\ 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
1151In Silico, In Vitro and In Cellulo Models for Monitoring SARS-CoV-2 Spike/Human ACE2 Complex, Viral Entry and Cell Fusion  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent responsible for the recent coronavirus disease 2019 (COVID-19) pandemic. Productive SARS-CoV-2 infection relies on viral entry into cells expressing angiotensin-converting enzyme 2 (ACE2). Indeed, viral entry into cells is mostly mediated by the early interaction between the viral spike protein S and its ACE2 receptor. The S/ACE2 complex is, thus, the first contact point between the incoming virus and its cellular target; consequently, it has been considered an attractive therapeutic target. To further characterize this interaction and the cellular processes engaged in the entry step of the virus, we set up various in silico, in vitro and in cellulo approaches that allowed us to specifically monitor the S/ACE2 association. We report here a computational model of the SARS-CoV-2 S/ACE2 complex, as well as its biochemical and biophysical monitoring using pulldown, AlphaLISA and biolayer interferometry (BLI) binding assays. This led us to determine the kinetic parameters of the S/ACE2 association and dissociation steps. In parallel to these in vitro approaches, we developed in cellulo transduction assays using SARS-CoV-2 pseudotyped lentiviral vectors and HEK293T-ACE2 cell lines generated in-house. This allowed us to recapitulate the early replication stage of the infection mediated by the S/ACE2 interaction and to detect cell fusion induced by the interaction. Finally, a cell imaging system was set up to directly monitor the S/ACE2 interaction in a cellular context and a flow cytometry assay was developed to quantify this association at the cell surface. Together, these different approaches are available for both basic and clinical research, aiming to characterize the entry step of the original SARS-CoV-2 strain and its variants as well as to investigate the possible chemical modulation of this interaction. All these models will help in identifying new antiviral agents and new chemical tools for dissecting the virus entry step.

Viruses2021       LitCov and CORD-19
1152Sleep problems among Chinese adolescents and young adults during the coronavirus-2019 pandemic  

OBJECTIVE: To assess the prevalence and sociodemographic correlates of insomnia symptoms among Chinese adolescents and young adults affected by the outbreak of coronavirus disease-2019 (COVID-19). METHODS: This cross-sectional study included Chinese adolescents and young adults 12–29 years of age during part of the COVID-19 epidemic period. An online survey was used to collect demographic data, and to assess recognition of COVID-19, insomnia, depression, and anxiety symptoms using the Pittsburgh Sleep Quality Index (PSQI), the Patient Health Questionnaire (PHQ-9), and the Generalized Anxiety Disorder (GAD-7) questionnaires, respectively. The Social Support Rate Scale was used to assess social support. RESULTS: Among 11,835 adolescents and young adults included in the study, the prevalence of insomnia symptoms during part of the COVID-19 epidemic period was 23.2%. Binomial logistic regression analysis revealed that female sex and residing in the city were greater risk factors for insomnia symptoms. Depression or anxiety were risk factors for insomnia symptoms; however, social support, both subjective and objective, was protective factors against insomnia symptoms. Furthermore, anxiety and depression symptoms were mediators of social support and insomnia symptoms. CONCLUSIONS: Results of this study revealed a high prevalence of sleep problems among adolescents and young adults during the COVID-19 epidemic, especially senior high school and college students, which were negatively associated with students’ projections of trends in COVID-19. The adverse impact of COVID-19 was a risk factor for insomnia symptoms; as such, the government must devote more attention to sleep disorders in this patient population while combating COVID-19.

Sleep Med2020       LitCov and CORD-19
1153Pro- and Anti-Inflammatory Responses in Severe COVID-19 induced Acute Respiratory Distress Syndrome-An Observational Pilot Study  

OBJECTIVES: The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). METHODS: This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14(th) and May 28(th) 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. RESULTS: All patients suffered from severe ARDS, 30.8% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and naïve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. CONCLUSIONS: Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience.

Front Immunol2020       LitCov and CORD-19
1154Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes  

N/A

JAMA Netw Open2022       LitCov
1155Maternal and perinatal characteristics and outcomes of pregnancies complicated with COVID-19 in Kuwait  

BACKGROUND: The effect of SARS-CoV-2 infection in pregnant women and newborns is incompletely understood. Preliminary data shows a rather fluctuating course of the disease from asymptomatic or mild symptoms to maternal death. However, it is not clear whether the disease increases the risk of pregnancy-related complications. The aim of the study is to describe the maternal and neonatal clinical characteristics and outcome of pregnancies with SARS-CoV-2 infection. METHODS: In this retrospective national-based study, we analyzed the medical records of all pregnant women infected with SARS-CoV-2 and their neonates who were admitted to New-Jahra Hospital (NJH), Kuwait, between March 15th 2020 and May 31st 2020. During the study period and as part of the public health measures, a total of 185 pregnant women infected with SARS-CoV-2, regardless of symptoms, were hospitalized at NJH, and were included. Maternal and neonatal clinical manifestations, laboratory tests and treatments were collected. The outcomes of pregnancies included miscarriage, intrauterine fetal death (IUFD), preterm birth and live birth were assessed until the end date of the outcomes follow-up (November 10th 2020). RESULTS: A total of 185 pregnant women infected with SARS-CoV-2 were enrolled with a median age of 31 years (interquartile range, IQR: 27.5–34), and median gestational age at diagnosis of SARS-CoV2 infection was 29 weeks (IQR: 18–34). The majority (88%) of these women had mild symptoms, with fever (58%) being the most common presenting symptom followed by cough (50.6%). At the time of the analysis, out of the 185, 3 (1.6%) of the pregnant women had a miscarriage, 1 (0.54%) had IUFD which was not related to COVID-19, 16 (8.6%) had ongoing pregnancies and 165 (89%) had a live birth. Only 2 (1.1%) of these women developed severe pneumonia and required intensive care. A total of 167 neonates with two sets of twins were born with median gestational age at birth was 38 (IQR: 36–39) weeks. Most of the neonates were asymptomatic, and only 2 of them tested positive on day 5 by nasopharyngeal swab testing. CONCLUSIONS: In this national-based study, most of the pregnant women infected with SARS-CoV-2 showed mild symptoms. Although mother-to-child vertical transmission of SARS-CoV-2 is possible, COVID-19 infection during pregnancy may not lead to unfavorable maternal and neonatal outcomes. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s12884-020-03461-2.

BMC Pregnancy Childbirth2020       LitCov and CORD-19
1156COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy and Follow-Up: JACC State-of-the-Art Review  

Abstract Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, we review the current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexisting thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

J Am Coll Cardiol2020       LitCov and CORD-19
1157Technical guidelines for seasonal influenza vaccination in China (2022-2023)  

N/A

Zhonghua Yu Fang Yi Xue Za Zhi2022       LitCov
1158Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic  

N/A

Circulation2020       LitCov and CORD-19
1159In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs  

Coronavirus disease‐2019 (COVID‐19) outbreak due to novel coronavirus or severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has come out as a major threat for mankind in recent times. It is continually taking an enormous toll on mankind by means of increasing number of deaths, associated comorbidities, and socioeconomic loss around the globe. Unavailability of chemotherapeutics/vaccine has posed tremendous challenges to scientists and doctors for developing an urgent therapeutic strategy. In this connection, the present in silico study aims to understand the sequence divergence of spike protein (the major infective protein of SARS‐CoV‐2), its mode of interaction with the angiotensin‐converting enzyme‐2 receptor (ACE2) receptor of human and related animal hosts/reservoir. Moreover, the involvement of the human Toll‐like receptors (TLRs) against the spike protein has also been demonstrated. Our data indicated that the spike glycoprotein of SARS‐CoV‐2 is phylogenetically close to bat coronavirus and strongly binds with ACE2 receptor protein from both human and bat origin. We have also found that cell surface TLRs, especially TLR4 is most likely to be involved in recognizing molecular patterns from SARS‐CoV‐2 to induce inflammatory responses. The present study supported the zoonotic origin of SARS‐CoV‐2 from a bat and also revealed that TLR4 may have a crucial role in the virus‐induced inflammatory consequences associated with COVID‐19. Therefore, selective targeting of TLR4‐spike protein interaction by designing competitive TLR4‐antagonists could pave a new way to treat COVID‐19. Finally, this study is expected to improve our understanding on the immunobiology of SARS‐CoV‐2 and could be useful in adopting spike protein, ACE2, or TLR‐guided intervention strategy against COVID‐19 shortly.

