\ 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
4501Protocol for a patient-reported experience measures (PREMs) survey of patients discharged during the COVID-19 pandemic and their family caregivers  

INTRODUCTION: In the Swiss canton of Valais, the first cases of SARS-CoV-2 were detected on 28 February 2020. Discharged patients’ and their family caregivers’ experiences in relation to safety, quality of care, trust and communication during the COVID-19 hospitalisation period remain unexplored. The study aims to collect the patient-reported experience measures (PREMs) survey of patients discharged during the COVID-19 pandemic and their family caregivers. METHODS AND ANALYSIS: Patients aged ≥18 years, hospitalised between 28 February and 11 May 2020 and then discharged home, plus their family caregivers will be invited to complete a self-administrated questionnaire made up of 14 closed questions and 1 open-ended question. The questionnaire will include items on the patient’s hospital trajectory and assess the interpersonal trust placed in nurses and physicians based on Krajewska-Kułak et al’s Trust in Nurse Scale and Anderson et al’s Trust in Physician Scale. Participants’ perceived stress will be assessed using Cohen et al’s Perceived Stress Scale. Feelings of safety will be examined based on Dryhurst et al’s questionnaire on Risk Perception During Pandemics. After ethical clearance, data will be collected using a postal paper questionnaire and via an online web link. Descriptive and inferential statistics will be computed, and the open question will undergo a qualitative thematic analysis. We will analyse perceptions of the different hospital trajectories experienced by patients undergoing surgery with and without a SARS-CoV-2 infection. ETHICS AND DISSEMINATION: The Human Research Ethics Committee of Vaud (2020-02025) authorised this study. Gathering experiences and learning about the impact of the COVID-19 pandemic on the social determinants of health among discharged patients and families fit in well with the Triple Aim framework and the PREMs survey. The study will formulate recommendations to support interventions in the face of the second wave of COVID-19 pandemic and their effects on patients’ and their family caregivers’ experiences.

BMJ Open2021       LitCov and CORD-19
4502Growth of Ambulatory Virtual Visits and Differential Use by Patient Sociodemographics at One Urban Academic Medical Center During the COVID-19 Pandemic: Retrospective Analysis  

BACKGROUND: Despite widespread interest in the use of virtual (ie, telephone and video) visits for ambulatory patient care during the COVID-19 pandemic, studies examining their adoption during the pandemic by race, sex, age, or insurance are lacking. Moreover, there have been limited evaluations to date of the impact of these sociodemographic factors on the use of telephone versus video visits. Such assessments are crucial to identify, understand, and address differences in care delivery across patient populations, particularly those that could affect access to or quality of care. OBJECTIVE: The aim of this study was to examine changes in ambulatory visit volume and type (ie, in-person vs virtual and telephone vs video visits) by patient sociodemographics during the COVID-19 pandemic at one urban academic medical center. METHODS: We compared volumes and patient sociodemographics (age, sex, race, insurance) for visits during the first 11 weeks following the COVID-19 national emergency declaration (March 15 to May 31, 2020) to visits in the corresponding weeks in 2019. Additionally, for visits during the COVID-19 study period, we examined differences in visit type (ie, in-person versus virtual, and telephone versus video visits) by sociodemographics using multivariate logistic regression. RESULTS: Total visit volumes in the COVID-19 study period comprised 51.4% of the corresponding weeks in 2019 (n=80,081 vs n=155,884 visits). Although patient sociodemographics between the COVID-19 study period in 2020 and the corresponding weeks in 2019 were similar, 60.5% (n=48,475) of the visits were virtual, compared to 0% in 2019. Of the virtual visits, 61.2% (n=29,661) were video based, and 38.8% (n=18,814) were telephone based. In the COVID-19 study period, virtual (vs in-person) visits were more likely among patients with race categorized as other (vs White) and patients with Medicare (vs commercial) insurance and less likely for men, patients aged 0-17 years, 65-74 years, or ≥75 years (compared to patients aged 18-45 years), and patients with Medicaid insurance or insurance categorized as other. Among virtual visits, compared to telephone visits, video visits were more likely to be adopted by patients aged 0-17 years (vs 18-45 years), but less likely for all other age groups, men, Black (vs White) patients, and patients with Medicare or Medicaid (vs commercial) insurance. CONCLUSIONS: Virtual visits comprised the majority of ambulatory visits during the COVID-19 study period, of which a majority were by video. Sociodemographic differences existed in the use of virtual versus in-person and video versus telephone visits. To ensure equitable care delivery, we present five policy recommendations to inform the further development of virtual visit programs and their reimbursement.

JMIR Med Inform2020       LitCov and CORD-19
4503COVID-19 Autopsies, Oklahoma, USA  

OBJECTIVES: To report the methods and findings of two complete autopsies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals who died in Oklahoma (United States) in March 2020. METHODS: Complete postmortem examinations were performed according to standard procedures in a negative-pressure autopsy suite/isolation room using personal protective equipment, including N95 masks, eye protection, and gowns. The diagnosis of coronavirus disease 2019 (COVID-19) was confirmed by real-time reverse transcriptase polymerase chain reaction testing on postmortem swabs. RESULTS: A 77-year-old obese man with a history of hypertension, splenectomy, and 6 days of fever and chills died while being transported for medical care. He tested positive for SARS-CoV-2 on postmortem nasopharyngeal and lung parenchymal swabs. Autopsy revealed diffuse alveolar damage and chronic inflammation and edema in the bronchial mucosa. A 42-year-old obese man with a history of myotonic dystrophy developed abdominal pain followed by fever, shortness of breath, and cough. Postmortem nasopharyngeal swab was positive for SARS-CoV-2; lung parenchymal swabs were negative. Autopsy showed acute bronchopneumonia with evidence of aspiration. Neither autopsy revealed viral inclusions, mucus plugging in airways, eosinophils, or myocarditis. CONCLUSIONS: SARS-CoV-2 testing can be performed at autopsy. Autopsy findings such as diffuse alveolar damage and airway inflammation reflect true virus-related pathology; other findings represent superimposed or unrelated processes.

Am J Clin Pathol2020       LitCov and CORD-19
4504ImmunosuppressiveTherapies Differently Modulate Humoral- and T-Cell-Specific Responses to COVID-19 mRNA Vaccine in Rheumatoid Arthritis Patients  

OBJECTIVE: To assess in rheumatoid arthritis (RA) patients, treated with different immunosuppressive therapies, the induction of SARS-CoV-2-specific immune response after vaccination in terms of anti-region-binding-domain (RBD)-antibody- and T-cell-specific responses against spike, and the vaccine safety in terms of clinical impact on disease activity. METHODS: Health care workers (HCWs) and RA patients, having completed the BNT162b2-mRNA vaccination in the last 2 weeks, were enrolled. Serological response was evaluated by quantifying anti-RBD antibodies, while the cell-mediated response was evaluated by a whole-blood test quantifying the interferon (IFN)-γ-response to spike peptides. FACS analysis was performed to identify the cells responding to spike stimulation. RA disease activity was evaluated by clinical examination through the DAS28crp, and local and/or systemic clinical adverse events were registered. In RA patients, the ongoing therapeutic regimen was modified during the vaccination period according to the American College of Rheumatology indications. RESULTS: We prospectively enrolled 167 HCWs and 35 RA patients. Anti-RBD-antibodies were detected in almost all patients (34/35, 97%), although the titer was significantly reduced in patients under CTLA-4-inhibitors (median: 465 BAU/mL, IQR: 103-1189, p<0.001) or IL-6-inhibitors (median: 492 BAU/mL, IQR: 161-1007, p<0.001) compared to HCWs (median: 2351 BAU/mL, IQR: 1389-3748). T-cell-specific response scored positive in most of RA patients [24/35, (69%)] with significantly lower IFN-γ levels in patients under biological therapy such as IL-6-inhibitors (median: 33.2 pg/mL, IQR: 6.1-73.9, p<0.001), CTLA-4-inhibitors (median: 10.9 pg/mL, IQR: 3.7-36.7, p<0.001), and TNF-α-inhibitors (median: 89.6 pg/mL, IQR: 17.8-224, p=0.002) compared to HCWs (median: 343 pg/mL, IQR: 188-756). A significant correlation between the anti-RBD-antibody titer and spike-IFN-γ-specific T-cell response was found in RA patients (rho=0.432, p=0.009). IFN-γ T-cell response was mediated by CD4(+) and CD8(+) T cells. Finally, no significant increase in disease activity was found in RA patients following vaccination. CONCLUSION: This study showed for the first time that antibody-specific and whole-blood spike-specific T-cell responses induced by the COVID-19 mRNA-vaccine were present in the majority of RA patients, who underwent a strategy of temporary suspension of immunosuppressive treatment during vaccine administration. However, the magnitude of specific responses was dependent on the immunosuppressive therapy administered. In RA patients, BNT162b2 vaccine was safe and disease activity remained stable.

Front Immunol2021       LitCov and CORD-19
4505Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies  

N/A

Nat Med2022       LitCov and CORD-19
4506Reduced Rate of Inpatient Hospital Admissions in 18 German University Hospitals During the COVID-19 Lockdown  

The COVID-19 pandemic has caused strains on health systems worldwide disrupting routine hospital services for all non-COVID patients. Within this retrospective study, we analyzed inpatient hospital admissions across 18 German university hospitals during the 2020 lockdown period compared to 2018. Patients admitted to hospital between January 1 and May 31, 2020 and the corresponding periods in 2018 and 2019 were included in this study. Data derived from electronic health records were collected and analyzed using the data integration center infrastructure implemented in the university hospitals that are part of the four consortia funded by the German Medical Informatics Initiative. Admissions were grouped and counted by ICD 10 chapters and specific reasons for treatment at each site. Pooled aggregated data were centrally analyzed with descriptive statistics to compare absolute and relative differences between time periods of different years. The results illustrate how care process adoptions depended on the COVID-19 epidemiological situation and the criticality of the disease. Overall inpatient hospital admissions decreased by 35% in weeks 1 to 4 and by 30.3% in weeks 5 to 8 after the lockdown announcement compared to 2018. Even hospital admissions for critical care conditions such as malignant cancer treatments were reduced. We also noted a high reduction of emergency admissions such as myocardial infarction (38.7%), whereas the reduction in stroke admissions was smaller (19.6%). In contrast, we observed a considerable reduction in admissions for non-critical clinical situations, such as hysterectomies for benign tumors (78.8%) and hip replacements due to arthrosis (82.4%). In summary, our study shows that the university hospital admission rates in Germany were substantially reduced following the national COVID-19 lockdown. These included critical care or emergency conditions in which deferral is expected to impair clinical outcomes. Future studies are needed to delineate how appropriate medical care of critically ill patients can be maintained during a pandemic.

