\ 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
2751Loneliness, physical activity and mental health during COVID-19: a longitudinal analysis of depression and anxiety in adults over the age of 50 between 2015 and 2020  

OBJECTIVE: Loneliness and physical activity are important targets for research into the impact of COVID-19 because they have established links with mental health, could be exacerbated by social distancing policies, and are potentially modifiable. In this study, we aimed to identify whether loneliness and physical activity were associated with worse mental health during a period of mandatory social distancing in the UK. DESIGN: Population-based observational cohort study. SETTING: Mental health data collected online during COVID-19 from an existing sample of adults aged 50 and over taking part in a longitudinal study of aging. All had comparable annual data collected between 2015 and 2019. PARTICIPANTS: Three-thousand two-hundred and eighty-one participants aged 50 and over. MEASUREMENTS: Trajectories of depression (measured by PHQ-9) and anxiety (measured by GAD-7) between 2015 and 2020 were analyzed with respect to loneliness, physical activity levels, and a number of socioeconomic and demographic characteristics using zero-inflated negative binomial regression. RESULTS: In 2020, PHQ-9 score for loneliness, adjusted for covariates, was 3.23 (95% CI: 3.01–3.44), an increase of around 1 point on all previous years in this group and 2 points higher than people not rated lonely, whose score did not change in 2020 (1.22, 95% CI: 1.12–1.32). PHQ-9 was 2.60 (95% CI: 2.43–2.78) in people with decreased physical activity, an increase of .5 on previous years. In contrast, PHQ-9 in 2020 for people whose physical activity had not decreased was 1.66, 95% CI: 1.56−1.75, similar to previous years. A similar relationship was observed for GAD-7 though the absolute burden of symptoms lower. CONCLUSION: After accounting for pre-COVID-19 trends, we show that experiencing loneliness and decreased physical activity are risk factors for worsening mental health during the pandemic. Our findings highlight the need to examine policies which target these potentially modifiable risk factors.

Int Psychogeriatr2020       LitCov and CORD-19
2752Assessment of SARS-CoV-2 serological tests for the diagnosis of COVID-19 through the evaluation of three immunoassays: Two automated immunoassays (Euroimmun and Abbott) and one rapid lateral flow immunoassay (NG Biotech)  

BACKGROUND: The emergence of new SARS-CoV-2 has promoted the development of new serological tests that could be complementary to RT-PCR. Nevertheless, the assessment of clinical performances of available tests is urgently required as their use has just been initiated for diagnose. OBJECTIVES: The aim of this study was to assess the performance of three immunoassays for the detection of SARS-CoV-2 antibodies. METHODS: Two automated immunoassays (Abbott SARS-CoV-2 CLIA IgG and Euroimmun Anti-SARS-CoV-2 ELISA IgG/IgA assays) and one lateral flow immunoassay (LFIA NG-Test® IgG-IgM COVID-19) were tested. 293 specimens were analyzed from patients with a positive RT-PCR response, from patients with symptoms consistent with COVID-19 but exhibiting a negative response to the RT-PCR detection test, and from control group specimens. Days since symptoms onset were collected from clinical information sheet associated with respiratory tract samples. RESULTS: Overall sensitivity for IgG was equivalent (around 80%) for CLIA, ELISA and LFIA. Sensitivity for IgG detection, >14 days after onset of symptoms, was 100.0% for all assays. Overall specificity for IgG was greater for CLIA and LFIA (more than 98%) compared to ELISA (95.8%). Specificity was significantly different between IgA ELISA (78.9%) and IgM LFIA (95.8%) (p < 0.05). The best agreement was observed between CLIA and LFIA assays (97%; k = 0.936). CONCLUSION: Excellent sensitivity for IgG detection was obtained >14 days after onset of symptoms for all immunoassays. Specificity was also excellent for IgG CLIA and IgG LFIA. Our study shows that NG-Test® is reliable and accurate for routine use in clinical laboratories.

J Clin Virol2020       LitCov and CORD-19
2753The Genome sequence of the SARS-associated coronavirus  

N/A

Science2003       CORD-19
2754Structural Evaluation of the Spike Glycoprotein Variants on SARS-CoV-2 Transmission and Immune Evasion  

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents significant social, economic and political challenges worldwide. SARS-CoV-2 has caused over 3.5 million deaths since late 2019. Mutations in the spike (S) glycoprotein are of particular concern because it harbours the domain which recognises the angiotensin-converting enzyme 2 (ACE2) receptor and is the target for neutralising antibodies. Mutations in the S protein may induce alterations in the surface spike structures, changing the conformational B-cell epitopes and leading to a potential reduction in vaccine efficacy. Here, we summarise how the more important variants of SARS-CoV-2, which include cluster 5, lineages B.1.1.7 (Alpha variant), B.1.351 (Beta), P.1 (B.1.1.28/Gamma), B.1.427/B.1.429 (Epsilon), B.1.526 (Iota) and B.1.617.2 (Delta) confer mutations in their respective spike proteins which enhance viral fitness by improving binding affinity to the ACE2 receptor and lead to an increase in infectivity and transmission. We further discuss how these spike protein mutations provide resistance against immune responses, either acquired naturally or induced by vaccination. This information will be valuable in guiding the development of vaccines and other therapeutics for protection against the ongoing coronavirus disease 2019 (COVID-19) pandemic.

Int J Mol Sci2021       LitCov and CORD-19
2755Impact of the COVID-19 pandemic on emergency department attendances and acute medical admissions  

BACKGROUND: To better understand the impact of the COVID-19 pandemic on hospital healthcare, we studied activity in the emergency department (ED) and acute medicine department of a major UK hospital. METHODS: Electronic patient records for all adult patients attending ED (n = 243,667) or acute medicine (n = 82,899) during the pandemic (2020–2021) and prior year (2019) were analysed and compared. We studied parameters including severity, primary diagnoses, co-morbidity, admission rate, length of stay, bed occupancy, and mortality, with a focus on non-COVID-19 diseases. RESULTS: During the first wave of the pandemic, daily ED attendance fell by 37%, medical admissions by 30% and medical bed occupancy by 27%, but all returned to normal within a year. ED attendances and medical admissions fell across all age ranges; the greatest reductions were seen for younger adults in ED attendances, but in older adults for medical admissions. Compared to non-COVID-19 pandemic admissions, COVID-19 admissions were enriched for minority ethnic groups, for dementia, obesity and diabetes, but had lower rates of malignancy. Compared to the pre-pandemic period, non-COVID-19 pandemic admissions had more hypertension, cerebrovascular disease, liver disease, and obesity. There were fewer low severity ED attendances during the pandemic and fewer medical admissions across all severity categories. There were fewer ED attendances with common non-respiratory illnesses including cardiac diagnoses, but no change in cardiac arrests. COVID-19 was the commonest diagnosis amongst medical admissions during the first wave and there were fewer diagnoses of pneumonia, myocardial infarction, heart failure, cellulitis, chronic obstructive pulmonary disease, urinary tract infection and other sepsis, but not stroke. Levels had rebounded by a year later with a trend to higher levels of stroke than before the pandemic. During the pandemic first wave, 7-day mortality was increased for ED attendances, but not for non-COVID-19 medical admissions. CONCLUSIONS: Reduced ED attendances in the first wave of the pandemic suggest opportunities for reducing low severity presentations to ED in the future, but also raise the possibility of harm from delayed or missed care. Reassuringly, recent rises in attendance and admissions indicate that any deterrent effect of the pandemic on attendance is diminishing. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12873-021-00529-w.

BMC Emerg Med2021       LitCov and CORD-19
2756Impact assessment of non-pharmaceutical interventions against COVID-19 and influenza in Hong Kong: an observational study  

BACKGROUND: A range of public health measures have been implemented to suppress local transmission of coronavirus disease 2019 (COVID-19) in Hong Kong. We examined the effect of these interventions and behavioural changes of the public on the incidence of COVID-19, as well as on influenza virus infections, which might share some aspects of transmission dynamics with COVID-19. METHODS: We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (R(t)) for COVID-19 and influenza A H1N1 to estimate changes in transmissibility over time. Attitudes towards COVID-19 and changes in population behaviours were reviewed through three telephone surveys done on Jan 20–23, Feb 11–14, and March 10–13, 2020. FINDINGS: COVID-19 transmissibility measured by R(t) has remained at approximately 1 for 8 weeks in Hong Kong. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% (95% CI 34–53%) reduction in transmissibility in the community, from an estimated R(t) of 1·28 (95% CI 1·26–1·30) before the start of the school closures to 0·72 (0·70–0·74) during the closure weeks. Similarly, a 33% (24–43%) reduction in transmissibility was seen based on paediatric hospitalisation rates, from an R(t) of 1·10 (1·06–1·12) before the start of the school closures to 0·73 (0·68–0·77) after school closures. Among respondents to the surveys, 74·5%, 97·5%, and 98·8% reported wearing masks when going out, and 61·3%, 90·2%, and 85·1% reported avoiding crowded places in surveys 1 (n=1008), 2 (n=1000), and 3 (n=1005), respectively. INTERPRETATION: Our study shows that non-pharmaceutical interventions (including border restrictions, quarantine and isolation, distancing, and changes in population behaviour) were associated with reduced transmission of COVID-19 in Hong Kong, and are also likely to have substantially reduced influenza transmission in early February, 2020. FUNDING: Health and Medical Research Fund, Hong Kong.

