\ 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
351Mental Health of Children and Adolescents Amidst COVID-19 and Past Pandemics: A Rapid Systematic Review  

Background: The COVID‑19 pandemic and associated public health measures have disrupted the lives of people around the world. It is already evident that the direct and indirect psychological and social effects of the COVID‑19 pandemic are insidious and affect the mental health of young children and adolescents now and will in the future. The aim and objectives of this knowledge-synthesis study were to identify the impact of the pandemic on children’s and adolescent’s mental health and to evaluate the effectiveness of different interventions employed during previous and the current pandemic to promote children’s and adolescents’ mental health. Methodology: We conducted the systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included experimental randomized and nonrandomized controlled trials, observational studies, and qualitative studies. Results: Of the 5828 articles that we retrieved, 18 articles met the inclusion criteria. We thematically analyzed them and put the major findings under the thematic areas of impact of the pandemic on children’s and adolescents’ mental health. These studies reported that pandemics cause stress, worry, helplessness, and social and risky behavioral problems among children and adolescents (e.g., substance abuse, suicide, relationship problems, academic issues, and absenteeism from work). Interventions such as art-based programs, support services, and clinician-led mental health and psychosocial services effectively decrease mental health issues among children and adolescents. Conclusion: Children and adolescents are more likely to experience high rates of depression and anxiety during and after a pandemic. It is critical that future researchers explore effective mental health strategies that are tailored to the needs of children and adolescents. Explorations of effective channels regarding the development and delivery of evidenced-based, age-appropriate services are vital to lessen the effects and improve long-term capacities for mental health services for children and adolescents. Key Practitioner Message: The COVID-19 pandemic’s physical restrictions and social distancing measures have affected each and every domain of life. Although the number of children and adolescents affected by the disease is small, the disease and the containment measures such as social distancing, school closure, and isolation have negatively impacted the mental health and well-being of children and adolescents. The impact of COVID-19 on the mental health of children and adolescents is of great concern. Anxiety, depression, disturbances in sleep and appetite, as well as impairment in social interactions are the most common presentations. It has been indicated that compared to adults, this pandemic may continue to have increased long term adverse consequences on children’s and adolescents’ mental health. As the pandemic continues, it is important to monitor the impact on children’s and adolescents’ mental health status and how to help them to improve their mental health outcomes in the time of the current or future pandemics.

Int J Environ Res Public Healt2021       LitCov and CORD-19
352Association Between Public Knowledge About COVID-19, Trust in Information Sources and Adherence to Social Distancing: Cross-Sectional Survey  

BACKGROUND: The success of behavioral interventions and policies designed to reduce the impact of the COVID-19 pandemic depends on how well individuals are informed about both the consequences of infection and the steps that should be taken to reduce the impact of the disease. OBJECTIVE: The aim of this study was to investigate associations between public knowledge about COVID-19, adherence to social distancing, and public trust in government information sources (eg, the US Centers for Disease Control and Prevention), private sources (eg, FOX and CNN), and social networks (eg, Facebook and Twitter) to inform future policies related to critical information distribution. METHODS: We conducted a cross-sectional survey (N=1243) between April 10 and 14, 2020. Data collection was stratified by US region and other demographics to ensure representativeness of the sample. RESULTS: Government information sources were the most trusted among the public. However, we observed trends in the data that suggested variations in trust by age and gender. White and older populations generally expressed higher trust in government sources, while non-White and younger populations expressed higher trust in private sources (eg, CNN) and social networks (eg, Twitter). Trust in government sources was positively associated with accurate knowledge about COVID-19 and adherence to social distancing. However, trust in private sources (eg, FOX and CNN) was negatively associated with knowledge about COVID-19. Similarly, trust in social networks (eg, Facebook and Twitter) was negatively associated with both knowledge and adherence to social distancing. CONCLUSIONS: During pandemics such as the COVID-19 outbreak, policy makers should carefully consider the quality of information disseminated through private sources and social networks. Furthermore, when disseminating urgent health information, a variety of information sources should be used to ensure that diverse populations have timely access to critical knowledge.

JMIR Public Health Surveill2020       LitCov and CORD-19
353Pediatric Mental and Behavioral Health in the Period of Quarantine and Social Distancing With COVID-19  

The coronavirus disease (COVID-19) pandemic has spread rapidly throughout the world and has had a long-term impact. The pandemic has caused great harm to society and caused serious psychological trauma to many people. Children are a vulnerable group in this global public health emergency, as their nervous systems, endocrine systems, and hypothalamic-pituitary-adrenal axes are not well developed. Psychological crises often cause children to produce feelings of abandonment, despair, incapacity, and exhaustion, and even raise the risk of suicide. Children with mental illnesses are especially vulnerable during the quarantine and social distancing period. The inclusion of psychosocial support for children and their families are part of the health responses to disaster and disaster recovery. Based on the biopsychosocial model, some children may have catastrophic thoughts and be prone to experience despair, numbness, flashbacks, and other serious emotional and behavioral reactions. In severe cases, there may be symptoms of psychosis or posttraumatic stress disorder. Timely and appropriate protections are needed to prevent the occurrence of psychological and behavioral problems. The emerging digital applications and health services such as telehealth, social media, mobile health, and remote interactive online education are able to bridge the social distance and support mental and behavioral health for children. Based on the psychological development characteristics of children, this study also illustrates interventions on the psychological impact from the COVID-19 pandemic. Even though the world has been struggling to curb the influences of the pandemic, the quarantine and social distancing policies will have long-term impacts on children. Innovative digital solutions and informatics tools are needed more than ever to mitigate the negative consequences on children. Health care delivery and services should envision and implement innovative paradigms to meet broad well-being needs and child health as the quarantine and social distancing over a longer term becomes a new reality. Future research on children's mental and behavioral health should pay more attention to novel solutions that incorporate cutting edge interactive technologies and digital approaches, leveraging considerable advances in pervasive and ubiquitous computing, human-computer interaction, and health informatics among many others. Digital approaches, health technologies, and informatics are supposed to be designed and implemented to support public health surveillance and critical responses to children’s growth and development. For instance, human-computer interactions, augmented reality, and virtual reality could be incorporated to remote psychological supporting service for children’s health; mobile technologies could be used to monitor children’s mental and behavioral health while protecting their individual privacy; big data and artificial intelligence could be used to support decision making on whether children should go out for physical activities and whether schools should be reopened. Implications to clinical practices, psychological therapeutic practices, and future research directions to address current effort gaps are highlighted in this study.

JMIR Pediatr Parent2020       LitCov and CORD-19
354Epidemiological characteristics of an outbreak of severe acute respiratory syndrome in Dongcheng District of Beijing from March to May 2003  

N/A

Biomed Environ Sci2003       CORD-19
355Maternal and infant outcomes of full-term pregnancy combined with COVID-2019 in Wuhan, China: retrospective case series  

OBJECTIVE: To investigate the maternal and infant outcomes of full-term pregnant patients in Wuhan, China, who were infected with 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is responsible for coronavirus disease 2019 (COVID-2019). DESIGN: Retrospective case series. SETTING: The Central Hospitals of Wuhan, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China. PARTICIPANTS: Twenty one full-term pregnant patients who were admitted to the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, confirmed SARS-CoV-2 infection and COVID-2019 with laboratorial and clinical methods, were reviewed by our medical team, and the data were collected from January 20, 2020 to February 29, 2020. MAIN CLINICAL DATA COLLECTION: Clinical data had been collecting using a standard case report form, such as epidemiological history, clinical manifestations, auxiliary examination of major laboratory and clinic, etc. All the information was collected and confirmed by our medical team. RESULTS: Twenty one full-term pregnant patients were reviewed (median age 29 years), and no patients were admitted to intensive care unit (ICU), and died during the treating progress. According to our review, all the cases were infected by human to human transmission, and the most common symptoms at onset of illness were cough in 17 (80.95%), fatigue in 10 (47.62%), fever in 7 (33.33%), expectoration in 1 (4.76%), and only one patient (4.76%) developed shortness of breath on admission. The median time from exposure to onset of illness was 10 days (interquartile range 7 –2 days), and from onset of symptoms to first hospital admission was 1 day (interquartile range 1–2 days). CONCLUSIONS: As of February 29, 2020, all the patients who were full-term pregnancy combined with COVID-2019 were cured and delivered successfully, and all the newborns were not infected with SARS-CoV-2, and there were no evidence of mother-to-child transmission.

Arch Gynecol Obstet2020       LitCov and CORD-19
356COVID-19 and the 5G Conspiracy Theory: Social Network Analysis of Twitter Data  

BACKGROUND: Since the beginning of December 2019, the coronavirus disease (COVID-19) has spread rapidly around the world, which has led to increased discussions across online platforms. These conversations have also included various conspiracies shared by social media users. Amongst them, a popular theory has linked 5G to the spread of COVID-19, leading to misinformation and the burning of 5G towers in the United Kingdom. The understanding of the drivers of fake news and quick policies oriented to isolate and rebate misinformation are keys to combating it. OBJECTIVE: The aim of this study is to develop an understanding of the drivers of the 5G COVID-19 conspiracy theory and strategies to deal with such misinformation. METHODS: This paper performs a social network analysis and content analysis of Twitter data from a 7-day period (Friday, March 27, 2020, to Saturday, April 4, 2020) in which the #5GCoronavirus hashtag was trending on Twitter in the United Kingdom. Influential users were analyzed through social network graph clusters. The size of the nodes were ranked by their betweenness centrality score, and the graph’s vertices were grouped by cluster using the Clauset-Newman-Moore algorithm. The topics and web sources used were also examined. RESULTS: Social network analysis identified that the two largest network structures consisted of an isolates group and a broadcast group. The analysis also revealed that there was a lack of an authority figure who was actively combating such misinformation. Content analysis revealed that, of 233 sample tweets, 34.8% (n=81) contained views that 5G and COVID-19 were linked, 32.2% (n=75) denounced the conspiracy theory, and 33.0% (n=77) were general tweets not expressing any personal views or opinions. Thus, 65.2% (n=152) of tweets derived from nonconspiracy theory supporters, which suggests that, although the topic attracted high volume, only a handful of users genuinely believed the conspiracy. This paper also shows that fake news websites were the most popular web source shared by users; although, YouTube videos were also shared. The study also identified an account whose sole aim was to spread the conspiracy theory on Twitter. CONCLUSIONS: The combination of quick and targeted interventions oriented to delegitimize the sources of fake information is key to reducing their impact. Those users voicing their views against the conspiracy theory, link baiting, or sharing humorous tweets inadvertently raised the profile of the topic, suggesting that policymakers should insist in the efforts of isolating opinions that are based on fake news. Many social media platforms provide users with the ability to report inappropriate content, which should be used. This study is the first to analyze the 5G conspiracy theory in the context of COVID-19 on Twitter offering practical guidance to health authorities in how, in the context of a pandemic, rumors may be combated in the future.