Front Public Health2020       LitCov and CORD-19
4507Impact of National Containment Measures on Decelerating the Increase in Daily New Cases of COVID-19 in 54 Countries and 4 Epicenters of the Pandemic: Comparative Observational Study  

BACKGROUND: Coronavirus disease (COVID-19) is a worldwide epidemic, and various countries have responded with different containment measures to reduce disease transmission, including stay-at-home orders, curfews, and lockdowns. Comparative studies have not yet been conducted to investigate the impact of these containment measures; these studies are needed to facilitate public health policy-making across countries. OBJECTIVE: The aim of this study was to describe and evaluate the impact of national containment measures and policies (stay-at-home orders, curfews, and lockdowns) on decelerating the increase in daily new cases of COVID-19 in 54 countries and 4 epicenters of the pandemic in different jurisdictions worldwide. METHODS: We reviewed the effective dates of the national containment measures (stay-at-home order, curfew, or lockdown) of 54 countries and 4 epicenters of the COVID-19 pandemic (Wuhan, New York State, Lombardy, and Madrid), and we searched cumulative numbers of confirmed COVID-19 cases and daily new cases provided by health authorities. Data were drawn from an open, crowdsourced, daily-updated COVID-19 data set provided by Our World in Data. We examined the trends in the percent increase in daily new cases from 7 days before to 30 days after the dates on which containment measures went into effect by continent, World Bank income classification, type of containment measures, effective date of containment measures, and number of confirmed cases on the effective date of the containment measures. RESULTS: We included 122,366 patients with confirmed COVID-19 infection from 54 countries and 24,071 patients from 4 epicenters on the effective dates on which stay-at-home orders, curfews, or lockdowns were implemented between January 23 and April 11, 2020. Stay-at-home, curfew, and lockdown measures commonly commenced in countries with approximately 30%, 20%, or 10% increases in daily new cases. All three measures were found to lower the percent increase in daily new cases to <5 within one month. Among the countries studied, 20% had an average percent increase in daily new cases of 30-49 over the seven days prior to the commencement of containment measures; the percent increase in daily new cases in these countries was curbed to 10 and 5 a maximum of 15 days and 23 days after the implementation of containment measures, respectively. CONCLUSIONS: Different national containment measures were associated with a decrease in daily new cases of confirmed COVID-19 infection. Stay-at-home orders, curfews, and lockdowns curbed the percent increase in daily new cases to <5 within a month. Resurgence in cases within one month was observed in some South American countries.

J Med Internet Res2020       LitCov and CORD-19
4508'Blue toes' following vaccination with the BNT162b2 mRNA COVID-19 vaccine  

Highlights: COVID toes can be encountered in young individuals during acute COVID-19 infection while it results from the direct action of Spike protein on vessels. We report the case of COVID toes during the French campaign of vaccination that occurred 4 days after the vaccination with the Pfizer-BioNTech mRNA vaccine against COVID-19.

J Travel Med2021       LitCov and CORD-19
4509The Century of mRNA Vaccines: COVID-19 Vaccines and Allergy  

N/A

J Investig Allergol Clin Immun2021       LitCov and CORD-19
4510Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19  

BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care–level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support–free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. CONCLUSIONS: In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.)

N Engl J Med2021       LitCov and CORD-19
4511Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Persons Aged ≥12 Years-United States, August 31-October 23, 2022  

N/A

MMWR Morb Mortal Wkly Rep2022       LitCov
4512Correlation Analysis of Anti-SARS-CoV-2 RBD IgG and Neutralizing Antibody against SARS-CoV-2 Omicron Variants after Vaccination  

N/A

Diagnostics (Basel)2022       LitCov
4513Global seroprevalence of SARS-CoV-2 antibodies: A systematic review and meta-analysis  

BACKGROUND: Many studies report the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We aimed to synthesize seroprevalence data to better estimate the level and distribution of SARS-CoV-2 infection, identify high-risk groups, and inform public health decision making. METHODS: In this systematic review and meta-analysis, we searched publication databases, preprint servers, and grey literature sources for seroepidemiological study reports, from January 1, 2020 to December 31, 2020. We included studies that reported a sample size, study date, location, and seroprevalence estimate. We corrected estimates for imperfect test accuracy with Bayesian measurement error models, conducted meta-analysis to identify demographic differences in the prevalence of SARS-CoV-2 antibodies, and meta-regression to identify study-level factors associated with seroprevalence. We compared region-specific seroprevalence data to confirmed cumulative incidence. PROSPERO: CRD42020183634. RESULTS: We identified 968 seroprevalence studies including 9.3 million participants in 74 countries. There were 472 studies (49%) at low or moderate risk of bias. Seroprevalence was low in the general population (median 4.5%, IQR 2.4–8.4%); however, it varied widely in specific populations from low (0.6% perinatal) to high (59% persons in assisted living and long-term care facilities). Median seroprevalence also varied by Global Burden of Disease region, from 0.6% in Southeast Asia, East Asia and Oceania to 19.5% in Sub-Saharan Africa (p<0.001). National studies had lower seroprevalence estimates than regional and local studies (p<0.001). Compared to Caucasian persons, Black persons (prevalence ratio [RR] 3.37, 95% CI 2.64–4.29), Asian persons (RR 2.47, 95% CI 1.96–3.11), Indigenous persons (RR 5.47, 95% CI 1.01–32.6), and multi-racial persons (RR 1.89, 95% CI 1.60–2.24) were more likely to be seropositive. Seroprevalence was higher among people ages 18–64 compared to 65 and over (RR 1.27, 95% CI 1.11–1.45). Health care workers in contact with infected persons had a 2.10 times (95% CI 1.28–3.44) higher risk compared to health care workers without known contact. There was no difference in seroprevalence between sex groups. Seroprevalence estimates from national studies were a median 18.1 times (IQR 5.9–38.7) higher than the corresponding SARS-CoV-2 cumulative incidence, but there was large variation between Global Burden of Disease regions from 6.7 in South Asia to 602.5 in Sub-Saharan Africa. Notable methodological limitations of serosurveys included absent reporting of test information, no statistical correction for demographics or test sensitivity and specificity, use of non-probability sampling and use of non-representative sample frames. DISCUSSION: Most of the population remains susceptible to SARS-CoV-2 infection. Public health measures must be improved to protect disproportionately affected groups, including racial and ethnic minorities, until vaccine-derived herd immunity is achieved. Improvements in serosurvey design and reporting are needed for ongoing monitoring of infection prevalence and the pandemic response.

PLoS One2021       LitCov and CORD-19
4514Evolutionary and Phenotypic Characterization of Two Spike Mutations in European Lineage 20E of SARS-CoV-2  

We have detected two mutations in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at amino acid positions 1163 and 1167 that appeared independently in multiple transmission clusters and different genetic backgrounds. Furthermore, both mutations appeared together in a cluster of 1,627 sequences belonging to clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information on the S protein in the pre- and postfusion conformations predicts that both mutations confer rigidity, which could potentially decrease viral fitness. Accordingly, we observed reduced infectivity of this spike genotype relative to the ancestral 20E sequence in vitro, and the levels of viral RNA in nasopharyngeal swabs were not significantly higher. Furthermore, the mutations did not impact thermal stability or antibody neutralization by sera from vaccinated individuals but moderately reduce neutralization by convalescent-phase sera from the early stages of the pandemic. Despite multiple successful appearances of the two spike mutations during the first year of SARS-CoV-2 evolution, the genotype with both mutations was displaced upon the expansion of the 20I (Alpha) variant. The midterm fate of the genotype investigated was consistent with the lack of advantage observed in the clinical and experimental data.

mBio2021       LitCov and CORD-19
4515COVID-19 in Children-United States, February 12-April 2, 2020  

As of April 2, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in >890,000 cases and >45,000 deaths worldwide, including 239,279 cases and 5,443 deaths in the United States (1,2). In the United States, 22% of the population is made up of infants, children, and adolescents aged <18 years (children) (3). Data from China suggest that pediatric COVID-19 cases might be less severe than cases in adults and that children might experience different symptoms than do adults (4,5); however, disease characteristics among pediatric patients in the United States have not been described. Data from 149,760 laboratory-confirmed COVID-19 cases in the United States occurring during February 12-April 2, 2020 were analyzed. Among 149,082 (99.6%) reported cases for which age was known, 2,572 (1.7%) were among children aged <18 years. Data were available for a small proportion of patients on many important variables, including symptoms (9.4%), underlying conditions (13%), and hospitalization status (33%). Among those with available information, 73% of pediatric patients had symptoms of fever, cough, or shortness of breath compared with 93% of adults aged 18-64 years during the same period; 5.7% of all pediatric patients, or 20% of those for whom hospitalization status was known, were hospitalized, lower than the percentages hospitalized among all adults aged 18-64 years (10%) or those with known hospitalization status (33%). Three deaths were reported among the pediatric cases included in this analysis. These data support previous findings that children with COVID-19 might not have reported fever or cough as often as do adults (4). Whereas most COVID-19 cases in children are not severe, serious COVID-19 illness resulting in hospitalization still occurs in this age group. Social distancing and everyday preventive behaviors remain important for all age groups as patients with less serious illness and those without symptoms likely play an important role in disease transmission (6,7).

MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
4516Demographic Characteristics of Persons Vaccinated During the First Month of the COVID-19 Vaccination Program-United States, December 14, 2020-January 14, 2021  

In December 2020, two COVID-19 vaccines (Pfizer-BioNTech and Moderna) were authorized for emergency use in the United States for the prevention of coronavirus disease 2019 (COVID-19).* Because of limited initial vaccine supply, the Advisory Committee on Immunization Practices (ACIP) prioritized vaccination of health care personnel† and residents and staff members of long-term care facilities (LTCF) during the first phase of the U.S. COVID-19 vaccination program (1). Both vaccines require 2 doses to complete the series. Data on vaccines administered during December 14, 2020-January 14, 2021, and reported to CDC by January 26, 2021, were analyzed to describe demographic characteristics, including sex, age, and race/ethnicity, of persons who received ≥1 dose of COVID-19 vaccine (i.e., initiated vaccination). During this period, 12,928,749 persons in the United States in 64 jurisdictions and five federal entities§ initiated COVID-19 vaccination. Data on sex were reported for 97.0%, age for 99.9%, and race/ethnicity for 51.9% of vaccine recipients. Among persons who received the first vaccine dose and had reported demographic data, 63.0% were women, 55.0% were aged ≥50 years, and 60.4% were non-Hispanic White (White). More complete reporting of race and ethnicity data at the provider and jurisdictional levels is critical to ensure rapid detection of and response to potential disparities in COVID-19 vaccination. As the U.S. COVID-19 vaccination program expands, public health officials should ensure that vaccine is administered efficiently and equitably within each successive vaccination priority category, especially among those at highest risk for infection and severe adverse health outcomes, many of whom are non-Hispanic Black (Black), non-Hispanic American Indian/Alaska Native (AI/AN), and Hispanic persons (2,3).

MMWR Morb Mortal Wkly Rep2021       LitCov and CORD-19
4517Global Infodemiology of COVID-19: Analysis of Google Web Searches and Instagram Hashtags  

BACKGROUND: Although “infodemiological” methods have been used in research on coronavirus disease (COVID-19), an examination of the extent of infodemic moniker (misinformation) use on the internet remains limited. OBJECTIVE: The aim of this paper is to investigate internet search behaviors related to COVID-19 and examine the circulation of infodemic monikers through two platforms—Google and Instagram—during the current global pandemic. METHODS: We have defined infodemic moniker as a term, query, hashtag, or phrase that generates or feeds fake news, misinterpretations, or discriminatory phenomena. Using Google Trends and Instagram hashtags, we explored internet search activities and behaviors related to the COVID-19 pandemic from February 20, 2020, to May 6, 2020. We investigated the names used to identify the virus, health and risk perception, life during the lockdown, and information related to the adoption of COVID-19 infodemic monikers. We computed the average peak volume with a 95% CI for the monikers. RESULTS: The top six COVID-19–related terms searched in Google were “coronavirus,” “corona,” “COVID,” “virus,” “corona virus,” and “COVID-19.” Countries with a higher number of COVID-19 cases had a higher number of COVID-19 queries on Google. The monikers “coronavirus ozone,” “coronavirus laboratory,” “coronavirus 5G,” “coronavirus conspiracy,” and “coronavirus bill gates” were widely circulated on the internet. Searches on “tips and cures” for COVID-19 spiked in relation to the US president speculating about a “miracle cure” and suggesting an injection of disinfectant to treat the virus. Around two thirds (n=48,700,000, 66.1%) of Instagram users used the hashtags “COVID-19” and “coronavirus” to disperse virus-related information. CONCLUSIONS: Globally, there is a growing interest in COVID-19, and numerous infodemic monikers continue to circulate on the internet. Based on our findings, we hope to encourage mass media regulators and health organizers to be vigilant and diminish the use and circulation of these infodemic monikers to decrease the spread of misinformation.

J Med Internet Res2020       LitCov and CORD-19
4518Hospital mortality in patients with rare diseases during pandemics: lessons learnt from the COVID-19 and SARS pandemics  

BACKGROUND: The threat and experience of pandemics occur differently for different groups. The rare disease population is at particular risk of being further marginalised during pandemics. In this study, our objective was to assess the hospital mortality patterns in the rare disease and the general populations during the coronavirus disease of 2019 (COVID-19) and severe acute respiratory syndrome (SARS) pandemics in Hong Kong. METHODS: All admission records during the COVID-19 pandemic (January 23–August 23, 2020) and SARS pandemic (March 11–June 30, 2003) were extracted from the local public healthcare database. Patients with rare diseases were identified using one or more of the 1084 10th version International Classification of Diseases and Related Health Problems (ICD-10) codes cross-referenced with 467 ORPHAcodes. Hospital mortality patterns were compared in patients with and without COVID-19/SARS infection. Admission records during the same period in 2019 and 2002 were retrieved for comparison. RESULTS: During the COVID-19 pandemic, 407,219 patients were admitted to one or more of the 43 public hospitals in Hong Kong, of which, 13,894 were patients with rare diseases (3.4%). A total of 4381 and 77 patients from the general and rare disease populations were infected with COVID-19. Rare disease patients had an adjusted 3.4 times odds of COVID-19-related hospital mortality compared with that of the general population (95% C.I. 1.24–9.41). COVID-19-related mortality was almost exclusively seen in patients ≥ 60 years. While age-related increase in mortality was also observed for the general population during the SARS pandemic, the pattern observed in the rare disease population was significantly different, with a 12.5 times higher SARS-related mortality observed in rare disease patients ≤ 18 years than those in the general population (12.5% vs 1.0%). Patients admitted during the same pandemic periods without coronavirus infection had a significantly higher hospital mortality compared with those admitted one year before the pandemic (p < 0.001). CONCLUSION: This population-based study demonstrated the differential impacts of the COVID-19 and SARS pandemics on the rare disease population. In the era of budget and resource scarcity, this study warrants cautious healthcare planning, with consideration of the rare disease population in healthcare prioritisation.

Orphanet J Rare Dis2021       LitCov and CORD-19
4519The Global Epidemic of the SARS-CoV-2 Delta Variant, Key Spike Mutations and Immune Escape  

During the COVID-19 pandemic, SARS-CoV-2 variants have emerged and spread worldwide. The Delta (B.1.617.2) variant was first reported in India in October 2020 and was classified as a “variant of concern (VOC)” by the WHO on 11 May, 2021. Compared to the wild-type strain, several studies have shown that the Delta variant is more transmissible and has higher viral loads in infected samples. COVID-19 patients infected with the Delta variant have a higher risk of hospitalization, intensive care unit (ICU) admission, and mortality. The Delta variant is becoming the dominant strain in many countries around the world. This review summarizes and analyses the biological characteristics of key amino acid mutations, the epidemic characteristics, and the immune escape of the Delta variant. We hope to provide scientific reference for the monitoring and prevention measures of the SARS-CoV-2 Delta variant and the development strategy of a second-generation vaccine.

Front Immunol2021       LitCov and CORD-19
4520Chest computed tomography findings of COVID-19 pneumonia  

OBJECTIVE: To retrospectively analyze the chest computed tomography (CT) features in patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: From January 9, 2020, to February 26, 2020, totally 56 laboratory-confirmed patients with COVID-19 underwent chest CT. For 40 patients, follow-up CT scans were obtained. The CT images were evaluated for the number, type and distribution of the opacity, and the affected lung lobes. Furthermore, the initial CT scan and the follow-up CT scans were compared. RESULTS: Forty patients (83.6%) had two or more opacities in the lung. Eighteen (32.7%) patients had only ground-glass opacities; twenty-nine patients (52.7%) had ground-glass and consolidative opacities; and eight patients (14.5%) had only consolidation. A total of 43 patients (78.2%) showed two or more lobes involved. The opacities tended to be both in peripheral and central (30/55, 54.5%) or purely peripheral distribution (25/55, 45.5%). Fifty patients (90.9%) had the lower lobe involved. The first follow-up CT scans showed that twelve patients (30%) had improvement, 26 (65%) patients had mild-moderate progression, and two patients (5%) had severe progression with “white lungs.” The second follow-up CT showed that 22 patients (71%) showed improvement compared with the first follow-up CT, four patients (12.9%) had aggravated progression, and five patients (16.1%) showed unchanged radiographic appearance. CONCLUSIONS: The common CT features of COVID-19 pneumonia are multiple lung opacities, multiple types of the opacity (ground-glass, ground-glass and consolidation, and consolidation alone), and multiple lobes especially the lower lobe involved. Follow-up CT could demonstrate the rapid progression of COVID-19 pneumonia (either in aggravation or absorption). KEY POINTS: • The predominant CT features of COVID-19 pneumonia are multiple ground-glass opacities with or without consolidation and, with both lungs, multiple lobes and especially the lower lobe affected. • CT plays a crucial role in early diagnosis and assessment of COVID-19 pneumonia progression. • CT findings of COVID-19 pneumonia may not be consistent with the clinical symptoms or the initial RT-PCR test results.