Lancet Public Health2020       LitCov and CORD-19
2757Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia  

BACKGROUND: Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti–interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear. METHODS: We randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28. RESULTS: A total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P=0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, –5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.)

N Engl J Med2020       LitCov and CORD-19
2758Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression  

BACKGROUND: Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infection caused by the delta variant with increasing time since vaccination. METHODS: This study was designed as a systematic review and meta-regression. We did a systematic review of preprint and peer-reviewed published article databases from June 17, 2021, to Dec 2, 2021. Randomised controlled trials of COVID-19 vaccine efficacy and observational studies of COVID-19 vaccine effectiveness were eligible. Studies with vaccine efficacy or effectiveness estimates at discrete time intervals of people who had received full vaccination and that met predefined screening criteria underwent full-text review. We used random-effects meta-regression to estimate the average change in vaccine efficacy or effectiveness 1–6 months after full vaccination. FINDINGS: Of 13 744 studies screened, 310 underwent full-text review, and 18 studies were included (all studies were carried out before the omicron variant began to circulate widely). Risk of bias, established using the risk of bias 2 tool for randomised controlled trials or the risk of bias in non-randomised studies of interventions tool was low for three studies, moderate for eight studies, and serious for seven studies. We included 78 vaccine-specific vaccine efficacy or effectiveness evaluations (Pfizer–BioNTech-Comirnaty, n=38; Moderna-mRNA-1273, n=23; Janssen-Ad26.COV2.S, n=9; and AstraZeneca-Vaxzevria, n=8). On average, vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21·0 percentage points (95% CI 13·9–29·8) among people of all ages and 20·7 percentage points (10·2–36·6) among older people (as defined by each study, who were at least 50 years old). For symptomatic COVID-19 disease, vaccine efficacy or effectiveness decreased by 24·9 percentage points (95% CI 13·4–41·6) in people of all ages and 32·0 percentage points (11·0–69·0) in older people. For severe COVID-19 disease, vaccine efficacy or effectiveness decreased by 10·0 percentage points (95% CI 6·1–15·4) in people of all ages and 9·5 percentage points (5·7–14·6) in older people. Most (81%) vaccine efficacy or effectiveness estimates against severe disease remained greater than 70% over time. INTERPRETATION: COVID-19 vaccine efficacy or effectiveness against severe disease remained high, although it did decrease somewhat by 6 months after full vaccination. By contrast, vaccine efficacy or effectiveness against infection and symptomatic disease decreased approximately 20–30 percentage points by 6 months. The decrease in vaccine efficacy or effectiveness is likely caused by, at least in part, waning immunity, although an effect of bias cannot be ruled out. Evaluating vaccine efficacy or effectiveness beyond 6 months will be crucial for updating COVID-19 vaccine policy. FUNDING: Coalition for Epidemic Preparedness Innovations.

Lancet2022       LitCov and CORD-19
2759Covid-19-related stressors, mental disorders, depressive and anxiety symptoms: a cross-sectional, nationally-representative, face-to-face survey in Serbia  

N/A

Epidemiol Psychiatr Sci2022       LitCov and CORD-19
2760Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis  

INTRODUCTION: An epidemic of Coronavirus Disease 2019 (COVID-19) began in December 2019 in China leading to a Public Health Emergency of International Concern (PHEIC). Clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews on COVID-19 have been published to date. METHODS: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies and also case reports, were included, and analyzed separately. We performed a random-effects model meta-analysis to calculate pooled prevalences and 95% confidence intervals (95%CI). RESULTS: 660 articles were retrieved for the time frame (1/1/2020-2/23/2020). After screening, 27 articles were selected for full-text assessment, 19 being finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5–92.9%), cough (57.6%, 95%CI 40.8–74.4%) and dyspnea (45.6%, 95%CI 10.9–80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0–30.6%) required intensive care unit (ICU), 32.8% presented with acute respiratory distress syndrome (ARDS) (95%CI 13.7–51.8), 6.2% (95%CI 3.1–9.3) with shock. Some 13.9% (95%CI 6.2–21.5%) of hospitalized patients had fatal outcomes (case fatality rate, CFR). CONCLUSION: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and hospitalization was associated with a CFR of >13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure and facilities to treat severe COVID-19.

Travel Med Infect Dis2020       LitCov and CORD-19
2761The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice  

N/A

Nature2020       LitCov and CORD-19
2762Online, Face-to-Face, or Blended Learning? Faculty and Medical Students' Perceptions During the COVID-19 Pandemic: A Mixed-Method Study  

BACKGROUND: COVID-19 pandemic forced educational institutions to adopt online methods which were inevitable to keep continuity of education across all academia after suspension of traditional educational systems. The aim of this study was to explore the experience of faculty and students of online and face-to-face learning, and their preference of the mode of learning after the pandemic. METHODS: This is a mixed-method study. Quantitative data was collected through a survey from 194 medical students and 33 faculty members, while qualitative data was collected through two focus group discussions with 9 students and another two with 13 faculty members. Quantitative variables were presented as means and standard deviations. Paired samples t-test and Chi-square test were used. Thematic analysis of qualitative data was used to code, interpret, and make sense of data. RESULTS: Mean scores of responses of faculty members and students were higher for face-to-face and blended learning compared to online learning in all survey statements with statistically significant differences. More than half of the students (53.1%) preferred the face-to-face mode of learning, while most of the faculty members (60.6%) preferred the blended mode of learning. Qualitative analysis identified five themes, namely: “Transforming the way theoretical teaching sessions are given,” “Face-to-face teaching at campus cannot be replaced for some types of education,” “Interaction in online sessions is limited,” “Problems and challenges of online examinations,” and “Technical issues and challenges of online education.” It revealed suggestions that at least 30% of the curriculum could be taught online post-COVID-19. Some aspects of clinically oriented teaching including history taking and case discussions can also be delivered online in the future. Faculty members and students reported that dealing with online education was not difficult, although the transition was not smooth. CONCLUSION: Medical students and faculty members were in favor of face-to-face and blended modes of learning. However, they perceived online mode of learning as an acceptable adaptation in theoretical teaching and in some clinically oriented teaching including history taking and clinical case discussions. Although face-to-face education in medicine is irreplaceable, the blended mode of learning remains an acceptable and practical solution for the post-COVID era.

Front Med (Lausanne)2022       LitCov and CORD-19
2763Psychological impact of COVID-19 on speech and language therapists working with adult dysphagia: A national survey  

