\ 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
901Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients  

BACKGROUND AND AIMS: Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk for lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. METHODS: LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. RESULTS: Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p=0.013) and mostly female (68%, p=0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p<0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/mL vs. 200.5 AU/mL in controls, p<0.001). Predictors for negative response among LT recipients were older age, lower eGFR, and treatment with high dose steroids and MMF. No serious adverse events were reported in both groups. CONCLUSION: LT recipients developed substantially lower immunological response to Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibodies response include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population. LAY SUMMARY: Liver Transplant recipients had a substantially inferior immunity to the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive, average antibody levels were two times less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.

J Hepatol2021       LitCov and CORD-19
902Effect of COVID-19 on maternal, perinatal and neonatal outcome: systematic review  

OBJECTIVE: To evaluate the effects of coronavirus disease 2019 (COVID‐19) on maternal, perinatal and neonatal outcomes by performing a systematic review of available published literature on pregnancies affected by COVID‐19. METHODS: We performed a systematic review to evaluate the effects of COVID‐19 on pregnancy, perinatal and neonatal outcomes. We conducted a comprehensive literature search using PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure Database and Wan Fang Data until 20 April 2020 (studies were identified through PubMed alert after that date). For the research strategy, combinations of the following keywords and MeSH terms were used: SARS‐CoV‐2, COVID‐19, coronavirus disease 2019, pregnancy, gestation, maternal, mothers, vertical transmission, maternal‐fetal transmission, intrauterine transmission, neonates, infant, delivery. Eligibility criteria included laboratory‐confirmed and/or clinically diagnosed COVID‐19, patient being pregnant on admission and availability of clinical characteristics, including at least one maternal, perinatal or neonatal outcome. Exclusion criteria were non‐peer‐reviewed or unpublished reports, unspecified date and location of the study, suspicion of duplicate reporting, and unreported maternal or perinatal outcomes. No language restrictions were applied. RESULTS: We identified a high number of relevant case reports and case series, but only 24 studies, including a total of 324 pregnant women with COVID‐19, met the eligibility criteria and were included in the systematic review. These comprised nine case series (eight consecutive) and 15 case reports. A total of 20 pregnant patients with laboratory‐confirmed COVID‐19 were included in the case reports. In the combined data from the eight consecutive case series, including 211 (71.5%) cases of laboratory‐confirmed and 84 (28.5%) of clinically diagnosed COVID‐19, the maternal age ranged from 20 to 44 years and the gestational age on admission ranged from 5 to 41 weeks. The most common symptoms at presentation were fever, cough, dyspnea/shortness of breath, fatigue and myalgia. The rate of severe pneumonia reported amongst the case series ranged from 0 to 14%, with the majority of the cases requiring admission to the intensive care unit. Almost all cases from the case series had positive computer tomography chest findings. All six and 22 cases that had nucleic‐acid testing in vaginal mucus and breast milk samples, respectively, were negative for SARS‐CoV‐2. Only four cases of spontaneous miscarriage or abortion were reported. In the consecutive case series, 219/295 women had delivered at the time of reporting, and the majority of these had Cesarean section. The gestational age at delivery ranged from 28 to 41 weeks. Apgar scores at 1 and 5 min ranged from 7 to 10 and 7 to 10, respectively. Only eight neonates had birth weight <2500 g and nearly one‐third of cases were transferred to the neonatal intensive care unit. There was one case each of neonatal asphyxia and neonatal death. In 155 neonates that had nucleic‐acid testing in throat swab, all, except three cases, were negative for SARS‐CoV‐2. There were seven maternal deaths, four intrauterine fetal deaths (one with twin pregnancy) and two neonatal deaths (twin pregnancy) reported in a non‐consecutive case series of nine cases with severe COVID‐19. From the case reports, two maternal deaths, one neonatal death and two cases of neonatal SARS‐CoV‐2 infection were reported. CONCLUSIONS: Despite the increasing number of published studies on COVID‐19 in pregnancy, there are insufficient good‐quality data to draw unbiased conclusions with regard to the severity of the disease or specific complications of COVID‐19 in pregnant women, as well as vertical transmission, perinatal and neonatal complications. In order to answer specific questions in relation to the impact of COVID‐19 on pregnant women and their fetuses through meaningful good‐quality research, we urge researchers and investigators to present complete outcome data and reference previously published cases in their publications, and to record such reporting when the data of a case are entered into a registry or several registries. This article is protected by copyright. All rights reserved.

Ultrasound Obstet Gynecol2020       LitCov and CORD-19
903SARS-beginning to understand a new virus  

The 114-day epidemic of the severe acute respiratory syndrome (SARS) swept 29 countries, affected a reported 8,098 people, left 774 patients dead and almost paralysed the Asian economy. Aggressive quarantine measures, possibly aided by rising summer temperatures, successfully terminated the first eruption of SARS and provided at least a temporal break, which allows us to consolidate what we have learned so far and plan for the future. Here, we review the genomics of the SARS coronavirus (SARS-CoV), its phylogeny, antigenic structure, immune response and potential therapeutic interventions should the SARS epidemic flare up again.

Nat Rev Microbiol2003       CORD-19
904Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC)  

N/A

MMWR Recomm Rep2003       CORD-19
905Recent progress and challenges in drug development against COVID-19 coronavirus-an update on the status  

Abstract Coronaviruses are a large group of viruses known to cause illnesses that vary between the common cold and more severe diseases to include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). A novel coronavirus was identified in December 2019 in Wuhan city, Hubei province, China. This virus represents a new strain that has not been previously identified in humans. The virus is now known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting disease is called coronavirus disease 2019 (COVID-19). The World Health Organization (WHO) declared the novel coronavirus outbreak a global pandemic in March 2020. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with more than 1,948,617 laboratory-confirmed cases and over 121,846 deaths worldwide. Currently, no specific medication is recommended to treat COVID-19 patients. However, governments and pharmaceutical companies are struggling to quickly find an effective drug to defeat the coronavirus. In the current review, we summarize the existing state of knowledge about COVID-19, available medications, and treatment options. Favilavir is an antiviral drug that is approved in Japan for common influenza treatment and is now approved to treat symptoms of COVID-19 in China. Moreover, Chloroquine and hydroxychloroquine, drugs used to treat malaria and arthritis, respectively, were recommended by the National Health Commission of the People's Republic of China for treatment of COVID-19. Presently, chloroquine and hydroxychloroquine are under investigation by the US Food and Drug Administration (FDA) as a treatment for COVID-19. The first COVID-19 vaccine is not expected to be ready for clinical trials before the end of the year.

Infect Genet Evol2020       LitCov and CORD-19
906Fear and Practice Modifications among Dentists to Combat Novel COVID-19 Outbreak  

An outbreak of novel coronavirus disease (COVID-19) in China has influenced every aspect of life. Healthcare professionals, especially dentists, are exposed to a higher risk of getting infected due to close contact with infected patients. The current study was conducted to assess anxiety and fear of getting infected among dentists while working during the current novel coronavirus diseases (COVID-19) outbreak. In addition, dentists’ knowledge about various practice modifications to combat COVID-19 has been evaluated. A cross-sectional study was conducted using an online survey from 10th to 17th March 2020. The well-constructed questionnaire was designed and registered at online website (Kwiksurveys) and validated. A total of 669 participants from 30 different countries across the world responded. After scrutiny, completed questionnaires (n = 650) were included in the study. Statistical analysis was performed using SPSS version 25. Chi-Square and Spearman correlation tests were applied to control confounders and assess the relation of dentists’ response with respect to gender and educational level. More than two-thirds of the general dental practitioners (78%) from 30 countries questioned were anxious and scared by the devastating effects of COVID-19. A large number of dentists (90%) were aware of recent changes in the treatment protocols. However, execution of amended treatment protocol was recorded as 61%. The majority of the dentists (76%) were working in the hospital setting out of which 74% were from private, and 20% were from government setups. Individually we received a large number of responses from Pakistan and Saudi Arabia, but collectively more than 50% of the responses were from other parts of the world. Despite having a high standard of knowledge and practice, dental practitioners around the globe are in a state of anxiety and fear while working in their respective fields due to the COVID-19 pandemic impact on humanity. A number of dental practices have either modified their services according to the recommended guidelines to emergency treatment only or closed down practices for an uncertain period.