Eur Radiol2020       LitCov and CORD-19
4521A systematic review of possible airborne transmission of the COVID-19 virus in the indoor air environment  

At the end of December 2019, the rapid spread of the COVID-19 (SARS-CoV-2) disease and, subsequently, deaths around the world, lead to the declaration of the pandemic situation in the world. At the beginning of the epidemic, much attention is paid to person-to-person transmission, disinfection of virus-contaminated surfaces, and social distancing. However, there is much debate about the routes of disease transmission, including airborne transmission, so it is important to elucidate the exact route of transmission of the COVID-19 disease. To this end, the first systematic review study was conducted to comprehensively search all databases to collect studies on airborne transmission of SARS-CoV-2 in indoor air environments. In total, 14 relevant and eligible studies were included. Based on the findings, there is a great possibility of airborne transmission of SARS-CoV-2 in indoor air environments. Therefore, some procedures are presented such as improving ventilation, especially in hospitals and crowded places, and observing the interpersonal distance of more than 2 meters so that experts in indoor air quality consider them to improve the indoor air environments. Finally, in addition to the recommendations of the centers and official authorities such as hand washing and observing social distancing, the route of air transmission should also be considered to further protect health personnel, patients in hospitals, and the public in other Public Buildings.

Environ Res2020       LitCov and CORD-19
4522The Psychological Impact of Epidemic and Pandemic Outbreaks on Healthcare Workers: Rapid Review of the Evidence  

PURPOSE OF REVIEW: We aim to provide quantitative evidence on the psychological impact of epidemic/pandemic outbreaks (i.e., SARS, MERS, COVID-19, ebola, and influenza A) on healthcare workers (HCWs). RECENT FINDINGS: Forty-four studies are included in this review. Between 11 and 73.4% of HCWs, mainly including physicians, nurses, and auxiliary staff, reported post-traumatic stress symptoms during outbreaks, with symptoms lasting after 1–3 years in 10–40%. Depressive symptoms are reported in 27.5–50.7%, insomnia symptoms in 34–36.1%, and severe anxiety symptoms in 45%. General psychiatric symptoms during outbreaks have a range comprised between 17.3 and 75.3%; high levels of stress related to working are reported in 18.1 to 80.1%. Several individual and work-related features can be considered risk or protective factors, such as personality characteristics, the level of exposure to affected patients, and organizational support. SUMMARY: Empirical evidence underlines the need to address the detrimental effects of epidemic/pandemic outbreaks on HCWs’ mental health. Recommendations should include the assessment and promotion of coping strategies and resilience, special attention to frontline HCWs, provision of adequate protective supplies, and organization of online support services. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11920-020-01166-z) contains supplementary material, which is available to authorized users.

Curr Psychiatry Rep2020       LitCov and CORD-19
4523Neutralisation of SARS-CoV-2 lineage P.1 by antibodies elicited through natural SARS-CoV-2 infection or vaccination with an inactivated SARS-CoV-2 vaccine: an immunological study  

BACKGROUND: Mutations accrued by SARS-CoV-2 lineage P.1—first detected in Brazil in early January, 2021—include amino acid changes in the receptor-binding domain of the viral spike protein that also are reported in other variants of concern, including B.1.1.7 and B.1.351. We aimed to investigate whether isolates of wild-type P.1 lineage SARS-CoV-2 can escape from neutralising antibodies generated by a polyclonal immune response. METHODS: We did an immunological study to assess the neutralising effects of antibodies on lineage P.1 and lineage B isolates of SARS-CoV-2, using plasma samples from patients previously infected with or vaccinated against SARS-CoV-2. Two specimens (P.1/28 and P.1/30) containing SARS-CoV-2 lineage P.1 (as confirmed by viral genome sequencing) were obtained from nasopharyngeal and bronchoalveolar lavage samples collected from patients in Manaus, Brazil, and compared against an isolate of SARS-CoV-2 lineage B (SARS.CoV2/SP02.2020) recovered from a patient in Brazil in February, 2020. Isolates were incubated with plasma samples from 21 blood donors who had previously had COVID-19 and from a total of 53 recipients of the chemically inactivated SARS-CoV-2 vaccine CoronaVac: 18 individuals after receipt of a single dose and an additional 20 individuals (38 in total) after receipt of two doses (collected 17–38 days after the most recent dose); and 15 individuals who received two doses during the phase 3 trial of the vaccine (collected 134–230 days after the second dose). Antibody neutralisation of P.1/28, P.1/30, and B isolates by plasma samples were compared in terms of median virus neutralisation titre (VNT(50), defined as the reciprocal value of the sample dilution that showed 50% protection against cytopathic effects). FINDINGS: In terms of VNT(50), plasma from individuals previously infected with SARS-CoV-2 had an 8·6 times lower neutralising capacity against the P.1 isolates (median VNT(50) 30 [IQR <20–45] for P.1/28 and 30 [<20–40] for P.1/30) than against the lineage B isolate (260 [160–400]), with a binominal model showing significant reductions in lineage P.1 isolates compared with the lineage B isolate (p≤0·0001). Efficient neutralisation of P.1 isolates was not seen with plasma samples collected from individuals vaccinated with a first dose of CoronaVac 20–23 days earlier (VNT(50)s below the limit of detection [<20] for most plasma samples), a second dose 17–38 days earlier (median VNT(50) 24 [IQR <20–25] for P.1/28 and 28 [<20–25] for P.1/30), or a second dose 134–260 days earlier (all VNT(50)s below limit of detection). Median VNT(50)s against the lineage B isolate were 20 (IQR 20–30) after a first dose of CoronaVac 20–23 days earlier, 75 (<20–263) after a second dose 17–38 days earlier, and 20 (<20–30) after a second dose 134–260 days earlier. In plasma collected 17–38 days after a second dose of CoronaVac, neutralising capacity against both P.1 isolates was significantly decreased (p=0·0051 for P.1/28 and p=0·0336 for P.1/30) compared with that against the lineage B isolate. All data were corroborated by results obtained through plaque reduction neutralisation tests. INTERPRETATION: SARS-CoV-2 lineage P.1 might escape neutralisation by antibodies generated in response to polyclonal stimulation against previously circulating variants of SARS-CoV-2. Continuous genomic surveillance of SARS-CoV-2 combined with antibody neutralisation assays could help to guide national immunisation programmes. FUNDING: São Paulo Research Foundation, Brazilian Ministry of Science, Technology and Innovation and Funding Authority for Studies, Medical Research Council, National Council for Scientific and Technological Development, National Institutes of Health. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Lancet Microbe2021       LitCov and CORD-19
4524Vaccination Hesitancy and Conspiracy Beliefs in the UK During the SARS-COV-2 Pandemic  

BACKGROUND: Conspiracy beliefs about vaccination along with vaccination hesitancy are threats to achieving population immunity during the SARS-COV-2 (COVID-19) pandemic. This longitudinal study aimed to clarify the association between these and non-monetary incentives to vaccination in the UK. METHOD: Data were collected at three points: (1) before and (2) after the development of a vaccine and (3) after the vaccination programme was underway. At Time 1, participants completed measures of general and COVID-19-specific concerns about vaccination and belief in conspiracy theories. At times 2 and 3, participants reported their intentions whether or not to have the SARS-CoV-2 vaccine. Those who were hesitant provided qualitative comments about what might change their decision. RESULTS: Vaccination hesitancy decreased between times 1 (54%) and 3 (13%). There were small effects of conspiracy beliefs on vaccine hesitancy, but only at time 1. Most concerns and reported incentives were related to safety, although at time 2, incentives included endorsement by trusted public figures. By time 3, only a minority of participants (N = 18) were adamantly against vaccination, stating that nothing would change their minds. CONCLUSION: Vaccination hesitancy declined in the UK during the course of the study. However, concerns about vaccine safety remained and could jeopardise the vaccination programme should any adverse effects be reported. Conspiracy beliefs seem to play only a minor role in hesitancy and may continue to decrease in importance with a successful vaccination programme. Understanding motivations behind vaccination hesitancy is vital if we are to achieve population immunity.

Int J Behav Med2021       LitCov and CORD-19
4525Distinct conformational states of SARS-CoV-2 spike protein  

Intervention strategies are urgently needed to control the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic. The trimeric viral spike (S) protein catalyzes fusion between viral and target cell membranes to initiate infection. Here we report two cryo-EM structures, derived from a preparation of the full-length S protein, representing its prefusion (2.9Å resolution) and postfusion (3.0Å resolution) conformations, respectively. The spontaneous transition to the postfusion state is independent of target cells. The prefusion trimer has three receptor-binding domains clamped down by a segment adjacent to the fusion peptide. The postfusion structure is strategically decorated by N-linked glycans, suggesting possible protective roles against host immune responses and harsh external conditions. These findings advance our understanding of SARS-CoV-2 entry and may guide development of vaccines and therapeutics.

Science2020       LitCov and CORD-19
4526Favipiravir for treating patients with novel coronavirus: protocol for a systematic review and meta-analysis of randomised clinical trials  

INTRODUCTION: An outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was reported in Wuhan, China, in mid-December 2019, and declared a pandemic by the WHO on 11 March 2020. Due to the unknown nature of the disease and the lack of specific drugs, several potential treatments were used for patients. This systematic review and meta-analysis will evaluate studies of the effects of favipiravir in COVID-19 pneumonia. METHODS AND ANALYSIS: We will search electronic databases including LitCovid hub, PubMed, Scopus, ISI Web of Sciences, Cochrane and Embase using keywords related to COVID-19 and favipiravir. We will search the reference lists of all included studies and reviews. We will also search for clinical trial registries, such as ClinicalTrials.gov, for the ongoing clinical trials. All randomised clinical trials investigating the safety and efficacy of favipiravir compared with other control groups for the treatment of patients with confirmed infection with SARS-CoV-2 will be included. Patients’ survival at the end of the treatment as well as the follow-up will be the primary outcome of the treatment, followed by the time and rate of the patient with a negative COVID-19 test. The desired secondary outcome will consist of a decreased rate of symptoms, proportion of intensive care unit (ICU) transfers, length of the hospital stay, ICU treatments, the quality of life and additional adverse events. Data synthesis will be conducted using CMA V.2. Two independent investigators will be screening titles, abstracts and full texts of included studies, based on eligibility criteria. These investigators will then independently extract the data and appraise the quality of said studies. All potential discrepancies will be resolved through consultation with the third reviewer. Statistical heterogeneity will be assessed using a standard I(2) test. A funnel plot, Egger’s test and Begg’s test will be used for detecting asymmetry to explore possible publication bias. ETHICS AND DISSEMINATION: All findings of this systematic review and meta-analysis will help identify the safety and efficacy of favipiravir for patients with COVID-19. Given that the design of the study is a systematic review, there is no need to follow the code of ethics protocol. The results of this study will be published in a reputable journal. PROSPERO REGISTRATION NUMBER: CRD42020180032.

