who are co-infected with HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses; 5. Female patients who have no sexual protection in the last 30 days prior to the screening assessment; 6. Pregnant or lactating women or women using estrogen contraception; 7. Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period; 8. Other conditions that the researchers consider not suitable for participating in this clinical trial. INTERVENTION AND COMPARATOR: There will be two study groups: experimental and control. Both will receive all necessary routine treatment for COVID-19. The experimental group will receive an intravenous injection of dental pulp stem cells suspension (3.0x10(7) human DPSCs in 30ml saline solution) on day 1, 4 and 7; The control group will receive an equal amount of saline (placebo) on the same days. Clinical and laboratory observations will be performed for analysis during a period of 28 days for each case since the commencement of the study. MAIN OUTCOMES: 1. Primary outcome The primary outcome is Time To Clinical Improvement (TTCI). By definition, TTCI is the time (days) it takes to downgrade two levels from the following six ordered grades [(grade 1) discharge to (grade 6) death] in the clinical state of admission to the start of study treatments (hDPSCs or placebo). Six grades of ordered variables: 2. Secondary outcomes 2.1 vital signs: heart rate, blood pressure (systolic blood pressure, diastolic blood pressure). During the screening period, hospitalization every day (additional time points of D1, D4, D7 30min before injection, 2h ± 30min, 24h ± 30min after the injection) and follow-up period D90 ± 3 days. 2.2 Laboratory examinations: during the screening period, 30 minutes before D1, D4, D7 infusion, 2h ± 30min, 24h ± 30min after the end of infusion, D10, D14, D28 during hospitalization or discharge day and follow-up period D90 ± 3 days. 2.3 Blood routine: white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, neutrophils, lymphocytes, monocytes, eosinophils Acidic granulocyte count, basophil count, red blood cell, hemoglobin, hematocrit, average volume of red blood cells, average red blood cell Hb content, average red blood cell Hb concentration, RDW standard deviation, RDW coefficient of variation, platelet count, platelet specific platelet average Volume, platelet distribution width,% of large platelets; 2.4 Liver and kidney function tests: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, prealbumin, total protein, albumin, globulin, white / globule ratio , Total bilirubin, direct bilirubin, cholinesterase, urea, creatinine, total carbon dioxide, uric acid glucose, potassium, sodium, chlorine, calcium, corrected calcium, magnesium, phosphorus, calcium and phosphorus product, anion gap, penetration Pressure, total cholesterol, triacylglycerol, high density lipoprotein cholesterol, Low density lipoprotein cholesterol, lipoprotein a, creatine kinase, lactate dehydrogenase, estimated glomerular filtration rate. 2.5 Inflammation indicators: hypersensitive C-reactive protein, serum amyloid (SAA); 2.6 Infectious disease testing: Hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb), Hepatitis C (Anti-HCV), AIDS (HIVcombin), syphilis (Anti-TP), cytomegalovirus CMV-IgM, cytomegalovirus CMV-IgG; only during the screening period and follow-up period D90 ± 3. 2.7 Immunological testing: Collect peripheral blood to detect the phenotype of T lymphocyte, B lymphocyte, natural killer cell, Macrophage and neutrophil by using flow cytometry. Collect peripheral blood to detect the gene profile of mononuclear cells by using single-cell analyses. Collect peripheral blood serum to detect various immunoglobulin changes: IgA, IgG, IgM, total IgE; Collect peripheral blood serum to explore the changes of cytokines, Th1 cytokines (IL-1 β, IL-2, TNF-a, ITN-γ), Th2 cytokines (IL-4, IL-6, IL -10). 2.8 Pregnancy test: blood β-HCG, female subjects before menopause are examined during the screening period and follow-up period D90 ± 3. 2.9 Urine routine: color, clarity, urine sugar, bilirubin, ketone bodies, specific gravity, pH, urobilinogen, nitrite, protein, occult blood, leukocyte enzymes, red blood cells, white blood cells, epithelial cells, non-squamous epithelial cells , Transparent cast, pathological cast, crystal, fungus; 2.10 Stool Routine: color, traits, white blood cells, red blood cells, fat globules, eggs of parasites, fungi, occult blood (chemical method), occult blood (immune method), transferrin (2h ± 30min after the injection and not detected after discharge). RANDOMIZATION: Block randomization method will be applied by computer to allocate the participants into experimental and control groups. The random ratio is 1:1. BLINDING (MASKING): Participants, outcomes assessors and investigators (including personnel in laboratory and imaging department who issue the sample report or image observations) will be blinded. Injections of cell suspension and saline will be coded in accordance with the patient’s randomisation group. The blind strategy is kept by an investigator who does not deliver the medical care or assess primary outcome results. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Twenty participants will be randomized to the experimental and control groups (10 per group). TRIAL STATUS: Protocol version number, hDPSC-CoVID-2019-02-2020 Version 2.0, March 13, 2020. Patients screening commenced on 16(th) April and an estimated date of the recruitment of the final participants will be around end of July. . TRIAL REGISTRATION: Registration: World Health Organization Trial Registry: ChiCTR2000031319; March 27,2020. ClinicalTrials.gov Identifier: NCT04336254; April 7, 2020 Other Study ID Numbers: hDPSC-CoVID-2019-02-2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19
175A cross-national study of factors associated with women's perinatal mental health and wellbeing during the COVID-19 pandemic  