Int J Environ Res Public Healt2020       LitCov and CORD-19
907Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2  

BACKGROUND: Coronavirus disease 2019 (COVID-19) linked with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause severe illness and life-threatening pneumonia in humans. The current COVID-19 pandemic demands an effective vaccine to acquire protection against the infection. Therefore, the present study was aimed to design a multiepitope-based subunit vaccine (MESV) against COVID-19. METHODS: Structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) of SARS-CoV-2 are responsible for its prime functions. Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast B- and T- cell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV. RESULTS: Predicted epitopes suggested high antigenicity, conserveness, substantial interactions with the human leukocyte antigen (HLA) binding alleles, and collective global population coverage of 88.40%. Taken together, 276 amino acids long MESV was designed by connecting 3 cytotoxic T lymphocytes (CTL), 6 helper T lymphocyte (HTL) and 4 B-cell epitopes with suitable adjuvant and linkers. The MESV construct was non-allergenic, stable, and highly antigenic. Molecular docking showed a stable and high binding affinity of MESV with human pathogenic toll-like receptors-3 (TLR3). Furthermore, in silico immune simulation revealed significant immunogenic response of MESV. Finally, MEV codons were optimized for its in silico cloning into the Escherichia coli K-12 system, to ensure its increased expression. CONCLUSION: The MESV developed in this study is capable of generating immune response against COVID-19. Therefore, if designed MESV further investigated experimentally, it would be an effective vaccine candidate against SARS-CoV-2 to control and prevent COVID-19.

Infect Dis Poverty2020       LitCov and CORD-19
908SARS-associated coronavirus  

N/A

N Engl J Med2003       CORD-19
909Hospitalization and Mortality among Black Patients and White Patients with Covid-19  

BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19–positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19–positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.

N Engl J Med2020       LitCov and CORD-19
910Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) study: an observational cohort study of SARS-CoV-2 infection and vaccination in healthcare workers  

BACKGROUND: SARS-CoV-2 is a recently emerged pandemic coronavirus (CoV) capable of causing severe respiratory illness. However, a significant number of infected people present as asymptomatic or pauci-symptomatic. In this prospective assessment of at-risk healthcare workers (HCWs) we seek to determine whether pre-existing antibody or T cell responses to previous seasonal human coronavirus (HCoV) infections affect immunological or clinical responses to SARS-CoV-2 infection or vaccination. METHODS: A cohort of 300 healthcare workers, confirmed negative for SARS-CoV-2 exposure upon study entry, will be followed for up to 1 year with monthly serology analysis of IgM and IgG antibodies against the spike proteins of SARS-CoV-2 and the four major seasonal human coronavirus - HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63. Participants will complete monthly questionnaires that ask about Coronavirus Disease 2019 (COVID-19) exposure risks, and a standardized, validated symptom questionnaire (scoring viral respiratory disease symptoms, intensity and severity) at least twice monthly and any day when any symptoms manifest. SARS-CoV-2 PCR testing will be performed any time participants develop symptoms consistent with COVID-19. For those individuals that seroconvert and/or test positive by SARS-CoV-2 PCR, or receive the SARS-CoV-2 vaccine, additional studies of T cell activation and cytokine production in response to SARS-CoV-2 peptide pools and analysis of Natural Killer cell numbers and function will be conducted on that participant’s cryopreserved baseline peripheral blood mononuclear cells (PBMCs). Following the first year of this study we will further analyze those participants having tested positive for COVID-19, and/or having received an authorized/licensed SARS-CoV-2 vaccine, quarterly (year 2) and semi-annually (years 3 and 4) to investigate immune response longevity. DISCUSSION: This study will determine the frequency of asymptomatic and pauci-symptomatic SARS-CoV-2 infection in a cohort of at-risk healthcare workers. Baseline and longitudinal assays will determine the frequency and magnitude of anti-spike glycoprotein antibodies to the seasonal HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, and may inform whether pre-existing antibodies to these human coronaviruses are associated with altered COVID-19 disease course. Finally, this study will evaluate whether pre-existing immune responses to seasonal HCoVs affect the magnitude and duration of antibody and T cell responses to SARS-CoV-2 vaccination, adjusting for demographic covariates. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06233-1.

BMC Infect Dis2021       LitCov and CORD-19
911Assessing the relationship between surface levels of PM2.5 and PM10 particulate matter impact on COVID-19 in Milan, Italy  

Abstract The novel coronavirus disease (COVID-19) is a highly pathogenic, transmittable and invasive pneumococcal disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which emerged in December 2019 and January 2020 in Wuhan city, Hubei province, China and fast spread later on the middle of February 2020 in the Northern part of Italy and Europe. This study investigates the correlation between the degree of accelerated diffusion and lethality of COVID-19 and the surface air pollution in Milan metropolitan area, Lombardy region, Italy. Daily average concentrations of inhalable particulate matter (PM) in two size fractions PM2.5, PM10 and maxima PM10 ground level atmospheric pollutants together air quality and climate variables (daily average temperature, relative humidity, wind speed, atmospheric pressure field and Planetary Boundary Layer-PBL height) collected during 1 January–30 April 2020 were analyzed. In spite of being considered primarily transmitted by indoor bioaerosols droplets and infected surfaces, or direct human-to-human personal contacts, it seems that high levels of urban air pollution, weather and specific climate conditions have a significant impact on the increased rates of confirmed COVID-19 Total number, Daily New and Total Deaths cases, possible attributed not only to indoor but also to outdoor airborne bioaerosols distribution. Our analysis demonstrates the strong influence of daily averaged ground levels of particulate matter concentrations, positively associated with average surface air temperature and inversely related to air relative humidity on COVID-19 cases outbreak in Milan. Being a novel pandemic coronavirus (SARS-CoV-2) version, COVID-19 might be ongoing during summer conditions associated with higher temperatures and low humidity levels. Presently is not clear if this protein “spike” of the new coronavirus COVID-19 is involved through attachment mechanisms on indoor or outdoor airborne aerosols in the infectious agent transmission from a reservoir to a susceptible host in some agglomerated urban areas like Milan is.

Sci Total Environ2020       LitCov and CORD-19
912Breath Regulation and yogic Exercise An online Therapy for calm and Happiness (BREATH) for frontline hospital and long-term care home staff managing the COVID-19 pandemic: A structured summary of a study protocol for a feasibility study for a randomised controlled trial  

OBJECTIVES: Objective 1: To determine if it is feasible to conduct an RCT of online Sudarshan Kriya Yoga (SKY) for frontline hospital and long-term care home staff under the constraints imposed by the COVID-19 pandemic and need for remote trial monitoring. Objective 2: To assess whether online versions of SKY and/or Health Enhancement Program (HEP) result in improvement in self-rated measures of insomnia, anxiety, depression, and resilience. TRIAL DESIGN: This is an open-label feasibility randomized controlled trial (RCT), comparing an online breath based yogic intervention SKY versus an online control mind-body intervention HEP in frontline hospital and long-term care home staff managing the COVID-19 pandemic. PARTICIPANTS: Participants will include frontline hospital and long-term care home staff that are involved in the management of COVID-19 patients in London, Ontario, Canada. Participants will be willing and able to attend via online video conferencing software to participate in the study interventions. Participants must have an adequate understanding of English and be able to sit without physical discomfort for 60 minutes. INTERVENTION AND COMPARATOR: Sudarshan Kriya Yoga (SKY): The online version of SKY will be delivered by at least one certified Canadian SKY teacher, with at least one back up teacher at all times, under the supervision of Ms. Ronnie Newman, Director of Research and Health Promotion, Art of Living Foundation, USA. The online version of SKY for healthcare workers has a total duration of 3 hours. Phase I will consist of 5 self-paced online modules of 4-10 minutes each to learn the breath control techniques. Participants will be sent an online survey in REDCap requesting that they self-confirm completion of the Phase I modules. In Phase II, 2 interactive online sessions of 1 hour each will be held on consecutive days with a certified SKY teacher, during which participants will learn the fast, medium and slow breaths. For ease of scheduling, multiple time windows will be offered for Phase II. There will be at least one back up teacher at all times. Both Phase I and II will be completed in the first week. Health Enhancement Program (HEP): The active control arm, HEP, will consist of time-matched online self-paced modules for Phase I. Phase II will consist of mindfulness-based meditation sessions delivered by mental health staff. HEP will be an active treatment program that incorporates mind-body interventions. HEP will consist of time-matched online self-paced modules with psychoeducation on healthy active living as well as interactive modules comprising of guided de-stressing exercises including music therapy, mindfulness and progressive muscle relaxation. Weekly follow up sessions will be offered to all recruited participants for 30 minutes each for the subsequent 4 weeks in both study arms. MAIN OUTCOMES: The following feasibility outcomes will be measured at the end of the study: (1) rate of participant recruitment, (2) rate of retention, (3) completeness of data entry, (4) cost of interventions, and (5) unexpected costs. Such measures will be collected on a daily basis through-out the study and tabulated 5 weeks later at the end of the study. RANDOMISATION: Participants will be randomized after they have electronically signed the consent form and the research staff have confirmed eligibility. We will use REDCap to perform randomization in a 1:1 ratio as well as allocation concealment. REDCap is widely used by health researchers worldwide to significantly reduce data entry and study management errors to improve data fidelity. BLINDING (MASKING): All study participants will be blinded to the study hypotheses so as to prevent any expectation bias. Group allocation will be masked during analysis. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This study will randomize a total of 60 participants in a 1:1 ratio to either SKY or HEP interventions. TRIAL STATUS: Protocol version number 2.0 (June 5, 2020). Recruitment is currently ongoing (starting June 25, 2020). We anticipate to complete recruitment by June 30, 2021 and complete the study by September 30, 2021. TRIAL REGISTRATION: ClinicalTrials.gov protocol ID NCT04368676 (posted April 30, 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
913Laparoscopic right hepatectomy with intrahepatic transection of the right bile duct  