J Med Virol2020       LitCov and CORD-19
1160Parental COVID-19 Testing of Hospitalized Children: Rethinking Infection Control in a Pandemic  

J Pediatric Infect Dis Soc2020       LitCov and CORD-19
1161Double-quencher probes improve detection sensitivity toward SARS-CoV-2 in a reverse-transcription polymerase chain reaction (RT-PCR) assay  

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

J Virol Methods2020       LitCov and CORD-19
1162Structured ICU resource management in a pandemic is associated with favorable outcome in critically ill COVID-19 patients  

INTRODUCTION: On February 25, 2020, the first 2 patients were tested positive for severe acute respiratory syndrome coronavirus‑2 (SARS-CoV-2) in Tyrol, Austria. Rapid measures were taken to ensure adequate intensive care unit (ICU) preparedness for a surge of critically ill coronavirus disease-2019 (COVID-19) patients. METHODS: This cohort study included all COVID-19 patients admitted to an ICU with confirmed or strongly suspected COVID-19 in the State of Tyrol, Austria. Patients were recorded in the Tyrolean COVID-19 intensive care registry. Date of final follow-up was July 17, 2020. RESULTS: A total of 106 critically ill patients with COVID-19 were admitted to 1 of 13 ICUs in Tyrol from March 9 to July 17, 2020. Median age was 64 years (interquartile range, IQR 54–74 years) and the majority of patients were male (76 patients, 71.7%). Median simplified acute physiology score III (SAPS III) was 56 points (IQR 49–64 points). The median duration from appearance of first symptoms to ICU admission was 8 days (IQR 5–11 days). Invasive mechanical ventilation was required in 72 patients (67.9%) and 6 patients (5.6%) required extracorporeal membrane oxygenation treatment. Renal replacement therapy was necessary in 21 patients (19.8%). Median ICU length of stay (LOS) was 18 days (IQR 5–31 days), median hospital LOS was 27 days (IQR 13–49 days). The ICU mortality was 21.7% (23 patients), hospital mortality was 22.6%. There was no significant difference in ICU mortality in patients receiving invasive mechanical ventilation and in those not receiving it (18.1% vs. 29.4%, p = 0.284). As of July 17th, 2020, two patients are still hospitalized, one in an ICU, one on a general ward. CONCLUSION: Critically ill COVID-19 patients in Tyrol showed high severity of disease often requiring complex treatment with increased lengths of ICU and hospital stay. Nevertheless, the mortality was found to be remarkably low, which may be attributed to our adaptive surge response providing sufficient ICU resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00508-020-01764-0) contains supplementary material, which is available to authorized users.

Wien Klin Wochenschr2020       LitCov and CORD-19
1163Adapting Neurosurgery Practice During the COVID-19 Pandemic in the Indian Subcontinent  

ABSTRACT Background The COVID-19 pandemic has changed the practice of neurosurgery. Significant resources have been dedicated to it. The pandemic in the Indian subcontinent, when compared to the rest of the world, is relatively delayed. The neurosurgical practice cannot remain unaffected by hugely disruptive measures such as a lockdown. The inevitable rise in covid infections with its gradual relaxation continues to pose a risk for health care providers. Therefore, it is imperative to evaluate whether the pandemic has had a discernible effect on the same especially in terms of practice modifications in private establishments and publicly funded hospitals, the emotional impact on the surgeon, and the influence of social media on the psyche of the surgeon. Material and Methods An online questionnaire-based survey was prepared, with questions related to the COVID specific themes of precautions taken in outpatient services and operation theaters, the influence of social media, the economic loss incurred, and the perceptible impact of telemedicine and webinars. The links to the survey were mailed to neurosurgeons in private and public practice all over the country. The responses were anonymized to ensure free and unbiased answers to the survey questions. Results A total of 176 responses were received from all over the Indian Sub-Continent. The median age of respondents was 39years (range 32-70 yrs) and the post-residency experience was 7years (range 0-34 yrs). Respondents were an equitable mix of public and private practitioners. 46% of the respondents were practicing restricted outpatient services, more in public institutions (p=0.22) which also had a higher incidence of tele-outpatient services(26% vs 17%). Wearing surgical masks, N-95 masks, and gloves were the most commonly practised precautionary measures in outpatient services(>60%). While private practitioners were continuing elective cases(40%), public institutes were more cautious with only emergencies being operated(29%). The greatest fear among all practitioners was passing the infection to the family (75%). Social media was helpful for brainstorming queries and updating practice modifications, but some surgeons admitted to receiving threats upon social media platforms(37.5%). Depression and economic losses were palpable for approximately 30% neurosurgeons. Conclusion The survey highlights the perception of the neurosurgeons towards the pandemic and the difference in public-private practice. Suspension of elective procedures, severe curtailment of the regular outpatient appointments, drastic modifications of the normal OPD/OR practices and apprehensions related to inadequacy of safety provided by PPE usage and financial losses of private establishments were some of the visible themes in our survey results. Though telemedicine has not been as widely adopted as expected, yet online education has been favourably received.

World Neurosurg2020       LitCov and CORD-19
1164Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa  

The SARS-CoV-2 epidemic in southern Africa has been characterized by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, while the second and third waves were driven by the Beta (B.1.351) and Delta (B.1.617.2) variants, respectively(1–3). In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron, B.1.1.529) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, which are predicted to influence antibody neutralization and spike function(4). Here we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.

Nature2022       LitCov and CORD-19
1165SARS-CoV-2-specific T-cell immunity in cases of COVID-19 and SARS and uninfected controls  

N/A

Nature2020       LitCov and CORD-19
1166Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From COVID-19  

Importance Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown. Objective To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness. Design, Setting, and Participants In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020. Exposure Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract. Main Outcomes and Measures Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57). Results Of the 100 included patients, 53 (53%) were male, and the median (interquartile range [IQR]) age was 49 (45-53) years. The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days. Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization. At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (3 pg/mL or greater) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (13.9 pg/mL or greater) in 5 patients (5%). Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, higher left ventricle mass, and raised native T1 and T2. A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), and pericardial enhancement (n = 22). There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1122 [1113-1132] ms vs 1143 [1131-1156] ms; P = .02) but not for native T2 mapping or hsTnT levels. None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = -0.07; P = .50). High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.35; P < .001) and native T2 mapping (r = 0.22; P = .03). Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation. Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology. Conclusions and Relevance In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

JAMA Cardiol2020       LitCov and CORD-19
1167Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study  

Summary Background Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in Shenzhen, China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control measures. Methods From Jan 14 to Feb 12, 2020, the Shenzhen Center for Disease Control and Prevention identified 391 SARS-CoV-2 cases and 1286 close contacts. We compared cases identified through symptomatic surveillance and contact tracing, and estimated the time from symptom onset to confirmation, isolation, and admission to hospital. We estimated metrics of disease transmission and analysed factors influencing transmission risk. Findings Cases were older than the general population (mean age 45 years) and balanced between males (n=187) and females (n=204). 356 (91%) of 391 cases had mild or moderate clinical severity at initial assessment. As of Feb 22, 2020, three cases had died and 225 had recovered (median time to recovery 21 days; 95% CI 20–22). Cases were isolated on average 4·6 days (95% CI 4·1–5·0) after developing symptoms; contact tracing reduced this by 1·9 days (95% CI 1·1–2·7). Household contacts and those travelling with a case were at higher risk of infection (odds ratio 6·27 [95% CI 1·49–26·33] for household contacts and 7·06 [1·43–34·91] for those travelling with a case) than other close contacts. The household secondary attack rate was 11·2% (95% CI 9·1–13·8), and children were as likely to be infected as adults (infection rate 7·4% in children <10 years vs population average of 6·6%). The observed reproductive number (R) was 0·4 (95% CI 0·3–0·5), with a mean serial interval of 6·3 days (95% CI 5·2–7·6). Interpretation Our data on cases as well as their infected and uninfected close contacts provide key insights into the epidemiology of SARS-CoV-2. This analysis shows that isolation and contact tracing reduce the time during which cases are infectious in the community, thereby reducing the R. The overall impact of isolation and contact tracing, however, is uncertain and highly dependent on the number of asymptomatic cases. Moreover, children are at a similar risk of infection to the general population, although less likely to have severe symptoms; hence they should be considered in analyses of transmission and control. Funding Emergency Response Program of Harbin Institute of Technology, Emergency Response Program of Peng Cheng Laboratory, US Centers for Disease Control and Prevention.

Lancet Infect Dis2020       LitCov and CORD-19
1168Online teaching in physiotherapy education during COVID-19 pandemic in Italy: a retrospective case-control study on students' satisfaction and performance  

BACKGROUND: During COVID-19 pandemic, physiotherapy lecturers faced the challenge of rapidly shifting from face-to-face to online education. This retrospective case-control study aims to compare students’ satisfaction and performances shown in an online course to a control group of students who underwent the same course delivered face-to-face in the previous five years. METHODS: Between March and April 2020, a class (n = 46) of entry-level physiotherapy students (University of Verona - Italy), trained by an experienced physiotherapist, had 24-hours online lessons. Students exposed to the same course in the previous five academic years (n = 112), delivered with face-to-face conventional lessons, served as a historical control. The course was organized in 3 sequential phases: (1) PowerPoint presentations were uploaded to the University online platform, (2) asynchronous video recorded lectures were provided on the same platform, and (3) between online lectures, the lecturer and students could communicate through an email chat to promote understanding, dispel any doubts and collect requests for supplementary material (e.g., scientific articles, videos, webinars, podcasts). Outcomes were: (1) satisfaction as routinely measured by University with a national instrument and populated in a database; (2) performance as measured with an oral examination. RESULTS: We compared satisfaction with the course, expressed on a 5-point Likert scale, resulting in no differences between online and face-to-face teaching (Kruskal-Wallis (2) = 0.24, df = 1, p = 0.62). We weighted up students’ results by comparing their mean performances with the mean performances of the same course delivered face-to-face in the previous five years, founding a statistical significance in favour of online teaching (Wilcoxon rank sum test W = 1665, p < 0.001). CONCLUSIONS: Online teaching in entry-level Physiotherapy seems to be a feasible option to face COVID-19 pandemic, as satisfies students as well as face-to-face courses and leading to a similar performance. Entry-level Bachelors in Physiotherapy may consider moving to eLearning to facilitate access to higher education. Universities will have to train lecturers to help them develop appropriate pedagogical skills, and supply suitable support in terms of economic, organizational, and technological issues, aimed at guaranteeing a high level of education to their students. TRIAL REGISTRATION: Retrospectively registered.