BACKGROUND: Speech and language therapists (SLTs) working with dysphagia have had to radically alter diagnostic and rehabilitation services during the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, hereafter referred to as coronavirus disease (COVID‐19). Given the aerosol‐generating procedures inherent in swallow assessment and interventions, these SLTs have also been particularly susceptible to virus exposure. AIMS: To investigate the psychological impact of COVID‐19 on SLTs working with adult dysphagia across the Republic of Ireland and to identify the personal and professional factors associated with depression, anxiety, stress and post‐traumatic stress disorder (PTSD). To explore SLT perspectives regarding their experiences during the COVID‐19 pandemic. METHODS & PROCEDURES: A cross‐sectional 34‐item online survey was developed and piloted. The survey collected demographic details and professional factors and it incorporated the Depression, Anxiety, and Stress Scale—21 (DASS‐21) and the Impact of Event Scale—Revised (IES‐R). The survey also sought SLT perspectives regarding their experiences during the pandemic. It was distributed to Irish SLT managers, the Irish Association of Speech and Language Therapists (IASLT) and the Irish Dysphagia Special Interest Group (SIG) for dissemination. OUTCOMES & RESULTS: A total of 94 SLTs working with adults with dysphagia across Ireland responded. In total, 60% of respondents screened positive for depression, anxiety, stress and/or PTSD. Based on the DASS‐21, 38% screened positive for depression (mean score = 8.0; SD = 6.3), 36% screened positive for anxiety (mean score = 6.5; SD = 6.0), and 49% screened positive for stress (mean score = 15.4; SD = 6.9). A total of 26% of respondents screened positive for PTSD (mean IES‐R total score = 22.6; SD = 16.0). Factors associated with depression, anxiety, stress and PTSD were young age (p = 0.002), limited clinical experience (p = 0.01) and not living with children (p = 0.02). A thematic analysis of SLT perspectives identified four main themes: ‘fear of COVID‐19 infection and transmission’, ‘uncertainty regarding policies and procedures’, ‘changes in SLT roles and responsibilities’ and ‘increased workload’. CONCLUSIONS & IMPLICATIONS: This study highlights the psychological impact of COVID‐19 on SLTs working with adults with dysphagia in Ireland and identifies SLTs who are at risk of depression, anxiety, stress and PTSD during the COVID‐19 pandemic. Findings may assist employers to identify staff who require psychological support and long‐term follow‐up during this pandemic and any future health emergencies. WHAT THIS PAPER ADDS: WHAT IS ALREADY KNOWN ON THE SUBJECT: Depression, anxiety, stress and PTSD are prevalent among nurses and other healthcare professionals internationally as a result of the COVID‐19 pandemic and associated factors have been identified in previous research. Despite this, no research has been conducted to establish the psychological impact of the first surge of COVID‐19 on SLTs working with dysphagia in relation to depression, anxiety, stress and PTSD and the associated factors. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE: A total of 60% of SLTs working with adults with dysphagia in this survey presented with depression, anxiety, stress and/or PTSD. Associated personal and professional factors amongst respondents included young age, limited clinical experience and not living with children. The perspectives of SLTs on their experiences during the first surge of COVID‐19 are also explored. WHAT ARE THE POTENTIAL OR ACTUAL CLINICAL IMPLICATIONS OF THIS WORK? The findings from this study may assist SLT managers to identify SLTs who are at a higher risk of depression, anxiety, stress and PTSD to ensure appropriate support can be provided.

Int J Lang Commun Disord2021       LitCov and CORD-19
2764Recent Advances in the Evaluation of Serological Assays for the Diagnosis of SARS-CoV-2 Infection and COVID-19  

Introduction: Few data on the diagnostic performance of serological tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are currently available. We evaluated sensitivity and specificity of five different widely used commercial serological assays for the detection of SARS-CoV-2–specific IgG, IgM, and IgA antibodies using reverse transcriptase-PCR assay in nasopharyngeal swab as reference standard test. Methods: A total of 337 plasma samples collected in the period April–June 2020 from SARS-CoV-2 RT-PCR positive (n = 207) and negative (n = 130) subjects were investigated by one point-of-care lateral flow immunochromatographic assay (LFIA IgG and IgM, Technogenetics) and four fully automated assays: two chemiluminescence immunoassays (CLIA-iFlash IgG and IgM, Shenzhen YHLO Biotech and CLIA-LIAISON(®) XL IgG, DiaSorin), one electrochemiluminescence immunoassay (ECLIA-Elecsys(®) total predominant IgG, Roche), and one enzyme-linked immunosorbent assay (ELISA IgA, Euroimmune). Results: The overall sensitivity of all IgG serological assays was >80% and the specificity was >97%. The sensitivity of IgG assays was lower within 2 weeks from the onset of symptoms ranging from 70.8 to 80%. The LFIA and CLIA-iFlash IgM showed an overall low sensitivity of 47.6 and 54.6%, while the specificity was 98.5 and 96.2%, respectively. The ELISA IgA yielded a sensitivity of 84.3% and specificity of 81.7%. However, the ELISA IgA result was indeterminate in 11.7% of cases. Conclusions: IgG serological assays seem to be a reliable tool for the retrospective diagnosis of SARS-CoV-2 infection. IgM assays seem to have a low sensitivity and IgA assay is limited by a substantial rate of indeterminate results.

Front Public Health2020       LitCov and CORD-19
2765Assessment of SARS-CoV-2 Screening Strategies to Permit the Safe Reopening of College Campuses in the United States  

IMPORTANCE: The coronavirus disease 2019 (COVID-19) pandemic poses an existential threat to many US residential colleges; either they open their doors to students in September or they risk serious financial consequences. OBJECTIVE: To define severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening performance standards that would permit the safe return of students to US residential college campuses for the fall 2020 semester. DESIGN, SETTING, AND PARTICIPANTS: This analytic modeling study included a hypothetical cohort of 4990 students without SARS-CoV-2 infection and 10 with undetected, asymptomatic SARS-CoV-2 infection at the start of the semester. The decision and cost-effectiveness analyses were linked to a compartmental epidemic model to evaluate symptom-based screening and tests of varying frequency (ie, every 1, 2, 3, and 7 days), sensitivity (ie, 70%-99%), specificity (ie, 98%-99.7%), and cost (ie, $10/test-$50/test). Reproductive numbers (R(t)) were 1.5, 2.5, and 3.5, defining 3 epidemic scenarios, with additional infections imported via exogenous shocks. The model assumed a symptomatic case fatality risk of 0.05% and a 30% probability that infection would eventually lead to observable COVID-19–defining symptoms in the cohort. Model projections were for an 80-day, abbreviated fall 2020 semester. This study adhered to US government guidance for parameterization data. MAIN OUTCOMES AND MEASURES: Cumulative tests, infections, and costs; daily isolation dormitory census; incremental cost-effectiveness; and budget impact. RESULTS: At the start of the semester, the hypothetical cohort of 5000 students included 4990 (99.8%) with no SARS-CoV-2 infection and 10 (0.2%) with SARS-CoV-2 infection. Assuming an R(t) of 2.5 and daily screening with 70% sensitivity, a test with 98% specificity yielded 162 cumulative student infections and a mean isolation dormitory daily census of 116, with 21 students (18%) with true-positive results. Screening every 2 days resulted in 243 cumulative infections and a mean daily isolation census of 76, with 28 students (37%) with true-positive results. Screening every 7 days resulted in 1840 cumulative infections and a mean daily isolation census of 121 students, with 108 students (90%) with true-positive results. Across all scenarios, test frequency was more strongly associated with cumulative infection than test sensitivity. This model did not identify symptom-based screening alone as sufficient to contain an outbreak under any of the scenarios we considered. Cost-effectiveness analysis selected screening with a test with 70% sensitivity every 2, 1, or 7 days as the preferred strategy for an R(t) of 2.5, 3.5, or 1.5, respectively, implying screening costs of $470, $910, or $120, respectively, per student per semester. CONCLUSIONS AND RELEVANCE: In this analytic modeling study, screening every 2 days using a rapid, inexpensive, and even poorly sensitive (>70%) test, coupled with strict behavioral interventions to keep R(t) less than 2.5, is estimated to maintain a controllable number of COVID-19 infections and permit the safe return of students to campus.

JAMA Netw Open2020       LitCov and CORD-19
2766Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world since the first cases of coronavirus disease 2019 (COVID-19) were observed in December 2019 in Wuhan, China. It has been suspected that infected persons who remain asymptomatic play a significant role in the ongoing pandemic, but their relative number and effect have been uncertain. The authors sought to review and synthesize the available evidence on asymptomatic SARS-CoV-2 infection. Asymptomatic persons seem to account for approximately 40% to 45% of SARS-CoV-2 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. Asymptomatic infection may be associated with subclinical lung abnormalities, as detected by computed tomography. Because of the high risk for silent spread by asymptomatic persons, it is imperative that testing programs include those without symptoms. To supplement conventional diagnostic testing, which is constrained by capacity, cost, and its one-off nature, innovative tactics for public health surveillance, such as crowdsourcing digital wearable data and monitoring sewage sludge, might be helpful.

Ann Intern Med2020       LitCov and CORD-19
2767Long-Term Humoral Response After a Second Dose of SARS-CoV-2 mRNA Vaccine in Japanese Kidney Transplant Recipients  

N/A

Front Microbiol2022       LitCov
2768Anti-Spike Protein Assays to Determine SARS-CoV-2 Antibody Levels: a Head-to-Head Comparison of Five Quantitative Assays  

Reliable quantification of the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly relevant, e.g., for identifying possible vaccine failure and estimating the time of protection. Therefore, we evaluated five different anti-SARS-CoV-2 antibody assays regarding the quantification of anti-spike (S) antibodies. Sera from 69 SARS-CoV-2-naive individuals 21 ± 1 days after vaccination with a single dose of BNT162b2 (Pfizer/BioNTech) were tested using the following quantitative assays: Roche S total antibody, DiaSorin trimeric spike IgG, DiaSorin S1/S2 IgG, Abbott II IgG, and Serion/Virion IgG. Results were further compared to the percent inhibition calculated from a surrogate virus neutralization test (sVNT). Individual values were distributed over several orders of magnitude for all assays. Although the assays were in good overall agreement (ρ = 0.80 to 0.94), Passing-Bablok regression revealed systematic constant and proportional differences, which could not be eliminated by converting the results to binding antibody units (BAU) per milliliter, as suggested by the manufacturers. Seven (10%) individuals had negative sVNT results (i.e., <30% inhibition). These samples were identified by most assays and yielded significantly lower binding antibody levels. Although all assays showed good correlation, they were not interchangeable, even when converted to BAU per milliliter using the WHO international standard for SARS-CoV-2 immunoglobulin. This highlights the need for further standardization of SARS-CoV-2 serology. IMPORTANCE Reliable quantification of the antibody response to SARS-CoV-2 is highly relevant, e.g., for identifying possible vaccine failure and estimating the time of protection. We compared the performance of five CE marked tests that quantify antibodies against the viral spike protein. Our findings suggest that, although all assays showed good correlation, their results were not interchangeable, even when converted to BAU per milliliter using the WHO international standard for SARS-CoV-2 immunoglobulin. This highlights the need for further standardization of SARS-CoV-2 serology.