N/A

Ann Surg Oncol2012       CORD-19
914Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis  

N/A

JAMA2020       LitCov and CORD-19
915Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways  

We previously identified the major pathological changes in the respiratory and immune systems of patients who died of severe acute respiratory syndrome (SARS) but gained little information on the organ distribution of SARS‐associated coronavirus (SARS‐CoV). In the present study, we used a murine monoclonal antibody specific for SARS‐CoV nucleoprotein, and probes specific for a SARS‐CoV RNA polymerase gene fragment, for immunohistochemistry and in situ hybridization, respectively, to detect SARS‐CoV systematically in tissues from patients who died of SARS. SARS‐CoV was found in lung, trachea/bronchus, stomach, small intestine, distal convoluted renal tubule, sweat gland, parathyroid, pituitary, pancreas, adrenal gland, liver and cerebrum, but was not detected in oesophagus, spleen, lymph node, bone marrow, heart, aorta, cerebellum, thyroid, testis, ovary, uterus or muscle. These results suggest that, in addition to the respiratory system, the gastrointestinal tract and other organs with detectable SARS‐CoV may also be targets of SARS‐CoV infection. The pathological changes in these organs may be caused directly by the cytopathic effect mediated by local replication of the SARS‐CoV; or indirectly as a result of systemic responses to respiratory failure or the harmful immune response induced by viral infection. In addition to viral spread through a respiratory route, SARS‐CoV in the intestinal tract, kidney and sweat glands may be excreted via faeces, urine and sweat, thereby leading to virus transmission. This study provides important information for understanding the pathogenesis of SARS‐CoV infection and sheds light on possible virus transmission pathways. This data will be useful for designing new strategies for prevention and treatment of SARS. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

J Pathol2004       CORD-19
916COVID-19 infection: Origin, transmission and characteristics of human coronaviruses  

The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. Genomic analysis revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) bat viruses, therefore bats could be the possible primary reservoir. The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery. In the current review, we summarize and comparatively analyze the emergence and pathogenicity of COVID-19 infection and previous human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). We also discuss the approaches for developing effective vaccines and therapeutic combinations to cope with this viral outbreak.

J Adv Res2020       LitCov and CORD-19
917Influence of Social Media Platforms on Public Health Protection Against the COVID-19 Pandemic via the Mediating Effects of Public Health Awareness and Behavioral Changes: Integrated Model  

BACKGROUND: Despite the growing body of literature examining social media in health contexts, including public health communication, promotion, and surveillance, limited insight has been provided into how the utility of social media may vary depending on the particular public health objectives governing an intervention. For example, the extent to which social media platforms contribute to enhancing public health awareness and prevention during epidemic disease transmission is currently unknown. Doubtlessly, coronavirus disease (COVID-19) represents a great challenge at the global level, aggressively affecting large cities and public gatherings and thereby having substantial impacts on many health care systems worldwide as a result of its rapid spread. Each country has its capacity and reacts according to its perception of threat, economy, health care policy, and the health care system structure. Furthermore, we noted a lack of research focusing on the role of social media campaigns in public health awareness and public protection against the COVID-19 pandemic in Jordan as a developing country. OBJECTIVE: The purpose of this study was to examine the influence of social media platforms on public health protection against the COVID-19 pandemic via public health awareness and public health behavioral changes as mediating factors in Jordan. METHODS: A quantitative approach and several social media platforms were used to collect data via web questionnaires in Jordan, and a total of 2555 social media users were sampled. This study used structural equation modeling to analyze and verify the study variables. RESULTS: The main findings revealed that the use of social media platforms had a significant positive influence on public health protection against COVID-19 as a pandemic. Public health awareness and public health behavioral changes significantly acted as partial mediators in this relationship. Therefore, a better understanding of the effects of the use of social media interventions on public health protection against COVID-19 while taking public health awareness and behavioral changes into account as mediators should be helpful when developing any health promotion strategy plan. CONCLUSIONS: Our findings suggest that the use of social media platforms can positively influence awareness of public health behavioral changes and public protection against COVID-19. Public health authorities may use social media platforms as an effective tool to increase public health awareness through dissemination of brief messages to targeted populations. However, more research is needed to validate how social media channels can be used to improve health knowledge and adoption of healthy behaviors in a cross-cultural context.

J Med Internet Res2020       LitCov and CORD-19
918Coronaviruses: An Overview of Their Replication and Pathogenesis  

Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, an unusually large RNA genome, and a unique replication strategy. Coronaviruses cause a variety of diseases in mammals and birds ranging from enteritis in cows and pigs and upper respiratory disease chickens to potentially lethal human respiratory infections. Here we provide a brief introduction to coronaviruses discussing their replication and pathogenicity, and current prevention and treatment strategies. We will also discuss the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the recently identified Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).

Coronaviruses2015       CORD-19
919Suicide risk and prevention during the COVID-19 pandemic  

Lancet Psychiatry2020       LitCov and CORD-19
920Application and Preliminary Outcomes of Remote Diagnosis and Treatment During the COVID-19 Outbreak: Retrospective Cohort Study  

BACKGROUND: The coronavirus disease (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in the self-quarantine of countless people due to possible infection. This situation makes telemedicine necessary as it can overcome geographical barriers, increase the number of people served, and provide online clinical support for patients. However, the outcomes of telemedicine have not yet been evaluated. OBJECTIVE: The aim of our study is to describe the epidemiological features and clinical symptoms of patients receiving remote diagnosis and treatment at the online outpatient clinic of our hospital, as well as to analyze the outcomes and advantages of telemedicine, during the COVID-19 pandemic. METHODS: Data from patients receiving remote diagnosis and treatment via consultation services for COVID-19 concerns at the online outpatient clinic of Henan Provincial People's Hospital from January 24 to February 17, 2020, were collected. A retrospective analysis was performed on epidemiological features, clinical symptoms, and preliminary outcomes. RESULTS: Online inquiry, consultation, and suggestions were provided for patient concerns related to COVID-19. Our hospital also offered offline noncontact drug delivery services following online ordering and payment. A total of 4589 patients receiving remote diagnosis and treatment were recruited. The daily number of online outpatient visits initially increased and then decreased, reaching its peak on January 28 when the daily number of online outpatient visits totaled 612. Of 4589 patients, 1940 (42.3%) were males and 2649 (57.7%) were females (age range: 78 days to 85 years). Most patients were aged 20-39 years (n=3714, 80.9%) and came from Henan Province (n=3898, 84.9%). The number of patients from other provinces was 691 (15.1%). During the online consultations, patients discussed the following symptoms: fever (n=2383), cough (n=1740), nasal obstruction (n=794), fatigue (n=503), and diarrhea (n=276). A total of 873 orders of noncontact drug delivery following online payment was completed. The daily number of such orders gradually stabilized after the initial, steady increase. For offline drug delivery orders, the median (IQR) was 36 (58). An online satisfaction survey was filled out postconsultation by patients; of the 985 responses received, 98.1% (n=966) of respondents were satisfied with the service they received. CONCLUSIONS: Remote diagnosis and treatment offered via online outpatient consultations effectively reduced the burden on hospitals, prevented overcrowding, reduced the risk of cross-infection, and relieved patients' anxiety during the COVID-19 outbreak. This plays an essential role in pandemic management.