BMC Med Educ2021       LitCov and CORD-19
1169Sharp increase in depression and anxiety among Brazilian adults during the COVID-19 pandemic: findings from the PAMPA cohort  

OBJECTIVES: We aimed to compare the prevalence of depression and anxiety symptoms before and during the pandemic and identify factors associated with aggravated mental health symptoms. STUDY DESIGN: Retrospective cohort study. METHODS: We identified the proportion of normal, mild, moderate, and severe symptoms of depression and anxiety before and during the social distancing restrictions in adults from southern Brazil. An online, self-administered questionnaire was delivered for residents within the state of Rio Grande do Sul. Depressive and anxiety symptoms were examined by the Hospital Anxiety and Depression Scale. RESULTS: Most of the participants (n = 2314) aged between 31 and 59 years (54.2%), were women (76.6%), White (90.6%) with a university degree (66.6%). Moderate-to-severe symptoms of depression and anxiety were reported in 3.9% and 4.5% of participants, respectively, before COVID-19. During the pandemic (June–July, 2020), these proportions increased to 29.1% (6.6-fold increase) and 37.8% (7.4-fold increase), respectively. Higher rates of depressive and anxiety symptoms were observed among women, those aged 18–30 years, diagnosed with chronic disease and participants who had their income negatively affected by social restrictions. Remaining active or becoming physically active during social distancing restrictions reduced the probability of aggravated mental health disorders. CONCLUSIONS: Depressive and anxiety symptoms had a 6.6- and 7.4-fold increase since the COVID-19 pandemic. Public policies such as physical activity promotion and strategies to reduce the economic strain caused by this pandemic are urgently needed to mitigate the impact of the pandemic on mental health.

Public Health2020       LitCov and CORD-19
1170Assessment of 135 794 Pediatric Patients Tested for SARS-CoV-2 Across the United States  

N/A

JAMA Pediatr2021       LitCov and CORD-19
1171The effect of the COVID pandemic lockdown measures on surgical emergencies: experience and lessons learned from a Greek tertiary hospital  

BACKGROUND: The COVID-19 pandemic caused a rise in healthcare demands leading to significant restructuring of hospital emergency departments worldwide. The aim of the present study is twofold: firstly, to discern any differences in regard to reason for surgical emergency department (SED) attendance and hospital admission during the pandemic and pre-pandemic eras in Greece, and secondly, to assess the impact of the lockdown measures implemented during the pandemic on SED patient attendance. METHODS: Since the beginning of the COVID-19 pandemic in Greece (1 March 2020) and up to 15 December 2020, the charts of all adult patients arriving at the SED of the third surgical department of the “Attikon” University Hospital (a tertiary referral center for surgical and COVID-19 cases) were retrospectively reviewed and broken down in four periods reflecting two nationwide lockdown (period A 1/3/2020 to 30/4/2020 and period D 16/10/2020 to 15/12/2020) and two interim (period B 1/5/2020 to 15/6/2020 and period C 15/9/2020 to 30/10/2020) periods. Demographic and clinical data were compared to those obtained from the same time periods of the year 2019. RESULTS: The total number of patients attending the SED decreased by 35.9% during the pandemic (from 2839 total patients in 2019 to 1819 in 2020). During the first lockdown, there was statistically significant reduction of motor vehicle accidents (p=0.04) and torso injuries (p=0.01). Contrarily, the rate of head injuries (p<0.001) and abdominal pain (p=0.04) were significantly increased. The same effect was observed regarding the rate of hospital admissions (p=0.002), although in terms of absolute numbers, admissions remained unchanged. During the second lockdown, there was a reduction in the number of perianal abscess cases (p=0.04) and hernia-related problems (p=0.001). An increase in the rate of fall injuries was also demonstrable (p=0.02). Overall, application of the lockdown led to a significant decrease in minor (p<0.001) and torso (p=0.001) injuries. CONCLUSION: The burden of the new COVID-19 disease has left a noticeable imprint in the function of emergency departments worldwide. In Greece, SED attendance was significantly reduced during the pandemic, an effect that was even more pronounced during the lockdown implementation; nevertheless, the overall rate of hospital admissions remained the same, denoting that patient care was not altered.

World J Emerg Surg2021       LitCov and CORD-19
1172Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents. METHODS: We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic. RESULTS: Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide. CONCLUSIONS: Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.

N Engl J Med2020       LitCov and CORD-19
1173Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study  

BACKGROUND: Since the coronavirus disease 2019 outbreak began in the Chinese city of Wuhan on Dec 31, 2019, 68 imported cases and 175 locally acquired infections have been reported in Singapore. We aimed to investigate options for early intervention in Singapore should local containment (eg, preventing disease spread through contact tracing efforts) be unsuccessful. METHODS: We adapted an influenza epidemic simulation model to estimate the likelihood of human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a simulated Singaporean population. Using this model, we estimated the cumulative number of SARS-CoV-2 infections at 80 days, after detection of 100 cases of community transmission, under three infectivity scenarios (basic reproduction number [R(0)] of 1·5, 2·0, or 2·5) and assuming 7·5% of infections are asymptomatic. We first ran the model assuming no intervention was in place (baseline scenario), and then assessed the effect of four intervention scenarios compared with a baseline scenario on the size and progression of the outbreak for each R(0) value. These scenarios included isolation measures for infected individuals and quarantining of family members (hereafter referred to as quarantine); quarantine plus school closure; quarantine plus workplace distancing; and quarantine, school closure, and workplace distancing (hereafter referred to as the combined intervention). We also did sensitivity analyses by altering the asymptomatic fraction of infections (22·7%, 30·0%, 40·0%, and 50·0%) to compare outbreak sizes under the same control measures. FINDINGS: For the baseline scenario, when R(0) was 1·5, the median cumulative number of infections at day 80 was 279 000 (IQR 245 000–320 000), corresponding to 7·4% (IQR 6·5–8·5) of the resident population of Singapore. The median number of infections increased with higher infectivity: 727 000 cases (670 000–776 000) when R(0) was 2·0, corresponding to 19·3% (17·8–20·6) of the Singaporean population, and 1 207 000 cases (1 164 000–1 249 000) when R(0) was 2·5, corresponding to 32% (30·9–33·1) of the Singaporean population. Compared with the baseline scenario, the combined intervention was the most effective, reducing the estimated median number of infections by 99·3% (IQR 92·6–99·9) when R(0) was 1·5, by 93·0% (81·5–99·7) when R(0) was 2·0, and by 78·2% (59·0 −94·4) when R(0) was 2·5. Assuming increasing asymptomatic fractions up to 50·0%, up to 277 000 infections were estimated to occur at day 80 with the combined intervention relative to 1800 for the baseline at R(0) of 1·5. INTERPRETATION: Implementing the combined intervention of quarantining infected individuals and their family members, workplace distancing, and school closure once community transmission has been detected could substantially reduce the number of SARS-CoV-2 infections. We therefore recommend immediate deployment of this strategy if local secondary transmission is confirmed within Singapore. However, quarantine and workplace distancing should be prioritised over school closure because at this early stage, symptomatic children have higher withdrawal rates from school than do symptomatic adults from work. At higher asymptomatic proportions, intervention effectiveness might be substantially reduced requiring the need for effective case management and treatments, and preventive measures such as vaccines. FUNDING: Singapore Ministry of Health, Singapore Population Health Improvement Centre.

Lancet Infect Dis2020       LitCov and CORD-19
1174The Vaccine Efficacy Against the SARS-CoV-2 Omicron: A Systemic Review and Meta-Analysis  

N/A

Front Public Health2022       LitCov
1175Vaccination-infection interval determines cross-neutralization potency to SARS-CoV-2 Omicron after breakthrough infection by other variants  

Background The immune profile against SARS-CoV-2 has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by the Omicron in individuals with various immune histories. Methods The neutralization susceptibility of the variants including the Omicron and their ancestor was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections by the Alpha/Delta with multiple time intervals following vaccination. Findings The Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against the Omicron were induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies. Conclusions Immune histories with breakthrough infections can overcome the resistance to infection by the Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against the Omicron and future variants. Funding This study was supported by grants from the Japan Agency for Medical Research and Development (AMED).