Microbiol Spectr2021       LitCov and CORD-19
2769Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells  

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused a large respiratory outbreak in Wuhan, China in December 2019, is currently spreading across many countries globally. Here, we show that a TMPRSS2-expressing VeroE6 cell line is highly susceptible to SARS-CoV-2 infection, making it useful for isolating and propagating SARS-CoV-2. Our results reveal that, in common with SARS- and Middle East respiratory syndrome-CoV, SARS-CoV-2 infection is enhanced by TMPRSS2.

Proc Natl Acad Sci U S A2020       LitCov and CORD-19
2770Safety and effectiveness of BNT162b2 mRNA Covid-19 vaccine in adolescents  

In South Korea, all 12th grade students (highs school seniors) were offered BNT162b2 vaccine starting July 19, 2021; while 10(th)-11(th) grade students were not eligible. We conducted a nationwide retrospective cohort study by to determine the safety and effectiveness of BNT162b2 mRNA Covid-19 vaccine in adolescents against SARS-CoV-2 infection. Among 444,313 persons who received the first dose of vaccine, reporting rate for myocarditis and/or pericarditis was 1.8 per 100,000 (95% C.I. 0.8 – 3.5) among first-dose recipients and 4.3 per 100,000 (95% C.I. 2.6 – 6.7) in second-dose recipients. Vaccine effectiveness against symptomatic/asymptomatic SARS-CoV-2 infection 14 days post-first dose vaccination was 91.1% (95% C.I. 89.6 – 92.5), and 14 days post-second dose was 99.1% (95% C.I. 98.5 – 99.5). In this retrospective cohort study, BNT162b2 vaccination was safe and was associated with a significantly lower risk of SARS-CoV-2 infection, suggesting that vaccination in adolescent may reduce the burden of Covid-19.

Vaccine2021       LitCov and CORD-19
2771Omicron: A Heavily Mutated SARS-CoV-2 Variant Exhibits Stronger Binding to ACE2 and Potently Escapes Approved COVID-19 Therapeutic Antibodies  

The new SARS-CoV-2 variant of concern “Omicron” was recently spotted in South Africa and spread quickly around the world due to its enhanced transmissibility. The variant became conspicuous as it harbors more than 30 mutations in the Spike protein with 15 mutations in the receptor-binding domain (RBD) alone, potentially dampening the potency of therapeutic antibodies and enhancing the ACE2 binding. More worrying, Omicron infections have been reported in vaccinees in South Africa and Hong Kong, and that post-vaccination sera poorly neutralize the new variant. Here, we investigated the binding strength of Omicron with ACE2 and monoclonal antibodies that are either approved by the FDA for COVID-19 therapy or undergoing phase III clinical trials. Computational mutagenesis and free energy perturbation could confirm that Omicron RBD binds ACE2 ~2.5 times stronger than prototype SARS-CoV-2. Notably, three substitutions, i.e., T478K, Q493K, and Q498R, significantly contribute to the binding energies and almost doubled the electrostatic potential (ELE) of the RBD(Omic)–ACE2 complex. Omicron also harbors E484A substitution instead of the E484K that helped neutralization escape of Beta, Gamma, and Mu variants. Together, T478K, Q493K, Q498R, and E484A substitutions contribute to a significant drop in the ELE between RBD(Omic)–mAbs, particularly in etesevimab, bamlanivimab, and CT-p59. AZD1061 showed a slight drop in ELE and sotrovimab that binds a conserved epitope on the RBD; therefore, it could be used as a cocktail therapy in Omicron-driven COVID-19. In conclusion, we suggest that the Spike mutations prudently devised by the virus facilitate the receptor binding, weakening the mAbs binding to escape the immune response.

Front Immunol2021       LitCov and CORD-19
2772Detection of SARS-CoV-2 VOC-Omicron using commercial sample-to-answer real-time RT-PCR platforms and melting curve-based SNP assays  

N/A

J Clin Virol Plus2022       LitCov
2773Comparison of SARS-CoV-2 Antibody Response Following Vaccination With BNT162b2 and mRNA-1273  

N/A

JAMA2021       LitCov and CORD-19
2774The Impact of the COVID-19 Outbreak on the Attendance of Patients with Surgical Complaints at a Tertiary Hospital Emergency Department  

N/A

J Laparoendosc Adv Surg Tech A2020       LitCov and CORD-19
2775The use of the health belief model to assess predictors of intent to receive the COVID-19 vaccine and willingness to pay  

N/A

Hum Vaccin Immunother2020       LitCov and CORD-19
2776Telehealth-Based Services During the COVID-19 Pandemic: A Systematic Review of Features and Challenges  

Background: As an ever-growing popular service, telehealth catered for better access to high-quality healthcare services. It is more valuable and cost-effective, particularly in the middle of the current COVID-19 pandemic. Accordingly, this study aimed to systematically review the features and challenges of telehealth-based services developed to support COVID-19 patients and healthcare providers. Methods: A comprehensive search was done for the English language and peer-reviewed articles published until November 2020 using PubMed and Scopus electronic databases. In this review paper, only studies focusing on the telehealth-based service to support COVID-19 patients and healthcare providers were included. The first author's name, publication year, country of the research, study objectives, outcomes, function type including screening, triage, prevention, diagnosis, treatment or follow-up, target population, media, communication type, guideline-based design, main findings, and challenges were extracted, classified, and tabulated. Results: Of the 5,005 studies identified initially, 64 met the eligibility criteria. The studies came from 18 countries. Most of them were conducted in the United States and China. Phone calls, mobile applications, videoconferencing or video calls, emails, websites, text messages, mixed-reality, and teleradiology software were used as the media for communication. The majority of studies used a synchronous communication. The articles addressed the prevention, screening, triage, diagnosis, treatment, and follow-up aspects of COVID-19 which the most common purpose was the patients' follow-up (34/64, 53%). Thirteen group barriers were identified in the literature, which technology acceptance and user adoption, concerns about the adequacy and accuracy of subjective patient assessment, and technical issues were the most frequent ones. Conclusion: This review revealed the usefulness of telehealth-based services during the COVID-19 outbreak and beyond. The features and challenges identified through the literature can be helpful for a better understanding of current telehealth approaches and pointed out the need for clear guidelines, scientific evidence, and innovative policies to implement successful telehealth projects.

Front Public Health2021       LitCov and CORD-19
2777Comparison of mRNA-1273 and BNT162b2 SARS-CoV-2 mRNA Vaccine Immunogenicity in Kidney Transplant Recipients  

Transpl Int2021       LitCov and CORD-19
2778Analysis of post-COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome  

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19) triggers the development of numerous pathologies and infection-linked complications and exacerbates existing pathologies in nearly all body systems. Aside from the primarily targeted respiratory organs, adverse SARS-CoV-2 effects were observed in nervous, cardiovascular, gastrointestinal/metabolic, immune, and other systems in COVID-19 survivors. Long-term effects of this viral infection have been recently observed and represent distressing sequelae recognised by the World Health Organisation (WHO) as a distinct clinical entity defined as post-COVID-19 condition. Considering the pandemic is still ongoing, more time is required to confirm post COVID-19 condition diagnosis in the COVID-19 infected cohorts, although many reported post COVID-19 symptoms overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). AIMS OF REVIEW: In this study, COVID-19 clinical presentation and associated post-infection sequelae (post-COVID-19 condition) were reviewed and compared with ME/CFS symptomatology. KEY SCIENTIFIC CONCEPTS OF REVIEW: The onset, progression, and symptom profile of post COVID-19 condition patients have considerable overlap with ME/CFS. Considering the large scope and range of pro-inflammatory effects of this virus, it is reasonable to expect development of post COVID-19 clinical complications in a proportion of the affected population. There are reports of a later debilitating syndrome onset three months post COVID-19 infection (often described as long-COVID-19), marked by the presence of fatigue, headache, cognitive dysfunction, post-exertional malaise, orthostatic intolerance, and dyspnoea. Acute inflammation, oxidative stress, and increased levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα), have been reported in SARS-CoV-2 infected patients. Longitudinal monitoring of post COVID-19 patients is warranted to understand the long-term effects of SARS-CoV-2 infection and the pathomechanism of post COVID-19 condition.