JMIR Mhealth Uhealth2020       LitCov and CORD-19
921Graft Cryopreservation Does Not Impact Overall Survival after Allogeneic Hematopoietic Cell Transplantation Using Post-Transplantation Cyclophosphamide for Graft-versus-Host Disease Prophylaxis  

ABSTRACT The COVID-19 pandemic has created significant barriers to timely donor evaluation, cell collection, and graft transport for allogeneic hematopoietic stem cell transplantation (allo-HCT). To ensure availability of donor cells on the scheduled date of infusion, many sites now collect cryopreserved grafts before the start of pretransplantation conditioning. Post-transplantation cyclophosphamide (ptCY) is an increasingly used approach for graft-versus-host disease (GVHD) prophylaxis, but the impact of graft cryopreservation on the outcomes of allo-HCT using ptCY is not known. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared the outcomes of HCT using cryopreserved versus fresh grafts in patients undergoing HCT for hematologic malignancy with ptCY. We analyzed 274 patients with hematologic malignancy undergoing allo-HCT between 2013 and 2018 with cryopreserved grafts and ptCY. Eighteen patients received bone marrow grafts and 256 received peripheral blood stem cell grafts. These patients were matched for age, graft type, disease risk index (DRI), and propensity score with 1080 patients who underwent allo-HCT with fresh grafts. The propensity score, which is an assessment of the likelihood of receiving a fresh graft versus a cryopreserved graft, was calculated using logistic regression to account for the following: disease histology, Karnofsky Performance Score (KPS), HCT Comorbidity Index, conditioning regimen intensity, donor type, and recipient race. The primary endpoint was overall survival (OS). Secondary endpoints included acute and chronic graft-versus-host disease (GVHD), non-relapse mortality (NRM), relapse/progression and disease-free survival (DFS). Because of multiple comparisons, only P values <.01 were considered statistically significant. The 2 cohorts (cryopreserved and fresh) were similar in terms of patient age, KPS, diagnosis, DRI, HCT-CI, donor/graft source, and conditioning intensity. One-year probabilities of OS were 71.1% (95% confidence interval [CI], 68.3% to 73.8%) with fresh grafts and 70.3% (95% CI, 64.6% to 75.7%) with cryopreserved grafts (P = .81). Corresponding probabilities of OS at 2 years were 60.6% (95% CI, 57.3% to 63.8%) and 58.7% (95% CI, 51.9% to 65.4%) (P = .62). In matched-pair regression analysis, graft cryopreservation was not associated with a significantly higher risk of mortality (hazard ratio [HR] for cryopreserved versus fresh, 1.05; 95% CI, .86 to 1.29; P = .60). Similarly, rates of neutrophil recovery (HR, .91; 95% CI, .80 to 1.02; P = .12), platelet recovery (HR, .88; 95% CI, .78 to 1.00; P = .05), grade III-IV acute GVHD (HR, .78; 95% CI, .50 to 1.22; P = .27), NRM (HR, 1.16; 95% CI, .86 to 1.55; P = .32) and relapse/progression (HR, 1.21; 95% CI, .97 to 1.50; P = .09) were similar with cryopreserved grafts versus fresh grafts. There were somewhat lower rates of chronic GVHD (HR, 78; 95% CI, .61 to .99; P = .04) and DFS (HR for treatment failure, 1.19; 95% CI, 1.01 to 1.29; P = .04) with graft cryopreservation that were of marginal statistical significance after adjusting for multiple comparisons. Overall, our data indicate that graft cryopreservation does not significantly delay hematopoietic recovery, increase the risk of acute GVHD or NRM, or decrease OS after allo-HCT using ptCY.

Biol Blood Marrow Transplant2020       LitCov and CORD-19
922Cardiovascular Considerations for Patients, Healthcare Workers and Health Systems During the COVID-19 Pandemic  

Abstract The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and preexisting cardiovascular disease (CVD) have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become host or vectors of virus transmission. We hereby review the peer-reviewed and preprint literature pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.

J Am Coll Cardiol2020       LitCov and CORD-19
923Severe acute respiratory syndrome coronavirus-2, a newly emerged pathogen: an overview  

Coronavirus disease 2019 (COVID-19) is a viral pneumonia, responsible for the recent pandemic, and originated from Wuhan, China, in December 2019. The causative agent of the outbreak was identified as coronavirus and designated as severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). Few years back, the severe acute respiratory syndrome coronavirus (SARS- CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) were reported to be highly pathogenic and caused severe infections in humans. In the current situation SARS-CoV-2 has become the third highly pathogenic coronavirus that is responsible for the present outbreak in human population. At the time of this review, there were more than 14 007 791 confirmed COVID-19 patients which associated with over 597 105 deaths in more then 216 countries across the globe (as reported by World Health Organization). In this review we have discussed about SARS-CoV, MERS-CoV and SARC-CoV-2, their reservoirs, role of spike proteins and immunogenicity. We have also covered the diagnosis, therapeutics and vaccine status of SARS-CoV-2.

Pathog Dis2020       LitCov and CORD-19
924Emerging coronaviruses: Genome structure, replication and pathogenesis  

The recent emergence of a novel coronavirus (2019‐nCoV), which is causing an outbreak of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this minireview, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats.

J Med Virol2020       LitCov and CORD-19
925Outbreak of severe acute respiratory syndrome in Hong Kong Special Administrative Region: case report  

N/A

BMJ2003       CORD-19
926Differential detection of rhinoviruses and enteroviruses RNA sequences associated with classical immunofluorescence assay detection of respiratory virus antigens in nasopharyngeal swabs from infants with bronchiolitis  

To define the role of enteroviruses and human rhinoviruses as etiological agents in childhood bronchiolitis, clinical aspirates from 84 infants admitted to hospital with symptoms of obstructive bronchiolitis were tested by picornavirus RT‐PCR assay, adenovirus PCR assay and classical immunofluorescence antigen detection of common respiratory viral agents. Respiratory syncytial viruses (A&B) were detectable in 45 of 84 (53.6%) nasopharyngeal aspirates from infants with bronchiolitis, whereas coronaviruses, influenza viruses, and parainfluenza viruses were not detectable in the same samples. Adenoviruses were detectable by PCR in 11 of 84 (13.1%) nasopharyngeal swabs. By using a picornavirus RT‐PCR assay followed by a differential molecular hybridisation, rhinovirus and enterovirus RNA sequences were detected in 16 of 84 (19%) and in 10 of 84 (11.9%) of the nasopharyngeal swabs tested. Positive human rhinovirus or enterovirus RT‐PCR assay, however, was the only evidence of respiratory infection in 8 of 84 (9.5%) and in 7 of 84 (8.33%) of the studied patients. Respiratory syncytial viruses, human rhinoviruses, adenoviruses, and enteroviruses occur in dual infections detected in 18 of 84 (21.4%) respiratory samples tested. The median duration of stay in hospital was not significantly different between the patients demonstrating a single viral infection and those with a dual viral infection (6.22 ± 2.07 vs. 5.04 ± 0.95 days; P > 0.05). In summary, combination of molecular and classical detection assays of common viruses can be used to demonstrate enterovirus and human rhinovirus respiratory infection in childhood bronchiolitis, and provides an improved approach to obtain new insights into concomitant viral respiratory tract infection in infants. J. Med. Virol. 61:341–346, 2000. © 2000 Wiley‐Liss, Inc.

J Med Virol2000       CORD-19
927Students under lockdown: Comparisons of students' social networks and mental health before and during the COVID-19 crisis in Switzerland  

This study investigates students’ social networks and mental health before and at the time of the COVID-19 pandemic in April 2020, using longitudinal data collected since 2018. We analyze change on multiple dimensions of social networks (interaction, friendship, social support, co-studying) and mental health indicators (depression, anxiety, stress, loneliness) within two cohorts of Swiss undergraduate students experiencing the crisis (N = 212), and make additional comparisons to an earlier cohort which did not experience the crisis (N = 54). In within-person comparisons we find that interaction and co-studying networks had become sparser, and more students were studying alone. Furthermore, students’ levels of stress, anxiety, loneliness, and depressive symptoms got worse, compared to measures before the crisis. Stressors shifted from fears of missing out on social life to worries about health, family, friends, and their future. Exploratory analyses suggest that COVID-19 specific worries, isolation in social networks, lack of interaction and emotional support, and physical isolation were associated with negative mental health trajectories. Female students appeared to have worse mental health trajectories when controlling for different levels of social integration and COVID-19 related stressors. As universities and researchers discuss future strategies on how to combine on-site teaching with online courses, our results indicate the importance of considering social contacts in students’ mental health and offer starting points to identify and support students at higher risk of social isolation and negative psychological effects during the COVID-19 pandemic.