Med (N Y)2022       LitCov and CORD-19
1176Evidence-Based Strategies for Clinical Organizations to Address COVID-19 Vaccine Hesitancy  

The success of vaccination programs is contingent upon irrefutable scientific safety data combined with high rates of public acceptance and population coverage. Vaccine hesitancy, characterized by lack of confidence in vaccination and/or complacency about vaccination that may lead to delay or refusal to vaccinate despite the availability of services, threatens to undermine the success of COVID-19 vaccination programs. The rapid pace of vaccine development, misinformation in popular and social media, the polarized sociopolitical environment, and the inherent complexities of large-scale vaccination efforts may undermine vaccination confidence and increase complacency about COVID-19 vaccination. While the experience of recent lethal surges of COVID-19 infections have underscored the value of COVID-19 vaccines, ensuring population uptake of COVID-19 vaccination will require application of multi-level, evidence-based strategies to influence behavior change and address vaccine hesitancy. Recent survey research evaluating public attitudes in the U.S. toward the COVID-19 vaccine reveals substantial vaccine hesitancy. Building upon efforts at the policy and community level to ensure population access to COVID-19 vaccination, a strong healthcare system response is critical to address vaccine hesitancy. Drawing on the evidence base in social, behavioral, communication, and implementation science, we review, summarize and encourage use of interpersonal, individual-level, and organizational interventions within clinical organizations to address this critical gap and improve population adoption of COVID-19 vaccination.

Mayo Clin Proc2020       LitCov and CORD-19
1177Prevalence of Gastrointestinal Symptoms and Fecal Viral Shedding in Patients With COVID-19: A Systematic Review and Meta-analysis  

IMPORTANCE: Coronavirus disease 2019 (COVID-19) is a global pandemic and can involve the gastrointestinal (GI) tract, including symptoms like diarrhea and shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces. OBJECTIVE: To provide a pooled estimate of GI symptoms, liver enzyme levels outside reference ranges, and fecal tests positive for SARS-CoV-2 among patients with COVID-19. DATA SOURCES: An electronic literature search was performed for published (using MEDLINE/PubMed and Embase) and preprint (using bioRxiv and medRxiv) studies of interest conducted from November 1, 2019, to March 30, 2020. Search terms included “COVID-19,” “SARS-Cov-2,” and/or “novel coronavirus.” STUDY SELECTION: Eligible studies were those including patients with SARS-CoV-2 infection who reported GI symptoms. DATA EXTRACTION AND SYNTHESIS: Data on patients with GI symptoms (ie, diarrhea, nausea, or vomiting), liver enzyme level changes, and fecal shedding of virus were extracted. Quality of studies was examined using methodological index for nonrandomized studies. Pooled estimates (%) were reported with 95% CIs with level of heterogeneity (I(2)). MAIN OUTCOMES AND MEASURES: Study and patient characteristics with pooled detection rates for diarrhea, nausea or vomiting, liver enzyme levels outside reference ranges, and SARS-CoV-2 positivity in feces tests were analyzed. RESULTS: Of 1484 records reviewed, 23 published and 6 preprint studies were included in the analysis, with a total of 4805 patients (mean [SD] age, 52.2 [14.8] years; 1598 [33.2%] women) with COVID-19. The pooled rates were 7.4% (95% CI, 4.3%-12.2%) of patients reporting diarrhea and 4.6% (95% CI, 2.6%-8.0%) of patients reporting nausea or vomiting. The pooled rate for aspartate aminotransferase levels outside reference ranges was 20% (95% CI, 15.3%-25.6%) of patients, and the pooled rate for alanine aminotransferase levels outside reference ranges was 14.6% (95% CI, 12.8%-16.6%) of patients. Fecal tests that were positive for SARS-CoV-2 were reported in 8 studies, and viral RNA shedding was detected in feces in 40.5% (95% CI, 27.4%-55.1%) of patients. There was high level of heterogeneity (I(2) = 94%), but no statistically significant publication bias noted. CONCLUSIONS AND RELEVANCE: These findings suggest that that 12% of patients with COVID-19 will manifest GI symptoms; however, SAR-CoV-2 shedding was observed in 40.5% of patients with confirmed SARS-CoV-2 infection. This highlights the need to better understand what measures are needed to prevent further spread of this highly contagious pathogen.

JAMA Netw Open2020       LitCov and CORD-19
1178Sociodemographic Determinants of COVID-19 Vaccine Hesitancy, Fear of Infection and Protection Self-Efficacy  

OBJECTIVES: Arkansas COVID-19 vaccine uptake has been lower than the national average. This study examined associations between sociodemographic factors and COVID-19 vaccine hesitancy, fear of infection, and protection self-efficacy. METHODS: Adults either residing, having employment, or receiving health care in Arkansas (n = 754) participated in an online survey between October 30, 2020 and January 16, 2021. Participants were recruited in both rural and urban areas from 6 Arkansas primary care clinics. Survey questions addressed sociodemographic factors, COVID-19 infection fear, protection self-efficacy, and COVID-19 vaccine attitudes. Bivariate and multivariable logistic regression models were used to assess associations between dependent variables and respondents’ sociodemographic characteristics, COVID-19 infection fear, and COVID-19 protection self-efficacy. RESULTS: About 38% of participants reported COVID-19 vaccine hesitancy. Age, sex, race, and education were significantly associated with COVID-19 and general vaccine attitudes. Odds of COVID-19 vaccine hesitancy decreased as age increased (OR = 0.98; P < .01). Women had higher odds of COVID-19 vaccine hesitancy than men (OR = 1.52; P < .05). Respondents with a high school diploma and below and respondents with some college or a technical degree had greater odds of COVID-19 vaccine hesitancy (OR = 2.58; P < .001; and OR = 1.97; P < .01, respectively) compared to respondents with a 4-year college degree. Black/African American respondents had greater odds of COVID-19 vaccine hesitancy compared to White respondents (OR = 3.08; P < .001). No significant difference was observed among rural and urban respondents regarding COVID-19 vaccine hesitancy; however, respondents in rural areas were more likely to report low general vaccine trust compared to those in urban areas (OR = 1.87; P < .01). Respondents reporting no fear (OR = 5.51; P < .001) and very little fear (OR = 1.95; P < .05) of COVID-19 had greater odds of COVID-19 vaccine hesitancy compared to respondents who feared COVID-19 infection to a great extent. CONCLUSIONS: COVID-19 vaccine hesitancy and general trust in vaccines differ significantly among age, sex, race, and education. These trust and hesitancy patterns are challenges for achieving population immunity and follow similar patterns of vulnerability to COVID-19. Vaccination programs and interventions must consider these differences in COVID-19 vaccine hesitancy and general vaccine trust to alleviate COVID-19 disparities. Findings make a significant contribution in evaluating vaccine hesitancy among a large, diverse sample from a rural state.

J Prim Care Community Health2021       LitCov and CORD-19
1179Computational Alanine Scanning and Structural Analysis of the SARS-CoV-2 Spike Protein/Angiotensin-Converting Enzyme 2 Complex  

[Image: see text] The recent emergence of the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent for the coronavirus disease 2019 (COVID-19), is causing a global pandemic that poses enormous challenges to global public health and economies. SARS-CoV-2 host cell entry is mediated by the interaction of the viral transmembrane spike glycoprotein (S-protein) with the angiotensin-converting enzyme 2 gene (ACE2), an essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis. Accordingly, this work reports an atomistic-based, reliable in silico structural and energetic framework of the interactions between the receptor-binding domain of the SARS-CoV-2 S-protein and its host cellular receptor ACE2 that provides qualitative and quantitative insights into the main molecular determinants in virus/receptor recognition. In particular, residues D38, K31, E37, K353, and Y41 on ACE2 and Q498, T500, and R403 on the SARS-CoV-2 S-protein receptor-binding domain are determined as true hot spots, contributing to shaping and determining the stability of the relevant protein–protein interface. Overall, these results could be used to estimate the binding affinity of the viral protein to different allelic variants of ACE2 receptors discovered in COVID-19 patients and for the effective structure-based design and development of neutralizing antibodies, vaccines, and protein/protein inhibitors against this terrible new coronavirus.

ACS Nano2020       LitCov and CORD-19
1180Epidemiology, outcomes and utilization of intensive care unit resources for critically ill COVID-19 patients in Libya: A prospective multi-center cohort study  

BACKGROUND: The coronavirus disease (COVID-19) pandemic has severely affected African countries, specifically the countries, such as Libya, that are in constant conflict. Clinical and laboratory information, including mortality and associated risk factors in relation to hospital settings and available resources, about critically ill patients with COVID-19 in Africa is not available. This study aimed to determine the mortality and morbidity of COVID-19 patients in intensive care units (ICU) following 60 days after ICU admission, and explore the factors that influence in‐ICU mortality rate. METHODS: This is a multicenter prospective observational study among COVID-19 critical care patients in 11 ICUs in Libya from May 29th to December 30th 2020. Basic demographic data, clinical characteristics, laboratory values, admission Sequential Organ Failure Assessment (SOFA) score, quick SOFA, and clinical management were analyzed. RESULT: We included 465 consecutive COVID-19 critically ill patients. The majority (67.1%) of the patients were older than 60 years, with a median (IQR) age of 69 (56.5–75); 240 (51.6%) were male. At 60 days of follow-up, 184 (39.6%) were discharged alive, while 281 (60.4%) died in the intensive care unit. The median (IQR) ICU length of stay was 7 days (4–10) and non-survivors had significantly shorter stay, 6 (3–10) days. The body mass index was 27.9 (24.1–31.6) kg/m2. At admission to the intensive care unit, quick SOFA median (IQR) score was 1 (1–2), whereas total SOFA score was 6 (4–7). In univariate analysis, the following parameters were significantly associated with increased/decreased hazard of mortality: increased age, BMI, white cell count, neutrophils, procalcitonin, cardiac troponin, C-reactive protein, ferritin, fibrinogen, prothrombin, and d-dimer levels were associated with higher risk of mortality. Decreased lymphocytes, and platelet count were associated with higher risk of mortality. Quick SOFA and total SOFA scores increase, emergency intubation, inotrope use, stress myocardiopathy, acute kidney injury, arrythmia, and seizure were associated with higher mortality. CONCLUSION: Our study reported the highest mortality rate (60.4%) among critically ill patients with COVID-19 60 days post-ICU admission. Several factors were found to be predictive of mortality, which may help to identify patients at risk of mortality during the ongoing COVID-19 pandemic.