Pregnant and postpartum women face unique challenges during the COVID-19 pandemic that may put them at elevated risk of mental health problems. However, few large-scale and no cross-national studies have been conducted to date that investigate modifiable pandemic-related behavioral or cognitive factors that may influence mental health in this vulnerable group. This international study sought to identify and measure the associations between pandemic-related information seeking, worries, and prevention behaviors on perinatal mental health during the COVID-19 pandemic. An anonymous, online, cross-sectional survey of pregnant and postpartum women was conducted in 64 countries between May 26, 2020 and June 13, 2020. The survey, available in twelve languages, was hosted on the Pregistry platform for COVID-19 studies (https://corona.pregistry.com) and advertised in social media channels and online parenting forums. Participants completed measures on demographics, COVID-19 exposure and worries, information seeking, COVID-19 prevention behaviors, and mental health symptoms including posttraumatic stress via the IES-6, anxiety/depression via the PHQ-4, and loneliness via the UCLA-3. Of the 6,894 participants, substantial proportions of women scored at or above the cut-offs for elevated posttraumatic stress (2,979 [43%]), anxiety/depression (2,138 [31%], and loneliness (3,691 [53%]). Information seeking from any source (e.g., social media, news, talking to others) five or more times per day was associated with more than twice the odds of elevated posttraumatic stress and anxiety/depression, in adjusted models. A majority of women (86%) reported being somewhat or very worried about COVID-19. The most commonly reported worries were related to pregnancy and delivery, including family being unable to visit after delivery (59%), the baby contracting COVID-19 (59%), lack of a support person during delivery (55%), and COVID-19 causing changes to the delivery plan (41%). Greater worries related to children (i.e., inadequate childcare, their infection risk) and missing medical appointments were associated with significantly higher odds of posttraumatic stress, anxiety/depression and loneliness. Engaging in hygiene-related COVID-19 prevention behaviors (face mask-wearing, washing hands, disinfecting surfaces) were not related to mental health symptoms or loneliness. Elevated posttraumatic stress, anxiety/depression, and loneliness are highly prevalent in pregnant and postpartum women across 64 countries during the COVID-19 pandemic. Excessive information seeking and worries related to children and medical care are associated with elevated symptoms, whereas engaging in hygiene-related preventive measures were not. In addition to screening and monitoring mental health symptoms, addressing excessive information seeking and women’s worries about access to medical care and their children’s well-being, and developing strategies to target loneliness (e.g., online support groups) should be part of intervention efforts for perinatal women. Public health campaigns and medical care systems need to explicitly address the impact of COVID-19 related stressors on mental health in perinatal women, as prevention of viral exposure itself does not mitigate the pandemic’s mental health impact.

PLoS One2021       LitCov and CORD-19
176Barriers and facilitators of adherence to social distancing recommendations during COVID-19 among a large international sample of adults  

BACKGROUND: Social distancing measures (e.g., avoiding travel, limiting physical contact with people outside of one’s household, and maintaining a 1 or 2-metre distance between self and others when in public, depending on the country) are the primary strategies used to prevent transmission of the SARS-Cov-2 virus that causes COVID-19. Given that there is no effective treatment or vaccine for COVID-19, it is important to identify barriers and facilitators to adherence to social distancing to inform ongoing and future public health campaigns. METHOD: This cross-sectional study was conducted online with a convenience sample of English-speaking adults. The survey was administered over the course of three weeks (March 30 –April 16, 2020) when social distancing measures were well-enforced in North America and Europe. Participants were asked to complete measures assessing socio-demographic characteristics, psychological constructs, including motivations to engage in social distancing, prosocial attitudes, distress, and social distancing behaviors. Descriptive (mean, standard deviation, percentage) and inferential statistics (logistic regression) were used to describes endorsement rates for various motivations, rates of adherence to social distancing recommendations, and predictors of adherence. RESULTS: Data were collected from 2013 adults living primarily in North America and Europe. Most frequently endorsed motivations to engage in social distancing (or facilitators) included “I want to protect others” (86%), “I want to protect myself” (84%), and I feel a sense of responsibility to protect our community” (84%). Most frequently endorsed motivations against social distancing (or barriers) included “There are many people walking on the streets in my area” (31%), “I have friends or family who need me to run errands for them” (25%), “I don’t trust the messages my government provides about the pandemic” (13%), and “I feel stressed when I am alone or in isolation” (13%). Adherence to social distancing recommendations ranged from 45% for “working from home or remotely” to 90% for “avoiding crowded places/non-essential travel”, with men and younger individuals (18–24 years) showing lower adherence compared to women and older individuals. CONCLUSION: This study found that adherence to social distancing recommendations vary depending on the behaviour, with none of the surveyed behaviours showing perfect adherence. Strongest facilitators included wanting to protect the self, feeling a responsibility to protect the community, and being able to work/study remotely; strongest barriers included having friends or family who needed help with running errands and socializing in order to avoid feeling lonely. Future interventions to improve adherence to social distancing measures should couple individual-level strategies targeting key barriers to social distancing identified herein, with effective institutional measures and public health interventions. Public health campaigns should continue to highlight compassionate attitudes towards social distancing.