J Med Internet Res2020       LitCov and CORD-19
357A national cross-sectional survey of public perceptions of the COVID-19 pandemic: Self-reported beliefs, knowledge and behaviors  

INTRODUCTION: Efforts to mitigate the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing Corona Virus Disease-19 (COVID-19) have largely relied on broad compliance with public health recommendations yet navigating the high volume of evolving information can be challenging. We assessed self-reported public perceptions related to COVID-19 including, beliefs (e.g., severity, concerns, health), knowledge (e.g., transmission, information sources), and behaviors (e.g., physical distancing) to understand perspectives in Canada and to inform future public health initiatives. METHODS: We administered a national online survey aiming to obtain responses from 2000 adults in Canada. Respondent sampling was stratified by age, sex, and region. We used descriptive statistics to summarize responses and tested for regional differences using chi-squared tests, followed by weighted logistic regression. RESULTS: We collected 1,996 eligible questionnaires between April 26(th) and May 1(st), 2020. One-fifth (20%) of respondents knew someone diagnosed with COVID-19, but few had tested positive themselves (0.6%). Negative impacts of pandemic conditions were evidenced in several areas, including concerns about healthcare (e.g. sufficient equipment, 52%), pandemic stress (45%), and worsening social (49%) and mental/emotional (39%) health. Most respondents (88%) felt they had good to excellent knowledge of virus transmission, and predominantly accessed (74%) and trusted (60%) Canadian news television, newspapers/magazines, or non-government news websites for COVID-19 information. We found high compliance with distancing measures (80% reported self-isolating or always physical distancing). We identified associations between region and self-reported beliefs, knowledge, and behaviors related to COVID-19. DISCUSSION: We found that information about COVID-19 is largely acquired through domestic news sources, which may explain high self-reported compliance with prevention measures. The results highlight the broader impact of a pandemic on the general public’s overall health and wellbeing, outside of personal infection. The study findings should be used to inform public health communications during COVID-19 and future pandemics.

PLoS One2020       LitCov and CORD-19
358Pre-exposure prophylaxis with hydroxychloroquine for high-risk healthcare workers during the COVID-19 pandemic: A structured summary of a study protocol for a multicentre, double-blind randomized controlled trial  

OBJECTIVES: The aim of this study is to assess the efficacy of the use of pre-exposure prophylaxis (PrEP) with hydroxychloroquine against placebo in healthcare workers with high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in reducing their risk of coronavirus disease 2019 (COVID-19) disease during an epidemic period. As secondary objectives, we would like to: i) assess the efficacy of the use of PrEP with hydroxychloroquine against placebo in healthcare workers with high risk of SARS-CoV-2 infection in reducing their risk of exposure to SARS-CoV-2 (defined by seroconversion) during an epidemic period, ii) evaluate the safety of PrEP with hydroxychloroquine in adults, iii) describe the incidence of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 infection, iv) identify clinical, analytical and microbiological predictors of COVID-19 among healthcare workers at high risk of SARS-CoV-2 infection, v) set up a repository of serum samples obtained from healthcare workers at high risk of SARS-CoV-2 infection for future research on blood markers to predict SARS-CoV-2 infection. TRIAL DESIGN: Multicentre double-blind parallel design (ratio 1:1) randomized controlled clinical trial. PARTICIPANTS: Approximately 440 healthcare workers of four Spanish hospitals (Hospital Clínic of Barcelona, Hospital de la Santa Creu i Sant Pau of Barcelona, Hospital Plató of Barcelona, Hospital General de Granollers, Barcelona) will be recruited. Participants are considered to be at high-risk of SARS-CoV-2 infection due to their frequent contact with suspected and confirmed cases of COVID-19. For eligibility, healthcare workers with 18 years old or older working at least 3 days a week in a hospital with both negative SARS-CoV-2 polymerase chain reaction (PCR) assays and serological COVID-19 rapid diagnostic tests (RDT) are invited to participate. Participants with any of the following conditions are excluded: pregnancy, breastfeeding, ongoing antiviral, antiretroviral or corticosteroids treatment, chloroquine or hydroxychloroquine uptake the last month or any contraindication to hydroxychloroquine treatment. INTERVENTION AND COMPARATOR: Intervention group (PrEP): participants will receive the standard of care and will take 400mg of hydroxychloroquine (2 tablets of 200 mg per Dolquine® tablet) daily the first four consecutive days, followed by 400 mg weekly for a period of 6 months. Control group: participants will receive placebo tablets with identical physical appearance to hydroxychloroquine 200 mg (Dolquine®) tablets following the same treatment schedule of the intervention group. Both groups will be encouraged to use the personal protection equipment (PPE) for COVID-19 prevention according to current hospital guidelines. MAIN OUTCOMES: The primary endpoint will be the number of confirmed cases of a COVID-19 (defined by a positive PCR for SARS-CoV-2 or symptoms compatible with COVID-19 with seroconversion) in the PrEP group compared to the placebo group at any time during the 6 months of the follow-up in healthcare workers with negative SARS-CoV-2 PCR and serology at day 0. As secondary endpoints, we will obtain: i) the SARS-CoV-2 seroconversion in the PrEP group compared to placebo during the 6 months of follow-up in healthcare workers with negative serology at day 0; ii) the occurrence of any adverse event related with hydroxychloroquine treatment; iii) the incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers in the non-PrEP group, among the total of healthcare workers included in the non-PrEP group during the study period; iv) the risk ratio for the different clinical, analytical and microbiological conditions to develop COVID-19; v) a repository of serum samples obtained from healthcare workers confirmed COVID-19 cases for future research on blood markers to predict SARS-CoV-2 infection. RANDOMISATION: Participants meeting all eligibility requirements will be allocated to one of the two study arms (PrEP with hydroxychloroquine or non-PrEP control group) in a 1:1 ratio using simple randomisation with computer generated random numbers. BLINDING (MASKING): Participants, doctors and nurses caring for participants, and investigators assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Each intervention group will have 220 participants, giving a total of 440 participants. TRIAL STATUS: The current protocol version is 1.5, 2(nd) of June 2020. Two hundred and seventy-fiveparticipants were recruited and completed first month follow-up until date. The estimated sample size could not be reached yet due to the declining national epidemic curve. Thus, 275 is the total number of participants included until date. The study has been suspended (26(th) of June) until new epidemic curve occurs. TRIAL REGISTRATION: This trial was registered on April 2(nd) 2020 at clinicaltrials.gov with the number NCT04331834. 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
359Testing the efficacy and safety of BIO101, for the prevention of respiratory deterioration, in patients with COVID-19 pneumonia (COVA study): a structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: As of December, 1(st), 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, resulted in more than 1 472 917 deaths worldwide and death toll is still increasing exponentially. Many COVID-19 infected people are asymptomatic or experience moderate symptoms and recover without medical intervention. However, older people and those with comorbid hypertension, diabetes, obesity, or heart disease are at higher risk of mortality. Because current therapeutic options for COVID-19 patients are limited specifically for this elderly population at risk, Biophytis is developing BIO101 (20-hydroxyecdysone, a Mas receptor activator) as a new treatment option for managing patients with SARS-CoV-2 infection at the severe stage. The angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2. Interaction between ACE2 and SARS-CoV2 spike protein seems to alter the function of ACE2, a key player in the renin-angiotensin system (RAS). The clinical picture of COVID-19 includes acute respiratory distress syndrome (ARDS), cardiomyopathy, multiorgan dysfunction and shock, all of which might result from an imbalance of the RAS. We propose that RAS balance could be restored in COVID-19 patients through MasR activation downstream of ACE2 activity, with 20-hydroxyecdysone (BIO101) a non-peptidic Mas receptor (MasR) activator. Indeed, MasR activation by 20-hydroxyecdysone harbours anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. BIO101, a 97% pharmaceutical grade 20-hydroxyecdysone could then offer a new therapeutic option by improving the respiratory function and ultimately promoting survival in COVID-19 patients that develop severe forms of this devastating disease. Therefore, the objective of this COVA study is to evaluate the safety and efficacy of BIO101, whose active principle is 20-hydroxyecdysone, in COVID-19 patients with severe pneumonia. TRIAL DESIGN: Randomized, double-blind, placebo-controlled, multi-centre, group sequential and adaptive which will be conducted in 2 parts. Part 1: Ascertain the safety and tolerability of BIO101 and obtain preliminary indication of the activity of BIO101, in preventing respiratory deterioration in the target population Part 2: Re-assessment of the sample size needed for the confirmatory part 2 and confirmation of the effect of BIO101 observed in part 1 in the target population. The study is designed as group sequential to allow an efficient run-through, from obtaining an early indication of activity to a final confirmation. And adaptive – to allow accumulation of early data and adapt sample size in part 2 in order to inform the final design of the confirmatory part of the trial. PARTICIPANTS: : 1. Age: 45 and above. 2. A confirmed diagnosis of COVID-19 infection, within the last 14 days, prior to randomization, as determined by PCR or other approved commercial or public health assay, in a specimen as specified by the test used. 3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration ≥3 days. 4. a. Clinical findings on a physical examination. b. Respiratory symptoms developed within the past 7 days. 5. a. Tachypnea: ≥25 breaths per minute. b. Arterial oxygen saturation ≤92%. c. A special note should be made if there is suspicion of COVID-19-related myocarditis or pericarditis, as the presence of these is a stratification criterion. 6. a. ALT and AST ≤ 5x upper limit of normal (ULN). b. Gamma-glutamyl transferase (GGT) ≤ 5x ULN. c. Total bilirubin ≤ 5×ULN. 7. Willing to participate and able to sign an informed consent form (ICF). Or, when relevant, a legally authorized representative (LAR) might sign the ICF on behalf of the study participant. 8. : a. Have a negative urine pregnancy test at screening. b. Be willing to use a contraceptive method as outlined in inclusion criterion 9 from screening to 30 days after last dose. 9. Male participants who are sexually active with a female partner must agree to the use of an effective method of birth control throughout the study and until 3 months after the last administration of the investigational product. (Note: medically acceptable methods of contraception that may be used by the participant and/or partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, each supplemented with a condom, as well as sterilization and vasectomy). 10. Female participants who are lactating must agree not to breastfeed during the study and up to 14 days after the intervention. 11. Male participants must agree not to donate sperm for the purpose of reproduction throughout the study and until 3 months after the last administration of the investigational product. 12. For France only: Being affiliated with a European Social Security. : 1. Not needing or not willing to remain in a healthcare facility during the study. 2. Moribund condition (death likely in days) or not expected to survive for >7 days – due to other and non-COVID-19 related conditions. 3. Participant on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO), or high-flow Oxygen (delivery of oxygen at a flow of ≥16 L/min.). 4. Participant is not able to take medications by mouth (as capsules or as a powder, mixed in water). 5. Disallowed concomitant medication: Consumption of any herbal products containing 20-hydroxyecdysone and derived from Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g. performance enhancing agents). 6. Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101. 7. Renal disease requiring dialysis, or known renal insufficiency (eGFR≤30 mL/min/1.73 m2, based on Cockcroft & Gault formula). 8. a. Non-affiliation to compulsory French social security scheme (beneficiary or right-holder). b. Being under tutelage or legal guardianship. Participants will be recruited from approximately 30 clinical centres in Belgium, France, the UK, USA and Brazil. Maximum patients’ participation in the study will last 28 days. Follow-up of participants discharged from hospital will be performed through post-intervention phone calls at 14 (± 2) and 60 (± 4) days. INTERVENTION AND COMPARATOR: Two treatment arms will be tested in this study: interventional arm 350 mg b.i.d. of BIO101 (AP 20-hydroxyecdysone) and placebo comparator arm 350 mg b.i.d of placebo. Administration of daily dose is the same throughout the whole treatment period. Participants will receive the study medication while hospitalized for up to 28 days or until a clinical endpoint is reached (i.e., ‘negative’ or ‘positive’ event). Participants who are officially discharged from hospital care will no longer receive study medication. MAIN OUTCOMES: Primary study endpoint: The proportion of participants with ‘negative’ events up to 28 days. Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage). Requiring extracorporeal membrane oxygenation (ECMO). Requiring high-flow oxygen defined as delivery of oxygen at a flow of ≥16 L/min. Only if the primary endpoint is significant at the primary final analysis the following Proportion of participants with events of respiratory failure at Day 28. Proportion of participants with ‘positive’ events at Day 28. Proportion of participants with events of all-cause mortality at Day 28. A ‘positive’ event is defined as the official discharge from hospital care by the department due to improvement in participant condition. Secondary and exploratory endpoints: In addition, a variety of functional measures and biomarkers (including the SpO2 / FiO2 ratio, viral load and markers related to inflammation, muscles, tissue and the RAS / MAS pathways) will also be collected. RANDOMIZATION: In part 1, randomization will be stratified by RAS pathway modulator use (yes/no) and co-morbidities (none vs. 1 and above). In Part 2, randomization will be stratified by centre, gender, RAS pathway modulator use (yes/no), co-morbidities (none vs. 1 and above), receiving Continuous Positive Airway Pressure/Bi-level Positive Airway Pressure (CPAP/BiPAP) at study entry (Yes/No) and suspicion of COVID-19 related myocarditis or pericarditis (present or not). BLINDING (MASKING): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. All therapeutic units (TU), BIO101 b.i.d. or placebo b.i.d., cannot be distinguished in compliance with the double-blind process. An independent data-monitoring committee (DMC) will conduct 2 interim analyses. A first one based on the data from part 1 and a second from the data from parts 1 and 2. The first will inform about BIO101 safety, to allow the start of recruitment into part 2 followed by an analysis of the efficacy data, to obtain an indication of activity. The second interim analysis will inform about the sample size that will be required for part 2, in order to achieve adequate statistical power. Numbers to be randomised (sample size) : Part 1: 50 (to obtain the proof of concept in COVID-19 patients). Part 2: 310, potentially increased by 50% (up to 465, based on interim analysis 2) (to confirm the effects of BIO101 observed in part 1). TRIAL STATUS: The current protocol Version is V 10.0, dated on 24.09.2020. The recruitment that started on September 1(st) 2020 is ongoing and is anticipated to finish for the whole study by March2021. TRIAL REGISTRATION: The trial was registered before trial start in trial registries: EudraCT, No. 2020-001498-63, registered May 18, 2020; and Clinicaltrials.gov, identifier NCT04472728, registered July 15, 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-020-04998-5.