BMJ Open2020       LitCov and CORD-19
4527Maternal-Fetal Implications of SARS CoV-2 Infection during Pregnancy, Viral, Serological Analyses of Placenta and Cord Blood  

Objective: There are few data on the maternal–fetal transmission of SARS-CoV-2 and its outcomes. This study aimed to evaluate pregnancy outcomes of pregnant women infected by SARS-CoV-2, to detect SARS-CoV-2 in placenta and different newborns’ samples and search antibodies in cord blood. Methods: This was a prospective study of pregnant women diagnosed with SARS-CoV-2 infection from May 2020 to May 2021. At delivery, the placentas were investigated for SARS-CoV-2 using RT-PCR, cord blood. Mothers’ blood samples were tested by SARS-CoV-2 serology. PCR of nasopharyngeal, anal and gastric swabs (NPSs) of newborns was performed according to pediatric indications. Results: Among 3626 pregnant women presenting at maternity to deliver, 45 mothers had COVID-19 during their pregnancy or at delivery (32 ± 4.8 years). Most of them were multiparous and in the third trimester. There were 35 (77%) women who remained in ambulatory, while 10 (22%) were hospitalized for severe pneumonia, digestive symptoms, and/or fetal tachycardia. Thirty-eight delivered vaginally, and 7 had a cesarean delivery with normal Apgar scores (9 ± 1.6 at 5 min) and umbilical artery pH (7.22 ± 0.08). Two mothers required ICU admission after cesarean section for fetal and maternal distress. Of the 46 newborns, 6 were premature births (13%) and 5 IUGR (intra-uterine growth restriction,11%). RT-PCR SARS-CoV-2 was positive for 1/30 placental, and 1/33 neonatal anal swabs and negative in all other cases and in gastric swabs. SARS-CoV-2 IgG was positive in 20/41 cord blood samples (49%) and their mothers’ samples. IgM was negative in the 23 cord blood samples. Conclusions: Pregnancy outcomes in women diagnosed with COVID-19 during their pregnancy were favorable in most cases. However, some women with severe clinical forms required hospitalization and ICU admission. Preterm births and intrauterine growth retardations were relatively frequent. Vaginal delivery was possible in most cases. SARS-CoV-2 IgG antibodies were positive and elevated in most cord blood samples of newborns. They are possibly of maternal origin, suggesting a probable mechanism of fetal protection against SARS-CoV-2 infection. No SARS-CoV-2 IgM was found in the cord blood samples. Detection of SARS-CoV-2 in placenta is rare.

Int J Environ Res Public Healt2022       LitCov and CORD-19
4528Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2  

IMPORTANCE: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. OBJECTIVE: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. EXPOSURES: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). MAIN OUTCOMES AND MEASURES: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. RESULTS: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). CONCLUSIONS AND RELEVANCE: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.

JAMA Netw Open2021       LitCov and CORD-19
4529Emergence of a Novel Coronavirus: Protocol for Extending Surveillance Used by the Royal College of General Practitioners Research and Surveillance Centre and Public Health England  

BACKGROUND: The Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) have successfully worked together on the surveillance of influenza and other infectious diseases for over 50 years, including three previous pandemics. With the emergence of the international outbreak of the coronavirus infection (COVID-19), a UK national approach to containment has been established to test people suspected of exposure to COVID-19. At the same time and separately, the RCGP RSC’s surveillance has been extended to monitor the temporal and geographical distribution of COVID-19 infection in the community as well as assess the effectiveness of the containment strategy. OBJECTIVES: The aims of this study are to surveil COVID-19 in both asymptomatic populations and ambulatory cases with respiratory infections, ascertain both the rate and pattern of COVID-19 spread, and assess the effectiveness of the containment policy. METHODS: The RCGP RSC, a network of over 500 general practices in England, extract pseudonymized data weekly. This extended surveillance comprises of five components: (1) Recording in medical records of anyone suspected to have or who has been exposed to COVID-19. Computerized medical records suppliers have within a week of request created new codes to support this. (2) Extension of current virological surveillance and testing people with influenza-like illness or lower respiratory tract infections (LRTI)—with the caveat that people suspected to have or who have been exposed to COVID-19 should be referred to the national containment pathway and not seen in primary care. (3) Serology sample collection across all age groups. This will be an extra blood sample taken from people who are attending their general practice for a scheduled blood test. The 100 general practices currently undertaking annual influenza virology surveillance will be involved in the extended virological and serological surveillance. (4) Collecting convalescent serum samples. (5) Data curation. We have the opportunity to escalate the data extraction to twice weekly if needed. Swabs and sera will be analyzed in PHE reference laboratories. RESULTS: General practice clinical system providers have introduced an emergency new set of clinical codes to support COVID-19 surveillance. Additionally, practices participating in current virology surveillance are now taking samples for COVID-19 surveillance from low-risk patients presenting with LRTIs. Within the first 2 weeks of setup of this surveillance, we have identified 3 cases: 1 through the new coding system, the other 2 through the extended virology sampling. CONCLUSIONS: We have rapidly converted the established national RCGP RSC influenza surveillance system into one that can test the effectiveness of the COVID-19 containment policy. The extended surveillance has already seen the use of new codes with 3 cases reported. Rapid sharing of this protocol should enable scientific critique and shared learning. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18606

JMIR Public Health Surveill2020       LitCov and CORD-19
4530Magnetic beads combined with carbon black-based screen-printed electrodes for COVID-19: A reliable and miniaturized electrochemical immunosensor for SARS-CoV-2 detection in saliva  

The diffusion of novel SARS-CoV-2 coronavirus over the world generated COVID-19 pandemic event as reported by World Health Organization on March 2020. The huge issue is the high infectivity and the absence of vaccine and customised drugs allowing for hard management of this outbreak, thus a rapid and on site analysis is a need to contain the spread of COVID-19. Herein, we developed an electrochemical immunoassay for rapid and smart detection of SARS-CoV-2 coronavirus in saliva. The electrochemical assay was conceived for Spike (S) protein or Nucleocapsid (N) protein detection using magnetic beads as support of immunological chain and secondary antibody with alkaline phosphatase as immunological label. The enzymatic by-product 1-naphtol was detected using screen-printed electrodes modified with carbon black nanomaterial. The analytical features of the electrochemical immunoassay were evaluated using the standard solution of S and N protein in buffer solution and untreated saliva with a detection limit equal to 19 ng/mL and 8 ng/mL in untreated saliva, respectively for S and N protein. Its effectiveness was assessed using cultured virus in biosafety level 3 and in saliva clinical samples comparing the data using the nasopharyngeal swab specimens tested with Real-Time PCR. The agreement of the data, the low detection limit achieved, the rapid analysis (30 min), the miniaturization, and portability of the instrument combined with the easiness to use and no-invasive sampling, confer to this analytical tool high potentiality for market entry as the first highly sensitive electrochemical immunoassay for SARS-CoV-2 detection in untreated saliva.

Biosens Bioelectron2020       LitCov and CORD-19
4531Experiences and perceptions of Turkish intensive care nurses providing care to Covid-19 patients: A qualitative study  

N/A

Int Nurs Rev2022       LitCov and CORD-19
4532SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo  

The spike D614G substitution is prevalent in global SARS-CoV-2 strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. The variant exhibits more efficient infection, replication, and competitive fitness in primary human airway epithelial cells, but maintains similar morphology and in vitro neutralization properties, compared with the ancestral wild-type virus. Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease. However, the D614G variant transmits significantly faster and displayed increased competitive fitness than the wild-type virus in hamsters. These data show that the D614G substitution enhances SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells and animal models.

Science2020       LitCov and CORD-19
4533Using Automated Machine Learning to Predict the Mortality of Patients With COVID-19: Prediction Model Development Study  

BACKGROUND: During a pandemic, it is important for clinicians to stratify patients and decide who receives limited medical resources. Machine learning models have been proposed to accurately predict COVID-19 disease severity. Previous studies have typically tested only one machine learning algorithm and limited performance evaluation to area under the curve analysis. To obtain the best results possible, it may be important to test different machine learning algorithms to find the best prediction model. OBJECTIVE: In this study, we aimed to use automated machine learning (autoML) to train various machine learning algorithms. We selected the model that best predicted patients’ chances of surviving a SARS-CoV-2 infection. In addition, we identified which variables (ie, vital signs, biomarkers, comorbidities, etc) were the most influential in generating an accurate model. METHODS: Data were retrospectively collected from all patients who tested positive for COVID-19 at our institution between March 1 and July 3, 2020. We collected 48 variables from each patient within 36 hours before or after the index time (ie, real-time polymerase chain reaction positivity). Patients were followed for 30 days or until death. Patients’ data were used to build 20 machine learning models with various algorithms via autoML. The performance of machine learning models was measured by analyzing the area under the precision-recall curve (AUPCR). Subsequently, we established model interpretability via Shapley additive explanation and partial dependence plots to identify and rank variables that drove model predictions. Afterward, we conducted dimensionality reduction to extract the 10 most influential variables. AutoML models were retrained by only using these 10 variables, and the output models were evaluated against the model that used 48 variables. RESULTS: Data from 4313 patients were used to develop the models. The best model that was generated by using autoML and 48 variables was the stacked ensemble model (AUPRC=0.807). The two best independent models were the gradient boost machine and extreme gradient boost models, which had an AUPRC of 0.803 and 0.793, respectively. The deep learning model (AUPRC=0.73) was substantially inferior to the other models. The 10 most influential variables for generating high-performing models were systolic and diastolic blood pressure, age, pulse oximetry level, blood urea nitrogen level, lactate dehydrogenase level, D-dimer level, troponin level, respiratory rate, and Charlson comorbidity score. After the autoML models were retrained with these 10 variables, the stacked ensemble model still had the best performance (AUPRC=0.791). CONCLUSIONS: We used autoML to develop high-performing models that predicted the survival of patients with COVID-19. In addition, we identified important variables that correlated with mortality. This is proof of concept that autoML is an efficient, effective, and informative method for generating machine learning–based clinical decision support tools.