PLoS One2020       LitCov and CORD-19
177Conversations and Medical News Frames on Twitter: Infodemiological Study on COVID-19 in South Korea  

BACKGROUND: SARS-CoV-2 (severe acute respiratory coronavirus 2) was spreading rapidly in South Korea at the end of February 2020 following its initial outbreak in China, making Korea the new center of global attention. The role of social media amid the current coronavirus disease (COVID-19) pandemic has often been criticized, but little systematic research has been conducted on this issue. Social media functions as a convenient source of information in pandemic situations. OBJECTIVE: Few infodemiology studies have applied network analysis in conjunction with content analysis. This study investigates information transmission networks and news-sharing behaviors regarding COVID-19 on Twitter in Korea. The real time aggregation of social media data can serve as a starting point for designing strategic messages for health campaigns and establishing an effective communication system during this outbreak. METHODS: Korean COVID-19-related Twitter data were collected on February 29, 2020. Our final sample comprised of 43,832 users and 78,233 relationships on Twitter. We generated four networks in terms of key issues regarding COVID-19 in Korea. This study comparatively investigates how COVID-19-related issues have circulated on Twitter through network analysis. Next, we classified top news channels shared via tweets. Lastly, we conducted a content analysis of news frames used in the top-shared sources. RESULTS: The network analysis suggests that the spread of information was faster in the Coronavirus network than in the other networks (Corona19, Shincheon, and Daegu). People who used the word “Coronavirus” communicated more frequently with each other. The spread of information was faster, and the diameter value was lower than for those who used other terms. Many of the news items highlighted the positive roles being played by individuals and groups, directing readers’ attention to the crisis. Ethical issues such as deviant behavior among the population and an entertainment frame highlighting celebrity donations also emerged often. There was a significant difference in the use of nonportal (n=14) and portal news (n=26) sites between the four network types. The news frames used in the top sources were similar across the networks (P=.89, 95% CI 0.004-0.006). Tweets containing medically framed news articles (mean 7.571, SD 1.988) were found to be more popular than tweets that included news articles adopting nonmedical frames (mean 5.060, SD 2.904; N=40, P=.03, 95% CI 0.169-4.852). CONCLUSIONS: Most of the popular news on Twitter had nonmedical frames. Nevertheless, the spillover effect of the news articles that delivered medical information about COVID-19 was greater than that of news with nonmedical frames. Social media network analytics cannot replace the work of public health officials; however, monitoring public conversations and media news that propagates rapidly can assist public health professionals in their complex and fast-paced decision-making processes.

J Med Internet Res2020       LitCov and CORD-19
178Using BCG vaccine to enhance non-specific protection of Healthcare workers during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial in Denmark  

Objectives: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism. The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. Hypothesis: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. Trial design: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. Participants: The trial will recruit 1,500 HCW at Danish hospitals. To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week. Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration. Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis); or other mycobacterial species. Previous confirmed COVID-19. Fever (>38 C) within the past 24 hours. Suspicion of active viral or bacterial infection. Pregnancy. Breastfeeding. Vaccination with other live attenuated vaccine within the last 4 weeks. Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1); b) subjects with solid organ transplantation; c) subjects with bone marrow transplantation; d) subjects under chemotherapy; e) subjects with primary immunodeficiency; f) subjects under treatment with any anti-cytokine therapy within the last year; g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months; h) Active solid or non-solid malignancy or lymphoma within the prior two years. Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial. Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. Main outcomes: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation. Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation. Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1. Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference. The physicians administering the treatment are not blinded. Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group. Trial Status: Current protocol version 5.1, from July 6, 2020. Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. Trial registration: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Keywords: COVID-19, Randomised controlled trial, Protocol, BCG vaccine, NSEs/Non-specific effects of vaccines, Heterologous effects of vaccines, Health care workers, Pandemic, Immune training.

Trials2020       LitCov and CORD-19
179Remdesivir for the Treatment of Covid-19-Final Report  

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)

N Engl J Med2020       LitCov and CORD-19
180Quantitative SARS-CoV-2 Serology in Children With Multisystem Inflammatory Syndrome (MIS-C)  

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Pediatrics2020       LitCov and CORD-19
181The British variant of the new coronavirus-19 (Sars-Cov-2) should not create a vaccine problem  

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J Biol Regul Homeost Agents2021       LitCov and CORD-19
182Human aminopeptidase N is a receptor for human coronavirus 229E  