Trials2021       LitCov and CORD-19
360Prone positioning in severe acute respiratory distress syndrome  

N/A

N Engl J Med2013       CORD-19
361Social and environmental risk factors in the emergence of infectious diseases  

Fifty years ago, the age-old scourge of infectious disease was receding in the developed world in response to improved public health measures, while the advent of antibiotics, better vaccines, insecticides and improved surveillance held the promise of eradicating residual problems. By the late twentieth century, however, an increase in the emergence and re-emergence of infectious diseases was evident in many parts of the world. This upturn looms as the fourth major transition in human–microbe relationships since the advent of agriculture around 10,000 years ago. About 30 new diseases have been identified, including Legionnaires' disease, human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), hepatitis C, bovine spongiform encephalopathy (BSE)/variant Creutzfeldt-Jakob disease (vCJD), Nipah virus, several viral hemorrhagic fevers and, most recently, severe acute respiratory syndrome (SARS) and avian influenza. The emergence of these diseases, and resurgence of old ones like tuberculosis and cholera, reflects various changes in human ecology: rural-to-urban migration resulting in high-density peri-urban slums; increasing long-distance mobility and trade; the social disruption of war and conflict; changes in personal behavior; and, increasingly, human-induced global changes, including widespread forest clearance and climate change. Political ignorance, denial and obduracy (as with HIV/AIDS) further compound the risks. The use and misuse of medical technology also pose risks, such as drug-resistant microbes and contaminated equipment or biological medicines. A better understanding of the evolving social dynamics of emerging infectious diseases ought to help us to anticipate and hopefully ameliorate current and future risks.

Nat Med2004       CORD-19
362Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission  

Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.

Elife2020       LitCov and CORD-19
363Barriers and facilitators to online medical and nursing education during the COVID-19 pandemic: perspectives from international students from low- and middle-income countries and their teaching staff  

BACKGROUND: The COVID-19 pandemic posed a huge challenge to the education systems worldwide, forcing many countries to provisionally close educational institutions and deliver courses fully online. The aim of this study was to explore the quality of the online education in China for international medical and nursing students from low- and middle-income countries (LMICs) as well as the factors that influenced their satisfaction with online education during the COVID-19 pandemic. METHODS: Questionnaires were developed and administered to 316 international medical and nursing students and 120 teachers at a university in China. The Chi-square test was used to detect the influence of participants’ personal characteristics on their satisfaction with online education. The Kruskal–Wallis rank-sum test was employed to identify the negative and positive factors influencing the online education satisfaction. A binary logistic regression model was performed for multiple-factor analysis to determine the association of the different categories of influential factors—crisis-, learner-, instructor-, and course-related categories, with the online education satisfaction. RESULTS: Overall, 230 students (response rate 72.8%) and 95 teachers (response rate 79.2%) completed the survey. It was found that 36.5% of students and 61.1% of teachers were satisfied with the online education. Teachers’ professional title, students’ year of study, continent of origin and location of current residence significantly influenced the online education satisfaction. The most influential barrier for students was the severity of the COVID-19 situation and for teachers it was the sense of distance. The most influential facilitating factor for students was a well-accomplished course assignment and for teachers it was the successful administration of the online courses. CONCLUSIONS: Several key factors have been identified that affected the attitudes of international health science students from LMICs and their teachers towards online education in China during the COVID-19 pandemic. To improve the online education outcome, medical schools are advised to promote the facilitating factors and cope with the barriers, by providing support for students and teaching faculties to deal with the anxiety caused by the pandemic, caring for the state of mind of in-China students away from home, maintaining the engagement of out-China students studying from afar and enhancing collaborations with overseas institutions to create practice opportunities at students’ local places.

Hum Resour Health2021       LitCov and CORD-19
364Preparedness and Responses Faced during the COVID-19 Pandemic in Belgium: An Observational Study and Using the National Open Data  

This study aimed to descript the Belgian COVID-19 responses process according to the WHO’s (World Health Organization) Health Emergency and Disaster Risk Management Framework (Health EDRM Framework) and to present the measures taken and epidemic impact in the different phases of COVID-19 in Belgium. The WHO’s EDRM Framework was used for reviewing the Belgian Public health emergency preparedness and responses in the context of COVID-19. Information on the measures taken was collected through the literature review including all government’s communication, reports, and scientific papers. All epidemic data were extracted from a national open database managed and published by the Sciensano. Additionally, two authors closely followed the Belgian situation since the beginning of the pandemic and updated the data every day. During the COVID-19 pandemic, the anti-epidemic strategy was mainly to avoid medical resources exceeding the upper limit. Belgium issued a series of emergency decrees to limit the spread of the virus. An existing structure of “federal-region-municipal” as the framework of public health emergency preparedness and response was adapted. The emergency response process in Belgium was divided into four phases: information-evaluation-coordination-decision-making at the region level and the final decision-making at the federal level. Belgium also implemented a phased plan in the process of setting up and lifting the lockdown. However, it was vulnerable in early response, due to the shortage of medical equipment supplies in general, and more particularly for the long term care facilities (LTCFs). Belgium has achieved an intensive cooperation between stakeholders based on an existing multisectoral emergency organization framework. Legislation, medical insurance, and good communication also played a role in limiting the spread of viruses. However, the authorities underestimated the risk of an epidemic and did not take quarantine measures among people suspected affected by SARS-COV-2 in the early stages, resulting in insufficient medical equipment supply and a large number of deaths in the LTCF. The implementation of the lockdown measure in Belgium also encountered obstacles. The lockdown and its exit strategy were both closely related to the pandemic situation and social and economic life. The authorities should strengthen information management, improve the public awareness of the measures, and find out the balance points between the social and economic life and infection control measures.