PLoS One2020       LitCov and CORD-19
928Single-cell analysis of SARS-CoV-2 receptor ACE2 and spike protein priming expression of proteases in the human heart  

AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly binds to ACE2 (angiotensin-converting enzyme 2) to facilitate cellular entry. Compared with the lung or respiratory tract, the human heart exhibits greater ACE2 expression. However, little substantial damage was found in the heart tissue, and no viral particles were observed in the cardiac myocytes. This study aims to analyse ACE2 and SARS-CoV-2 spike (S) protein proteases at the single-cell level, to explore the cardiac involvement in COVID-19 and improve our understanding of the potential cardiovascular implications of COVID-19. METHODS AND RESULTS: With meta-analysis, the prevalence of cardiac injury in COVID-19 patients varies from 2% [95% confidence interval (CI) 0–5%, I(2) = 0%] in non-ICU patients to 59% (95% CI 48–71%, I(2) = 85%) in non-survivors. With public single-cell sequence data analysis, ACE2 expression in the adult human heart is higher than that in the lung (adjusted P < 0.0001). Inversely, the most important S protein cleavage protease TMPRSS2 (transmembrane protease serine protease-2) in the heart exhibits an extremely lower expression than that in the lung (adjusted P < 0.0001), which may restrict entry of SARS-CoV-2 into cardiac cells. Furthermore, we discovered that other S protein proteases, CTSL (cathepsin L) and FURIN (furin, paired basic amino acid cleaving enzyme), were expressed in the adult heart at a similar level to that in the lung, which may compensate for TMPRSS2, mediating cardiac involvement in COVID-19. CONCLUSION: Compared with the lung, ACE2 is relatively more highly expressed in the human heart, while the key S protein priming protease, TMPRSS2, is rarely expressed. The low percentage of ACE2(+)/TMPRSS2(+) cells reduced heart vulnerability to SARS-CoV-2 to some degree. CTSL and FURIN may compensate for S protein priming to mediate SARS-CoV-2 infection of the heart.

Cardiovasc Res2020       LitCov and CORD-19
929Early prediction of level-of-care requirements in patients with COVID-19  

This study examined records of 2566 consecutive COVID-19 patients at five Massachusetts hospitals and sought to predict level-of-care requirements based on clinical and laboratory data. Several classification methods were applied and compared against standard pneumonia severity scores. The need for hospitalization, ICU care, and mechanical ventilation were predicted with a validation accuracy of 88%, 87%, and 86%, respectively. Pneumonia severity scores achieve respective accuracies of 73% and 74% for ICU care and ventilation. When predictions are limited to patients with more complex disease, the accuracy of the ICU and ventilation prediction models achieved accuracy of 83% and 82%, respectively. Vital signs, age, BMI, dyspnea, and comorbidities were the most important predictors of hospitalization. Opacities on chest imaging, age, admission vital signs and symptoms, male gender, admission laboratory results, and diabetes were the most important risk factors for ICU admission and mechanical ventilation. The factors identified collectively form a signature of the novel COVID-19 disease.

Elife2020       LitCov and CORD-19
930Tropism, replication competence and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis. METHODS: We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls. FINDINGS: SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV. INTERPRETATION: The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens. FUNDING: US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.

Lancet Respir Med2020       LitCov and CORD-19
931Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic  

N/A

Circulation2020       LitCov and CORD-19
932Conspiracy theories as barriers to controlling the spread of COVID-19 in the U.S  

RATIONALE: The COVID-19 pandemic poses extraordinary challenges to public health. OBJECTIVE: Because the novel coronavirus is highly contagious, the widespread use of preventive measures such as masking, physical distancing, and eventually vaccination is needed to bring it under control. We hypothesized that accepting conspiracy theories that were circulating in mainstream and social media early in the COVID-19 pandemic in the US would be negatively related to the uptake of preventive behaviors and also of vaccination when a vaccine becomes available. METHOD: A national probability survey of US adults (N = 1050) was conducted in the latter half of March 2020 and a follow-up with 840 of the same individuals in July 2020. The surveys assessed adoption of preventive measures recommended by public health authorities, vaccination intentions, conspiracy beliefs, perceptions of threat, belief about the safety of vaccines, political ideology, and media exposure patterns. RESULTS: Belief in three COVID-19-related conspiracy theories was highly stable across the two periods and inversely related to the (a) perceived threat of the pandemic, (b) taking of preventive actions, including wearing a face mask, (c) perceived safety of vaccination, and (d) intention to be vaccinated against COVID-19. Conspiracy beliefs in March predicted subsequent mask-wearing and vaccination intentions in July even after controlling for action taken and intentions in March. Although adopting preventive behaviors was predicted by political ideology and conservative media reliance, vaccination intentions were less related to political ideology. Mainstream television news use predicted adopting both preventive actions and vaccination. CONCLUSIONS: Because belief in COVID-related conspiracy theories predicts resistance to both preventive behaviors and future vaccination for the virus, it will be critical to confront both conspiracy theories and vaccination misinformation to prevent further spread of the virus in the US. Reducing those barriers will require continued messaging by public health authorities on mainstream media and in particular on politically conservative outlets that have supported COVID-related conspiracy theories.

Soc Sci Med2020       LitCov and CORD-19
933Things must not fall apart: the ripple effects of the COVID-19 pandemic on children in sub-Saharan Africa  

ABSTRACT: Zero to 19 year-old children in sub-Saharan Africa bear a disproportionate proportion of the global burden of communicable and non-communicable diseases. Significant public health gains have been made in the fight against these diseases, however, factors such as underequipped health systems, disease outbreaks, conflict, and political instability continue to challenge prevention and control. The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introduces new challenges to public health programs in sub-Saharan Africa. Of particular concern are programs targeting major conditions among children, such as undernutrition, vaccine-preventable pneumonia and diarrhea, malaria, tuberculosis, HIV, and sickle cell disease. This article focuses on the impact of the COVID-19 pandemic on child health in sub-Saharan Africa. We review the epidemiology of major pediatric diseases and, referencing modeling projections, discuss the short- and long-term impact of the pandemic on major disease control. We deliberate on potential complications of SARS-CoV-2 co-infections/co-morbidities and identify critical social and ethical issues. Furthermore, we highlight the paucity of COVID-19 data and clinical trials in this region and the lack of child participants in ongoing studies. Lastly, approaches and interventions to mitigate the pandemic’s impact on child health outcomes are discussed. IMPACT: Children in sub-Saharan Africa bear a disproportionate burden of communicable and non-communicable diseases globally; this remains true even as the COVID-19 pandemic persists. Amidst the fast-expanding COVID-19 literature, there is little comprehensive coverage of the pandemic’s indirect impact on child health in sub-Saharan Africa. This article comprehensively outlines the threat that the pandemic poses to major disease prevention and control for children in sub-Saharan Africa. It discusses the potential impact of SARS-CoV-2 co-infections/co-morbidities, highlights research gaps, and advocates for data and action to mitigate the ripple effects of the pandemic on this population.

Pediatr Res2020       LitCov and CORD-19
934Role of infection in chronic bronchitis  

N/A

Am Rev Respir Dis1976       CORD-19
935The impact of the Severe Acute Respiratory Syndrome on hotels: a case study of Hong Kong  

Hotel business in Hong Kong has been badly affected by the outbreak of the Severe Acute Respiratory Syndrome (SARS) since March 2003. Medical reports suggest that a direct contact with the secretion or respiratory droplets from a patient through a short distance is very likely to be the possible way of transmitting the disease. World Health Organization (WHO), hence, has advised international travellers to avoid visiting several regions that have the most number of SARS cases, including Hong Kong. Since then, the number of hotel guests has largely dropped to a level that Hong Kong has never experienced before. As a totally new experience to the hotel industry in Hong Kong and elsewhere, hoteliers basically do not have enough knowledge to respond to epidemic crisis. In view of the lack of published articles in the hospitality literature that examine the issue, this paper investigates the impact of the SARS outbreak on the hotel industry in Hong Kong. In addition, this paper addresses the issue of SARS crisis management in risk identification, assessment and alleviation. The paper is expected to benefit the entire hotel industry from better understanding and planning to face the mysterious illness.