HUMAN coronaviruses (HCV) in two serogroups represented by HCV-229E and HCV-OC43 are an important cause of upper respiratory tract infections(1). Here we report that human aminopeptidase N, a cell-surface metalloprotease on intestinal, lung and kidney epithelial cells(2–5), is a receptor for human coronavirus strain HCV-229E, but not for HCV-OC43. A monoclonal antibody, RBS, blocked HCV-229E virus infection of human lung fibroblasts, immunoprecipitated aminopeptidase N and inhibited its enzymatic activity. HCV-229E-resistant murine fibroblasts became susceptible after transfection with complementary DNA encoding human aminopeptidase N. By contrast, infection of human cells with HCV-OC43 was not inhibited by antibody RBS and expression of aminopeptidase N did not enhance HCV-OC43 replication in mouse cells. A mutant aminopeptidase lacking the catalytic site of the enzyme did not bind HCV-229E or RBS and did not render murine cells susceptible to HCV-229E infection, suggesting that the virus-binding site may lie at or near the active site of the human aminopeptidase molecule.

Nature1992       CORD-19
183COVID-19-Related Mental Health Effects in the Workplace: A Narrative Review  

The Coronavirus Disease 2019 (COVID-19) pandemic has deeply altered social and working environments in several ways. Social distancing policies, mandatory lockdowns, isolation periods, and anxiety of getting sick, along with the suspension of productive activity, loss of income, and fear of the future, jointly influence the mental health of citizens and workers. Workplace aspects can play a crucial role on moderating or worsening mental health of people facing this pandemic scenario. The purpose of this literature review is to deepen the psychological aspects linked to workplace factors, following the epidemic rise of COVID-19, in order to address upcoming psychological critical issues in the workplaces. We performed a literature search using Google Scholar, PubMed, and Scopus, selecting papers focusing on workers’ psychological problems that can be related to the workplace during the pandemic. Thirty-five articles were included. Mental issues related to the health emergency, such as anxiety, depression, post-traumatic stress disorder (PTSD), and sleep disorders are more likely to affect healthcare workers, especially those on the frontline, migrant workers, and workers in contact with the public. Job insecurity, long periods of isolation, and uncertainty of the future worsen the psychological condition, especially in younger people and in those with a higher educational background. Multiple organizational and work-related interventions can mitigate this scenario, such as the improvement of workplace infrastructures, the adoption of correct and shared anti-contagion measures, including regular personal protective equipment (PPE) supply, and the implementation of resilience training programs. This review sets the basis for a better understanding of the psychological conditions of workers during the pandemic, integrating individual and social perspectives, and providing insight into possible individual, social, and occupational approaches to this “psychological pandemic”.

Int J Environ Res Public Healt2020       LitCov and CORD-19
184Clinical Characteristics and Outcome of Hospitalized COVID-19 Patients in a MERS-CoV Endemic Area  

Background: The Kingdom of Saudi Arabia (KSA) reported 170,639 cases and 1430 deaths from COVID-19 since the first case emerged in the country on March 2 through June 25, 2020. The objective of this report is to describe the characteristics and outcome observed among 99 hospitalized COVID-19 patients in the largest academic hospital in KSA, and assess co-infection with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Methods: This single-center case series data included select epidemiological, clinical, radiological features and laboratory findings of all confirmed hospitalized cases of COVID-19 in King Saud University Medical City (KSUMC), Riyadh, KSA, from March 22 until May 31, 2020, followed through June 6, 2020. We conducted retrospective analysis of listed data from 99 hospitalized patients and present characteristics and factors associated with severity in percentages and univariate odds ratios. Cases were confirmed using nasopharyngeal or throat swab by real-time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and MERS-CoV by RT-PCR. Results: The 99 hospitalized COVID-19 patients included in this analysis constitute 16% of 632 positive SARS-CoV-2 among 6633 persons who were tested at the KSUMC (positivity rate, 9.4%). MERS-CoV PCR was negative in all 99 patients tested. The majority of these 99 hospitalized patients were males (66%), had a mean age of 44 years (range, 19–87), and a quarter (25.3%) were health care workers. Patients with comorbid conditions accounted for 52.5% of patients including the 8.1% who were asymptomatic; diabetes mellitus being the most frequent (31.3%), followed by hypertension (22.2%). The most common presenting symptoms were fever (67.7%), cough (60.6%), dyspnea (43.4%), upper respiratory symptoms (27.3%), fatigue (26.3%), diarrhea (19.2%) and loss of smell (9.1%). The clinical conditions among these 99 patients included upper respiratory tract infection (47.5%), abnormal chest X-ray, lymphopenia, high inflammatory markers a fifth (21%) of patients had moderate pneumonia, while 7% had severe pneumonia with 22.2% requiring admission to the intensive care unit and 12.1% died. Late presentation with severe disease, an abnormal chest X-ray, lymphopenia, high inflammatory markers (C-reactive protein, ferritin, and procalcitonin), and end organ damage (high creatinine or high aspartate aminotransferase) were predictors for admission to critical care unit or died. Conclusion: We observed no MERS-CoV co-infection in this early cohort of hospitalized COVID-19 patients who were relatively young, more than half had comorbid conditions, presented with fever and/or cough, an abnormal chest X-ray, lymphopenia, and high inflammatory markers. Given MERS-CoV endemicity in the country, co-monitoring of MERS-CoV and SARS-CoV-2 coinfection is critical.