PLoS One2021       LitCov and CORD-19
1181Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study  

BACKGROUND: Assessing the burden of COVID-19 on the basis of medically attended case numbers is suboptimal given its reliance on testing strategy, changing case definitions, and disease presentation. Population-based serosurveys measuring anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies provide one method for estimating infection rates and monitoring the progression of the epidemic. Here, we estimate weekly seroprevalence of anti-SARS-CoV-2 antibodies in the population of Geneva, Switzerland, during the epidemic. METHODS: The SEROCoV-POP study is a population-based study of former participants of the Bus Santé study and their household members. We planned a series of 12 consecutive weekly serosurveys among randomly selected participants from a previous population-representative survey, and their household members aged 5 years and older. We tested each participant for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA. We estimated seroprevalence using a Bayesian logistic regression model taking into account test performance and adjusting for the age and sex of Geneva's population. Here we present results from the first 5 weeks of the study. FINDINGS: Between April 6 and May 9, 2020, we enrolled 2766 participants from 1339 households, with a demographic distribution similar to that of the canton of Geneva. In the first week, we estimated a seroprevalence of 4·8% (95% CI 2·4–8·0, n=341). The estimate increased to 8·5% (5·9–11·4, n=469) in the second week, to 10·9% (7·9–14·4, n=577) in the third week, 6·6% (4·3–9·4, n=604) in the fourth week, and 10·8% (8·2–13·9, n=775) in the fifth week. Individuals aged 5–9 years (relative risk [RR] 0·32 [95% CI 0·11–0·63]) and those older than 65 years (RR 0·50 [0·28–0·78]) had a significantly lower risk of being seropositive than those aged 20–49 years. After accounting for the time to seroconversion, we estimated that for every reported confirmed case, there were 11·6 infections in the community. INTERPRETATION: These results suggest that most of the population of Geneva remained uninfected during this wave of the pandemic, despite the high prevalence of COVID-19 in the region (5000 reported clinical cases over <2·5 months in the population of half a million people). Assuming that the presence of IgG antibodies is associated with immunity, these results highlight that the epidemic is far from coming to an end by means of fewer susceptible people in the population. Further, a significantly lower seroprevalence was observed for children aged 5–9 years and adults older than 65 years, compared with those aged 10–64 years. These results will inform countries considering the easing of restrictions aimed at curbing transmission. FUNDING: Swiss Federal Office of Public Health, Swiss School of Public Health (Corona Immunitas research program), Fondation de Bienfaisance du Groupe Pictet, Fondation Ancrage, Fondation Privée des Hôpitaux Universitaires de Genève, and Center for Emerging Viral Diseases.

Lancet2020       LitCov and CORD-19
1182CoroNet: A deep neural network for detection and diagnosis of COVID-19 from chest x-ray images  

BACKGROUND AND OBJECTIVE: The novel Coronavirus also called COVID-19 originated in Wuhan, China in December 2019 and has now spread across the world. It has so far infected around 1.8 million people and claimed approximately 114698 lives overall. As the number of cases are rapidly increasing, most of the countries are facing shortage of testing kits and resources. The limited quantity of testing kits and increasing number of daily cases encouraged us to come up with a Deep Learning model that can aid radiologists and clinicians in detecting COVID-19 cases using chest X-rays. METHODS: In this study, we propose CoroNet, a Deep Convolutional Neural Network model to automatically detect COVID-19 infection from chest X-ray images. The proposed model is based on Xception architecture pre-trained on ImageNet dataset and trained end-to-end on a dataset prepared by collecting COVID-19 and other chest pneumonia X-ray images from two different publically available databases. RESULTS: CoroNet has been trained and tested on the prepared dataset and the experimental results show that our proposed model achieved an overall accuracy of 89.6%, and more importantly the precision and recall rate for COVID-19 cases are 93% and 98.2% for 4-class cases (COVID vs Pneumonia bacterial vs pneumonia viral vs normal). For 3-class classification (COVID vs Pneumonia vs normal), the proposed model produced a classification accuracy of 95%. The preliminary results of this study look promising which can be further improved as more training data becomes available. CONCLUSION: CoroNet achieved promising results on a small prepared dataset which indicates that given more data, the proposed model can achieve better results with minimum pre-processing of data. Overall, the proposed model substantially advances the current radiology based methodology and during COVID-19 pandemic, it can be very helpful tool for clinical practitioners and radiologists to aid them in diagnosis, quantification and follow-up of COVID-19 cases.

Comput Methods Programs Biomed2020       LitCov and CORD-19
1183Epidemiology of COVID-19 Among Children in China  

N/A

Pediatrics2020       LitCov
1184Flexible, Freely Available Stochastic Individual Contact Model for Exploring COVID-19 Intervention and Control Strategies: Development and Simulation  

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

JMIR Public Health Surveill2020       LitCov and CORD-19
1185Risk factors for severe outcomes for COVID-19 patients hospitalised in Switzerland during the first pandemic wave, February to August 2020: prospective observational cohort study  

N/A

Swiss Med Wkly2021       LitCov and CORD-19
1186Correlation of Immunogenicity and Reactogenicity of BNT162b2 and CoronaVac SARS-CoV-2 Vaccines  

COVID-19 infection is a global health issue, and vaccination is the main strategy to control this pandemic. In this study, 189 participants received BNT162b2 or CoronaVac vaccine, and 133 of them recorded adverse events (AEs) daily for 4 weeks after vaccination. Their neutralizing antibody against SARS-CoV-2 was determined with live virus microneutralization (vMN) assay. The vMN geometric mean titer (GMT) on day 56 was 129.9 (95% confidence interval [CI],108.6 to 155.2) in the BNT162b2 group and 13.1 (95% CI, 11.2 to 15.3) in the CoronaVac group. Day 56 vMN GMT was 147.9 (95% CI, 118.9 to 184.1) in females and 129.9 (95% CI, 108.6 to 155.2) in males receiving BNT162b2, while it was 14.0 (95% CI, 11.6 to 17.0) in females and 11.4 (95% CI, 8.7 to 15.0) in males receiving CoronaVac. Injection site pain (88.8%) and redness (77.5%) were the most commonly BNT162b2-related AEs, and injection site pain (37.7%) and tiredness (26.4%) were more frequent in the CoronaVac group. Women showed a higher frequency of headache (45.7% versus 29.4%) and joint pain (26.1 versus 14.7%) than men in BTN162b2 group. Headache (26.5% versus 0%) and tiredness (38.2% versus 5.3%) were more common in women than in men vaccinated with CoronaVac. No correlation between any AE and antibody response was observed in BNT162b2 or CoronaVac platforms. After taking the gender factor into account, in the BNT162b2 group, a low correlation between day 21 vMN titer and redness (rho = 0.34) or itching (rho = 0.32) was presented in females, and a low correlation between day 56 vMN titer and fever (rho = 0.35) was presented in males. Taken together, AEs could have a low correlation with BNT162b2 vaccine response. IMPORTANCE Effective vaccines against SARS-CoV-2 are vital tools for containing the COVID-19 pandemic by increasing population immunity. While currently available vaccines can elicit antibody response against SARS-CoV-2 with high efficacy, the associated side effects may cause vaccine hesitancy. Our work is important in that we have thoroughly analyzed the correlation between immunogenicity and reactogenicity of two COVID-19 vaccines (BNT162b2 and CoronaVac) in the study. Our results showed that women had higher levels of neutralizing antibodies than men after receiving BNT162b2 or CoronaVac. Furthermore, a low correlation was observed between day 21 vMN titer and local reactions (redness and itching) in females, as well as between day 56 vMN titer and fever in males receiving BNT162b2. Thus, common side effects are not always a negative impact of vaccination but may serve as an indicator of immunogenicity of vaccines. Our study may help in increasing the public’s acceptance and confidence over COVID-19 vaccination and ultimately achieving the goal of containing COVID-19 pandemic.

mSphere2022       LitCov and CORD-19
1187Patterns of Media Use, Strength of Belief in COVID-19 Conspiracy Theories and the Prevention of COVID-19 From March to July 2020 in the United States: Survey Study  