Int J Hosp Manag2003       CORD-19
936Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals  

In the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for potential transfusion to coronavirus disease 2019 (COVID-19) patients. The therapy has been deemed safe, and several clinical trials assessing its efficacy are ongoing. While it remains to be formally proven, the presence of neutralizing antibodies is thought to play a positive role in the efficacy of this treatment. Indeed, neutralizing titers of ≥1:160 have been recommended in some convalescent plasma trials for inclusion. Here, we performed repeated analyses at 1-month intervals on 31 convalescent individuals to evaluate how the humoral responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein, including neutralization, evolve over time. We observed that the levels of receptor-binding-domain (RBD)-specific IgG and IgA slightly decreased between 6 and 10 weeks after the onset of symptoms but that RBD-specific IgM levels decreased much more abruptly. Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing wild-type SARS-CoV-2 S or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, our results suggest that plasma from convalescent donors should be recovered rapidly after resolution of symptoms.

mBio2020       LitCov and CORD-19
937Unique transcriptional changes in coagulation cascade genes in SARS-CoV-2-infected lung epithelial cells: A potential factor in COVID-19 coagulopathies  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. In addition to the acute pulmonary symptoms of COVID-19 (the disease associated with SARS-CoV-2 infection), pulmonary and distal coagulopathies have caused morbidity and mortality in many patients. Currently, the molecular pathogenesis underlying COVID-19 associated coagulopathies are unknown. While there are many theories for the cause of this pathology, including hyper inflammation and excess tissue damage, the cellular and molecular underpinnings are not yet clear. By analyzing transcriptomic data sets from experimental and clinical research teams, we determined that changes in the gene expression of genes important in the extrinsic coagulation cascade in the lung epithelium may be important triggers for COVID-19 coagulopathy. This regulation of the extrinsic blood coagulation cascade is not seen with influenza A virus (IAV)-infected NHBEs suggesting that the lung epithelial derived coagulopathies are specific to SARS-Cov-2 infection. This study is the first to identify potential lung epithelial cell derived factors contributing to COVID-19 associated coagulopathy.

bioRxiv2020       CORD-19
938Novel coronavirus 2019-nCoV: prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV  

N/A

Eur Rev Med Pharmacol Sci2020       LitCov and CORD-19
939Artificial intelligence in clinical care amidst COVID-19 pandemic: A systematic review  

The worldwide health crisis caused by the SARS-Cov-2 virus has resulted in>3 million deaths so far. Improving early screening, diagnosis and prognosis of the disease are critical steps in assisting healthcare professionals to save lives during this pandemic. Since WHO declared the COVID-19 outbreak as a pandemic, several studies have been conducted using Artificial Intelligence techniques to optimize these steps on clinical settings in terms of quality, accuracy and most importantly time. The objective of this study is to conduct a systematic literature review on published and preprint reports of Artificial Intelligence models developed and validated for screening, diagnosis and prognosis of the coronavirus disease 2019. We included 101 studies, published from January 1st, 2020 to December 30th, 2020, that developed AI prediction models which can be applied in the clinical setting. We identified in total 14 models for screening, 38 diagnostic models for detecting COVID-19 and 50 prognostic models for predicting ICU need, ventilator need, mortality risk, severity assessment or hospital length stay. Moreover, 43 studies were based on medical imaging and 58 studies on the use of clinical parameters, laboratory results or demographic features. Several heterogeneous predictors derived from multimodal data were identified. Analysis of these multimodal data, captured from various sources, in terms of prominence for each category of the included studies, was performed. Finally, Risk of Bias (RoB) analysis was also conducted to examine the applicability of the included studies in the clinical setting and assist healthcare providers, guideline developers, and policymakers.

Comput Struct Biotechnol J2021       LitCov and CORD-19
940Severe acute respiratory syndrome (SARS)-paradigm of an emerging viral infection  

An acute and often severe respiratory illness emerged in southern China in late 2002 and rapidly spread to different areas of the Far East as well as several countries around the globe. When the outbreak of this apparently novel infectious disease termed severe acute respiratory syndrome (SARS) came to an end in July 2003, it had caused over 8000 probable cases worldwide and more than 700 deaths. Starting in March 2003, the World Health Organization (WHO) organised an unprecedented international effort by leading laboratories working together to find the causative agent. Little more than one week later, three research groups from this WHO-coordinated network simultaneously found evidence of a hitherto unknown coronavirus in SARS patients, using different approaches. After Koch’s postulates had been fulfilled, WHO officially declared on 16 April 2003 that this virus never before seen in humans is the cause of SARS. Ever since, progress around SARS-associated coronavirus (SARS-CoV) has been swift. Within weeks of the first isolate being obtained, its complete genome was sequenced. Diagnostic tests based on the detection of SARS-CoV RNA were developed and made available freely and widely; nevertheless the SARS case definition still remains based on clinical and epidemiological criteria. The agent’s environmental stability, methods suitable for inactivation and disinfection, and potential antiviral compounds have been studied, and development of vaccines and immunotherapeutics is ongoing. Despite its grave consequences in humanitarian, political and economic terms, SARS may serve as an example of how much can be achieved through a well-coordinated international approach, combining the latest technological advances of molecular virology with more “traditional” techniques carried out to an excellent standard.

J Clin Virol2003       CORD-19
941Health Center Testing for SARS-CoV-2 During the COVID-19 Pandemic-United States, June 5-October 2, 2020  

Long-standing social inequities and health disparities have resulted in increased risk for coronavirus disease 2019 (COVID-19) infection, severe illness, and death among racial and ethnic minority populations. The Health Resources and Services Administration (HRSA) Health Center Program supports nearly 1,400 health centers that provide comprehensive primary health care* to approximately 30 million patients in 13,000 service sites across the United States.† In 2019, 63% of HRSA health center patients who reported race and ethnicity identified as members of racial ethnic minority populations (1). Historically underserved communities and populations served by health centers have a need for access to important information and resources for preventing exposure to SARS-CoV-2, the virus that causes COVID-19, to testing for those at risk, and to follow-up services for those with positive test results.§ During the COVID-19 public health emergency, health centers¶ have provided and continue to provide testing and follow-up care to medically underserved populations**; these centers are capable of reaching areas disproportionately affected by the pandemic.†† HRSA administers a weekly, voluntary Health Center COVID-19 Survey§§ to track health center COVID-19 testing capacity and the impact of COVID-19 on operations, patients, and personnel. Potential respondents can include up to 1,382 HRSA-funded health centers.¶¶ To assess health centers' capacity to reach racial and ethnic minority groups at increased risk for COVID-19 and to provide access to testing, CDC and HRSA analyzed survey data for the weeks June 5-October 2, 2020*** to describe all patients tested (3,194,838) and those who received positive SARS-CoV-2 test results (308,780) by race/ethnicity and state of residence. Among persons with known race/ethnicity who received testing (2,506,935), 36% were Hispanic/Latino (Hispanic), 38% were non-Hispanic White (White), and 20% were non-Hispanic Black (Black); among those with known race/ethnicity with positive test results, 56% were Hispanic, 24% were White, and 15% were Black. Improving health centers' ability to reach groups at increased risk for COVID-19 might reduce transmission by identifying cases and supporting contact tracing and isolation. Efforts to improve coordination of COVID-19 response-related activities between state and local public health departments and HRSA-funded health centers can increase access to testing and follow-up care for populations at increased risk for COVID-19.

MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
942COVID-19, Renin-Angiotensin System and Endothelial Dysfunction  

The newly emergent novel coronavirus disease 2019 (COVID-19) outbreak, which is caused by SARS-CoV-2 virus, has posed a serious threat to global public health and caused worldwide social and economic breakdown. Angiotensin-converting enzyme 2 (ACE2) is expressed in human vascular endothelium, respiratory epithelium, and other cell types, and is thought to be a primary mechanism of SARS-CoV-2 entry and infection. In physiological condition, ACE2 via its carboxypeptidase activity generates angiotensin fragments (Ang 1–9 and Ang 1–7), and plays an essential role in the renin-angiotensin system (RAS), which is a critical regulator of cardiovascular homeostasis. SARS-CoV-2 via its surface spike glycoprotein interacts with ACE2 and invades the host cells. Once inside the host cells, SARS-CoV-2 induces acute respiratory distress syndrome (ARDS), stimulates immune response (i.e., cytokine storm) and vascular damage. SARS-CoV-2 induced endothelial cell injury could exacerbate endothelial dysfunction, which is a hallmark of aging, hypertension, and obesity, leading to further complications. The pathophysiology of endothelial dysfunction and injury offers insights into COVID-19 associated mortality. Here we reviewed the molecular basis of SARS-CoV-2 infection, the roles of ACE2, RAS signaling, and a possible link between the pre-existing endothelial dysfunction and SARS-CoV-2 induced endothelial injury in COVID-19 associated mortality. We also surveyed the roles of cell adhesion molecules (CAMs), including CD209L/L-SIGN and CD209/DC-SIGN in SARS-CoV-2 infection and other related viruses. Understanding the molecular mechanisms of infection, the vascular damage caused by SARS-CoV-2 and pathways involved in the regulation of endothelial dysfunction could lead to new therapeutic strategies against COVID-19.

Cells2020       LitCov and CORD-19
943Evaluation of SARS-CoV-2 PCR Positive Cases in the Pediatric Emergency Department  

N/A

Mikrobiyol Bul2020       LitCov and CORD-19
944SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues  

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.

Cell2020       LitCov and CORD-19
945Hydroxychloroquine efficacy and safety in preventing SARS-CoV-2 infection and COVID-19 disease severity during pregnancy (COVID-Preg): a structured summary of a study protocol for a randomised placebo controlled trial  

OBJECTIVES: The primary objectives of the study are: 1. To assess the effect of hydroxychloroquine (HCQ) in reducing SARS-CoV-2 viral shedding by PCR in infected pregnant women with mild symptoms. 2. To assess the efficacy of HCQ to prevent SARS-CoV-2 infection in pregnant women in contact with an infected or suspected case. 3. To evaluate the effect of HCQ in preventing the development of the COVID-19 disease in asymptomatic SARS-CoV-2-infected pregnant women. The secondary objectives are: 1. To determine the effect of HCQ on the clinical course and duration of the COVID-19 disease in SARS-CoV-2-infected pregnant women. 2. To determine the impact of HCQ on the risk of hospitalization and mortality of SARS-CoV-2-infected pregnant women. 3. To assess the safety and tolerability of HCQ in pregnant women. 4. To describe the clinical presentation of SARS-CoV-2 infection during pregnancy. 5. To describe the effects of maternal SARS-CoV-2 infection on pregnancy and perinatal outcomes by treatment group. 6. To determine the risk of vertical transmission (intra-utero and intra-partum) of SARS-CoV-2. TRIAL DESIGN: Randomized double-blind placebo-controlled two-arm multicentre clinical trial to evaluate the safety and efficacy of HCQ to prevent and/or minimize SARS-CoV-2 infection during pregnancy. Participants will be randomized to receive a 14-day oral treatment course of HCQ or placebo, ratio 1:1. PARTICIPANTS: Study population: pregnant women undergoing routine prenatal follow up or attending emergency units at the participating hospitals who report either symptoms/signs suggestive of COVID-19 disease or close contact with a suspected or confirmed COVID-19 case. Inclusion criteria Women will be invited to participate in the trial and sign an informed consent if they meet the following inclusion criteria. • Presenting with fever (≥37.5°C) and/or one mild symptom suggestive of COVID-19 disease (cough, dyspnoea, chills, odynophagia, diarrhoea, muscle pain, anosmia, dysgeusia, headache) OR being contact* of a SARS-CoV-2 confirmed or suspected case in the past 14 days • More than 12 weeks of gestation (dated by ultrasonography) • Agreement to deliver in the study hospitals Exclusion criteria • Known hypersensitivity to HCQ or other 4-amonoquinoline compounds • History of retinopathy of any aetiology • Concomitant use of digoxin, cyclosporine, cimetidine • Known liver disease • Clinical history of cardiac pathology including known long QT syndrome • Unable to cooperate with the requirements of the study • Participating in other intervention studies • Delivery onset (characterized by painful uterine contractions and variable changes of the cervix, including some degree of effacement and slower progression of dilatation up to 5 cm for first and subsequent labours) The study participants will be stratified by clinical presentation and SARS-CoV-2 PCR results. Assignment of participants to study groups will be as follows: • SARS-CoV-2-PCR confirmed, infected pregnant women: a. symptomatic (n=100) b. asymptomatic (n=100) • SARS-CoV-2 PCR negative pregnant women in contact* with a SARS-CoV-2-infected confirmed or suspected case (n=514). *The ECDC definition of close contact will be followed. The trial will be conducted in five hospitals in Spain: Hospital Clínic of Barcelona, Hospital Sant Joan de Déu and Hospital de la Santa Creu i Sant Pau, in Barcelona, and HM Puerta del Sur and Hospital Universitario de Torrejón, in Madrid. INTERVENTION AND COMPARATOR: Participants will be randomized to HCQ (400 mg/day for three days, followed by 200 mg/day for 11 days) or placebo (2 tablets for three days, followed by one tablet for 11 days). MAIN OUTCOMES: The primary outcome is the number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start (one week after treatment is completed). RANDOMISATION: Allocation of participants to study arms will be done centrally by the trial’s Sponsor (the Barcelona Institute for Global Health, ISGlobal) by block randomization. This method will ensure balanced allocation to both arms. The electronic CRF will automatically assign a study number to each participant, depending on her study group and recruitment site. Each number will be related to a treatment number, which assigns them to one of the study arms. BLINDING (MASKING): Participants, caregivers, investigators and those assessing the outcomes will be blinded to group assignment. Study tablets (HCQ and placebo) will be identically packaged in small opaque bottles. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This study requires 200 SARS-CoV-2 infected and 514 contact pregnant women, randomised 1:1 with 100 and 227 respectively in each study arm. TRIAL STATUS: Protocol version 1.0, from May 8(th), 2020. Recruitment is ongoing (first patient recruited the 19(th) May 2020 and recruitment end anticipated by December 2020). TRIAL REGISTRATION: EudraCT number: 2020-001587-29, registered 2 April 2020. Clinicaltrials.gov identifier: NCT04410562, retrospectively registered 1 June 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
946An investigation of transmission control measures during the first 50 days of the COVID-19 epidemic in China  

Responding to an outbreak of a novel coronavirus (agent of COVID-19) in December 2019, China banned travel to and from Wuhan city on 23 January and implemented a national emergency response. We investigated the spread and control of COVID-19 using a unique data set including case reports, human movement and public health interventions. The Wuhan shutdown was associated with the delayed arrival of COVID-19 in other cities by 2.91 days (95%CI: 2.54-3.29). Cities that implemented control measures pre-emptively reported fewer cases, on average, in the first week of their outbreaks (13.0; 7.1-18.8) compared with cities that started control later (20.6; 14.5-26.8). Suspending intra-city public transport, closing entertainment venues and banning public gatherings were associated with reductions in case incidence. The national emergency response appears to have delayed the growth and limited the size of the COVID-19 epidemic in China, averting hundreds of thousands of cases by 19 February (day 50).

Science2020       LitCov and CORD-19
947Risk factors for severe illness in hospitalized Covid-19 patients at a regional hospital  

BACKGROUND: The Covid-19 pandemic threatens to overwhelm scarce clinical resources. Risk factors for severe illness must be identified to make efficient resource allocations. OBJECTIVE: To evaluate risk factors for severe illness. DESIGN: Retrospective, observational case series. SETTING: Single-institution. PARTICIPANTS: First 117 consecutive patients hospitalized for Covid-19 from March 1 to April 12, 2020. EXPOSURE: None. MAIN OUTCOMES AND MEASURES: Intensive care unit admission or death. RESULTS: In-hospital mortality was 24.8% and average total length of stay was 11.82 days (95% CI: 10.01 to 13.63 days). 30.8% of patients required intensive care unit admission and 29.1% required mechanical ventilation. Multivariate regression identified the amount of supplemental oxygen required at admission (OR: 1.208, 95% CI: 1.011–1.443, p = .037), sputum production (OR: 6.734, 95% CI: 1.630–27.812, p = .008), insulin dependent diabetes mellitus (OR: 11.873, 95% CI: 2.218–63.555, p = .004) and chronic kidney disease (OR: 4.793, 95% CI: 1.528–15.037, p = .007) as significant risk factors for intensive care unit admission or death. Of the 48 patients who were admitted to the intensive care unit or died, this occurred within 3 days of arrival in 42%, within 6 days in 71%, and within 9 days in 88% of patients. CONCLUSIONS: At our regional medical center, patients with Covid-19 had an average length of stay just under 12 days, required ICU care in 31% of cases, and had a 25% mortality rate. Patients with increased sputum production and higher supplemental oxygen requirements at admission, and insulin dependent diabetes or chronic kidney disease may be at increased risk for severe illness. A model for predicting intensive care unit admission or death with excellent discrimination was created that may aid in treatment decisions and resource allocation. Early identification of patients at increased risk for severe illness may lead to improved outcomes in patients hospitalized with Covid-19.