J Med Internet Res2021       LitCov and CORD-19
4534What We Have Learned from Two Decades of Epidemics and Pandemics: A Systematic Review and Meta-Analysis of the Psychological Burden of Frontline Healthcare Workers  

In light of the current coronavirus disease 2019 (COVID-19) pandemic and potential future infectious disease outbreaks, a comprehensive understanding of the negative effects of epidemics and pandemics on healthcare workers' mental health could inform appropriate support interventions. Thus, we aimed to synthesize and quantify the psychological and psychosomatic symptoms among frontline medical staff. We searched four databases up to March 19, 2020 and additional literature, with daily search alerts set up until October 26, 2020. Studies reporting psychological and/or psychosomatic symptoms of healthcare workers caring for patients with severe acute respiratory syndrome, H1N1, Ebola, Middle East respiratory syndrome, or COVID-19 were eligible for inclusion. Two reviewers independently conducted the search, study selection, quality appraisal, data extraction, and synthesis and involved a third reviewer in case of disagreement. We used random effects modeling to estimate the overall prevalence rates of psychological/psychosomatic symptoms and the I(2) statistic. We included 86 studies, reporting data from 75,991 participants. Frontline staff showed a wide range of symptoms, including concern about transmitting the virus to the family (60.39%, 95% CI 42.53–76.96), perceived stress (56.77%, 95% CI 34.21–77.95), concerns about own health (45.97%, 95% CI 31.08–61.23), sleeping difficulties (39.88%, 95% CI 27.70–52.72), burnout (31.81%, 95% CI 13.32–53.89), symptoms of depression (25.72%, 95% CI 18.34–33.86), symptoms of anxiety (25.36%, 95% CI 17.90–33.64), symptoms of posttraumatic stress disorder (24.51%, 95% CI 18.16–31.46), mental health issues (23.11%, 95% CI 15.98–31.10), and symptoms of somatization (14.68%, 95% CI 10.67–19.18). We found consistent evidence for the pervasive and profound impact of large-scale outbreaks on the mental health of frontline healthcare workers. As the CO­VID-19 crisis continues to unfold, guaranteeing easy access to support structures for the entire healthcare workforce is vitally important.

Psychother Psychosom2021       LitCov and CORD-19
4535SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology  

Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2–activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19.

J Exp Med2020       LitCov and CORD-19
4536Acute kidney injury in patients hospitalized with COVID-19  

The rate of acute kidney injury (AKI) associated with patients hospitalized with Covid-19, and associated outcomes are not well understood. This study describes the presentation, risk factors and outcomes of AKI in patients hospitalized with Covid-19. We reviewed the health records for all patients hospitalized with Covid-19 between March 1, and April 5, 2020, at 13 academic and community hospitals in metropolitan New York. Patients younger than 18 years of age, with end stage kidney disease or with a kidney transplant were excluded. AKI was defined according to KDIGO criteria. Of 5,449 patients admitted with Covid-19, AKI developed in 1,993 (36.6%). The peak stages of AKI were stage 1 in 46.5%, stage 2 in 22.4% and stage 3 in 31.1%. Of these, 14.3% required renal replacement therapy (RRT). AKI was primarily seen in Covid-19 patients with respiratory failure, with 89.7% of patients on mechanical ventilation developing AKI compared to 21.7% of non-ventilated patients. 276/285 (96.8%) of patients requiring RRT were on ventilators. Of patients who required ventilation and developed AKI, 52.2% had the onset of AKI within 24 hours of intubation. Risk factors for AKI included older age, diabetes mellitus, cardiovascular disease, black race, hypertension and need for ventilation and vasopressor medications. Among patients with AKI, 694 died (35%), 519 (26%) were discharged and 780 (39%) were still hospitalized. AKI occurs frequently among patients with Covid-19 disease. It occurs early and in temporal association with respiratory failure and is associated with a poor prognosis.

Kidney Int2020       LitCov and CORD-19
4537SARS-CoV-2 Spike Mutations, L452R, T478K, E484Q and P681R, in the Second Wave of COVID-19 in Maharashtra, India  

As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being used to investigate its transmission and evolution. Against the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches were undertaken to identify possible new variants and gauge the fitness of the current circulating strains. Phylogenetic analysis revealed that newly identified lineages B.1.617.1 and B.1.617.2 were predominantly circulating. The signature mutations possessed by these strains were L452R, T478K, E484Q, D614G and P681R in the spike protein, including within the receptor-binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R, T478K and E484Q revealed that these may possibly result in increased ACE2 binding while P681R in the furin cleavage site could increase the rate of S1-S2 cleavage, resulting in better transmissibility. The two RBD mutations, L452R and E484Q, indicated decreased binding to select monoclonal antibodies (mAbs) and may affect their neutralization potential. Further in vitro/in vivo studies would help confirm the phenotypic changes of the mutant strains. Overall, the study revealed that the newly emerged variants were responsible for the second wave of COVID-19 in Maharashtra. Lineage B.1.617.2 has been designated as a VOC delta and B.1.617.1 as a variant of interest kappa, and they are being widely reported in the rest of the country as well as globally. Continuous monitoring of these and emerging variants in India is essential.

Microorganisms2021       LitCov and CORD-19
4538The Sensitivity and Costs of Testing for SARS-CoV-2 Infection With Saliva Versus Nasopharyngeal Swabs: A Systematic Review and Meta-analysis  

BACKGROUND: Nasopharyngeal swabs are the primary sampling method used for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but they require a trained health care professional and extensive personal protective equipment. PURPOSE: To determine the difference in sensitivity for SARS-CoV-2 detection between nasopharyngeal swabs and saliva and estimate the incremental cost per additional SARS-CoV-2 infection detected with nasopharyngeal swabs. DATA SOURCES: Embase, Medline, medRxiv, and bioRxiv were searched from 1 January to 1 November 2020. Cost inputs were from nationally representative sources in Canada and were converted to 2020 U.S. dollars. STUDY SELECTION: Studies including at least 5 paired nasopharyngeal swab and saliva samples and reporting diagnostic accuracy for SARS-CoV-2 detection. DATA EXTRACTION: Data were independently extracted using standardized forms, and study quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). DATA SYNTHESIS: Thirty-seven studies with 7332 paired samples were included. Against a reference standard of a positive result on either sample, the sensitivity of saliva was 3.4 percentage points lower (95% CI, 9.9 percentage points lower to 3.1 percentage points higher) than that of nasopharyngeal swabs. Among persons with previously confirmed SARS-CoV-2 infection, saliva's sensitivity was 1.5 percentage points higher (CI, 7.3 percentage points lower to 10.3 percentage points higher) than that of nasopharyngeal swabs. Among persons without a previous SARS-CoV-2 diagnosis, saliva was 7.9 percentage points less (CI, 14.7 percentage points less to 0.8 percentage point more) sensitive. In this subgroup, if testing 100 000 persons with a SARS-CoV-2 prevalence of 1%, nasopharyngeal swabs would detect 79 more (95% uncertainty interval, 5 fewer to 166 more) persons with SARS-CoV-2 than saliva, but with an incremental cost per additional infection detected of $8093. LIMITATION: The reference standard was imperfect, and saliva collection procedures varied. CONCLUSION: Saliva sampling seems to be a similarly sensitive and less costly alternative that could replace nasopharyngeal swabs for collection of clinical samples for SARS-CoV-2 testing. PRIMARY FUNDING SOURCE: McGill Interdisciplinary Initiative in Infection and Immunity. (PROSPERO: CRD42020203415)

Ann Intern Med2021       LitCov and CORD-19
4539Association between social media use and the acceptance of COVID-19 vaccination among the general population in Saudi Arabia-a cross-sectional study  

BACKGROUND: The Coronavirus Disease of 2019 (COVID-19) pandemic is a worldwide global public health threat. Although acceptance of COVID-19 vaccination will be a critical step in combating the pandemic, achieving high uptake will be difficult, and potentially made more difficult by social media misinformation. This study aimed to examine the association between social media use and acceptance of receiving COVID-19 vaccine among the general population in Saudi Arabia. METHODOLOGY: A cross-sectional study was conducted from June 17 to June 19, 2021 among 504 participants of the general population in Saudi Arabia. The data were collected using a three-part online questionnaire (sociodemographic characteristics, medical and vaccination history, pattern of social media use). RESULTS: Among 504 participants who completed the survey, 477 participants were acceptant of the vaccine and 27 were non-accepting. A total of 335 individuals had already received the vaccine, 142 were willing to receive the vaccine and 27 were unwilling. One hundred and thirty participants denied using social media for COVID-19 news. Four factors were found to be significant in influencing vaccine acceptance in univariate analysis: having a chronic condition (odds ratio (OR) = 0.367, P = 0.019), believing that infertility is a side effect of the COVID-19 vaccine (OR = 0.298, P = 0.009), being concerned about a serious side effect from the vaccine (somewhat concerned: OR = 0.294, P = 0.022, very concerned: OR = 0.017, P < 0.0001), and basing the decision to be vaccinated on social media information (OR = 0.260, P = 0.006). Two of these factors fell away on multivariate analysis: basing the decision on social media information (OR = 0.356, P = 0.071), and a belief that vaccination causes infertility (OR = 0.0333, P = 0.054), suggesting that the associations are dependent on other factors. CONCLUSION: ‏In conclusion, there was no significant independent relationship between social media usage and people's willingness to receive a COVID-19 vaccination. Further studies to explore the association between social media use and vaccine decisions are required to generalize this observation to the Saudi population.