J Epidemiol Glob Health2020       LitCov and CORD-19
185Identification of a new human coronavirus  

Three human coronaviruses are known to exist: human coronavirus 229E (HCoV-229E), HCoV-OC43 and severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV). Here we report the identification of a fourth human coronavirus, HCoV-NL63, using a new method of virus discovery. The virus was isolated from a 7-month-old child suffering from bronchiolitis and conjunctivitis. The complete genome sequence indicates that this virus is not a recombinant, but rather a new group 1 coronavirus. The in vitro host cell range of HCoV-NL63 is notable because it replicates on tertiary monkey kidney cells and the monkey kidney LLC-MK2 cell line. The viral genome contains distinctive features, including a unique N-terminal fragment within the spike protein. Screening of clinical specimens from individuals suffering from respiratory illness identified seven additional HCoV-NL63-infected individuals, indicating that the virus was widely spread within the human population. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1024) contains supplementary material, which is available to authorized users.

Nat Med2004       CORD-19
186Lung pathology of fatal severe acute respiratory syndrome  

BACKGROUND: Severe acute respiratory syndrome (SARS) is a novel infectious disease with global impact. A virus from the family Coronaviridae has been identified as the cause, but the pathogenesis is still unclear. METHODS: Post-mortem tissue samples from six patients who died from SARS in February and March, 2003, and an open lung biopsy from one of these patients were studied by histology and virology. Only one full autopsy was done. Evidence of infection with the SARS-associated coronavirus (SARS-CoV) and human metapneumovirus was sought by reverse-transcriptase PCR and serology. Pathological samples were examined by light and electron microscopy and immunohistochemistry. FINDINGS: All six patients had serological evidence of recent infection with SARS-CoV. Diffuse alveolar damage was common but not universal. Morphological changes identified were bronchial epithelial denudation, loss of cilia, and squamous metaplasia. Secondary bacterial pneumonia was present in one case. A giant-cell infiltrate was seen in four patients, with a pronounced increase in macrophages in the alveoli and the interstitium of the lung. Haemophagocytosis was present in two patients. The alveolar pneumocytes also showed cytomegaly with granular amphophilic cytoplasm. The patient for whom full autopsy was done had atrophy of the white pulp of the spleen. Electron microscopy revealed viral particles in the cytoplasm of epithelial cells corresponding to coronavirus. INTERPRETATION: SARS is associated with epithelial-cell proliferation and an increase in macrophages in the lung. The presence of haemophagocytosis supports the contention that cytokine dysregulation may account, at least partly, for the severity of the clinical disease. The case definition of SARS should acknowledge the range of lung pathology associated with this disease. Published online May 16, 2003 http://image.thelancet.com/extras/03art4347web.pdf

Lancet2003       CORD-19
187COVID-19 in Africa: care and protection for frontline healthcare workers  

Medical staff caring for COVID-19 patients face mental stress, physical exhaustion, separation from families, stigma, and the pain of losing patients and colleagues. Many of them have acquired SARS-CoV-2 and some have died. In Africa, where the pandemic is escalating, there are major gaps in response capacity, especially in human resources and protective equipment. We examine these challenges and propose interventions to protect healthcare workers on the continent, drawing on articles identified on Medline (Pubmed) in a search on 24 March 2020. Global jostling means that supplies of personal protective equipment are limited in Africa. Even low-cost interventions such as facemasks for patients with a cough and water supplies for handwashing may be challenging, as is ‘physical distancing’ in overcrowded primary health care clinics. Without adequate protection, COVID-19 mortality may be high among healthcare workers and their family in Africa given limited critical care beds and difficulties in transporting ill healthcare workers from rural to urban care centres. Much can be done to protect healthcare workers, however. The continent has learnt invaluable lessons from Ebola and HIV control. HIV counselors and community healthcare workers are key resources, and could promote social distancing and related interventions, dispel myths, support healthcare workers, perform symptom screening and trace contacts. Staff motivation and retention may be enhanced through carefully managed risk ‘allowances’ or compensation. International support with personnel and protective equipment, especially from China, could turn the pandemic’s trajectory in Africa around. Telemedicine holds promise as it rationalises human resources and reduces patient contact and thus infection risks. Importantly, healthcare workers, using their authoritative voice, can promote effective COVID-19 policies and prioritization of their safety. Prioritizing healthcare workers for SARS-CoV-2 testing, hospital beds and targeted research, as well as ensuring that public figures and the population acknowledge the commitment of healthcare workers may help to maintain morale. Clearly there are multiple ways that international support and national commitment could help safeguard healthcare workers in Africa, essential for limiting the pandemic’s potentially devastating heath, socio-economic and security impacts on the continent.

