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)
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*More details on these impact measures can be found here.
Exceptional score (in top 0.01%).
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CORD-19 dataset(1) (list of papers)
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| Title | Venue | Year | Impact | Source | |
|---|---|---|---|---|---|
| 651 | SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19 BACKGROUND: Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk. Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear. METHODS: Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients. We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl(3)-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo. RESULTS: We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count. Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients. Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming. SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo. Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation. SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte–platelet aggregates. Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation. CONCLUSIONS: Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2. SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients. | J Hematol Oncol | 2020 | LitCov and CORD-19 | |
| 652 | Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China | Lancet Oncol | 2020 | LitCov and CORD-19 | |
| 653 | People's Experiences and Satisfaction With Telehealth During the COVID-19 Pandemic in Australia: Cross-Sectional Survey Study BACKGROUND: In response to the COVID-19 pandemic, telehealth has rapidly been adopted to deliver health care services around the world. To date, studies have not compared people’s experiences with telehealth services during the pandemic in Australia to their experiences with traditional in-person visits. OBJECTIVE: This study aimed to compare participants’ perceptions of telehealth consults to their perceptions of traditional in-person visits and investigate whether people believe that telehealth services would be useful after the pandemic. METHODS: A national, cross-sectional, community survey was conducted between June 5 and June 12, 2020 in Australia. In total, 1369 participants who were aged ≥18 years and lived in Australia were recruited via targeted advertisements on social media (ie, Facebook and Instagram). Participants responded to survey questions about their telehealth experience, which included a free-text response option. A generalized linear model was used to estimate the adjusted relative risks of having a poorer telehealth experience than a traditional in-person visit experience. Content analysis was performed to determine the reasons why telehealth experiences were worse than traditional in-person visit experiences. RESULTS: Of the 596 telehealth users, the majority of respondents (n=369, 61.9%) stated that their telehealth experience was “just as good as” or “better than” their traditional in-person medical appointment experience. On average, respondents perceived that telehealth would be moderately useful to very useful for medical appointments after the COVID-19 pandemic ends (mean 3.67, SD 1.1). Being male (P=.007), having a history of both depression and anxiety (P=.016), and lower patient activation scores (ie, individuals’ willingness to take on the role of managing their health/health care) (P=.036) were significantly associated with a poor telehealth experience. In total, 6 overarching themes were identified from free-text responses for why participants’ telehealth experiences were poorer than their traditional in-person medical appointment experiences, as follows: communication is not as effective, limitations with technology, issues with obtaining prescriptions and pathology results, reduced confidence in their doctor, additional burden for complex care, and inability to be physically examined. CONCLUSIONS: Based on our sample’s responses, telehealth appointment experiences were comparable to traditional in-person medical appointment experiences. Telehealth may be worthwhile as a mode of health care delivery while the pandemic continues, and it may continue to be worthwhile after the pandemic. | J Med Internet Res | 2020 | LitCov and CORD-19 | |