BACKGROUND: Holding conspiracy beliefs regarding the COVID-19 pandemic in the United States has been associated with reductions in both actions to prevent the spread of the infection (eg, mask wearing) and intentions to accept a vaccine when one becomes available. Patterns of media use have also been associated with acceptance of COVID-19 conspiracy beliefs. Here we ask whether the type of media on which a person relies increased, decreased, or had no additional effect on that person’s COVID-19 conspiracy beliefs over a 4-month period. OBJECTIVE: We used panel data to explore whether use of conservative and social media in the United States, which were previously found to be positively related to holding conspiracy beliefs about the origins and prevention of COVID-19, were associated with a net increase in the strength of those beliefs from March to July of 2020. We also asked whether mainstream news sources, which were previously found to be negatively related to belief in pandemic-related conspiracies, were associated with a net decrease in the strength of such beliefs over the study period. Additionally, we asked whether subsequent changes in pandemic conspiracy beliefs related to the use of media were also related to subsequent mask wearing and vaccination intentions. METHODS: A survey that we conducted with a national US probability sample in March of 2020 and again in July with the same 840 respondents assessed belief in pandemic-related conspiracies, use of various types of media information sources, actions taken to prevent the spread of the disease and intentions to vaccinate, and various demographic characteristics. Change across the two waves was analyzed using path analytic techniques. RESULTS: We found that conservative media use predicted an increase in conspiracy beliefs (β=.17, 99% CI .10-.25) and that reliance on mainstream print predicted a decrease in their belief (β=–.08, 99% CI –.14 to –.02). Although many social media platforms reported downgrading or removing false or misleading content, ongoing use of such platforms by respondents predicted growth in conspiracy beliefs as well (β=.072, 99% CI .018-.123). Importantly, conspiracy belief changes related to media use between the two waves of the study were associated with the uptake of mask wearing and changes in vaccination intentions in July. Unlike other media, use of mainstream broadcast television predicted greater mask wearing (β=.17, 99% CI .09-.26) and vaccination intention (β=.08, 95% CI .02-.14), independent of conspiracy beliefs. CONCLUSIONS: The findings point to the need for greater efforts on the part of commentators, reporters, and guests on conservative media to report verifiable information about the pandemic. The results also suggest that social media platforms need to be more aggressive in downgrading, blocking, and counteracting claims about COVID-19 vaccines, claims about mask wearing, and conspiracy beliefs that have been judged problematic by public health authorities.

J Med Internet Res2021       LitCov and CORD-19
1188Sensitivity in Detection of Antibodies to Nucleocapsid and Spike Proteins of SARS-CoV-2 in Patients With COVID-19  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is associated with respiratory-related disease and death. Assays to detect virus-specific antibodies are important to understand the prevalence of infection and the course of the immune response. METHODS: Quantitative measurements of plasma or serum antibodies to the nucleocapsid and spike proteins were analyzed using luciferase immunoprecipitation system assays in 100 cross-sectional or longitudinal samples from patients with SARS-CoV-2 infection. A subset of samples was tested both with and without heat inactivation. RESULTS: At >14 days after symptom onset, antibodies against SARS-CoV-2 nucleocapsid protein showed 100% sensitivity and 100% specificity, whereas antibodies to spike protein were detected with 91% sensitivity and 100% specificity. Neither antibody levels nor the rate of seropositivity were significantly reduced by heat inactivation of samples. Analysis of daily samples from 6 patients with COVID-19 showed anti-nucleocapsid and spike protein antibodies appearing between days 8 and 14 after initial symptoms. Immunocompromised patients generally had a delayed antibody response to SARS-CoV-2, compared with immunocompetent patients. CONCLUSIONS: Antibody to the nucleocapsid protein of SARS-CoV-2 is more sensitive than spike protein antibody for detecting early infection. Analyzing heat-inactivated samples with a luciferase immunoprecipitation system assay is a safe and sensitive method for detecting SARS-CoV-2 antibodies.

J Infect Dis2020       LitCov and CORD-19
1189The first consecutive 5000 patients with COVID-19 from Qatar; a nation-wide cohort study  

BACKGROUND: There are limited data on Coronavirus Disease 2019 (COVID-19) outcomes at a national level, and none after 60 days of follow up. The aim of this study was to describe national, 60-day all-cause mortality associated with COVID-19, and to identify risk factors associated with admission to an intensive care unit (ICU). METHODS: This was a retrospective cohort study including the first consecutive 5000 patients with COVID-19 in Qatar who completed 60 days of follow up by June 17, 2020. The primary outcome was all-cause mortality at 60 days after COVID-19 diagnosis. In addition, we explored risk factors for admission to ICU. RESULTS: Included patients were diagnosed with COVID-19 between February 28 and April 17, 2020. The majority (4436, 88.7%) were males and the median age was 35 years [interquartile range (IQR) 28–43]. By 60 days after COVID-19 diagnosis, 14 patients (0.28%) had died, 10 (0.2%) were still in hospital, and two (0.04%) were still in ICU. Fatal COVID-19 cases had a median age of 59.5 years (IQR 55.8–68), and were mostly males (13, 92.9%). All included pregnant women (26, 0.5%), children (131, 2.6%), and healthcare workers (135, 2.7%) were alive and not hospitalized at the end of follow up. A total of 1424 patients (28.5%) required hospitalization, out of which 108 (7.6%) were admitted to ICU. Most frequent co-morbidities in hospitalized adults were diabetes (23.2%), and hypertension (20.7%). Multivariable logistic regression showed that older age [adjusted odds ratio (aOR) 1.041, 95% confidence interval (CI) 1.022–1.061 per year increase; P < 0.001], male sex (aOR 4.375, 95% CI 1.964–9.744; P < 0.001), diabetes (aOR 1.698, 95% CI 1.050–2.746; P 0.031), chronic kidney disease (aOR 3.590, 95% CI 1.596–8.079, P 0.002), and higher BMI (aOR 1.067, 95% CI 1.027–1.108 per unit increase; P 0.001), were all independently associated with increased risk of ICU admission. CONCLUSIONS: In a relatively younger national cohort with a low co-morbidity burden, COVID-19 was associated with low all-cause mortality. Independent risk factors for ICU admission included older age, male sex, higher BMI, and co-existing diabetes or chronic kidney disease. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s12879-020-05511-8.

BMC Infect Dis2020       LitCov and CORD-19
1190Global health on the front lines: an innovative medical student elective combining education and service during the COVID-19 pandemic  

BACKGROUND: An innovative medical student elective combined student-directed, faculty-supported online learning with COVID-19 response field placements. This study evaluated students’ experience in the course, the curriculum content and format, and its short-term impact on students’ knowledge and attitudes around COVID-19. METHODS: Students responded to discussion board prompts throughout the course and submitted pre−/post-course reflections. Pre−/post-course questionnaires assessed pandemic knowledge and attitudes using 4-point Likert scales. Authors collected aggregate data on enrollment, discussion posts, field placements, and scholarly work resulting from course activities. After the elective, authors conducted a focus group with a convenience sample of 6 participants. Institutional elective evaluation data was included in analysis. Authors analyzed questionnaire data with summary statistics and paired t-tests comparing knowledge and attitudes before and after the elective. Reflection pieces, discussion posts, and focus group data were analyzed using content analysis with a phenomenological approach. RESULTS: Twenty-seven students enrolled. Each student posted an average of 2.4 original discussion posts and 3.1 responses. Mean knowledge score increased from 43.8 to 60.8% (p < 0.001) between pre- and post-course questionnaires. Knowledge self-assessment also increased (2.4 vs. 3.5 on Likert scale, p < 0.0001), and students reported increased engagement in the pandemic response (2.7 vs. 3.6, p < 0.0001). Students reported increased fluency in discussing the pandemic and increased appreciation for the field of public health. There was no difference in students’ level of anxiety about the pandemic after course participation (3.0 vs. 3.1, p = 0.53). Twelve students (44.4%) completed the institutional evaluation. All rated the course “very good” or “excellent.” Students favorably reviewed the field placements, suggested readings, self-directed research, and learning from peers. They suggested more clearly defined expectations and improved balance between volunteer and educational hours. CONCLUSIONS: The elective was well-received by students, achieved stated objectives, and garnered public attention. Course leadership should monitor students’ time commitment closely in service-learning settings to ensure appropriate balance of service and education. Student engagement in a disaster response is insufficient to address anxiety related to the disaster; future course iterations should include a focus on self-care during times of crisis. This educational innovation could serve as a model for medical schools globally. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12909-021-02616-9.