Global Health2020       LitCov and CORD-19
188Detection of SARS-CoV-2 in Different Types of Clinical Specimens  

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JAMA2020       LitCov and CORD-19
189Determining the optimal strategy for reopening schools, the impact of test and trace interventions and the risk of occurrence of a second COVID-19 epidemic wave in the UK: a modelling study  

BACKGROUND: As lockdown measures to slow the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection begin to ease in the UK, it is important to assess the impact of any changes in policy, including school reopening and broader relaxation of physical distancing measures. We aimed to use an individual-based model to predict the impact of two possible strategies for reopening schools to all students in the UK from September, 2020, in combination with different assumptions about relaxation of physical distancing measures and the scale-up of testing. METHODS: In this modelling study, we used Covasim, a stochastic individual-based model for transmission of SARS-CoV-2, calibrated to the UK epidemic. The model describes individuals' contact networks stratified into household, school, workplace, and community layers, and uses demographic and epidemiological data from the UK. We simulated six different scenarios, representing the combination of two school reopening strategies (full time and a part-time rota system with 50% of students attending school on alternate weeks) and three testing scenarios (68% contact tracing with no scale-up in testing, 68% contact tracing with sufficient testing to avoid a second COVID-19 wave, and 40% contact tracing with sufficient testing to avoid a second COVID-19 wave). We estimated the number of new infections, cases, and deaths, as well as the effective reproduction number (R) under different strategies. In a sensitivity analysis to account for uncertainties within the stochastic simulation, we also simulated infectiousness of children and young adults aged younger than 20 years at 50% relative to older ages (20 years and older). FINDINGS: With increased levels of testing (between 59% and 87% of symptomatic people tested at some point during an active SARS-CoV-2 infection, depending on the scenario), and effective contact tracing and isolation, an epidemic rebound might be prevented. Assuming 68% of contacts could be traced, we estimate that 75% of individuals with symptomatic infection would need to be tested and positive cases isolated if schools return full-time in September, or 65% if a part-time rota system were used. If only 40% of contacts could be traced, these figures would increase to 87% and 75%, respectively. However, without these levels of testing and contact tracing, reopening of schools together with gradual relaxing of the lockdown measures are likely to induce a second wave that would peak in December, 2020, if schools open full-time in September, and in February, 2021, if a part-time rota system were adopted. In either case, the second wave would result in R rising above 1 and a resulting second wave of infections 2·0–2·3 times the size of the original COVID-19 wave. When infectiousness of children and young adults was varied from 100% to 50% of that of older ages, we still found that a comprehensive and effective test–trace–isolate strategy would be required to avoid a second COVID-19 wave. INTERPRETATION: To prevent a second COVID-19 wave, relaxation of physical distancing, including reopening of schools, in the UK must be accompanied by large-scale, population-wide testing of symptomatic individuals and effective tracing of their contacts, followed by isolation of diagnosed individuals. FUNDING: None.

Lancet Child Adolesc Health2020       LitCov and CORD-19
190Covid-19 in Critically Ill Patients in the Seattle Region-Case Series  

BACKGROUND: Community transmission of coronavirus 2019 (Covid-19) was detected in the state of Washington in February 2020. METHODS: We identified patients from nine Seattle-area hospitals who were admitted to the intensive care unit (ICU) with confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data were obtained through review of medical records. The data reported here are those available through March 23, 2020. Each patient had at least 14 days of follow-up. RESULTS: We identified 24 patients with confirmed Covid-19. The mean (±SD) age of the patients was 64±18 years, 63% were men, and symptoms began 7±4 days before admission. The most common symptoms were cough and shortness of breath; 50% of patients had fever on admission, and 58% had diabetes mellitus. All the patients were admitted for hypoxemic respiratory failure; 75% (18 patients) needed mechanical ventilation. Most of the patients (17) also had hypotension and needed vasopressors. No patient tested positive for influenza A, influenza B, or other respiratory viruses. Half the patients (12) died between ICU day 1 and day 18, including 4 patients who had a do-not-resuscitate order on admission. Of the 12 surviving patients, 5 were discharged home, 4 were discharged from the ICU but remained in the hospital, and 3 continued to receive mechanical ventilation in the ICU. CONCLUSIONS: During the first 3 weeks of the Covid-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both. Mortality among these critically ill patients was high. (Funded by the National Institutes of Health.)

N Engl J Med2020       LitCov and CORD-19
191Barriers and facilitators to healthcare workers' adherence with infection prevention and control (IPC) guidelines for respiratory infectious diseases: a rapid qualitative evidence synthesis  

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Cochrane Database Syst Rev2020       LitCov and CORD-19
192Effects of the lockdown on the mental health of the general population during the COVID-19 pandemic in Italy: Results from the COMET collaborative network  