PLoS One2020       LitCov and CORD-19
948Staff SARS-CoV-2 Seroprevalence and Mental Health as Key Factors in University Response to COVID-19 Pandemic  

Background: In response to rapid global spread of the newly emerged coronavirus disease 2019 (COVID-19), universities transitioned to online learning and telework to decrease risks of inter-person contact. To help administrators respond to the COVID-19 pandemic and better understand its impacts, we surveyed SARS-CoV-2 seroprevalence among NOVA University employees and assessed community mental health. Methods: Data were collected from voluntary participants at six NOVA University locations, in the Lisbon metropolitan area, from June 15–30, 2020. All subjects provided written informed consent. Of 1,627 recruited participants (mean age 42.0 ± 12.3 years), 1,624 were tested. Prior to blood collection, participants completed a questionnaire that assessed: COVID-19 symptoms during the previous 14 days, chronic non-communicable diseases, chronic medication, anxiety, and depression symptoms. SARS-CoV-2 serology tests were then performed, and results communicated approximately 4 days after blood draw. Participants with positive serology tests were contacted to assess COVID-19 symptoms since February. Results: Estimated prevalence of SARS-CoV-2 IgG antibodies was 3.1% (n = 50), of which 43.5% reported symptoms in the previous 4 months. The Medical School had the highest seroprevalence (6.2%). Participants reported having at least one chronic disease (63.7%), depression-like symptoms (2.1%), and anxiety symptoms (8.1%). Rates of depression and anxiety symptoms were significantly higher in women, with sleep hours and occasional alcohol consumption negatively associated with depression. Male gender, older age, and sleep hours negatively associated with anxiety symptoms. School of employment and presence of comorbidities positively associated with anxiety. Conclusion: By measuring seroprevalence of SARS-CoV-2 antibodies among NOVA employees and assessing subjects' mental health, we aim to help administrators at European public universities in urban areas, such as Lisbon, Portugal, better understand the needs of their communities. This study resulted in implementation of a stricter contingency plan in the Medical School, while other schools continued to follow Government mitigation guidelines. These findings may also guide the development of tailored strategies to ensure physical and mental health of the academic community during this pandemic crisis. We conclude that, together with COVID-19 contingency plans, psychological support services and facilities to help people effectively face pandemic-associated challenges and minimise anxiety and depression should be implemented.

Front Public Health2021       LitCov and CORD-19
949Double-quencher probes improve detection sensitivity toward SARS-CoV-2 in a reverse-transcription polymerase chain reaction (RT-PCR) assay  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in the city of Wuhan, Hubei Province, China, has spread worldwide and is threatening human life. The detection of SARS-CoV-2 is critical for preventing new outbreaks, curbing disease spread, and managing patients. Currently, a reverse-transcription polymerase chain reaction (RT-PCR) assay is used to detect the virus in clinical laboratories. However, although this assay is considered to have high specificity, its sensitivity is reportedly as low as 60–70%. Improved sensitivity is, therefore, urgently required. METHODS: We used the primers and single-quencher probes recommended by the CDC (N1, N2 and N3) in the USA and the NIID (N1 and N2) in Japan. In addition, we designed double-quencher probes according to the virus sequence provided by the NIID to develop a further assay (termed the YCH assay [N1 and N2]). Using these assays, we conducted RT-PCR with serially diluted DNA positive controls to assess and compare the detection sensitivity of the three assays. Furthermore, 66 nasopharyngeal swabs were tested to determine the diagnostic performances. RESULTS: The threshold cycle (Ct) value of the RT-PCR was relatively low for the CDC and YCH assays compared with the NIID assay. Serial dilution assays showed that both the CDC and YCH assays could detect low copy numbers of the DNA positive control. The background fluorescence signal at the baseline was lower for the YCH assay compared with the NIID assay. We assessed the diagnostic performance between single- (NIID) and double-quencher (YCH) probes using 66 nasopharyngeal swabs. When the results of YCH-N2 assay were used as a reference, each assay detected SARS-CoV-2 with positive percent agreements of 56% for NIID-N1, 61% for YCH-N1, and 94% for NIID-N2, and 100% negative percent agreements for NIID-N1, YCH-N1 and NIID-N2. CONCLUSION: Double-quencher probes decreased the background fluorescence and improved the detection sensitivity of RT-PCR for SARS-CoV-2.

J Virol Methods2020       LitCov and CORD-19
950Prevalence of Sars-Cov-2 Infection in Health Workers (HWs) and Diagnostic Test Performance: The Experience of a Teaching Hospital in Central Italy  

(1) Background: Health workers (HWs) are at high risk of acquiring SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infections. Therefore, health authorities further recommend screening strategies for SARS-CoV-2 infection in exposed or high-risk HWs. Nevertheless, to date, the best/optimal method to screen HWs for SARS-CoV-2 infection is still under debate, and data on the prevalence of SARS-CoV-2 infection in HWs are still scarce. The present study aims to assess the SARS-CoV-2 infection rate amongst HWs in a teaching hospital in Central Italy and the diagnostic performance of SARS-CoV-2 serology (index test) in comparison with the SARS-CoV-2 RNA PCR assay (reference standard). (2) Methods: A cross-sectional study on the retrospective data of HWs tested for SARS-CoV-2 by RNA-RT-PCR on nasopharyngeal swabs and by an IgM/IgG serology assay on venous blood samples, irrespective of exposure and/or symptoms, was carried out. (3) Results: A total of 2057 HWs (median age 46, 19–69 years, females 60.2%) were assessed by the RNA RT-PCR assay and 58 (2.7%) tested positive for SARS-CoV-2 infection. Compared with negative HWs, SARS-CoV-2-positives were younger (mean age 41.7 versus 45.2, p < 0.01; 50% versus 31% under or equal to 40 years old, p < 0.002) and had a shorter duration of employment (64 versus 125 months, p = 0.02). Exposure to SARS-CoV-2 was more frequent in positive HWs than in negatives (55.2% versus 27.5%, p < 0.0001). In 44.8% of positive HWs, no exposure was traced. None of the positive HWs had a fatal outcome, none of them had acute respiratory distress syndrome, and only one required hospitalization for mild/moderate pneumonia. In 1084 (51.2%) HWs, nasopharyngeal swabs and an IgM/IgG serology assay were performed. With regard to IgM serology, sensitivity was 0% at a specificity of 98.99% (positive predictive value, PPV 0%, negative predictive value, NPV 99.2%). Concerning IgG serology and irrespective of the time interval between nasopharyngeal swab and serology, sensitivity was 50% at a specificity of 99.1% (PPV 28.6%, NPV 99.6%). IgG serology showed a higher diagnostic performance when performed at least two weeks after testing SARS-CoV-2-positive at the RNA RT-PCR assay by a nasopharyngeal swab. (4) Conclusions: Our experience in Central Italy demonstrated a low prevalence of SARS-CoV-2 infection amongst HWs, but higher than in the general population. Nearly half of the positive HWs reported no previous exposure to SARS-CoV-2-infected subjects and were diagnosed thanks to the proactive screening strategy implemented. IgG serology seems useful when performed at least two weeks after an RNA RT-PCR assay. IgM serology does not seem to be a useful test for the diagnosis of active SARS-CoV-2 infection. High awareness of SARS-CoV-2 infection is mandatory for all people, but especially for HWs, irrespective of symptoms, to safeguard their health and that of patients.

Int J Environ Res Public Healt2020       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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