BMC Med Educ2021       LitCov and CORD-19
1191Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil  

BACKGROUND: Reports suggest that COVID-19 vaccine effectiveness is decreasing, but whether this reflects waning or new SARS-CoV-2 variants—especially delta (B.1.617.2)—is unclear. We investigated the association between time since two doses of ChAdOx1 nCoV-19 vaccine and risk of severe COVID-19 outcomes in Scotland (where delta was dominant), with comparative analyses in Brazil (where delta was uncommon). METHODS: In this retrospective, population-based cohort study in Brazil and Scotland, we linked national databases from the EAVE II study in Scotland; and the COVID-19 Vaccination Campaign, Acute Respiratory Infection Suspected Cases, and Severe Acute Respiratory Infection/Illness datasets in Brazil) for vaccination, laboratory testing, clinical, and mortality data. We defined cohorts of adults (aged ≥18 years) who received two doses of ChAdOx1 nCoV-19 and compared rates of severe COVID-19 outcomes (ie, COVID-19 hospital admission or death) across fortnightly periods, relative to 2–3 weeks after the second dose. Entry to the Scotland cohort started from May 19, 2021, and entry to the Brazil cohort started from Jan 18, 2021. Follow-up in both cohorts was until Oct 25, 2021. Poisson regression was used to estimate rate ratios (RRs) and vaccine effectiveness, with 95% CIs. FINDINGS: 1 972 454 adults received two doses of ChAdOx1 nCoV-19 in Scotland and 42 558 839 in Brazil, with longer follow-up in Scotland because two-dose vaccination began earlier in Scotland than in Brazil. In Scotland, RRs for severe COVID-19 increased to 2·01 (95% CI 1·54–2·62) at 10–11 weeks, 3·01 (2·26–3·99) at 14–15 weeks, and 5·43 (4·00–7·38) at 18–19 weeks after the second dose. The pattern of results was similar in Brazil, with RRs of 2·29 (2·01–2·61) at 10–11 weeks, 3·10 (2·63–3·64) at 14–15 weeks, and 4·71 (3·83–5·78) at 18–19 weeks after the second dose. In Scotland, vaccine effectiveness decreased from 83·7% (95% CI 79·7–87·0) at 2–3 weeks, to 75·9% (72·9–78·6) at 14–15 weeks, and 63·7% (59·6–67·4) at 18–19 weeks after the second dose. In Brazil, vaccine effectiveness decreased from 86·4% (85·4–87·3) at 2–3 weeks, to 59·7% (54·6–64·2) at 14–15 weeks, and 42·2% (32·4–50·6) at 18–19 weeks. INTERPRETATION: We found waning vaccine protection of ChAdOx1 nCoV-19 against COVID-19 hospital admissions and deaths in both Scotland and Brazil, this becoming evident within three months of the second vaccine dose. Consideration needs to be given to providing booster vaccine doses for people who have received ChAdOx1 nCoV-19. FUNDING: UK Research and Innovation (Medical Research Council), Scottish Government, Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Fiocruz, Fazer o Bem Faz Bem Programme; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Lancet2022       LitCov and CORD-19
1192Re-emergence of Gamma-like-II and emergence of Gamma-S:E661D SARS-CoV-2 lineages in the south of Brazil after the 2021 outbreak  

BACKGROUND: We report a genomic surveillance of SARS-CoV-2 lineages circulating in Paraná, southern Brazil, from March 2020 to April 2021. Our analysis, based on 333 genomes, revealed that the first variants detected in the state of Paraná in March 2020 were the B.1.1.33 and B.1.1.28 variants. The variants B.1.1.28 and B.1.1.33 were predominant throughout 2020 until the introduction of the variant P.2 in August 2020 and a variant of concern (VOC), Gamma (P.1), in January 2021. The VOC Gamma, a ramification of the B.1.1.28 lineage first detected in Manaus (northern Brazil), has grown rapidly since December 2020 and was thought to be responsible for the deadly second wave of COVID-19 throughout Brazil. METHODS: The 333 genomic sequences of SARS-CoV-2 from March 2020 to April 2021 were generated as part of the genomic surveillance carried out by Fiocruz in Brazil Genomahcov Fiocruz. SARS-CoV-2 sequencing was performed using representative samples from all geographic areas of Paraná. Phylogenetic analyses were performed using the 333 genomes also included other SARS-CoV-2 genomes from the state of Paraná and other states in Brazil that were deposited in the GISAID. In addition, the time-scaled phylogenetic tree was constructed with up to 3 random sequences of the Gamma variant from each state in Brazil in each month of 2021. In this analysis we also added the sequences identified as the B.1.1.28 lineage of the Amazonas state and and the Gamma-like-II (P.1-like-II) lineage identified in different regions of Brazil. RESULTS: Phylogenetic analyses of the SARS-CoV-2 genomes that were previously classified as the VOC Gamma lineage by WHO/PANGO showed that some genomes from February to April 2021 branched in a monophyletic clade and that these samples grouped together with genomes recently described with the lineage Gamma-like-II. Additionally, a new mutation (E661D) in the spike (S) protein has been identified in nearly 10% of the genomes classified as the VOC Gamma from Paraná in March and April 2021.Finally, we analyzed the correlation between the lineage and the Gamma variant frequency, age group (patients younger or older than 60 years old) and the clinical data of 86 cases from the state of Paraná. CONCLUSIONS: Our results provided a reliable picture of the evolution of the SARS-CoV-2 pandemic in the state of Paraná characterized by the dominance of the Gamma strain, as well as a high frequencies of the Gamma-like-II lineage and the S:E661D mutation. Epidemiological and genomic surveillance efforts should be continued to unveil the biological relevance of the novel mutations detected in the VOC Gamma in Paraná. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12985-021-01690-1.

Virol J2021       LitCov and CORD-19
1193Digestive system involvement and clinical outcomes among COVID-19 patients: A retrospective cohort study from Qatar  

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 virus most commonly presents with respiratory symptoms. While gastrointestinal (GI) manifestations either at presentation or during hospitalization are also common, their impact on clinical outcomes is controversial. Some studies have described worse outcomes in COVID-19 patients with GI symptoms, while others have shown either no association or a protective effect. There is a need for consistent standards to describe GI symptoms in COVID-19 patients and to assess their effect on clinical outcomes, including mortality and disease severity. AIM: To investigate the prevalence of GI symptoms in hospitalized COVID-19 patients and their correlation with disease severity and clinical outcomes. METHODS: We retrospectively reviewed 601 consecutive adult COVID-19 patients requiring hospitalization between May 1-15, 2020. GI symptoms were recorded at admission and during hospitalization. Demographic, clinical, laboratory, and treatment data were retrieved. Clinical outcomes included all-cause mortality, disease severity at presentation, need for intensive care unit (ICU) admission, development of acute respiratory distress syndrome, and need for mechanical ventilation. Multivariate logistic regression model was used to identify independent predictors of the adverse outcomes. RESULTS: The prevalence of any GI symptom at admission was 27.1% and during hospitalization was 19.8%. The most common symptoms were nausea (98 patients), diarrhea (76 patients), vomiting (73 patients), and epigastric pain or discomfort (69 patients). There was no difference in the mortality between the two groups (6.21% vs 5.5%, P = 0.7). Patients with GI symptoms were more likely to have severe disease at presentation (33.13% vs 22.5%, P < 0.001) and prolonged hospital stay (15 d vs 14 d, P = 0.04). There was no difference in other clinical outcomes, including ICU admission, development of acute respiratory distress syndrome, or need for mechanical ventilation. Drugs associated with the development of GI symptoms during hospitalization were ribavirin (diarrhea 26.37% P < 0.001, anorexia 17.58%, P = 0.02), hydroxychloroquine (vomiting 28.52%, P = 0.009) and lopinavir/ritonavir (nausea 32.65% P = 0.049, vomiting 31.47% P = 0.004, and epigastric pain 12.65% P = 0.048). In the multivariate regression analysis, age > 65 years was associated with increased mortality risk [odds ratio (OR) 7.53, confidence interval (CI): 3.09-18.29, P < 0.001], ICU admission (OR: 1.79, CI: 1.13-2.83, P = 0.012), and need for mechanical ventilation (OR: 1.89, CI:1.94-2.99, P = 0.007). Hypertension was an independent risk factor for ICU admission (OR: 1.82, CI:1.17-2.84, P = 0.008) and need for mechanical ventilation (OR: 1.66, CI: 1.05-2.62, P = 0.028). CONCLUSION: Patients with GI symptoms are more likely to have severe disease at presentation; however, mortality and disease progression is not different between the two groups.

World J Gastroenterol2021       LitCov and CORD-19
1194The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic  

The rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike-protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodies but remained susceptible to inhibition by Sotrovimab. Similarly, the Omicron spike evaded neutralization by antibodies from convalescent or BNT162b2-vaccinated individuals with 10- to 44-fold higher efficiency than the spike of the Delta variant. Neutralization of the Omicron spike by antibodies induced upon heterologous ChAdOx1/BNT162b2-vaccination or vaccination with three doses of BNT162b2 was more efficient, but the Omicron spike still evaded neutralization more efficiently than the Delta spike. These findings indicate that most therapeutic antibodies will be ineffective against the Omicron variant and that double immunization with BNT162b2 might not adequately protect against severe disease induced by this variant.