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic is an unprecedented traumatic event influencing the healthcare, economic, and social welfare systems worldwide. In order to slow the infection rates, lockdown has been implemented almost everywhere. Italy, one of the countries most severely affected, entered the “lockdown” on March 8, 2020. METHODS: The COvid Mental hEalth Trial (COMET) network includes 10 Italian university sites and the National Institute of Health. The whole study has three different phases. The first phase includes an online survey conducted between March and May 2020 in the Italian population. Recruitment took place through email invitation letters, social media, mailing lists of universities, national medical associations, and associations of stakeholders (e.g., associations of users/carers). In order to evaluate the impact of lockdown on depressive, anxiety and stress symptoms, multivariate linear regression models were performed, weighted for the propensity score. RESULTS: The final sample consisted of 20,720 participants. Among them, 12.4% of respondents (N = 2,555) reported severe or extremely severe levels of depressive symptoms, 17.6% (N = 3,627) of anxiety symptoms and 41.6% (N = 8,619) reported to feel at least moderately stressed by the situation at the DASS-21. According to the multivariate regression models, the depressive, anxiety and stress symptoms significantly worsened from the week April 9–15 to the week April 30 to May 4 (p < 0.0001). Moreover, female respondents and people with pre-existing mental health problems were at higher risk of developing severe depression and anxiety symptoms (p < 0.0001). CONCLUSIONS: Although physical isolation and lockdown represent essential public health measures for containing the spread of the COVID-19 pandemic, they are a serious threat for mental health and well-being of the general population. As an integral part of COVID-19 response, mental health needs should be addressed.

Eur Psychiatry2020       LitCov and CORD-19
193Top Concerns of Tweeters During the COVID-19 Pandemic: Infoveillance Study  

BACKGROUND: The recent coronavirus disease (COVID-19) pandemic is taking a toll on the world’s health care infrastructure as well as the social, economic, and psychological well-being of humanity. Individuals, organizations, and governments are using social media to communicate with each other on a number of issues relating to the COVID-19 pandemic. Not much is known about the topics being shared on social media platforms relating to COVID-19. Analyzing such information can help policy makers and health care organizations assess the needs of their stakeholders and address them appropriately. OBJECTIVE: This study aims to identify the main topics posted by Twitter users related to the COVID-19 pandemic. METHODS: Leveraging a set of tools (Twitter’s search application programming interface (API), Tweepy Python library, and PostgreSQL database) and using a set of predefined search terms (“corona,” “2019-nCov,” and “COVID-19”), we extracted the text and metadata (number of likes and retweets, and user profile information including the number of followers) of public English language tweets from February 2, 2020, to March 15, 2020. We analyzed the collected tweets using word frequencies of single (unigrams) and double words (bigrams). We leveraged latent Dirichlet allocation for topic modeling to identify topics discussed in the tweets. We also performed sentiment analysis and extracted the mean number of retweets, likes, and followers for each topic and calculated the interaction rate per topic. RESULTS: Out of approximately 2.8 million tweets included, 167,073 unique tweets from 160,829 unique users met the inclusion criteria. Our analysis identified 12 topics, which were grouped into four main themes: origin of the virus; its sources; its impact on people, countries, and the economy; and ways of mitigating the risk of infection. The mean sentiment was positive for 10 topics and negative for 2 topics (deaths caused by COVID-19 and increased racism). The mean for tweet topics of account followers ranged from 2722 (increased racism) to 13,413 (economic losses). The highest mean of likes for the tweets was 15.4 (economic loss), while the lowest was 3.94 (travel bans and warnings). CONCLUSIONS: Public health crisis response activities on the ground and online are becoming increasingly simultaneous and intertwined. Social media provides an opportunity to directly communicate health information to the public. Health systems should work on building national and international disease detection and surveillance systems through monitoring social media. There is also a need for a more proactive and agile public health presence on social media to combat the spread of fake news.

J Med Internet Res2020       LitCov and CORD-19
194Global, regional and national incidence, prevalence and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016  

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Lancet2017       CORD-19
195Clinical trials and the COVID-19 pandemic  

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Hell J Nucl Med2020       LitCov and CORD-19
196The Incubation Period of COVID-19 From Publicly Reported Confirmed Cases: Estimation and Application  

BACKGROUND: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. OBJECTIVE: To estimate the length of the incubation period of COVID-19 and describe its public health implications. DESIGN: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. SETTING: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. PARTICIPANTS: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. MEASUREMENTS: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. RESULTS: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. LIMITATION: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. CONCLUSION: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases. PRIMARY FUNDING SOURCE: U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.

Ann Intern Med2020       LitCov and CORD-19
197Neurological manifestations associated with SARS-CoV-2 and other coronaviruses: A narrative review for clinicians  