J Adv Res2021       LitCov and CORD-19
2779The Impact of Public Health Events on COVID-19 Vaccine Hesitancy on Chinese Social Media: National Infoveillance Study  

BACKGROUND: The ongoing COVID-19 pandemic has brought unprecedented challenges to every country worldwide. A call for global vaccination for COVID-19 plays a pivotal role in the fight against this virus. With the development of COVID-19 vaccines, public willingness to get vaccinated has become an important public health concern, considering the vaccine hesitancy observed worldwide. Social media is powerful in monitoring public attitudes and assess the dissemination, which would provide valuable information for policy makers. OBJECTIVE: This study aimed to investigate the responses of vaccine positivity on social media when major public events (major outbreaks) or major adverse events related to vaccination (COVID-19 or other similar vaccines) were reported. METHODS: A total of 340,783 vaccine-related posts were captured with the poster’s information on Weibo, the largest social platform in China. After data cleaning, 156,223 posts were included in the subsequent analysis. Using pandas and SnowNLP Python libraries, posts were classified into 2 categories, positive and negative. After model training and sentiment analysis, the proportion of positive posts was computed to measure the public positivity toward the COVID-19 vaccine. RESULTS: The positivity toward COVID-19 vaccines in China tends to fluctuate over time in the range of 45.7% to 77.0% and is intuitively correlated with public health events. In terms of gender, males were more positive (70.0% of the time) than females. In terms of region, when regional epidemics arose, not only the region with the epidemic and surrounding regions but also the whole country showed more positive attitudes to varying degrees. When the epidemic subsided temporarily, positivity decreased with varying degrees in each region. CONCLUSIONS: In China, public positivity toward COVID-19 vaccines fluctuates over time and a regional epidemic or news on social media may cause significant variations in willingness to accept a vaccine. Furthermore, public attitudes toward COVID-19 vaccination vary from gender and region. It is crucial for policy makers to adjust their policies through the use of positive incentives with prompt responses to pandemic-related news to promote vaccination acceptance.

JMIR Public Health Surveill2021       LitCov and CORD-19
2780Delay or Avoidance of Medical Care Because of COVID-19-Related Concerns-United States, June 2020  

Temporary disruptions in routine and nonemergency medical care access and delivery have been observed during periods of considerable community transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). However, medical care delay or avoidance might increase morbidity and mortality risk associated with treatable and preventable health conditions and might contribute to reported excess deaths directly or indirectly related to COVID-19 (2). To assess delay or avoidance of urgent or emergency and routine medical care because of concerns about COVID-19, a web-based survey was administered by Qualtrics, LLC, during June 24-30, 2020, to a nationwide representative sample of U.S. adults aged ≥18 years. Overall, an estimated 40.9% of U.S. adults have avoided medical care during the pandemic because of concerns about COVID-19, including 12.0% who avoided urgent or emergency care and 31.5% who avoided routine care. The estimated prevalence of urgent or emergency care avoidance was significantly higher among the following groups: unpaid caregivers for adults* versus noncaregivers (adjusted prevalence ratio [aPR] = 2.9); persons with two or more selected underlying medical conditions† versus those without those conditions (aPR = 1.9); persons with health insurance versus those without health insurance (aPR = 1.8); non-Hispanic Black (Black) adults (aPR = 1.6) and Hispanic or Latino (Hispanic) adults (aPR = 1.5) versus non-Hispanic White (White) adults; young adults aged 18-24 years versus adults aged 25-44 years (aPR = 1.5); and persons with disabilities§ versus those without disabilities (aPR = 1.3). Given this widespread reporting of medical care avoidance because of COVID-19 concerns, especially among persons at increased risk for severe COVID-19, urgent efforts are warranted to ensure delivery of services that, if deferred, could result in patient harm. Even during the COVID-19 pandemic, persons experiencing a medical emergency should seek and be provided care without delay (3).

MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
2781Discrimination of False Negative Results in RT-PCR Detection of SARS-CoV-2 RNAs in Clinical Specimens by Using an Internal Reference  

Reverse transcription-polymerase chain reaction (RT-PCR) is an essential method for specific diagnosis of SARS-CoV-2 infection. Unfortunately, false negative test results are often reported. In this study, we attempted to determine the principal causes leading to false negative results of RT-PCR detection of SARS-CoV-2 RNAs in respiratory tract specimens. Multiple sputum and throat swab specimens from 161 confirmed COVID-19 patients were tested with a commercial fluorescent RT-PCR kit targeting the ORF1ab and N regions of SARS-CoV-2 genome. The RNA level of a cellular housekeeping gene ribonuclease P/MRP subunit p30 (RPP30) in these specimens was also assessed by RT-PCR. Data for a total of 1052 samples were retrospectively re-analyzed and a strong association between positive results in SARS-CoV-2 RNA tests and high level of RPP30 RNA in respiratory tract specimens was revealed. By using the ROC-AUC analysis, we identified Ct cutoff values for RPP30 RT-PCR which predicted false negative results for SARS-CoV-2 RT-PCR with high sensitivity (95.03%–95.26%) and specificity (83.72%–98.55%) for respective combination of specimen type and amplification reaction. Using these Ct cutoff values, false negative results could be reliably identified. Therefore, the presence of cellular materials, likely infected host cells, are essential for correct SARS-CoV-2 RNA detection by RT-PCR in patient specimens. RPP30 could serve as an indicator for cellular content, or a surrogate indicator for specimen quality. In addition, our results demonstrated that false negativity accounted for a vast majority of contradicting results in SARS-CoV-2 RNA test by RT-PCR. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-020-00273-8) contains supplementary material, which is available to authorized users.

Virol Sin2020       LitCov and CORD-19
2782Evaluation of stress and anxiety caused by the COVID-19 pandemic in pediatric radiology  

BACKGROUND: Work-related stress and burnout were documented to be high among pediatric radiologists prior to the coronavirus disease 2019 (COVID-19) pandemic. New challenges arose from the COVID-19 pandemic, potentially introducing new stressors and anxieties. OBJECTIVE: To evaluate potential sources of stress and anxiety for pediatric radiology faculty during the early phase of the COVID-19 pandemic. MATERIALS AND METHODS: We conducted a survey of attending physician members of the Society for Pediatric Radiology in North America from April 27, 2020, to May 22, 2020. The response rate was 21% (251/1,206). Survey questions included demographic information and questions regarding working remotely, personal protective equipment, redeployment, personal wellness, wellness resources and financial concerns. A psychometrician reviewed the questions to ensure minimal risk of misinterpretation. RESULTS: Median age of respondents was 48 years (range 33–70 years) with median number of years in practice of 14 (range 1–45 years). Fifty-three percent of respondents were women and 46% were men. Because of an increase in remote work, 69% of respondents endorsed feeling more isolated from a lack of regular interaction with colleagues. Fifty-three percent of respondents indicated that it is challenging to work remotely while overseeing home schooling for children. In comparison to men, women reported overall higher work-related stress and anxiety (P=0.02), higher feelings of guilt from radiology staff (i.e. technologists and nurses) being more exposed to COVID-19 (P=0.02) and higher levels of stress providing for dependents (P=0.04). Most respondents thought that departmental leadership was effective and respondents were not concerned about meeting financial obligations or job loss. CONCLUSION: The early phase of the COVID-19 pandemic caused additional stress and anxiety for pediatric radiology faculty and disproportionally affected women. Given the continuously evolving state of the COVID-19 pandemic, these results could aid in planning and implementation of future strategies to combat burnout in radiology. Specific attention should be directed to different stressors experienced by female versus male radiologists, especially in regard to dependent care. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00247-021-05088-7.