BMC Public Health2022       LitCov and CORD-19
4540Coronavirus Disease Caused by Infections: A Real Challenge for Human Gut Microbiota  

The current COVID-19 pandemic is a great challenge for worldwide researchers in the human microbiota area because the mechanisms and long-term effects of the infection at the GI level are not yet deeply understood. In the current review, scientific literature including original research articles, clinical studies, epidemiological reports, and review-type articles concerning human intestinal infection with SARS-CoV-2 and the possible consequences on the microbiota were reviewed. Moreover, the following aspects pertaining to COVID-19 have also been discussed: transmission, resistance in the human body, the impact of nutritional status in relation to the intestinal microbiota, and the impact of comorbid metabolic disorders such as inflammatory bowel disease (IBS), obesity, and type two diabetes (T2D). The articles investigated show that health, age, and nutritional status are associated with specific communities of bacterial species in the gut, which could influence the clinical course of COVID-19 infection. Fecal microbiota alterations were associated with fecal concentrations of SARS-CoV-2 and COVID-19 severity. Patients suffering from metabolic and gastrointestinal (GI) disorders are thought to be at a moderate-to-high risk of infection with SARS-CoV-2, indicating the direct implication of gut dysbiosis in COVID-19 severity. However, additional efforts are required to identify the initial GI symptoms of COVID-19 for possible early intervention.

Front Cell Infect Microbiol2020       LitCov and CORD-19
4541Comparative Performance of Private Equity-Owned US Nursing Homes During the COVID-19 Pandemic  

IMPORTANCE: It is not known whether nursing homes with private equity (PE) ownership have performed better or worse than other nursing homes during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To evaluate the comparative performance of PE-owned nursing homes on COVID-19 outcomes. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of 11 470 US nursing homes used the Nursing Home COVID-19 Public File from May 17, 2020, to July 2, 2020, to compare outcomes of PE-owned nursing homes with for-profit, nonprofit, and government-owned homes, adjusting for facility characteristics. EXPOSURE: Nursing home ownership status. MAIN OUTCOMES AND MEASURES: Self-reported number of COVID-19 cases and deaths and deaths by any cause per 1000 residents; possessing 1-week supplies of personal protective equipment (PPE); staffing shortages. RESULTS: Of 11 470 nursing homes, 7793 (67.9%) were for-profit; 2523 (22.0%), nonprofit; 511 (5.3%), government-owned; and 543 (4.7%), PE-owned; with mean (SD) COVID-19 cases per 1000 residents of 88.3 [2.1], 67.0 [3.8], 39.8 [7.6] and 110.8 [8.1], respectively. Mean (SD) COVID-19 deaths per 1000 residents were 61.9 [1.6], 66.4 [3.0], 56.2 [7.3], and 78.9 [5.9], respectively; mean deaths by any cause per 1000 residents were 78.1 [1.3], 91.5 [2.2], 67.6 [4.5], and 87.9 [4.8], respectively. In adjusted analyses, government-owned homes had 35.5 (95% CI, −69.2 to −1.8; P = .03) fewer COVID-19 cases per 1000 residents than PE-owned nursing homes. Cases in PE-owned nursing homes were not statistically different compared with for-profit and nonprofit facilities; nor were there statistically significant differences in COVID-19 deaths or deaths by any cause between PE-owned nursing homes and for-profit, nonprofit, and government-owned facilities. For-profit, nonprofit, and government-owned nursing homes were 10.5% (9.1 percentage points; 95% CI, 1.8 to 16.3 percentage points; P = .006), 15.0% (13.0 percentage points; 95% CI, 5.5 to 20.6 percentage points; P < .001), and 17.0% (14.8 percentage points; 95% CI, 6.5 to 23.0 percentage points; P < .001), respectively, more likely to have at least a 1-week supply of N95 masks than PE-owned nursing homes. They were 24.3% (21.3 percentage points; 95% CI, 11.8 to 30.8 percentage points; P < .001), 30.7% (27.0 percentage points; 95% CI, 17.7 to 36.2 percentage points; P < .001), and 29.2% (25.7 percentage points; 95% CI, 16.1 to 35.3 percentage points; P < .001) more likely to have a 1-week supply of medical gowns than PE-owned nursing homes. Government nursing homes were more likely to have a shortage of nurses (6.9 percentage points; 95% CI, 0.0 to 13.9 percentage points; P = .049) than PE-owned nursing homes. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, PE-owned nursing homes performed comparably on staffing levels, resident cases, and deaths with nursing homes with other types of ownership, although their shortages of PPE may warrant monitoring.

JAMA Netw Open2020       LitCov and CORD-19
4542Psychosocial impact of the COVID-19 pandemic on 4378 UK healthcare workers and ancillary staff: initial baseline data from a cohort study collected during the first wave of the pandemic  

OBJECTIVES: This study reports preliminary findings on the prevalence of, and factors associated with, mental health and well-being outcomes of healthcare workers during the early months (April–June) of the COVID-19 pandemic in the UK. METHODS: Preliminary cross-sectional data were analysed from a cohort study (n=4378). Clinical and non-clinical staff of three London-based NHS Trusts, including acute and mental health Trusts, took part in an online baseline survey. The primary outcome measure used is the presence of probable common mental disorders (CMDs), measured by the General Health Questionnaire. Secondary outcomes are probable anxiety (seven-item Generalised Anxiety Disorder), depression (nine-item Patient Health Questionnaire), post-traumatic stress disorder (PTSD) (six-item Post-Traumatic Stress Disorder checklist), suicidal ideation (Clinical Interview Schedule) and alcohol use (Alcohol Use Disorder Identification Test). Moral injury is measured using the Moray Injury Event Scale. RESULTS: Analyses showed substantial levels of probable CMDs (58.9%, 95% CI 58.1 to 60.8) and of PTSD (30.2%, 95% CI 28.1 to 32.5) with lower levels of depression (27.3%, 95% CI 25.3 to 29.4), anxiety (23.2%, 95% CI 21.3 to 25.3) and alcohol misuse (10.5%, 95% CI 9.2 to 11.9). Women, younger staff and nurses tended to have poorer outcomes than other staff, except for alcohol misuse. Higher reported exposure to moral injury (distress resulting from violation of one’s moral code) was strongly associated with increased levels of probable CMDs, anxiety, depression, PTSD symptoms and alcohol misuse. CONCLUSIONS: Our findings suggest that mental health support for healthcare workers should consider those demographics and occupations at highest risk. Rigorous longitudinal data are needed in order to respond to the potential long-term mental health impacts of the pandemic.

Occup Environ Med2021       LitCov and CORD-19
4543Rise of the phoenix: Mucormycosis in COVID-19 times  

PURPOSE: Rhino-orbital mucormycosis in times of ongoing COVID-19 pandemic. AIMS: The aim of the study was to document cases of rhino-orbital mucormycosis seen at our Regional Institute of Ophthalmology during COVID-19 (coronavirus disease 2019) times. METHODS: The study is a retrospective, institutional cohort, interventional study. It was carried out at our Regional Institute of Ophthalmology from September 2020 to mid-March 2021. All patients of biopsy-proven mucormycosis were enrolled in the study. The patients were subjected to complete history taking, ophthalmological examination, and imaging studies. The patients were treated via a multidisciplinary approach with intravenous liposomal amphotericin B and debridement of local necrotic tissue. Exenteration was done when indicated. A minimum 75-day follow-up period was accorded to all study patients. Statistical analysis was done using Chi-square test. A P value ≤0.05 was taken as significant. RESULTS: Thirty-one patients were seen, with a mean age of 56.3 years. The major risk factors included uncontrolled diabetes (96.7%) and COVID-19 positivity (61.2%), with concomitant steroid use in 61.2% patients. The most common presentation was diminution of vision (<6/60 in 80.64% patients) and ophthalmoplegia (77.4%). The most common imaging findings were orbital cellulitis (61.29%) and pansinusitis (77.4%). Intravenous liposomal amphotericin B was given to all patients for an average 18.93 days. Exenteration was required in (n = 4) 12.9% of cases. Twenty-eight patients recovered and were alive on follow-up. Mortality was seen in three patients. The presence of cerebral involvement and a HbA1c value of ≥8 were found to be significant in the prediction of survival of patients with mucormycosis. CONCLUSION: We present the largest institutional cohort of rhino-orbital mucormycosis patients during the ongoing COVID-19 pandemic era from our unique perspective.

Indian J Ophthalmol2021       LitCov and CORD-19
4544COVID-19 Pandemic Stressors and Psychological Symptoms in Breast Cancer Patients  

Background. The current Coronavirus disease 2019 (COVID-19) pandemic is a highly stressful event that may lead to significant psychological symptoms, particularly in cancer patients who are at a greater risk of contracting viruses. This study examined the frequency of stressors experienced in relation to the ongoing coronavirus pandemic and its relationship with psychological symptoms (i.e., anxiety, depression, insomnia, fear of cancer recurrence) in breast cancer patients. Methods. Thirty-six women diagnosed with a non-metastatic breast cancer completed the Insomnia Severity Index, the Hospital Anxiety and Depression Scale, the severity subscale of the Fear of Cancer Recurrence Inventory, and the COVID-19 Stressors Questionnaire developed by our research team. Participants either completed the questionnaires during (30.6%) or after (69.4%) their chemotherapy treatment. Results. Results revealed that most of the participants (63.9%) have experienced at least one stressor related to the COVID-19 pandemic (one: 27.8%, two: 22.2%, three: 11.1%). The most frequently reported stressor was increased responsibilities at home (33.3%). Higher levels of concerns related to the experienced stressors were significantly correlated with higher levels of anxiety, depressive symptoms, insomnia, and fear of cancer recurrence, rs(32) = 0.36 to 0.59, all ps < 0.05. Conclusions. Cancer patients experience a significant number of stressors related to the COVID-19 pandemic, which are associated with increased psychological symptoms. These results contribute to a better understanding of the psychological consequences of a global pandemic in the context of cancer and they highlight the need to better support patients during such a challenging time.