| 654 | Use of Asynchronous Virtual Mental Health Resources for COVID-19 Pandemic-Related Stress Among the General Population in Canada: Cross-Sectional Survey Study BACKGROUND: The COVID-19 pandemic has resulted in profound mental health impacts among the general population worldwide. As many in-person mental health support services have been suspended or transitioned online to facilitate physical distancing, there have been numerous calls for the rapid expansion of asynchronous virtual mental health (AVMH) resources. These AVMH resources have great potential to provide support for people coping with negative mental health impacts associated with the pandemic; however, literature examining use prior to COVID-19 illustrates that the uptake of these resources is consistently low. OBJECTIVE: The aim of this paper is to examine the use of AVMH resources in Canada during the COVID-19 pandemic among the general population and among a participant subgroup classified as experiencing an adverse mental health impact related to the pandemic. METHODS: Data from this study were drawn from the first wave of a large multiwave cross-sectional monitoring survey, distributed from May 14 to 29, 2020. Participants (N=3000) were adults living in Canada. Descriptive statistics were used to characterize the sample, and bivariate cross-tabulations were used to examine the relationships between the use of AVMH resources and self-reported indicators of mental health that included a range of emotional and coping-related responses to the pandemic. Univariate and fully adjusted multivariate logistic regression models were used to examine associations between sociodemographic and health-related characteristics and use of AVMH resources in the subgroup of participants who reported experiencing one or more adverse mental health impacts identified in the set of self-reported mental health indicators. RESULTS: Among the total sample, 2.0% (n=59) of participants reported accessing AVMH resources in the prior 2 weeks to cope with stress related to the COVID-19 pandemic, with the highest rates of use among individuals who reported self-harm (n=5, 10.4%) and those who reported coping “not well” with COVID-19–related stress (n=22, 5.5%). Within the subgroup of 1954 participants (65.1% of the total sample) who reported an adverse mental health impact related to COVID-19, 54 (2.8%) reported use of AVMH resources. Individuals were more likely to have used AVMH resources if they had reported receiving in-person mental health supports, were connecting virtually with a mental health worker or counselor, or belonged to a visible minority group. CONCLUSIONS: Despite substantial government investment into AVMH resources, uptake is low among both the general population and individuals who may benefit from the use of these resources as a means of coping with the adverse mental health impacts of the COVID-19 pandemic. Further research is needed to improve our understanding of the barriers to use. | J Med Internet Res | 2020 | LitCov and CORD-19 | |
| 655 | Comparative evaluation of six nucleic acid amplification kits for SARS-CoV-2 RNA detection BACKGROUND: SARS-CoV-2 is a newly emerged coronavirus, causing the coronavirus disease 2019 (COVID-19) outbreak in December, 2019. As drugs and vaccines of COVID-19 remain in development, accurate virus detection plays a crucial role in the current public health crisis. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) kits have been reliably used for detection of SARS-CoV-2 RNA since the beginning of the COVID-19 outbreak, whereas isothermal nucleic acid amplification-based point-of-care automated kits have also been considered as a simpler and rapid alternative. However, as these kits have only been developed and applied clinically within a short timeframe, their clinical performance has not been adequately evaluated to date. We describe a comparative study between a newly developed cross-priming isothermal amplification (CPA) kit (Kit A) and five RT-qPCR kits (Kits B–F) to evaluate their sensitivity, specificity, predictive values and accuracy. METHODS: Fifty-two clinical samples were used including throat swabs (n = 30), nasal swabs (n = 7), nasopharyngeal swabs (n = 7) and sputum specimens (n = 8), comprising confirmed (n = 26) and negative cases (n = 26). SARS-CoV-2 detection was simultaneously performed on each sample using six nucleic acid amplification kits. The sensitivity, specificity, positive/negative predictive values (PPV/NPV) and the accuracy for each kit were assessed using clinical manifestation and molecular diagnoses as the reference standard. Reproducibility for RT-qPCR kits was evaluated in triplicate by three different operators using a SARS-CoV-2 RNA-positive sample. On the basis of the six kits’ evaluation results, CPA kit (Kit A) and two RT-qPCR Kits (Kit B and F) were applied to the SARS-CoV-2 detection in close-contacts of COVID-19 patients. RESULTS: For Kit A, the sensitivity, specificity, PPV/NPV and accuracy were 100%. Among the five RT-qPCR kits, Kits B, C and F had good agreement with the clinical diagnostic reports (Kappa ≥ 0.75); Kits D and E were less congruent (0.4 ≤ Kappa < 0.75). Differences between all kits were statistically significant (P < 0.001). The reproducibility of RT-qPCR kits was determined using a coefficients of variation (CV) between 0.95% and 2.57%, indicating good reproducibility. CONCLUSIONS: This is the first comparative study to evaluate CPA and RT-qPCR kits’ specificity and sensitivity for SARS-CoV-2 detection, and could serve as a reference for clinical laboratories, thus informing testing protocols amid the rapidly progressing COVID-19 pandemic. | Ann Clin Microbiol Antimicrob | 2021 | LitCov and CORD-19 | |