Pediatr Radiol2021       LitCov and CORD-19
2783Comparison of Patients Infected With Delta Versus Omicron COVID-19 Variants Presenting to Paris Emergency Departments: A Retrospective Cohort Study  

BACKGROUND: At the end of 2021, the B.1.1.529 SARS-CoV-2 variant (Omicron) wave superseded the B.1.617.2 variant (Delta) wave. OBJECTIVE: To compare baseline characteristics and in-hospital outcomes of patients with SARS-CoV-2 infection with the Delta variant versus the Omicron variant in the emergency department (ED). DESIGN: Retrospective chart reviews. SETTING: 13 adult EDs in academic hospitals in the Paris area from 29 November 2021 to 10 January 2022. PATIENTS: Patients with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test result for SARS-CoV-2 and variant identification. MEASUREMENTS: Main outcome measures were baseline clinical and biological characteristics at ED presentation, intensive care unit (ICU) admission, mechanical ventilation, and in-hospital mortality. RESULTS: A total of 3728 patients had a positive RT-PCR test result for SARS-CoV-2 during the study period; 1716 patients who had a variant determination (818 Delta and 898 Omicron) were included. Median age was 58 years, and 49% were women. Patients infected with the Omicron variant were younger (54 vs. 62 years; difference, 8.0 years [95% CI, 4.6 to 11.4 years]), had a lower rate of obesity (8.0% vs. 12.5%; difference, 4.5 percentage points [CI, 1.5 to 7.5 percentage points]), were more vaccinated (65% vs. 39% for 1 dose and 22% vs. 11% for 3 doses), had a lower rate of dyspnea (26% vs. 50%; difference, 23.6 percentage points [CI, 19.0 to 28.2 percentage points]), and had a higher rate of discharge home from the ED (59% vs. 37%; difference, 21.9 percentage points [−26.5 to −17.1 percentage points]). Compared with Delta, Omicron infection was independently associated with a lower risk for ICU admission (adjusted difference, 11.4 percentage points [CI, 8.4 to 14.4 percentage points]), mechanical ventilation (adjusted difference, 3.6 percentage points [CI, 1.7 to 5.6 percentage points]), and in-hospital mortality (adjusted difference, 4.2 percentage points [CI, 2.0 to 6.5 percentage points]). LIMITATION: Patients with COVID-19 illness and no SARS-CoV-2 variant determination in the ED were excluded. CONCLUSION: Compared with the Delta variant, infection with the Omicron variant in patients in the ED had different clinical and biological patterns and was associated with better in-hospital outcomes, including higher survival. PRIMARY FUNDING SOURCE: None.

Ann Intern Med2022       LitCov and CORD-19
2784Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19  

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate these deleterious events by inciting inflammatory and microvascular thrombotic processes. Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein. In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction. Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells. Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process.

Viruses2020       LitCov and CORD-19
2785Factors Associated With Death in Critically Ill Patients With COVID-19 in the US  

N/A

JAMA Intern Med2020       LitCov and CORD-19
2786Adolescent psychiatric disorders during the COVID-19 pandemic and lockdown  

The aim of this paper was to review the literature on adolescent psychiatric disorders related to the COVID-19 pandemic and lockdown. Stressful life events, extended home confinement, brutal grief, intrafamilial violence, overuse of the Internet and social media are factors that could influence the mental health of adolescents during this period. The COVID-19 pandemic could result in increased psychiatric disorders such as Post-Traumatic Stress, Depressive, and Anxiety Disorders, as well as grief-related symptoms. Adolescents with psychiatric disorders are at risk of a break or change in their care and management; they may experience increased symptoms. The COVID-19 pandemic and lockdown may have a negative impact on the mental health of adolescents, although there is still no data on the long term impact of this crisis. Adolescents’ individual, familial, and social vulnerability, as well as individual and familial coping abilities, are factors related to adolescent mental health in times of crisis. Adolescents are often vulnerable and require careful consideration by caregivers and healthcare system adaptations to allow for mental health support despite the lockdown. Research on adolescent psychiatric disorders in times of pandemics is necessary, as such a global situation could be prolonged or repeated.

Psychiatry Res2020       LitCov and CORD-19
2787Association of initial COVID-19 vaccine hesitancy with subsequent vaccination among pregnant and postpartum individuals  

OBJECTIVE: To examine the association between initial COVID‐19 vaccine hesitancy and subsequent vaccination among pregnant and postpartum individuals. DESIGN: Prospective cohort SETTING: A Midwestern tertiary care academic medical center. Individuals completed a baseline vaccine hesitancy assessment from 03/22/21 to 04/02/21, with subsequent ascertainment of vaccination status at 3 to 6 months follow‐up. METHODS: We used multivariable Poisson regression to estimate the relative risk of vaccination by baseline vaccine hesitancy status, and then characteristics associated with vaccination. MAIN OUTCOMES: Self‐report of COVID‐19 vaccination, and secondarily, consideration of COVID‐19 vaccination among those not vaccinated. RESULTS: Of 456 individuals (93% pregnant, 7% postpartum) initially surveyed, 290 individuals (64%; 23% pregnant, 77% postpartum) provided subsequent vaccination status (median=17 weeks). Forty percent (116/290) reported COVID‐19 vaccine hesitancy at enrollment, of whom 52% reported subsequent vaccination at follow‐up. Few individuals transitioned during the study period from vaccine hesitant to vaccinated (10%); in comparison, 80% of those who were not vaccine hesitant were vaccinated at follow‐up (aRR: 0.19; 95% CI: 0.11, 0.33). Among those who remained unvaccinated at follow‐up, 38% who were vaccine hesitant at baseline were considering vaccination compared to 71% who were not vaccine hesitant (aRR: 0.48; 95% CI: 0.33, 0.67). Individuals who were older, parous, employed, and of higher educational attainment were more likely to be vaccinated, and those who identified as non‐Hispanic Black, were Medicaid beneficiaries, and still pregnant at follow‐up were less likely to be vaccinated. CONCLUSIONS: COVID‐19 vaccine hesitancy persisted over time in the peripartum period, and few individuals who reported hesitancy at baseline were later vaccinated. Interventions that address vaccine hesitancy in pregnancy are needed. FUNDING: Ms. Germann was supported by the New York Academy of Medicine David E. Rogers Fellowship Program. Dr. Venkatesh was supported by the Care Innovation and Community Improvement Program and the Division of Maternal Fetal Medicine at The Ohio State University Wexner Medical Center.

BJOG2022       LitCov and CORD-19
2788Hospitalization and Critical Care of 109 Decedents with COVID-19 Pneumonia in Wuhan, China  

Rationale: The current outbreak of coronavirus disease (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, spreads across national and international borders. The overall death rate of COVID-19 pneumonia in the Chinese population was 4%. Objectives: To describe the process of hospitalization and critical care of patients who died of COVID-19 pneumonia. Methods: This was a multicenter observational study of 109 decedents with COVID-19 pneumonia from three hospitals in Wuhan. Demographic, clinical, laboratory, and treatment data were collected and analyzed, and the final date of follow-up was February 24, 2020. Results: The mean age of 109 decedents with COVID-19 pneumonia was 70.7 years, 35 patients (32.1%) were female, and 85 patients (78.0%) suffered from one or more underlying comorbidities. Multiple organ failure, especially respiratory failure and heart failure, appeared in all patients even at the early stage of disease. Overall, the mean time from onset of symptoms to death was 22.3 days. All 109 hospitalized patients needed admission to an intensive care unit (ICU); however, because of limited availability, only 51 (46.8%) could be admitted. The period from hospitalization to death in the ICU group and non-ICU group was 15.9 days (standard deviation = 8.8 d) and 12.5 days (8.6 d, P = 0.044), respectively. Conclusions: Mortality due to COVID-19 pneumonia was concentrated in patients above the age of 65 years, especially those with major comorbidities. Patients who were admitted to the ICU lived longer than those who were not. Our findings should aid in the recognition and clinical management of such infections, especially with regard to ICU resource allocation.

Ann Am Thorac Soc2020       LitCov and CORD-19
2789Quantifying the impact of quarantine duration on COVID-19 transmission  

The large number of individuals placed into quarantine because of possible severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) exposure has high societal and economic costs. There is ongoing debate about the appropriate duration of quarantine, particularly since the fraction of individuals who eventually test positive is perceived as being low. We use empirically determined distributions of incubation period, infectivity, and generation time to quantify how the duration of quarantine affects onward transmission from traced contacts of confirmed SARS-CoV-2 cases and from returning travellers. We also consider the roles of testing followed by release if negative (test-and-release), reinforced hygiene, adherence, and symptoms in calculating quarantine efficacy. We show that there are quarantine strategies based on a test-and-release protocol that, from an epidemiological viewpoint, perform almost as well as a 10-day quarantine, but with fewer person-days spent in quarantine. The findings apply to both travellers and contacts, but the specifics depend on the context.

Elife2021       LitCov and CORD-19
2790Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China  

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China has been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients in and outside of Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicenter as well the administrative center of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: Upon data cut-off (Jan 31st, 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597/647, 92.3%) were older (mean: 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations, and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei [severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, hazards ratio (HR) for critical illness 1.59, 95%CI 1.05–2.41] have a poorer prognosis compared with patients outside of Hubei after adjusting for age and comorbidity. However, among patients outside of Hubei, the duration from symptom onset to hospitalisation (mean: 4.4 versus 4.7 days) and prognosis (HR 0.84, 95%CI 0.40–1.80) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR 1.05, 1.01–1.08). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicenter. Future studies to determine the reason for delaying hospitalisation are warranted.