Int J Environ Res Public Healt2020       LitCov and CORD-19
365pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN  

N/A

J Virol2004       CORD-19
366Prevalence and Predictors of Anxiety and Depression Symptoms during the COVID-19 Pandemic and Compliance with Precautionary Measures: Age and Sex Matter  

Effective management of the global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (also known as COVID-19), resulted in the implementation of severe restrictions in movement and enforcement of social distancing measures. This study aimed to understand and characterize the psychosocial effects of the COVID-19 pandemic in the general population and to identify risks and protective factors that predict changes in mental health status. In addition, the study investigated compliance with precautionary measures (PM) to halt the spread of the virus. The online anonymous survey collected information on sociodemographic data, compliance with PM, quality of life (QOL), and mental health via the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). A total of 1642 adult participants (71.6% women, 28.4% men) completed the survey in the European island country, Cyprus. A large percentage (48%) reported significant financial concerns and 66.7% significant changes in their QOL. About 41% reported symptoms associated with mild anxiety; 23.1% reported moderate-severe anxiety symptoms. Concerning depression, 48% reported mild and 9.2% moderate-severe depression symptoms. Women, younger age (18–29), student status, unemployment status, prior psychiatric history, and those reporting greater negative impact on their QOL, were at higher risk for increased anxiety and depression symptoms (p < 0.05). The youngest age group and males also reported lower levels of compliance with PM. Higher compliance with PM predicted lower depression scores (p < 0.001) but higher anxiety for measures related to personal hygiene. The results of this study provide important data on the effects of the COVID-19 outbreak on mental health and QOL and identify a variety of personal and social determinants that serve as risks and protective factors. Furthermore, it has implications for policy makers demonstrating the need for effective mental health programs and guidance for the implementation of PM as a public health strategy.

Int J Environ Res Public Healt2020       LitCov and CORD-19
367Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis  

Abstract Background An outbreak of Novel Coronavirus (COVID -19) in Wuhan, China, the epidemic is more widespread than initially estimated, with cases now confirmed in multiple countries. Aims The aim of the meta-analysis was to assess the prevalence of comorbidities in the COVID-19 infection patients and the risk of underlying diseases in severe patients compared to non-severe patients. Methods A literature search was conducted using the databases PubMed, EMBASE, and Web of sciences until February 25, 2020. Risk ratio (OR) and 95% confidence intervals (CIs) were pooled using random-effects models. Results Eight studies were included in the meta- analysis, including 46248 infected patients. The result showed the most prevalent clinical symptom was fever ( 91 ± 3, 95% CI 86-97% ), followed by cough (67 ± 7, 95% CI 59-76%), fatigue ( 51 ± 0, 95% CI 34-68% ) and dyspnea ( 30 ± 4, 95% CI 21-40%). The most prevalent comorbidity were hypertension (17 ± 7, 95% CI 14-22%) and diabetes ( 8 ± 6, 95% CI 6-11% ), followed by cardiovascular diseases ( 5 ± 4, 95% CI 4-7% ) and respiratory system disease( 2 ± 0, 95% CI 1-3% ). Compared with the Non-severe patient, the pooled odds ratio of hypertension, respiratory system disease, cardiovascular disease in severe patients were (OR 2.36, 95% CI: 1.46-3.83), (OR 2.46, 95% CI: 1.76-3.44) and (OR 3.42, 95% CI: 1.88-6.22)respectively. Conclusion We assessed the prevalence of comorbidities in the COVID-19 infection patients and found underlying disease, including hypertension, respiratory system disease and cardiovascular, may be a risk factor for severe patients compared with Non-severe patients.

Int J Infect Dis2020       LitCov and CORD-19
368Microbial agents associated with waterborne diseases  

N/A

Crit Rev Microbiol2002       CORD-19
369Patient Satisfaction With Telemedicine During the COVID-19 Pandemic: Retrospective Cohort Study  

BACKGROUND: New York City was the international epicenter of the COVID-19 pandemic. Health care providers responded by rapidly transitioning from in-person to video consultations. Telemedicine (ie, video visits) is a potentially disruptive innovation; however, little is known about patient satisfaction with this emerging alternative to the traditional clinical encounter. OBJECTIVE: This study aimed to determine if patient satisfaction differs between video and in-person visits. METHODS: In this retrospective observational cohort study, we analyzed 38,609 Press Ganey patient satisfaction survey outcomes from clinic encounters (620 video visits vs 37,989 in-person visits) at a single-institution, urban, quaternary academic medical center in New York City for patients aged 18 years, from April 1, 2019, to March 31, 2020. Time was categorized as pre–COVID-19 and COVID-19 (before vs after March 4, 2020). Wilcoxon-Mann-Whitney tests and multivariable linear regression were used for hypothesis testing and statistical modeling, respectively. RESULTS: We experienced an 8729% increase in video visit utilization during the COVID-19 pandemic compared to the same period last year. Video visit Press Ganey scores were significantly higher than in-person visits (94.9% vs 92.5%; P<.001). In adjusted analyses, video visits (parameter estimate [PE] 2.18; 95% CI 1.20-3.16) and the COVID-19 period (PE 0.55; 95% CI 0.04-1.06) were associated with higher patient satisfaction. Younger age (PE –2.05; 95% CI –2.66 to –1.22), female gender (PE –0.73; 95% CI –0.96 to –0.50), and new visit type (PE –0.75; 95% CI –1.00 to –0.49) were associated with lower patient satisfaction. CONCLUSIONS: Patient satisfaction with video visits is high and is not a barrier toward a paradigm shift away from traditional in-person clinic visits. Future research comparing other clinic visit quality indicators is needed to guide and implement the widespread adoption of telemedicine.

J Med Internet Res2020       LitCov and CORD-19
370Characterization of an efficient coronavirus ribosomal frameshifting signal: Requirement for an RNA pseudoknot  

Abstract The genomic RNA of the coronavirus IBV contains an efficient ribosomal frameshifting signal at the junction of two overlapping open reading frames. We have defined by deletion analysis an 86 nucleotide sequence encompassing the overlap region which is sufficient to allow frameshifting in a heterologous context. The upstream boundary of the signal consists of the sequence UUUAAAC, which is the likely site of ribosomal slippage. We show by creation of complementary nucleotide changes that the RNA downstream of this “slippery” sequence folds into a tertiary structure termed a pseudoknot, the formation of which is essential for efficient frameshifting.

Cell1989       CORD-19
371Fatal outcome of human influenza A H5N1 is associated with high viral load and hypercytokinemia  

Avian influenza A (H5N1) viruses cause severe disease in humans(1,2), but the basis for their virulence remains unclear. In vitro and animal studies indicate that high and disseminated viral replication is important for disease pathogenesis(3,4,5). Laboratory experiments suggest that virus-induced cytokine dysregulation may contribute to disease severity(6,7,8,9). To assess the relevance of these findings for human disease, we performed virological and immunological studies in 18 individuals with H5N1 and 8 individuals infected with human influenza virus subtypes. Influenza H5N1 infection in humans is characterized by high pharyngeal virus loads and frequent detection of viral RNA in rectum and blood. Viral RNA in blood was present only in fatal H5N1 cases and was associated with higher pharyngeal viral loads. We observed low peripheral blood T-lymphocyte counts and high chemokine and cytokine levels in H5N1-infected individuals, particularly in those who died, and these correlated with pharyngeal viral loads. Genetic characterization of H5N1 viruses revealed mutations in the viral polymerase complex associated with mammalian adaptation and virulence. Our observations indicate that high viral load, and the resulting intense inflammatory responses, are central to influenza H5N1 pathogenesis. The focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1477) contains supplementary material, which is available to authorized users.

Nat Med2006       CORD-19
372Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant-National Healthcare Safety Network, March 1-August 1, 2021  

Nursing home and long-term care facility residents live in congregate settings and are often elderly and frail, putting them at high risk for infection with SARS-CoV-2, the virus that causes COVID-19, and severe COVID-19-associated outcomes; therefore, this population was prioritized for early vaccination in the United States (1). Following rapid distribution and administration of the mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) under an Emergency Use Authorization by the Food and Drug Administration (2), observational studies among nursing home residents demonstrated vaccine effectiveness (VE) ranging from 53% to 92% against SARS-CoV-2 infection (3-6). However, concerns about the potential for waning vaccine-induced immunity and the recent emergence of the highly transmissible SARS-CoV-2 B.1.617.2 (Delta) variant† highlight the need to continue to monitor VE (7). Weekly data reported by the Centers for Medicaid & Medicare (CMS)-certified skilled nursing facilities or nursing homes to CDC's National Healthcare Safety Network (NHSN)§ were analyzed to evaluate effectiveness of full vaccination (2 doses received ≥14 days earlier) with any of the two currently authorized mRNA COVID-19 vaccines during the period soon after vaccine introduction and before the Delta variant was circulating (pre-Delta [March 1-May 9, 2021]), and when the Delta variant predominated¶ (Delta [June 21-August 1, 2021]). Using 17,407 weekly reports from 3,862 facilities from the pre-Delta period, adjusted effectiveness against infection for any mRNA vaccine was 74.7% (95% confidence interval [CI] = 70.0%-78.8%). Analysis using 33,160 weekly reports from 11,581 facilities during an intermediate period (May 10-June 20) found that the adjusted effectiveness was 67.5% (95% CI = 60.1%-73.5%). Analysis using 85,593 weekly reports from 14,917 facilities during the Delta period found that the adjusted effectiveness was 53.1% (95% CI = 49.1%-56.7%). Effectiveness estimates were similar for Pfizer-BioNTech and Moderna vaccines. These findings indicate that mRNA vaccines provide protection against SARS-CoV-2 infection among nursing home residents; however, VE was lower after the Delta variant became the predominant circulating strain in the United States. This analysis assessed VE against any infection, without being able to distinguish between asymptomatic and symptomatic presentations. Additional evaluations are needed to understand protection against severe disease in nursing home residents over time. Because nursing home residents might remain at some risk for SARS-CoV-2 infection despite vaccination, multiple COVID-19 prevention strategies, including infection control, testing, and vaccination of nursing home staff members, residents, and visitors, are critical. An additional dose of COVID-19 vaccine might be considered for nursing home and long-term care facility residents to optimize a protective immune response.