Cell2021       LitCov and CORD-19
1195Efficacy of corticosteroids in non-intensive care unit patients with COVID-19 pneumonia from the New York Metropolitan region  

INTRODUCTION: The role of systemic corticosteroid as a therapeutic agent for patients with COVID-19 pneumonia is controversial. OBJECTIVE: The purpose of this study was to evaluate the effect of corticosteroids in non-intensive care unit (ICU) patients with COVID-19 pneumonia complicated by acute hypoxemic respiratory failure (AHRF). METHODS: This was a single-center retrospective cohort study, from 16(th) March, 2020 to 30(th) April, 2020; final follow-up on 10(th) May, 2020. 265 patients consecutively admitted to the non-ICU wards with laboratory-confirmed COVID-19 pneumonia were screened for inclusion. 205 patients who developed AHRF (SpO(2)/FiO(2) ≤ 440 or PaO(2)/FiO(2) ≤ 300) were only included in the final study. Direct admission to the Intensive care unit (ICU), patients developing composite primary outcome within 24 hours of admission, and patients who never became hypoxic during their stay in the hospital were excluded. Patients were divided into two cohorts based on corticosteroid. The primary outcome was a composite of ICU transfer, intubation, or in-hospital mortality. Secondary outcomes were ICU transfer, intubation, in-hospital mortality, discharge, length of stay, and daily trend of SpO(2)/FiO(2) (SF) ratio from the index date. Cox-proportional hazard regression was implemented to analyze the time to event outcomes. RESULT: Among 205 patients, 60 (29.27%) were treated with corticosteroid. The mean age was ~57 years, and ~75% were men. Thirteen patients (22.41%) developed a primary composite outcome in the corticosteroid cohort vs. 54 (37.5%) patients in the non-corticosteroid cohort (P = 0.039). The adjusted hazard ratio (HR) for the development of the composite primary outcome was 0.15 (95% CI, 0.07–0.33; P <0.001). The adjusted hazard ratio for ICU transfer was 0.16 (95% CI, 0.07 to 0.34; P < 0.001), intubation was 0.31 (95% CI, 0.14 to 0.70; P– 0.005), death was 0.53 (95% CI, 0.22 to 1.31; P– 0.172), composite of death or intubation was 0.31 (95% CI, 0.15 to 0.66; P– 0.002) and discharge was 3.65 (95% CI, 2.20 to 6.06; P<0.001). The corticosteroid cohort had increasing SpO(2)/FiO(2) over time compared to the non-corticosteroid cohort who experience decreasing SpO(2)/FiO(2) over time. CONCLUSION: Among non-ICU patients hospitalized with COVID-19 pneumonia complicated by AHRF, treatment with corticosteroid was associated with a significantly lower risk of the primary composite outcome of ICU transfer, intubation, or in-hospital death, composite of intubation or death and individual components of the primary outcome.

PLoS One2020       LitCov and CORD-19
1196Comparison of Generalized Anxiety and Sleep Disturbance among Frontline and Second-Line Healthcare Workers during the COVID-19 Pandemic  

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, also known as COVID-19, has developed into an alarming situation around the world. Healthcare workers are playing the role of frontline defense to safeguard the lives of everyone during the COVID-19 pandemic. The present study aimed to investigate the anxiety levels and sleep quality among frontline and second-line healthcare workers during the COVID-19 pandemic. In this cross-sectional study, a validated, self-administered, electronic questionnaire was distributed through email to healthcare workers. The selection of 1678 healthcare workers was based on a convenience sampling technique. The General Anxiety Disorder-7 (GAD-7) and Pittsburgh Sleep Quality Index (PSQI) instrument scales were used to assess healthcare workers’ anxiety levels and sleep quality during the COVID-19 pandemic. Out of 1678 respondents, 1200 (71.5%) were frontline healthcare workers, while 478 (28.5%) were second-line healthcare workers. Among all the healthcare workers, 435 (25.92%) were experiencing moderate to severe anxiety. Among them, 713 (59.4%) frontline healthcare workers were experiencing anxiety in comparison with 277 (57.9%) second-line healthcare workers. Severe anxiety symptoms were seen in 137 (11.41%) frontline healthcare workers compared to 44 (9.20%) second-line healthcare workers. In total, 1376 (82.0%) healthcare workers were found to have poor sleep quality; 975 (58.10%) were frontline, and 407 (23.89%) were second-line healthcare workers. The highest poor sleep quality levels were found among 642 (84.6%) of the healthcare workers who work in frontline areas (emergency departments, intensive care units, and wards) compared to 734 (79.9%) of the healthcare workers who work in second-line areas. These findings provide a substantial contribution to the consolidation of evidence concerning the negative impact of the pandemic on the mental health of healthcare workers (HCWs). These results have established an association that the COVID-19 pandemic causes larger negative psychological symptoms in frontline healthcare workers, such as severe anxiety and poor sleep quality. Preventive measures to minimize anxiety levels and maintain sleep quality, addressing this issue nationally and globally, are essential to support the healthcare workers who are sacrificing their mental health for the future of our nations.

Int J Environ Res Public Healt2021       LitCov and CORD-19
1197A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines  

N/A

Front Immunol2022       LitCov
1198Predictors of Severity in Covid-19 Patients in Casablanca, Morocco  

Background Morocco was affected, as were other countries, by the coronavirus disease 2019 (COVID-19) pandemic. Many risk factors of COVID-19 severity have been described, but data on infected patients in North Africa are limited. We aimed to explore the predictive factors of disease severity in COVID-19 patients in a tertiary hospital in Casablanca. Methods In this single-center, retrospective, observational study, we included all adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, admitted to Sheikh Khalifa International University Hospital in Casablanca between March 18 and May 20, 2020. Patients were separated into two groups: Non-severe patients were those with mild or moderate forms of COVID-19, and severe patients were those admitted to the intensive care unit (ICU) who had one of the following signs-respiratory rate > 30 breaths/min; oxygen saturation < 93% on room air; acute respiratory distress syndrome (ARDS); or required mechanical ventilation. Demographic, clinical, laboratory data, and outcomes were reviewed. We used univariable and multivariable logistic regression to explore predictive factors of severity. Results We reported 134 patients with confirmed SARS-CoV-2 infection. The median age was 53 years (interquartile range [IQR], 36-64), and 73 (54.5%) were men. Eighty-nine non-severe patients (66.4%) were admitted to single bedrooms, and 45 (33.6%) were placed in the ICU. The median time from illness onset to hospital admission was seven days (IQR, 3.0-7.2). Ninety-nine patients (74%) were admitted directly to the hospital, and 35 (26%) were transferred from other structures. Also, 68 patients (65.4%) were infected in clusters. Of the 134 patients, 61 (45.5%) had comorbidities, such as hypertension (n = 36; 26.9%), diabetes (n = 19; 14.2%), and coronary heart disease (n = 16; 11.9%). The most frequent symptoms were fever (n = 61; 45.5%), dry cough (n = 59; 44%), and dyspnea (n = 39; 29%). A total of 127 patients received hydroxychloroquine and azithromycin (95%). Eleven critical cases received lopinavir/ritonavir (8.2%). Five patients received tocilizumab (3.7%). We reported 13 ARDS cases in ICU patients (29%), eight with acute kidney injury (17.8%), and four thromboembolic events (8.8%). Fourteen ICU patients (31.1%) died at 28 days. In univariable analysis, older men with one or more comorbidities, infection in a cluster, chest scan with the COVID-19 Reporting and Data System (CO-RADS) 5, lymphopenia, high rates of ferritin, C-reactive protein (CRP), D-dimer, and lactate dehydrogenase were associated with severe forms of COVID-19. Multivariable logistic regression model founded increasing odds of severity associated with older age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01-1.09, P = .0039), men (OR 3.19, CI 1.06-9.60, P = .016), one or more comorbidities (OR 4.36, CI 1.32-14.45, P = .016), CRP > 10 mg/L (OR 5.47, CI 1.57-19.10, P = .008), and lymphopenia lower than 0.8 x10(9)/L (OR 6.65, CI 1.43-30.92, P = .016). Conclusions Clinicians should consider older male patients with comorbidities, lymphopenia, and a high CRP rate as factors to predict severe forms of COVID-19 earlier. The higher severity of infected patients in clusters must be confirmed by epidemiological and genetic studies.

Cureus2020       LitCov and CORD-19
1199Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination  

Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naive subjects after the second vaccine dose, though the memory B cell response declined slightly with age. In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose. This robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells in recovered individuals, identifying a key role for memory B cells in mounting recall responses to SARS-CoV-2 antigens. Together, our data demonstrated robust serological and cellular priming by mRNA vaccines and revealed distinct responses based on prior SARS-CoV-2 exposure, whereby COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses. These findings also highlight the utility of defining cellular responses in addition to serologies and may inform SARS-CoV-2 vaccine distribution in a resource-limited setting.

Sci Immunol2021       LitCov and CORD-19
1200Mask use, risk-mitigation behaviours and pandemic fatigue during the COVID-19 pandemic in five cities in Australia, the UK and USA: A cross-sectional survey  

Objectives To determine patterns of mask wearing and other infection prevention behaviours in cities where mask wearing is not a cultural norm, over two time periods of the pandemic. Methods A cross-sectional survey of masks and other preventive behaviours in adults ≥18 years was conducted in five cities (Sydney, Melbourne, London, Phoenix and New York). Data was analysed according to the epidemiology of COVID-19, mask mandates and a range of predictors of mask wearing. Results The most common measures used were avoiding public areas (80.4%), hand hygiene (76.4%), masks (71.8%) and distancing (67.6%). Over 40% of people avoided medical facilities. These measures decreased from March-July 2020. Pandemic fatigue was associated with younger age, low perceived severity of COVID-19 and declining COVID-19 prevalence. Predictors of mask wearing were location (US, UK), mandates, age <50 years, education, having symptoms and knowing someone with COVID-19. Negative experiences with mask wearing and low perceived severity of COVID-19 reduced mask wearing. Most respondents (98%) believed that hand washing and distancing were necessary, and 80% reported no change or stricter adherence to these measures when wearing masks. Conclusion Pandemic mitigation measures were widely reported across all cities, but decreased between March and July 2020. Pandemic fatigue was more common in younger people. Cities with mandates had higher rates of mask wearing. Promotion of mask use for older people may be useful. Masks did not result in reduction of other hygiene measures.

Int J Infect Dis2021       LitCov and CORD-19

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