Eur Respir J2020       LitCov and CORD-19
2791Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders  

BACKGROUND: To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset. METHODS: SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins. RESULTS: Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset. CONCLUSIONS: Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.

PLoS One2020       LitCov and CORD-19
2792Coinfections with Other Respiratory Pathogens among Patients with COVID-19  

Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are at an increased risk for coinfections; therefore, physicians need to be cognizant about excluding other treatable respiratory pathogens. Here, we report coinfection with SARS-CoV-2 and other respiratory pathogens in patients admitted to the coronavirus disease (COVID) care facilities of an Indian tertiary care hospital. From June 2020 through January 2021, we tested 191 patients with SARS-CoV-2 for 33 other respiratory pathogens using an fast track diagnostics respiratory pathogen 33 (FTD-33) assay. Additionally, information regarding other relevant respiratory pathogens was collected by reviewing their laboratory data. Overall, 13 pathogens were identified among patients infected with SARS-CoV-2, and 46.6% (89/191) of patients had coinfection with one or more additional pathogens. Bacterial coinfections (41.4% [79/191]) were frequent, with Staphylococcus aureus being the most common, followed by Klebsiella pneumoniae. Coinfections with SARS-CoV-2 and Pneumocystis jirovecii or Legionella pneumophila were also identified. The viral coinfection rate was 7.3%, with human adenovirus and human rhinovirus being the most common. Five patients in our cohort had positive cultures for Acinetobacter baumannii and K. pneumoniae, and two patients had active Mycobacterium tuberculosis infection. In total, 47.1% (90/191) of patients with coinfections were identified. The higher proportion of patients with coinfections in our cohort supports the systemic use of antibiotics in patients with severe SARS-CoV-2 pneumonia with rapid de-escalation based on respiratory PCR/culture results. The timely and simultaneous identification of coinfections can contribute to improved health of COVID-19 patients and enhanced antibiotic stewardship during the pandemic. IMPORTANCE Coinfections in COVID-19 patients may worsen disease outcomes and need further investigation. We found that a higher proportion of patients with COVID-19 were coinfected with one or more additional pathogens. A better understanding of the prevalence of coinfection with other respiratory pathogens in COVID-19 patients and the profile of pathogens can contribute to effective patient management and antibiotic stewardship during the current pandemic.

Microbiol Spectr2021       LitCov and CORD-19
2793The Cross-Sectional Relations of COVID-19 Fear and Stress to Psychological Distress among Frontline Healthcare Workers in Selangor, Malaysia  

Previous pandemics have demonstrated short and long-term impacts on healthcare workers’ mental health, causing knock-on effects on patient care and professional functioning. Indeed, the present COVID-19 pandemic has created unprecedented disruption in social interactions and working conditions. Malaysia has been under the Recovery Movement Control Order since June 2020; however, with the upsurge of cases, healthcare workers face pressure not only from working in resource-deprived settings but also from the increasing patient load. The primary objective of the present study was to examine the cross-sectional relationship of COVID-19 fear and stress to psychological distress (operationalized as anxiety and depression) in healthcare workers. The present sample included 286 frontline healthcare workers from three hospitals in Selangor, Malaysia. Self-administered questionnaires containing sociodemographic and occupational items, the Malay versions of the Coronavirus Stress Measure scale, the Fear of Coronavirus-19 scale, the Generalized Anxiety Disorder-7, and the Patient Health Questionnaire-9 were distributed via online platforms. Hierarchical multiple regression findings suggest that age, shift work, and COVID-19 stress consistently predicted anxiety and depression among frontline healthcare workers after adjusting for sociodemographic and occupational variables. The present findings suggest that frontline healthcare workers are not only inoculated against COVID-19 itself but also against the psychological sequelae of the pandemic.

Int J Environ Res Public Healt2021       LitCov and CORD-19
2794Jordanians' willingness to receive heterologous prime-boost COVID-19 vaccination and vaccine boosters  

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Eur Rev Med Pharmacol Sci2021       LitCov and CORD-19
2795Plant-Produced Glycosylated and In Vivo Deglycosylated Receptor Binding Domain Proteins of SARS-CoV-2 Induce Potent Neutralizing Responses in Mice  

The COVID-19 pandemic, caused by SARS-CoV-2, has rapidly spread to more than 222 countries and has put global public health at high risk. The world urgently needs cost-effective and safe SARS-CoV-2 vaccines, antiviral, and therapeutic drugs to control it. In this study, we engineered the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein and produced it in the plant Nicotiana benthamiana in a glycosylated and deglycosylated form. Expression levels of both glycosylated (gRBD) and deglycosylated (dRBD) RBD were greater than 45 mg/kg fresh weight. The purification yields were 22 mg of pure protein/kg of plant biomass for gRBD and 20 mg for dRBD, which would be sufficient for commercialization of these vaccine candidates. The purified plant-produced RBD protein was recognized by an S protein-specific monoclonal antibody, demonstrating specific reactivity of the antibody to the plant-produced RBD proteins. The SARS-CoV-2 RBD showed specific binding to angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 receptor. In mice, the plant-produced RBD antigens elicited high titers of antibodies with a potent virus-neutralizing activity. To our knowledge, this is the first report demonstrating that mice immunized with plant-produced deglycosylated RBD form elicited high titer of RBD-specific antibodies with potent neutralizing activity against SARS-CoV-2 infection. Thus, obtained data support that plant-produced glycosylated and in vivo deglycosylated RBD antigens, developed in this study, are promising vaccine candidates for the prevention of COVID-19.

Viruses2021       LitCov and CORD-19
2796Clinical, radiological and laboratory characteristics and risk factors for severity and mortality of 289 hospitalized COVID-19 patients  

BACKGROUND: The coronavirus disease 2019 (COVID‐19) has become a global pandemic, with 10‐20% of severe cases and over 508,000 deaths worldwide. OBJECTIVE: This study aims to address the risk factors associated with the severity of COVID‐19 patients and the mortality of severe patients. METHODS: 289 hospitalized laboratory‐confirmed COVID‐19 patients were included in this study. Electronic medical records, including patient demographics, clinical manifestation, comorbidities, laboratory tests results, and radiological materials were collected and analyzed. According to the severity and outcomes of the patients, they were divided into three groups: non‐survived (n=49), survived severe (n=78), and non‐severe (n=162) groups. Clinical, laboratory and radiological data were compared among these groups. Principal component analysis (PCA) was applied to reduce the dimensionality and visualize the patients on a low‐dimensional space. Correlations between clinical, radiological and laboratory parameters were investigated. Univariate and multivariate logistic regression methods were used to determine the risk factors associated with mortality in severe patients. Longitudinal changes of laboratory findings of survived severe cases and non‐survived cases during hospital stay were also collected. RESULTS: Of the 289 patients, the median age was 57 years (range, 22 ‐ 88) and 155 (53.4%) patients were male. As of the final follow‐up date of this study, 240 (83.0%) patients were discharged from the hospital and 49 (17.0%) patients died. Elder age, underlying comorbidities, and increased laboratory variables, such as leucocyte count, neutrophil count, neutrophil‐to‐lymphocyte ratio (NLR), C‐reactive protein (CRP), procalcitonin (PCT), D‐dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) on admission were found in survived severe cases compared to non‐severe cases. According to the multivariate logistic regression analysis, elder age, a higher number of affected lobes, elevated CRP levels on admission, increased prevalence of chest tightness/dyspnea and smoking history were independent risk factors for death of severe patients. A trajectory in PCA was observed from non‐severe towards non‐survived via severe and survived patients. Strong correlations between the age of patients, the affected lobe numbers and laboratory variables were identified. Dynamic changes of laboratory findings of survived severe cases and non‐survived cases during hospital stay showed that continuing increase of leucocytes and neutrophil count, sustained lymphopenia and eosinopenia, progressing decrease in platelet count, as well as high levels of NLR, CRP, PCT, AST, BUN, and serum creatinine were associated with in‐hospital death. CONCLUSIONS: Survived severe and non‐survived COVID‐19 patients had distinct clinical and laboratory characteristics, which were separated by principle component analysis. Elder age, increased number of affected lobes, higher levels of serum CRP, chest tightness/dyspnea, and smoking history were risk factors for mortality of severe COVID‐19 patients. Longitudinal changes of laboratory findings may be helpful in predicting disease progression and clinical outcome of severe patients.