Curr Oncol2021       LitCov and CORD-19
4545Gender differences of depression and anxiety among social media users during the COVID-19 outbreak in China:a cross-sectional study  

BACKGROUND: Studies have shown that the outbreak of infectious diseases would result in mental health problems. Females are in greater risk for psychological problems than males. The present study investigated gender differences of depression and anxiety and explored associated factors during the COVID-19 epidemic among Chinese social media users. METHODS: We recruited 3088 participants through social media cross China. Participants completed sociodemographic and the COVID-19 epidemic related questions, the 2-item Patient Health Questionnaire (PHQ-2), and the 2-item Generalized Anxiety Disorder Scale (GAD-2), the Chinese version of the 10-item Connor-Davidson Resilience Scale. We applied Chi-square test and ANOVA for data description and linear regression analysis for exploring factors associated with depression and anxiety. RESULTS: Of 3063 participants eligible for analysis, the total prevalence of depression and anxiety was 14.14 and 13.25%. Females were experiencing more severe stress and anxiety symptoms, while males showed better resilience to stress. The severity of depression symptoms would decrease with the increase of age resilience, and it would increase if being unemployed, feeling less adapted, being more stressed. The severity of anxiety symptoms would decrease with higher education and better resilience, and it would increase if being female, spending over 60 min on COVID-19 related information, less adapted, and being more stressed. CONCLUSION: The findings show the increased prevalence of depression and anxiety in Chinese population during the COVID-19 epidemic, and females are experiencing more severe anxiety symptoms than males. As social media is the current main resource of information related to COVID-19, interventions should be implemented to help users to limit the time they spend on social media and to get key information related to the epidemic from authoritative and authentic resource to avoid infodemic and prevent mental health problems.

BMC Public Health2020       LitCov and CORD-19
4546Drug Discovery Strategies for SARS-CoV-2  

Coronavirus disease 2019 (COVID-19) is a novel disease caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus that was first detected in December of 2019 in Wuhan, China, and has rapidly spread worldwide. The search for a suitable vaccine as well as effective therapeutics for the treatment of COVID-19 is underway. Drug repurposing screens provide a useful and effective solution for identifying potential therapeutics against SARS-CoV-2. For example, the experimental drug remdesivir, originally developed for Ebola virus infections, has been approved by the US Food and Drug Administration as an emergency use treatment of COVID-19. However, the efficacy and toxicity of this drug need further improvements. In this review, we discuss recent findings on the pathology of coronaviruses and the drug targets for the treatment of COVID-19. Both SARS-CoV-2–specific inhibitors and broad-spectrum anticoronavirus drugs against SARS-CoV, Middle East respiratory syndrome coronavirus, and SARS-CoV-2 will be valuable additions to the anti–SARS-CoV-2 armament. A multitarget treatment approach with synergistic drug combinations containing different mechanisms of action may be a practical therapeutic strategy for the treatment of severe COVID-19. SIGNIFICANCE STATEMENT: Understanding the biology and pathology of RNA viruses is critical to accomplish the challenging task of developing vaccines and therapeutics against SARS-CoV-2. This review highlights the anti–SARS-CoV-2 drug targets and therapeutic development strategies for COVID-19 treatment.

J Pharmacol Exp Ther2020       LitCov and CORD-19
4547Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study  

BACKGROUND: The role of prone positioning in intubated subjects with acute respiratory distress syndrome caused by coronavirus disease 2019 (COVID-19) remains unclear. METHODS: We conducted an observational cohort study of intubated patients admitted to our academic medical centre intensive care unit with COVID-19 between March 18-31 2020. Exclusion criteria were pregnancy, reintubation and previous prone positioning at a referring hospital. Patients that were placed in the prone position were followed up until hospital discharge. The primary outcome was oxygenation assessed by arterial oxygen tension/fraction of inspired oxygen ratio (PaO(2)/F(I)O(2)). Secondary outcomes included PaO(2)/F(I)O(2) ratio improvement ≥20%. Treatment failure of prone positioning was defined as death or requirement for extracorporeal membrane oxygenation (ECMO). RESULTS: Forty-two subjects (29 males; mean age:58.5 [12.7] years) were eligible for analysis. Nine subjects were placed in the prone position only once, with 25 requiring prone positioning on ≥3 occasions. 31/42 (74%) subjects survived to discharge, with 5 requiring ECMO; 11/42 (26.2%) subjects died. Following the first prone positioning session, mean (SD) PaO(2)/F(I)O(2) ratio increased from 17.9kPa (7.2) to 28.2kPa (12.2) (p<0.01). With repeated prone positioning sessions, 31/42 (73.8%) subjects who were discharged from hospital had PaO(2)/F(I)O(2) ratio improvement of ≥20%, compared to 11/42 subjects who either died or required ECMO (odds ratio:XX (95% confidence intervals:xx-xx)). CONCLUSION: Patients with COVID-19 ARDS frequently responded to initial prone positioning with improved oxygenation. Subsequent prone positioning in subjects discharged from hospital was associated with greater improvements in oxygenation.

Br J Anaesth2020       LitCov and CORD-19
4548Cellular and Humoral Immune Response to a Third Dose of BNT162b2 COVID-19 Vaccine-A Prospective Observational Study  

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Front Immunol2022       LitCov
4549Towards Achieving a Vaccine-Derived Herd Immunity Threshold for COVID-19 in the U.S  

A novel coronavirus emerged in December of 2019 (COVID-19), causing a pandemic that inflicted unprecedented public health and economic burden in all nooks and corners of the world. Although the control of COVID-19 largely focused on the use of basic public health measures (primarily based on using non-pharmaceutical interventions, such as quarantine, isolation, social-distancing, face mask usage, and community lockdowns) initially, three safe and highly-effective vaccines (by AstraZeneca Inc., Moderna Inc., and Pfizer Inc.), were approved for use in humans in December 2020. We present a new mathematical model for assessing the population-level impact of these vaccines on curtailing the burden of COVID-19. The model stratifies the total population into two subgroups, based on whether or not they habitually wear face mask in public. The resulting multigroup model, which takes the form of a deterministic system of nonlinear differential equations, is fitted and parameterized using COVID-19 cumulative mortality data for the third wave of the COVID-19 pandemic in the United States. Conditions for the asymptotic stability of the associated disease-free equilibrium, as well as an expression for the vaccine-derived herd immunity threshold, are rigorously derived. Numerical simulations of the model show that the size of the initial proportion of individuals in the mask-wearing group, together with positive change in behavior from the non-mask wearing group (as well as those in the mask-wearing group, who do not abandon their mask-wearing habit) play a crucial role in effectively curtailing the COVID-19 pandemic in the United States. This study further shows that the prospect of achieving vaccine-derived herd immunity (required for COVID-19 elimination) in the U.S., using the Pfizer or Moderna vaccine, is quite promising. In particular, our study shows that herd immunity can be achieved in the U.S. if at least 60% of the population are fully vaccinated. Furthermore, the prospect of eliminating the pandemic in the U.S. in the year 2021 is significantly enhanced if the vaccination program is complemented with non-pharmaceutical interventions at moderate increased levels of compliance (in relation to their baseline compliance). The study further suggests that, while the waning of natural and vaccine-derived immunity against COVID-19 induces only a marginal increase in the burden and projected time-to-elimination of the pandemic, adding the impacts of therapeutic benefits of the vaccines into the model resulted in a dramatic reduction in the burden and time-to-elimination of the pandemic.

Front Public Health2021       LitCov and CORD-19
4550Perception of the study situation and mental burden during the COVID-19 pandemic among undergraduate medical students with and without mentoring  

Objectives: The COVID-19 pandemic caused drastic changes in medical education and might affect students’ mental health and perception of study conditions. Mentoring may have mediating effects by enhancing social support. The University Medical Center Hamburg-Eppendorf (UKE) offers a voluntary general mentoring program (g-mentoring) for all interested students and a mentoring program for students with excellent course results and scientific interest (e-mentoring) We aimed to investigate the mental burden and views of their study situation during COVID-19 among students who did or did not participate in one of the formal mentoring programs. Method: We conducted a cross-sectional online survey (May 2020) examining students’ mental burden using the Patient Health Questionnaire (PHQ-4), and assessing their perception of study conditions and digital teaching using self-developed items. Results: Of 1193 invited students, 543 (45.5%) completed the survey. 35% of those participated in the g-mentoring and 7% in the e-mentoring. 59% did not participate in any program. More e-mentees than g-mentees and nonparticipants reported clinically unproblematic levels of anxiety and depression symptoms. The majority of students (55%) was somewhat worried about the impact of the pandemic on their study situation. Regarding digital teaching students did not feel overburdened by the lack of a fixed schedule and structure, e-mentees even less than g-mentees and nonparticipants. Both g-mentees and nonparticipants were significantly more appreciative of the possible repeated use of the digital teaching materials than e-mentees (both groups M=5.7 vs. M=5.4 in e-mentees, p=.045). Conclusion: The results indicate that while students feel substantially burdened by the situation and the majority worries about the impact of the pandemic on their studies, they also seem to cope well with the digital course format. Study motivation during COVID-19 decreased among the majority of students with and without mentoring. These aspects may be important to address by medical schools interested in developing effective interventions to support students during a pandemic and continuous online teaching.

GMS J Med Educ2020       LitCov and CORD-19

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(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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