MMWR Morb Mortal Wkly Rep2021       LitCov and CORD-19
373Putative roles of vitamin D in modulating immune response and immunopathology associated with COVID-19  

The first incidence of COVID-19 was reported in the Wuhan city of Hubei province in China in late December 2019. Because of failure in timely closing of borders of the affected region, COVID-19 spread across like a wildfire through air travel initiating a pandemic. It is a serious lower respiratory track viral infection caused by highly contagious, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Coronavirus including COVID-19 causing SARS-CoV-2 causes zoonotic diseases and thought to be originated from bats. Since its first incidence, the virus has spread all across the world, causing serious human casualties, economic losses, and disrupting global supply chains. As with SARS-CoV, COVID-19 causing SARS-CoV-2 follows a similar path of airborne infection, but is less lethal and more infectious than SARS and MERS. This review focusses on the pathogenesis of SARS-CoV-2, especially on the dysfunctional immune responses following a cytokine storm in severely affected persons. The mode of entry of SARS-CoV-2 is via the angiotensin converting enzyme 2 (ACE-2) receptors present on the epithelial lining of lungs, gastrointestinal tract, and mucus membranes. Older persons with weaker immune system and associated co-morbidities are more vulnerable to have dysfunctional immune responses, as most of them concomitantly have severe hypovitaminosis D. Consequently, causing severe damage to key organs of the body including lungs and the cardiovascular system. Since, vast majority of persons enters to the intensive care units and died, had severe vitamin D deficiency, thus, this area must be investigated seriously. In addition, this article assesses the role of vitamin D in reducing the risk of COVID-19. Vitamin D is a key regulator of the renin-angiotensin system that is exploited by SARS-CoV-2 for entry into the host cells. Further, vitamin D modulates multiple mechanisms of the immune system to contain the virus that includes dampening the entry and replication of SARS-CoV-2, reduces concentration of pro-inflammatory cytokines and increases levels of anti-inflammatory cytokines, enhances the production of natural antimicrobial peptide and activates defensive cells such as macrophages that could destroy SARS-CoV-2. Thus, this article provides the urgency of needed evidences through large population based randomized controlled trials and ecological studies to evaluate the potential role of vitamin D in COVID-19.

Virus Res2020       LitCov and CORD-19
374Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors  

N/A

Nature2020       LitCov and CORD-19
375Factors associated with hospital admission and critical illness among 5279 people with COVID-19 in New York City: prospective cohort study  

OBJECTIVE: To describe outcomes of people admitted to hospital with coronavirus disease 2019 (covid-19) in the United States, and the clinical and laboratory characteristics associated with severity of illness. DESIGN: Prospective cohort study. SETTING: Single academic medical center in New York City and Long Island. PARTICIPANTS: 5279 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection between 1 March 2020 and 8 April 2020. The final date of follow up was 5 May 2020. MAIN OUTCOME MEASURES: Outcomes were admission to hospital, critical illness (intensive care, mechanical ventilation, discharge to hospice care, or death), and discharge to hospice care or death. Predictors included patient characteristics, medical history, vital signs, and laboratory results. Multivariable logistic regression was conducted to identify risk factors for adverse outcomes, and competing risk survival analysis for mortality. RESULTS: Of 11 544 people tested for SARS-Cov-2, 5566 (48.2%) were positive. After exclusions, 5279 were included. 2741 of these 5279 (51.9%) were admitted to hospital, of whom 1904 (69.5%) were discharged alive without hospice care and 665 (24.3%) were discharged to hospice care or died. Of 647 (23.6%) patients requiring mechanical ventilation, 391 (60.4%) died and 170 (26.2%) were extubated or discharged. The strongest risk for hospital admission was associated with age, with an odds ratio of >2 for all age groups older than 44 years and 37.9 (95% confidence interval 26.1 to 56.0) for ages 75 years and older. Other risks were heart failure (4.4, 2.6 to 8.0), male sex (2.8, 2.4 to 3.2), chronic kidney disease (2.6, 1.9 to 3.6), and any increase in body mass index (BMI) (eg, for BMI >40: 2.5, 1.8 to 3.4). The strongest risks for critical illness besides age were associated with heart failure (1.9, 1.4 to 2.5), BMI >40 (1.5, 1.0 to 2.2), and male sex (1.5, 1.3 to 1.8). Admission oxygen saturation of <88% (3.7, 2.8 to 4.8), troponin level >1 (4.8, 2.1 to 10.9), C reactive protein level >200 (5.1, 2.8 to 9.2), and D-dimer level >2500 (3.9, 2.6 to 6.0) were, however, more strongly associated with critical illness than age or comorbidities. Risk of critical illness decreased significantly over the study period. Similar associations were found for mortality alone. CONCLUSIONS: Age and comorbidities were found to be strong predictors of hospital admission and to a lesser extent of critical illness and mortality in people with covid-19; however, impairment of oxygen on admission and markers of inflammation were most strongly associated with critical illness and mortality. Outcomes seem to be improving over time, potentially suggesting improvements in care.

BMJ2020       LitCov and CORD-19
376The Morphology of Virus-Antibody Interaction  

In the field of virus study, the electron microscope technique of negative staining is now more than 10 years old, and during these years the knowledge of virus fine structure has changed beyond all recognition. This chapter describes that the immune aggregate should be incubated for 1 hour at 37°C and then left in the cold overnight. This is the optimum approach for a system, where the concentration of neither the antigen nor the antiserum is known, and maximum clumping is needed. However, with many systems these parameters have been established, and if it is known that clumping can be obtained readily, for example, as with the avian infectious bronchitis system, then incubation for 1 hour at 37°C is sufficient, followed by spinning at 10,000 rpm for half an hour. Viruses in the small to intermediate size range are ideal for immune studies, as the particles are not disproportionately larger than the antibody molecules attached to them, and interaction between them can be visualized with better than 10 a resolution. Particles as large as the poxviruses are becoming too large for good resolution of antibody molecules to be obtained, and aggregates of poxvirus particles are usually too dense to be recorded photographically except at low power. In the field of clinical virology, there is a possibility that the electron microscope technique of negative staining will become a standard method of diagnosis. As far as research is concerned, the present article seems to have described the beginnings that have been made in the visualization of several aspects of antigen-antibody interaction. Each line investigated has yielded a few answers, but of much greater importance, has led to a better understanding of what questions should be asked. At present, viral antigens can only occasionally be obtained in pure form, such that there are only a very few systems where controlled and specific virus-antigen-antibody systems can be visualized.

Adv Virus Res1969       CORD-19
377Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC  

Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals(1). However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread(2). Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection(3,4). Viral genome analysis revealed close relatedness to coronaviruses found in bats(5). Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (Pipistrellus pipistrellus) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoV-EMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature12005) contains supplementary material, which is available to authorized users.

Nature2013       CORD-19
378Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19  

Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.

Cell2020       LitCov and CORD-19
379Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003  

BACKGROUND: An epidemic of severe acute respiratory syndrome (SARS) has been associated with an outbreak of atypical pneumonia originating in Guangdong Province, People's Republic of China. We aimed to identify the causative agent in the Guangdong outbreak and describe the emergence and spread of the disease within the province. METHODS: We analysed epidemiological information and collected serum and nasopharyngeal aspirates from patients with SARS in Guangdong in mid-February, 2003. We did virus isolation, serological tests, and molecular assays to identify the causative agent. FINDINGS: SARS had been circulating in other cities of Guangdong Province for about 2 months before causing a major outbreak in Guangzhou, the province's capital. A novel coronavirus, SARS coronavirus (CoV), was isolated from specimens from three patients with SARS. Viral antigens were also directly detected in nasopharyngeal aspirates from these patients. 48 of 55 (87%) patients had antibodies to SARS CoV in their convalescent sera. Genetic analysis showed that the SARS CoV isolates from Guangzhou shared the same origin with those in other countries, and had a phylogenetic pathway that matched the spread of SARS to the other parts of the world. INTERPRETATION: SARS CoV is the infectious agent responsible for the epidemic outbreak of SARS in Guangdong. The virus isolated from patients in Guangdong is the prototype of the SARS CoV in other regions and countries.

Lancet2003       CORD-19
380SARS-CoV-2 infection associated acute kidney injury in patients with pre-existing chronic renal disease: A report of two cases  

BACKGROUND: The 2019 novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]) is driving a novel atypical pneumonia (coronavirus disease 2019 [COVID‐19]) outbreak in Wuhan, causing huge public health challenges both in China and globally. Limited data are available for information and prognosis on COVID‐19 patients with pre‐existing chronic kidney disease. CASE PRESENTATION: Here we described the clinical characteristics and outcomes from two patients—a female aged 40‐year‐old and an 83‐year‐old male—who were subjected to SARS‐CoV‐2 infection, with history of chronic renal insufficiency. The female was admitted for dry cough and shortness of breath and the male was admitted for fever. The thorax computed tomography revealed patchy consolidation and ground‐glass opacity in both scattered lobes and the throat swab sample for coronavirus nucleic acid was positive. They were diagnosed with COVID‐19 and their renal function became progressively worse after infection with COVID‐19. After symptomatic support treatment, in both the patients, renal function was obviously restored, and both recovered from this pneumonia and conformed to the discharge criteria. CONCLUSION: SARS‐CoV‐2 infection may aggravate renal function impairment. It is crucial to monitor changes of renal function in patients with COVID‐19, especially those with primary kidney disease. Kidney protection interventions should be taken as early as possible, thereby improving the prognosis of patients with COVID‐19.