Allergy2020       LitCov and CORD-19
2797Multisystem inflammatory syndrome in children during the COVID-19 pandemic in Turkey: first report from the Eastern Mediterranean  

OBJECTIVE: We aimed to describe the typical clinical and laboratory features and treatment of children diagnosed with multisystem inflammatory syndrome in children (MIS-C) and to understand the differences as compared to severe/critical pediatric cases with COVID-19 in an eastern Mediterranean country. METHODS: Children (aged <18 years) who diagnosed with MIS-C and severe/critical pediatric cases with COVID-19 and were admitted to hospital between March 26 and November 3, 2020 were enrolled in the study. RESULTS: A total of 52 patients, 22 patients diagnosed with COVID-19 with severe/critical disease course and 30 patients diagnosed with MIS-C, were included in the study. Although severe COVID-19 cases and cases with MIS-C share many clinical and laboratory features, MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe cases (p<0.001 for each). Of all, 53.3% of MIS-C cases had the evidence of myocardial involvement as compared to severe cases (27.2%). Additionally, C-reactive protein (CRP) and white blood cell (WBC) are the independent predictors for the diagnosis of MIS-C, particularly in the existence of conjunctival injection and rash. Corticosteroids, intravenous immunoglobulin (IVIG), and biologic immunomodulatory treatments were mainly used in MIS-C cases rather than cases with severe disease course. There were only three deaths among 52 patients, one of whom had Burkitt lymphoma and the two cases with severe COVID-19 of late referral. CONCLUSION: Differences between clinical presentations, acute phase responses, organ involvements, and management strategies indicate that MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19. Conjunctival injection and higher CRP and low WBC count are reliable diagnostic parameters for MIS-C cases.

Clin Rheumatol2021       LitCov and CORD-19
2798Student-led curricular approaches in medical education: the educational effects of a virtual fundamentals of COVID-19 course  

BACKGROUND: As the field of education was adapting to virtual learning during the COVID-19 pandemic, a need quickly emerged for a course to prepare medical students for future clinical practice. This call to action was answered by creating an innovative Fundamentals of COVID-19 course at the Indiana University School of Medicine (IUSM). As a group of medical student leaders at IUSM, we developed this online course in order to support our fellow students and the community. METHODS: The study examined the educational effects of completing the Fundamentals of COVID-19 course. In order to examine these effects, the study asked enrolled students to complete both a pre- and post-course self-assessment survey. Students were asked an identical set of questions on each survey about their knowledge, skills, and abilities (KSA) regarding COVID-19. Composite scores were created for each KSA learning domain. Responses were provided using a five-point Likert scale ranging from 1 = strongly disagree to 5 = strongly agree. RESULTS: Out of the 724 students enrolled, 645 students completed both the pre- and post-course assessment surveys. Findings show that there were both meaningful and statistically significant differences in students’ responses to the pre- and post-course surveys. Results show 1.) a significant mean increase in the knowledge composite score of 1.01, 95% CI [0.95, 1.06], t(644) = 36.4, p < .001, d = 1.43; 2.) a significant mean increase in the skills composite score of .55, 95% CI [0.50, 0.60], t(644) = 20.70, p < .001, d = 0.81. and 3.) a significant mean increase of the abilities composite score of 1.02, 95% CI [.97, 1.07], t(644) = 36.56, p < .001, d = 1.44. CONCLUSIONS: These findings demonstrate that the student-developed, online Fundamentals of COVID-19 course resulted in notable and statistically significant educational effects. The increase in students’ self-reported ratings, especially in the knowledge and abilities domains, indicate that meaningful learning occurred within the course. These findings have notable implications for medical student training during healthcare emergencies, such as a pandemic, as well as within modern clerkship environments. Overall, our findings provide evidence that student-led curricular design and virtual delivery of course content can be effective tools in undergraduate medical education. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12909-021-03076-x.

BMC Med Educ2022       LitCov and CORD-19
2799The Influence of Social Distancing Behaviors and Psychosocial Factors on Physical Activity During the COVID-19 Pandemic: Cross-sectional Survey Study  

BACKGROUND: The COVID-19 pandemic has arguably facilitated a shift toward increased sedentariness and reduced physical activity. Moreover, there is mounting evidence that mental health has also declined during the pandemic. However, it remains unknown to what extent social distancing (SD) behaviors and mental health have affected the physical activity levels of the general population. OBJECTIVE: The purpose of this study was to determine the influence of SD behaviors and prevailing mental health on the odds of being physically active during the early COVID-19 pandemic response. METHODS: A total of 4819 adults (2474/4819, 51.3%, female) from the US population with a median age of 46 (IQR 35-59) completed an online survey during the early pandemic response (April-June 2020). The survey included questions on adherence to 11 SD behaviors, and validated questionnaires which assessed self-reported physical activity, depression, anxiety, and mental well-being. Respondents were categorized into 2 physical activity groups: inactive (0-599 metabolic equivalent of task [MET]-minutes/week) and active (≥600 MET-minutes/week). A logistic generalized additive model (GAM) was used to determine which SD factors and mental health outcomes were associated with physical activity level. RESULTS: The GAM analysis revealed that wearing a facemask in public (odds ratio [OR] 1.46, 95% CI 1.14-1.79; P=.003), limiting the use of public transport (OR 1.47, 95% CI 1.19-1.83; P=.001), and restricting travel outside the house (OR 1.56, 95% CI 1.19-2.05; P=.002) were SD behaviors associated with higher odds of being more physically active. Conversely, avoiding physical activity outside the house was associated with higher odds of being inactive (OR 0.52, 95% CI 0.46-0.63; P<.001). Leaving the house more frequently, and a higher mental well-being were associated with increasing odds of being physically active (P<.001). Engaging with a moderate number of SD behaviors (3-7 total) was positively associated with physical activity, whereas a very high SD vigilance (ie, engaging with ≥10 total behaviors) decreased the odds of being active during the early pandemic response. CONCLUSIONS: Based on the findings of our study, we suggest that future public health messaging of SD guidelines should include (1) a clear portrayal of the benefits of regular exercise on mental health; and (2) a specific focus on how to be physically active outdoors in a COVID-safe manner.

JMIR Public Health Surveill2021       LitCov and CORD-19
2800Flow controlled ventilation in Acute Respiratory Distress Syndrome associated with COVID-19: A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: This study aims to demonstrate the positive effects on oxygenation of flow-controlled ventilation compared to conventionally ventilated patients in patients suffering from Acute respiratory distress syndrome (ARDS) associated with COVID-19.We define ARDS according to the “Berlin” definition integrating the oxygenation index (P/F ratio), the level of Positive End Expiratory Pressure (PEEP), radiological and clinical findings. TRIAL DESIGN: This is a prospective, randomized (1:1 ratio), parallel group feasibility study in adult patients with proven COVID-19 associated ARDS. PARTICIPANTS: All adult patients admitted to the ICU of Hamad Medical Corporation facilities in Qatar because of COVID-19 infection who develop moderate to severe ARDS are eligible. The inclusion criteria are above 18 years of age, proven COVID-19 infection, respiratory failure necessitating intubation and mechanical ventilation, ARDS with a P/F ratio of at least 200mmHg or less and a minimum PEEP 5cmH2O, BMI less 30 kg/ m2. The following exclusion criteria: no written consent, chronic respiratory disease, acute or chronic cardiovascular disease, pregnancy or need for special therapy (prone position and/or Extracorporeal membrane oxygenation). INTERVENTION AND COMPARATOR: After randomisation, the group A patients will be ventilated with the test-device for 48 hours. The settings will be started with the pre-existing-PEEP. The upper pressure will be determined to achieve a tidal volume of 6 ml/kg lean body mass, while the respiratory rate will be set to maintain an arterial pH above 7.2. In group B, the ventilator settings will be adjusted by the attending ICU team in accordance with lung-protective ventilation strategy. All other treatment will be unchanged and according to our local policies/guidelines. MAIN OUTCOMES: The primary end point is PaO2. As this is a dynamic parameter, we will record it every 6-8 hours and analyse it sequentially. RANDOMISATION: The study team screens the ventilated patients who fulfil the inclusion criteria and randomise using a 1:1 allocation ratio after consenting using a closed envelope method. The latter were prepared and sealed in advance by an independent person. BLINDING (MASKING): Due to the technical nature of the study (use of a specific ventilator) blinding is only possible for the data-analysts and the patients. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size calculation based on the assumption of an effect size (change in PaO2) of 1.5 SDS in the primary endpoint (PaO2), an intended power of 80%, an alpha error of 5% and an equal sample ratio results in n=7 patients needed to treat. However, to compensate for dropouts we will include 10 patients in each group, which means in total 20 patients. TRIAL STATUS: The local registration number is MRC-05-018 with the protocol version number 3. The date of approval is 14(th) April 2020. Recruitment began 28th May 2020 and is expected to end in September 2020. TRIAL REGISTRATION: The protocol was registered before starting subject recruitment under the title: “Flow controlled ventilation in ARDS associated with COVID-19” in ClinicalTrials.org with the registration number: NCT04399317. Registered on 22 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19

(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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