| 656 | COVID-19 and lombardy: TESTing the impact of the first wave of the pandemic BACKGROUND: Italy was the first western country to experience a large Coronavirus Disease 2019 (COVID-19) outbreak and the province of Bergamo experienced one of the deadliest COVID-19 outbreaks in the world. Following the peak of the epidemic in mid-March, the curve has slowly fallen thanks to the strict lockdown imposed by the Italian government on 9th March 2020. METHODS: We performed a cross-sectional study to assess the prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in 423 workers in Bergamo province who returned to the workplace after the end of the Italian lockdown on 5th May 2020. To this end, we performed an enzyme-linked immunosorbent assay (ELISA) to detect the humoral response against SARS-CoV-2 and a nasopharyngeal swab to assess the presence of SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction (rRT-PCR). As a secondary aim of the study, we validated a lateral flow immunochromatography assay (LFIA) for the detection of anti-SARS-CoV-2 antibodies. FINDINGS: ELISA identified 38.5% positive subjects, of whom 51.5% were positive for both IgG and IgM, 47.3% were positive only for IgG, but only 1.2% were positive for IgM alone. Only 23 (5.4%) participants tested positive for SARS-CoV-2 by rRT-PCR, although with high cycle thresholds (between 34 and 39), indicating a very low residual viral load that was not able to infect cultured cells. All these rRT-PCR positive subjects had already experienced seroconversion. When the ELISA was used as the comparator, the estimated specificity and sensitivity of the rapid LFIA for IgG were 98% and 92%, respectively. INTERPRETATION: the prevalence of SARS-CoV-2 infection in the province of Bergamo reached 38.5%, significantly higher than has been reported for most other regions worldwide. Few nasopharyngeal swabs tested positive in fully recovered subjects, though with a very low SARS-CoV-2 viral load, with implications for infectivity and discharge policies for positive individuals in the post-pandemic period. The rapid LFIA used in this study is a valuable tool for rapid serologic surveillance of COVID-19 for population studies. FUNDING: The study was supported by Regione Lombardia, Milano Serravalle - Milano Tangenziali S.p.A., Brembo S.p.A, and by MEI System. | EBioMedicine | 2020 | LitCov and CORD-19 | |
| 657 | Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting OBJECTIVES: We investigate the incidence of bacterial and fungal co-infection of hospitalised patients with confirmed SARS-CoV-2 in this retrospective observational study across two London hospitals during the first UK wave of COVID-19. METHODS: A retrospective case-series of hospitalised patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (February 20–April 20; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza positive patients admitted during 2019/20 flu season. Patient demographics, microbiology, and clinical outcomes were analysed. RESULTS: 836 patients with confirmed SARS-CoV-2 were included; 27/836(3.2%) had early confirmed bacterial isolates identified (0-5 days post-admission) rising to 51/836(6.1%) throughout admission. Blood cultures, respiratory samples, pneumococcal or legionella urinary antigens, and respiratory viral PCR panels were obtained from 643(77%), 112(13%), 249(30%), 246(29%) and 250(30%) COVID-19 patients, respectively. A positive blood culture was identified in 60(7.1%) patients, of which 39/60 were classified as contaminants. Bacteraemia secondary to respiratory infection was confirmed in two cases (1 community-acquired K. pneumoniae and 1 ventilator-associated E. cloacae). Line-related bacteraemia was identified in six patients (3 candida, 2 Enterococcus spp. and 1 Pseudomonas aeruginosa). All other community acquired bacteraemias(16) were attributed to non-respiratory infection. Zero concomitant pneumococcal, legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; S. aureus the most common respiratory pathogen isolated in community-acquired coinfection (4/24;16.7%) with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n=3) were attributed to line related infections. Comparable rates of positive co-infection were identified in the control group of confirmed influenza infection; clinically relevant bacteraemias (2/141;1.4%), respiratory cultures (10/38;26.1%) and pneumococcal-positive antigens (1/19;5.2%) were low. CONCLUSION: We find a low frequency of bacterial co-infection in early COVID hospital presentation, and no evidence of concomitant fungal infection, at least in the early phase of COVID-19. | Clin Microbiol Infect | 2020 | LitCov and CORD-19 | |