Immun Inflamm Dis2020       LitCov and CORD-19
381Isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV) outbreak  

Public health measures were decisive in controlling the SARS epidemic in 2003. Isolation is the separation of ill persons from non-infected persons. Quarantine is movement restriction, often with fever surveillance, of contacts when it is not evident whether they have been infected but are not yet symptomatic or have not been infected. Community containment includes measures that range from increasing social distancing to community-wide quarantine. Whether these measures will be sufficient to control 2019-nCoV depends on addressing some unanswered questions.

J Travel Med2020       LitCov and CORD-19
382Telehealth transformation: COVID-19 and the rise of virtual care  

The novel coronavirus disease-19 (COVID-19) pandemic has altered our economy, society and healthcare system. While this crisis has presented the US healthcare delivery system with unprecedented challenges, the pandemic has catalyzed rapid adoption of telehealth or the entire spectrum of activities used to deliver care at a distance. Using examples reported by US healthcare organizations including ours, we describe the role telehealth has played in transforming healthcare delivery during the three phases of the US COVID-19 pandemic: 1) Stay-at-Home Outpatient Care; 2) Initial COVID-19 Hospital Surge, and 3) Post-Pandemic Recovery. Within each of these three phases, we examine how people, process and technology work together to support a successful telehealth transformation. Whether healthcare enterprises are ready or not, the new reality is that virtual care has arrived.

J Am Med Inform Assoc2020       LitCov and CORD-19
383Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico  

N/A

N Engl J Med2009       CORD-19
384A Genome Epidemiological Study of SARS-CoV-2 Introduction into Japan  

After the first case of coronavirus disease 2019 (COVID-19) in Japan on 15 January 2020, multiple nationwide COVID-19 clusters were identified by the end of February. The Japanese government focused on mitigating the emerging COVID-19 clusters by conducting active nationwide epidemiological surveillance. However, an increasing number of cases continued to appear until early April 2020, many with unclear infection routes and no recent history of travel outside Japan. We aimed to evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences from the COVID-19 cases that appeared until early April 2020 and to characterize their genealogical networks in order to demonstrate possible routes of spread in Japan. Nasopharyngeal specimens were collected from patients, and reverse transcription-quantitative PCR tests for SARS-CoV-2 were performed. Positive RNA samples were subjected to whole-genome sequencing, and a haplotype network analysis was performed. Some of the primary clusters identified during January and February 2020 in Japan descended directly from the Wuhan-Hu-1-related isolates from China and other distinct clusters. Clusters were almost contained until mid-March; the haplotype network analysis demonstrated that the COVID-19 cases from late March through early April may have created an additional large cluster related to the outbreak in Europe, leading to additional spread within Japan. In conclusion, genome surveillance has suggested that there were at least two distinct SARS-CoV-2 introductions into Japan from China and other countries. IMPORTANCE This study aimed to evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences from COVID-19 cases and to characterize their genealogical networks to demonstrate possible routes of spread in Japan. We found that there were at least two distinct SARS-CoV-2 introductions into Japan, initially from China and subsequently from other countries, including Europe. Our findings can help understand how SARS-CoV-2 entered Japan and contribute to increased knowledge of SARS-CoV-2 in Asia and its association with implemented stay-at-home/shelter-in-place/self-restraint/lockdown measures. This study suggested that it is necessary to formulate a more efficient containment strategy using real-time genome surveillance to support epidemiological field investigations in order to highlight potential infection linkages and mitigate the next wave of COVID-19 in Japan.

mSphere2020       LitCov and CORD-19
385An mRNA Vaccine against SARS-CoV-2-Preliminary Report  

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. METHODS: We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group. RESULTS: After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events. CONCLUSIONS: The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).

N Engl J Med2020       LitCov and CORD-19
386Thoracic imaging tests for the diagnosis of COVID-19  

N/A

Cochrane Database Syst Rev2020       LitCov and CORD-19
387Aminopeptidase N is a major receptor for the enteropathogenic coronavirus TGEV  

CORONAVIRUSES, like many animal viruses, are characterized by a restricted host range and tissue tropism(1). Transmissible gastroenteritis virus (TGEV), a major pathogen causing a fatal diarrhoea in newborn pig, replicates selectively in the differentiated enterocytes covering the villi of the small intestine(2). To investigate the molecular determinants of the infection, we characterized the surface molecule used by the virus for binding and entry into host cells. Here we report that aminopeptidase N, an ectoenzyme abundantly expressed at the apical membrane of the enterocytes, serves as a receptor for TGEV. Monoclonal antibodies were selected for their ability to block infection by TGEV of porcine cell lines. They recognized a brush-border membrane protein of M(r), 150K, which was identified as aminopeptidase N by ammo-terminal sequencing. Two lines of evidence supported the view that the peptidase itself acts as a receptor. First, virions bound specifically to aminopep-tidase N that was purified to homogeneity. Second, recombinant expression of aminopeptidase N conferred infectivity by TGEV to an otherwise non-permissive cell line.

Nature1992       CORD-19
388Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial  

BACKGROUND: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19, in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older. METHODS: In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18–55 years, 56–69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 10(10) virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18–55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56–69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5–6·5 × 10(10) virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18–55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA(80)). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. FINDINGS: Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18–55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56–69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18–55 years group, 22 (73%) of 30 in the 56–69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18–55 years group, 23 (77%) in the 56–69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18–55 years, 20 713 arbitrary units [AU]/mL [IQR 13 898–33 550], n=39; 56–69 years, 16 170 AU/mL [10 233–40 353], n=26; and ≥70 years 17 561 AU/mL [9705–37 796], n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA(80) at day 42 in the standard-dose groups: 18–55 years, 193 [IQR 113–238], n=39; 56–69 years, 144 [119–347], n=20; and ≥70 years, 161 [73–323], n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18–55 years: median 1187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841–2428], n=24; 56–69 years: 797 SFCs [383–1817], n=29; and ≥70 years: 977 SFCs [458–1914], n=48). INTERPRETATION: ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.

Lancet2020       LitCov and CORD-19
389The psychological impact of the COVID-19 epidemic on college students in China  

A COVID-19 epidemic has been spreading in China and other parts of the world since December 2019. The epidemic has brought not only the risk of death from infection but also unbearable psychological pressure. We sampled college students from Changzhi medical college by using cluster sampling. They responded to a questionnaire packet that included the 7-item Generalized Anxiety Disorder Scale (GAD-7) and those inquiring the participants’ basic information. We received 7,143 responses. Results indicated that 0.9% of the respondents were experiencing severe anxiety, 2.7% moderate anxiety, and 21.3% mild anxiety. Moreover, living in urban areas (OR = 0.810, 95% CI = 0.709 - 0.925), family income stability (OR = 0.726, 95% CI = 0.645 - 0.817) and living with parents (OR = 0.752, 95% CI = 0.596 - 0.950) were protective factors against anxiety. Moreover, having relatives or acquaintances infected with COVID-19 was a risk factor for increasing the anxiety of college students (OR = 3.007, 95% CI = 2.377 - 3.804). Results of correlation analysis indicated that economic effects, and effects on daily life, as well as delays in academic activities, were positively associated with anxiety symptoms (P < .001). However, social support was negatively correlated with the level of anxiety (P < .001). It is suggested that the mental health of college students should be monitored during epidemics.

Psychiatry Res2020       LitCov and CORD-19
390Universal screening for SARS-CoV-2 infection: a rapid review  

N/A

Cochrane Database Syst Rev2020       LitCov and CORD-19
391Position Paper for the State of the Art Application of Respiratory Support in Patients with COVID-19-German Respiratory Society  

Against the background of the pandemic caused by infection with the SARS-CoV-2, the German Society for Pneumology and Respiratory Medicine (DGP e.V.), in cooperation with other associations, has designated a team of experts in order to answer the currently pressing questions about therapy strategies in dealing with COVID-19 patients suffering from acute respiratory insufficiency (ARI). The position paper is based on the current knowledge that is evolving daily. Many of the published and cited studies require further review, also because many of them did not undergo standard review processes.Therefore, this position paper is also subject to a continuous review process and will be further developed in cooperation with the other professional societies. This position paper is structured into the following five topics: 1. Pathophysiology of acute respiratory insufficiency in patients without immunity infected with SARS-CoV-2 2. Temporal course and prognosis of acute respiratory insufficiency during the course of the disease 3. Oxygen insufflation, high-flow oxygen, non-invasive ventilation and invasive ventilation with special consideration of infectious aerosol formation 4. Non-invasive ventilation in ARI 5. Supply continuum for the treatment of ARI Key points have been highlighted as core statements and significant observations. Regarding the pathophysiological aspects of acute respiratory insufficiency (ARI), the pulmonary infection with SARS-CoV-2 COVID-19 runs through three phases: early infection, pulmonary manifestation and severe hyperinflammatory phase. There are differences between advanced COVID-19-induced lung damage and those changes seen in Acute Respiratory Distress Syndromes (ARDS) as defined by the Berlin criteria. In a pathophysiologically plausible - but currently not yet histopathologically substantiated – model, two types (L-type and H-type) are distinguished, which correspond to an early and late phase. This distinction can be taken into consideration in the differential instrumentation in the therapy of ARI. The assessment of the extent of ARI should be carried out by an arterial or capillary blood gas analysis under room air conditions and must include the calculation of the oxygen supply (measured from the variables of oxygen saturation, the Hb value, the corrected values of the Hüfner number and the cardiac output). In principle, aerosols can cause transmission of infectious viral particles. Open systems or leakage systems (so-called vented masks) can prevent the release of respirable particles. Procedures in which the invasive ventilation system must be opened, and endotracheal intubation must be carried out are associated with an increased risk of infection. The protection of personnel with personal protective equipment should have very high priority because fear of contagion must not be a primary reason for intubation. If the specifications for protective equipment (eye protection, FFP2 or FFP-3 mask, gown) are adhered to, inhalation therapy, nasal high-flow (NHF) therapy, CPAP therapy or NIV can be carried out according to the current state of knowledge without increased risk of infection to the staff. A significant proportion of patients with respiratory failure presents with relevant hypoxemia, often also caused by a high inspiratory oxygen fraction (FiO2) including NHF, and this hypoxemia cannot be not completely corrected. In this situation, CPAP/NIV therapy can be administered under use of a mouth and nose mask or a respiratory helmet as therapy escalation, as long as the criteria for endotracheal intubation are not fulfilled. In acute hypoxemic respiratory insufficiency, NIV should be performed in an intensive care unit or in a comparable unit by personnel with appropriate expertise. Under CPAP/NIV, a patient can deteriorate rapidly. For this reason, continuous monitoring with readiness to carry out intubation must be ensured at all times. If CPAP/NIV leads to further progression of ARI, intubation and subsequent invasive ventilation should be carried out without delay if no DNI order is in place. In the case of patients in whom invasive ventilation, after exhausting all guideline-based measures, is not sufficient, extracorporeal membrane oxygenation procedure (ECMO) should be considered to ensure sufficient oxygen supply and to remove CO (2) .