INTRODUCTION: The past two decades have been marked by three epidemics linked to emerging coronaviruses. The COVID-19 pandemic highlighted the existence of neurological manifestations associated with SARS-CoV-2 infection and raised the question of the neuropathogenicity of coronaviruses. The aim of this review was to summarize the current data about neurological manifestations and diseases linked to human coronaviruses. MATERIAL AND METHODS: Articles have been identified by searches of PubMed and Google scholar up to September 25, 2020, using a combination of coronavirus and neurology search terms and adding relevant references in the articles. RESULTS: We found five cohorts providing prevalence data of neurological symptoms among a total of 2533 hospitalized COVID-19 patients, and articles focusing on COVID-19 patients with neurological manifestations including a total of 580 patients. Neurological symptoms involved up to 73% of COVID-19 hospitalized patients, and were mostly headache, myalgias and impaired consciousness. Central nervous system (CNS) manifestations reported in COVID-19 were mostly non-specific encephalopathies that represented between 13% and 40% of all neurological manifestations; post-infectious syndromes including acute demyelinating encephalomyelitis (ADEM, n = 13), acute necrotizing encephalopathy (ANE, n = 4), Bickerstaff's encephalitis (n = 5), generalized myoclonus (n = 3) and acute transverse myelitis (n = 7); other encephalitis including limbic encephalitis (n = 9) and miscellaneous encephalitis with variable radiologic findings (n = 26); acute cerebrovascular diseases including ischemic strokes (between 1.3% and 4.7% of COVID-19 patients), hemorrhagic strokes (n = 17), cerebral venous thrombosis (n = 8) and posterior reversible encephalopathy (n = 5). Peripheral nervous system (PNS) manifestations reported in COVID-19 were the following: Guillain–Barré syndrome (n = 31) and variants including Miller Fisher syndrome (n = 3), polyneuritis cranialis (n = 2) and facial diplegia (n = 2); isolated oculomotor neuropathy (n = 6); critical illness myopathy (n = 6). Neuropathological studies in COVID-19 patients demonstrated different patterns of CNS damage, mostly ischemic and hemorrhagic changes with few cases of inflammatory injuries. Only one case suggested SARS-CoV-2 infiltration in endothelial and neural cells. We found 10 case reports or case series describing 22 patients with neurological manifestations associated with other human coronaviruses. Among them we found four MERS patients with ADEM or Bickerstaff's encephalitis, two SARS patients with encephalitis who had a positive SARS-CoV PCR in cerebrospinal fluid, five patients with ischemic strokes associated with SARS, eight MERS patients with critical illness neuromyopathy and one MERS patient with Guillain–Barré Syndrome. An autopsy study on SARS-CoV patients demonstrated the presence of the virus in the brain of eight patients. CONCLUSION: The wide range of neurological manifestations and diseases associated with SARS-CoV-2 is consistent with multiple pathogenic pathways including post-infectious mechanisms, septic-associated encephalopathies, coagulopathy or endothelitis. There was no definite evidence to support direct neuropathogenicity of SARS-CoV-2.

Rev Neurol (Paris)2020       LitCov and CORD-19
198Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong  

BACKGROUND: Health authorities worldwide, especially in the Asia Pacific region, are seeking effective public-health interventions in the continuing epidemic of severe acute respiratory syndrome (SARS). We assessed the epidemiology of SARS in Hong Kong. METHODS: We included 1425 cases reported up to April 28, 2003. An integrated database was constructed from several sources containing information on epidemiological, demographic, and clinical variables. We estimated the key epidemiological distributions: infection to onset, onset to admission, admission to death, and admission to discharge. We measured associations between the estimated case fatality rate and patients’age and the time from onset to admission. FINDINGS: After the initial phase of exponential growth, the rate of confirmed cases fell to less than 20 per day by April 28. Public-health interventions included encouragement to report to hospital rapidly after the onset of clinical symptoms, contact tracing for confirmed and suspected cases, and quarantining, monitoring, and restricting the travel of contacts. The mean incubation period of the disease is estimated to be 6.4 days (95% Cl 5.2–7.7). The mean time from onset of clinical symptoms to admission to hospital varied between 3 and 5 days, with longer times earlier in the epidemic. The estimated case fatality rate was 13.2% (9.8–16.8) for patients younger than 60 years and 43.3% (35.2–52.4) for patients aged 60 years or older assuming a parametric γ distribution. A non-parametric method yielded estimates of 6.8% (4.0–9.6) and 55.0% (45.3–64.7), respectively. Case clusters have played an important part in the course of the epidemic. INTERPRETATION: Patients’age was strongly associated with outcome. The time between onset of symptoms and admission to hospital did not alter outcome, but shorter intervals will be important to the wider population by restricting the infectious period before patients are placed in quarantine. Published online May 7, 2003 http://image.thelancet.com/extras/03art4453web.pdf

Lancet2003       CORD-19
199SARS-CoV-2 and Microbiological Diagnostic Dynamics in COVID-19 Pandemic  

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Mikrobiyol Bul2020       LitCov and CORD-19
200Virtually Perfect? Telemedicine for Covid-19  

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N Engl J Med2020       LitCov and CORD-19

(1) COVID-19 Open Research Dataset (CORD-19). 2020. Version 2022-06-02. Retrieved from https://ai2-semanticscholar-cord-19.s3-us-west-2.amazonaws.com/historical_releases.html. Accessed 2022-06-05. doi:10.5281/zenodo.3715506
(2) Chen Q, Allot A, & Lu Z. (2020) Keep up with the latest coronavirus research, Nature 579:193 and Chen Q, Allot A, Lu Z. LitCovid: an open database of COVID-19 literature. Nucleic Acids Research. 2020. (version 2023-01-10)
(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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