Pneumologie2020       LitCov and CORD-19
392What Media Helps, What Media Hurts: A Mixed Methods Survey Study of Coping with COVID-19 Using the Media Repertoire Framework and the Appraisal Theory of Stress  

BACKGROUND: Social and physical distancing in response to the coronavirus disease (COVID-19) pandemic has made screen-mediated information and communication technologies (media) indispensable. Whether an increase in screen use is a source of or a relief for stress remains to be seen. OBJECTIVE: In the immediate aftermath of the COVID-19 lockdowns, we investigated the relation between subjective stress and changes in the pattern of media use. Based on Lazarus’s transactional model of appraisal and coping, and building on an earlier similar survey, we hypothesize that individual differences in the appraisal of media predict variations in approach or avoidance of media for coping with COVID-19 stress. METHODS: Between March 20 and April 20, 2020, a brief snowball survey entitled: “What media helps, what media hurts: coping with COVID19 through screens” was distributed via Concordia University’s mailing lists and social media (PERFORM Centre, EngAGE Centre, and Media Health Lab). Using a media repertoire method, we asked questions about preferences, changes in use, and personal appraisal of media experiences (approach, avoid, and ignore) as a result of the COVID-19 pandemic and investigated interindividual differences in media use by factors such as subjective stress, age, gender, and self-reported mental health. RESULTS: More than 90% of the survey respondents were in Canada and the east coast of the United States. From 685 completed responses, 169 respondents were “very stressed” and 452 were “slightly worried” about the pandemic. COVID-19 stress led to increased use of Facebook (χ(2)(3)=11.76, P=.008), television (χ(2)(3)=12.40, P=.006), YouTube (χ(2)(3)=8.577, P=.04), and streaming services such as Netflix (χ(2)(3)=10.71, P=.01). Respondents who considered their mental health “not good” were twice as likely to prefer streaming services as a coping tool for self-isolation. Women and nonbinary respondents were twice as likely than men to pick social media for coping. Individuals younger than 35 years were 3 times more likely to pick computer games, and individuals older than 55 years were more likely to pick network television or print media. Gender affected the appraisal of media (less in men than others) in terms of avoid (F(1,637)=5.84, P=.02) and approach scores (F(1,637)=14.31, P<.001). Subjective mental health affected the ignore score (less in those who said “good” than others; F(1,637)=13.88, P<.001). The appraisal score and use increase explained variations in worrying about physical and mental health stress due to increased screen time. A qualitative analysis of open-ended questions revealed that media (especially social networks) were important for coping if they provided support and connection through the dissemination of factual and positive information while avoiding the overflow of sensational and false news. CONCLUSIONS: The relationship between appraisal of media’s positive and negative facets vary with demographic differences in mental health resiliency. The media repertoire approach is an important tool in studies that focus on assessing the benefits and harms of screen overuse in different populations, especially in the context of the COVID-19 pandemic.

J Med Internet Res2020       LitCov and CORD-19
393Epidemiological, clinical and virological characteristics of 465 hospitalized cases of COVID-19 from Zhejiang province in China  

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the associated coronavirus disease (COVID‐19) have spread throughout China. Previous studies predominantly focused on its place of origin, Wuhan, causing over estimation of the disease severity due to selection bias. We analyzed 465 confirmed cases in Zhejiang province to determine the epidemiological, clinical, and virological characteristics of COVID‐19. METHODS: Epidemiological, demographic, clinical, laboratory, and management data from qRT‐PCR confirmed COVID‐19 patients from January 17, 2020, to January 31, 2020, were collected, followed by multivariate logistic regression analysis for independent predictors of severe/critical‐type COVID‐19 and bioinformatic analysis for features of SARS‐CoV‐2 from Zhejiang province. RESULTS: Among 465 COVID‐19 patients, median age was 45 years, while hypertension, diabetes, and chronic liver disease were the most common comorbidities. History of exposure to the epidemic area was present in 170 (36.56%) and 185 (39.78%) patients were clustered in 77 families. Severe/critical‐type of COVID‐19 developed in 49 (10.54%) patients. Fever and cough were the most common symptoms, while diarrhea/vomiting was reported in 58 (12.47%) patients. Multivariate analysis revealed eight risk factors for severe/critical COVID‐19. Glucocorticoids and antibiotics were administered to 60 (12.90%) and 218(46.88%) patients, respectively. Bioinformatics showed four single amino acid mutations and one amino acid position loss in SARS‐CoV‐2 from Zhejiang province, with more similarity to humans than to viruses. CONCLUSIONS: SARS‐CoV‐2 showed virological mutations and more human transmission in Zhejiang province, indicating considerable epidemiological and clinical changes. Caution in glucocorticoid and antibiotics use is advisable.

Influenza Other Respir Viruses2020       LitCov and CORD-19
394Analysis of Genomic Characteristics and Transmission Routes of Patients With Confirmed SARS-CoV-2 in Southern California During the Early Stage of the US COVID-19 Pandemic  

IMPORTANCE: In late December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. Data on the routes of transmission to Los Angeles, California, the US West Coast epicenter for coronavirus disease 2019 (COVID-19), and subsequent community spread are limited. OBJECTIVE: To determine the transmission routes of SARS-CoV-2 to Southern California and elucidate local community spread within the Los Angeles metropolitan area. DESIGN, SETTING, AND PARTICIPANTS: This case series included 192 consecutive patients with reverse transcription–polymerase chain reaction (RT-PCR) test results positive for SARS-CoV-2 who were evaluated at Cedars-Sinai Medical Center in Los Angeles, California, from March 22 to April 15, 2020. Data analysis was performed from April to May 2020. MAIN OUTCOMES AND MEASURES: SARS-CoV-2 viral genomes were sequenced. Los Angeles isolates were compared with genomes from global subsampling and from New York, New York; Washington state; and China to determine potential sources of viral dissemination. Demographic data and outcomes were collected. RESULTS: The cohort included 192 patients (median [interquartile range] age, 59.5 [43-75] years; 110 [57.3%] men). The genetic characterization of SARS-CoV-2 isolates in the Los Angeles population pinpointed community transmission of 13 patients within a 3.81 km(2) radius. Variation landscapes of this case series also revealed a cluster of 10 patients that contained 5 residents at a skilled nursing facility, 1 resident of a nearby skilled nursing facility, 3 health care workers, and a family member of a resident of one of the skilled nursing facilities. Person-to-person transmission was detected in a cluster of 5 patients who shared the same single-nucleotide variation in their SARS-CoV-2 genomes. High viral genomic diversity was identified: 20 Los Angeles isolates (15.0%) resembled SARS-CoV-2 genomes from Asia, while 109 Los Angeles isolates (82.0%) were similar to isolates originating from Europe. Analysis of other common respiratory viral pathogens did not reveal coinfection in the cohort. CONCLUSIONS AND RELEVANCE: These findings highlight the precision of detecting person-to-person transmission and accurate contact tracing directly through SARS-CoV-2 genome isolation and sequencing. Development and application of phylogenetic analyses from the Los Angeles population established connections between COVID-19 clusters locally and throughout the US.

JAMA Netw Open2020       LitCov and CORD-19
395Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS)  

We did a case-control study in five Hong Kong hospitals, with 241 non-infected and 13 infected staff with documented exposures to 11 index patients with severe acute respiratory syndrome (SARS) during patient care. All participants were surveyed about use of mask, gloves, gowns, and hand-washing, as recommended under droplets and contact precautions when caring for index patients with SARS. 69 staff who reported use of all four measures were not infected, whereas all infected staff had omitted at least one measure (p=0·0224). Fewer staff who wore masks (p=0·0001), gowns (p=0·006), and washed their hands (p=0·047) became infected compared with those who didn't, but stepwise logistic regression was significant only for masks (p=0·011). Practice of droplets precaution and contact precaution is adequate in significantly reducing the risk of infection after exposures to patients with SARS. The protective role of the mask suggests that in hospitals, infection is transmitted by droplets.

Lancet2003       CORD-19
396Flexible, Freely Available Stochastic Individual Contact Model for Exploring COVID-19 Intervention and Control Strategies: Development and Simulation  

BACKGROUND: Throughout March 2020, leaders in countries across the world were making crucial decisions about how and when to implement public health interventions to combat the coronavirus disease (COVID-19). They urgently needed tools to help them to explore what will work best in their specific circumstances of epidemic size and spread, and feasible intervention scenarios. OBJECTIVE: We sought to rapidly develop a flexible, freely available simulation model for use by modelers and researchers to allow investigation of how various public health interventions implemented at various time points might change the shape of the COVID-19 epidemic curve. METHODS: “COVOID” (COVID-19 Open-Source Infection Dynamics) is a stochastic individual contact model (ICM), which extends the ICMs provided by the open-source EpiModel package for the R statistical computing environment. To demonstrate its use and inform urgent decisions on March 30, 2020, we modeled similar intervention scenarios to those reported by other investigators using various model types, as well as novel scenarios. The scenarios involved isolation of cases, moderate social distancing, and stricter population “lockdowns” enacted over varying time periods in a hypothetical population of 100,000 people. On April 30, 2020, we simulated the epidemic curve for the three contiguous local areas (population 287,344) in eastern Sydney, Australia that recorded 5.3% of Australian cases of COVID-19 through to April 30, 2020, under five different intervention scenarios and compared the modeled predictions with the observed epidemic curve for these areas. RESULTS: COVOID allocates each member of a population to one of seven compartments. The number of times individuals in the various compartments interact with each other and their probability of transmitting infection at each interaction can be varied to simulate the effects of interventions. Using COVOID on March 30, 2020, we were able to replicate the epidemic response patterns to specific social distancing intervention scenarios reported by others. The simulated curve for three local areas of Sydney from March 1 to April 30, 2020, was similar to the observed epidemic curve in terms of peak numbers of cases, total numbers of cases, and duration under a scenario representing the public health measures that were actually enacted, including case isolation and ramp-up of testing and social distancing measures. CONCLUSIONS: COVOID allows rapid modeling of many potential intervention scenarios, can be tailored to diverse settings, and requires only standard computing infrastructure. It replicates the epidemic curves produced by other models that require highly detailed population-level data, and its predicted epidemic curve, using parameters simulating the public health measures that were enacted, was similar in form to that actually observed in Sydney, Australia. Our team and collaborators are currently developing an extended open-source COVOID package comprising of a suite of tools to explore intervention scenarios using several categories of models.

JMIR Public Health Surveill2020       LitCov and CORD-19
397Modelling of hypothetical SARS-CoV-2 point-of-care tests on admission to hospital from A&E: rapid cost-effectiveness analysis  

N/A

Health Technol Assess2021       LitCov and CORD-19
398COVID-19 and Italy: what next?  

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already taken on pandemic proportions, affecting over 100 countries in a matter of weeks. A global response to prepare health systems worldwide is imperative. Although containment measures in China have reduced new cases by more than 90%, this reduction is not the case elsewhere, and Italy has been particularly affected. There is now grave concern regarding the Italian national health system's capacity to effectively respond to the needs of patients who are infected and require intensive care for SARS-CoV-2 pneumonia. The percentage of patients in intensive care reported daily in Italy between March 1 and March 11, 2020, has consistently been between 9% and 11% of patients who are actively infected. The number of patients infected since Feb 21 in Italy closely follows an exponential trend. If this trend continues for 1 more week, there will be 30 000 infected patients. Intensive care units will then be at maximum capacity; up to 4000 hospital beds will be needed by mid-April, 2020. Our analysis might help political leaders and health authorities to allocate enough resources, including personnel, beds, and intensive care facilities, to manage the situation in the next few days and weeks. If the Italian outbreak follows a similar trend as in Hubei province, China, the number of newly infected patients could start to decrease within 3–4 days, departing from the exponential trend. However, this cannot currently be predicted because of differences between social distancing measures and the capacity to quickly build dedicated facilities in China.

Lancet2020       LitCov and CORD-19
399BNT162b2 COVID-19 vaccine and correlates of humoral immune responses and dynamics: a prospective, single center, longitudinal cohort study in health-care workers  

BACKGROUND: Concurrent with the Pfizer–BioNTech BNT162b2 COVID-19 vaccine roll-out in Israel initiated on Dec 19, 2020, we assessed the early antibody responses and antibody kinetics after each vaccine dose in health-care workers of different ages and sexes, and with different comorbidities. METHODS: We did a prospective, single-centre, longitudinal cohort study at the Sheba Medical Centre (Tel-Hashomer, Israel). Eligible participants were health-care workers at the centre who had a negative anti-SARS-CoV-2 IgG assay before receiving the first dose of the intramuscular vaccine, and at least one serological antibody test after the first dose of the vaccine. Health-care workers with a positive SARS-CoV-2 PCR test before vaccination, a positive anti-SARS-CoV-2 IgG serology test before vaccination, or infection with COVID-19 after vaccination were excluded from the study. Participants were followed up weekly for 5 weeks after the first vaccine dose; a second dose was given at week 3. Serum samples were obtained at baseline and at each weekly follow-up, and antibodies were tested at 1–2 weeks after the first vaccine dose, at week 3 with the administration of the second vaccine dose, and at weeks 4–5 (ie, 1–2 weeks after the second vaccine dose). Participants with comorbidities were approached to participate in an enriched comorbidities subgroup, and at least two neutralising assays were done during the 5 weeks of follow-up in those individuals. IgG assays were done for the entire study population, whereas IgM, IgA, and neutralising antibody assays were done only in the enriched comorbidities subgroup. Concentrations of IgG greater than 0·62 sample-to-cutoff (s/co) ratio and of IgA greater than 1·1 s/co, and titres of neutralising antibodies greater than 10 were considered positive. Scatter plot and correlation analyses, logistic and linear regression analyses, and linear mixed models were used to investigate the longitudinal antibody responses. FINDINGS: Between Dec 19, 2020, and Jan 30, 2021, we obtained 4026 serum samples from 2607 eligible, vaccinated participants. 342 individuals were included in the enriched comorbidities subgroup. The first vaccine dose elicited positive IgG and neutralising antibody responses at week 3 in 707 (88·0%) of 803 individuals, and 264 (71·0%) of 372 individuals, respectively, which were rapidly increased at week 4 (ie, 1 week after the second vaccine dose) in 1011 (98·4%) of 1027 and 357 (96·5%) of 370 individuals, respectively. Over 4 weeks of follow-up after vaccination, a high correlation (r=0·92) was detected between IgG against the receptor-binding domain and neutralising antibody titres. First-dose induced IgG response was significantly lower in individuals aged 66 years and older (ratio of means 0·25, 95% CI 0·19–0·31) and immunosuppressed individuals (0·21, 0·14–0·31) compared with individuals aged 18·00–45·99 years and individuals with no immunosuppression, respectively. This disparity was partly abrogated following the second dose. Overall, endpoint regression analysis showed that lower antibody concentrations were consistently associated with male sex (ratio of means 0·84, 95% CI 0·80–0·89), older age (ie, ≥66 years; 0·64, 0·58–0·71), immunosuppression (0·44, 0·33–0·58), and other specific comorbidities: diabetes (0·88, 0·79–0·98), hypertension (0·90, 0·82–0·98), heart disease (0·86, 0·75–1·00), and autoimmune diseases (0·82, 0·73–0·92). INTERPRETATION: BNT162b2 vaccine induces a robust and rapid antibody response. The significant correlation between receptor-binding domain IgG antibodies and neutralisation titres suggests that IgG antibodies might serve as a correlate of neutralisation. The second vaccine dose is particularly important for older and immunosuppressed individuals, highlighting the need for timely second vaccinations and potentially a revaluation of the long gap between doses in some countries. Antibody responses were reduced in susceptible populations and therefore they might be more prone to breakthrough infections. FUNDING: Sheba Medical Center, Israel Ministry of Health.

Lancet Respir Med2021       LitCov and CORD-19
400People's Willingness to Vaccinate Against COVID-19 Despite Their Safety Concerns: Twitter Poll Analysis  

BACKGROUND: On January 30, 2020, the World Health Organization’s Emergency Committee declared the rapid, worldwide spread of COVID-19 a global health emergency. Since then, tireless efforts have been made to mitigate the spread of the disease and its impact, and these efforts have mostly relied on nonpharmaceutical interventions. By December 2020, the safety and efficacy of the first COVID-19 vaccines were demonstrated. The large social media platform Twitter has been used by medical researchers for the analysis of important public health topics, such as the public’s perception on antibiotic use and misuse and human papillomavirus vaccination. The analysis of Twitter-generated data can be further facilitated by using Twitter’s built-in, anonymous polling tool to gain insight into public health issues and obtain rapid feedback on an international scale. During the fast-paced course of the COVID-19 pandemic, the Twitter polling system has provided a viable method for gaining rapid, large-scale, international public health insights on highly relevant and timely SARS-CoV-2–related topics. OBJECTIVE: The purpose of this study was to understand the public’s perception on the safety and acceptance of COVID-19 vaccines in real time by using Twitter polls. METHODS: We developed 2 Twitter polls to explore the public’s views on available COVID-19 vaccines. The surveys were pinned to the Digital Health and Patient Safety Platform Twitter timeline for 1 week in mid-February 2021, and Twitter users and influencers were asked to participate in and retweet the polls to reach the largest possible audience. RESULTS: The adequacy of COVID-19 vaccine safety (ie, the safety of currently available vaccines; poll 1) was agreed upon by 1579 out of 3439 (45.9%) Twitter users. In contrast, almost as many Twitter users (1434/3439, 41.7%) were unsure about the safety of COVID-19 vaccines. Only 5.2% (179/3439) of Twitter users rated the available COVID-19 vaccines as generally unsafe. Poll 2, which addressed the question of whether users would undergo vaccination, was answered affirmatively by 82.8% (2862/3457) of Twitter users, and only 8% (277/3457) categorically rejected vaccination at the time of polling. CONCLUSIONS: In contrast to the perceived high level of uncertainty about the safety of the available COVID-19 vaccines, we observed an elevated willingness to undergo vaccination among our study sample. Since people's perceptions and views are strongly influenced by social media, the snapshots provided by these media platforms represent a static image of a moving target. Thus, the results of this study need to be followed up by long-term surveys to maintain their validity. This is especially relevant due to the circumstances of the fast-paced pandemic and the need to not miss sudden rises in the incidence of vaccine hesitancy, which may have detrimental effects on the pandemic’s course.

J Med Internet Res2021       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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