| 658 | Development of a Fluorescence-Based, High-Throughput SARS-CoV-2 3CLpro Reporter Assay In late 2019, a human coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, likely from a zoonotic reservoir. This virus causes COVID-19, has infected millions of people, and has led to hundreds of thousands of deaths across the globe. While the best interventions to control and ultimately stop the pandemic are prophylactic vaccines, antiviral therapeutics are important to limit morbidity and mortality in those already infected. At this time, only one FDA-approved anti-SARS-CoV-2 antiviral drug, remdesivir, is available, and unfortunately, its efficacy appears to be limited. Thus, the identification of new and efficacious antivirals is of the highest importance. In order to facilitate rapid drug discovery, flexible, sensitive, and high-throughput screening methods are required. With respect to drug targets, most attention is focused on either the viral RNA-dependent RNA polymerase or the main viral protease, 3CL(pro). 3CL(pro) is an attractive target for antiviral therapeutics, as it is essential for processing newly translated viral proteins and the viral life cycle cannot be completed without protease activity. In this work, we report a new assay to identify inhibitors of 3CL(pro). Our reporter is based on a green fluorescent protein (GFP)-derived protein that fluoresces only after cleavage by 3CL(pro). This experimentally optimized reporter assay allows for antiviral drug screening in human cell culture at biosafety level 2 (BSL2) with high-throughput compatible protocols. Using this screening approach in combination with existing drug libraries may lead to the rapid identification of novel antivirals to suppress SARS-CoV-2 replication and spread. IMPORTANCE The COVID-19 pandemic has already led to more than 700,000 deaths and innumerable changes to daily life worldwide. Along with development of a vaccine, identification of effective antivirals to treat infected patients is of the highest importance. However, rapid drug discovery requires efficient methods to identify novel compounds that can inhibit the virus. In this work, we present a method for identifying inhibitors of the SARS-CoV-2 main protease, 3CL(pro). This reporter-based assay allows for antiviral drug screening in human cell culture at biosafety level 2 (BSL2) with high-throughput compatible sample processing and analysis. This assay may help identify novel antivirals to control the COVID-19 pandemic. | J Virol | 2020 | LitCov and CORD-19 | |
| 659 | Comparative performance of SARS-CoV-2 lateral flow antigen tests and association with detection of infectious virus in clinical specimens: a single-center laboratory evaluation study BACKGROUND: Lateral flow devices (LFDs) for rapid antigen testing are set to become a cornerstone of SARS-CoV-2 mass community testing, although their reduced sensitivity compared with PCR has raised questions of how well they identify infectious cases. Understanding their capabilities and limitations is, therefore, essential for successful implementation. We evaluated six commercial LFDs and assessed their correlation with infectious virus culture and PCR cycle threshold (Ct) values. METHODS: In a single-centre, laboratory evaluation study, we did a head-to-head comparison of six LFDs commercially available in the UK: Innova Rapid SARS-CoV-2 Antigen Test, Spring Healthcare SARS-CoV-2 Antigen Rapid Test Cassette, E25Bio Rapid Diagnostic Test, Encode SARS-CoV-2 Antigen Rapid Test Device, SureScreen COVID-19 Rapid Antigen Test Cassette, and SureScreen COVID-19 Rapid Fluorescence Antigen Test. We estimated the specificities and sensitivities of the LFDs using stored naso-oropharyngeal swabs collected at St Thomas' Hospital (London, UK) for routine diagnostic SARS-CoV-2 testing by real-time RT-PCR (RT-rtPCR). Swabs were from inpatients and outpatients from all departments of St Thomas' Hospital, and from health-care staff (all departments) and their household contacts. SARS-CoV-2-negative swabs from the same population (confirmed by RT-rtPCR) were used for comparative specificity determinations. All samples were collected between March 23 and Oct 27, 2020. We determined the limit of detection (LOD) for each test using viral plaque-forming units (PFUs) and viral RNA copy numbers of laboratory-grown SARS-CoV-2. Additionally, LFDs were selected to assess the correlation of antigen test result with RT-rtPCR Ct values and positive viral culture in Vero E6 cells. This analysis included longitudinal swabs from five infected inpatients with varying disease severities. Furthermore, the sensitivities of available LFDs were assessed in swabs (n=23; collected from Dec 4, 2020, to Jan 12, 2021) confirmed to be positive (RT-rtPCR and whole-genome sequencing) for the B.1.1.7 variant, which was the dominant genotype in the UK at the time of study completion. FINDINGS: All LFDs showed high specificity (≥98·0%), except for the E25Bio test (86·0% [95% CI 77·9–99·9]), and most tests reliably detected 50 PFU/test (equivalent SARS-CoV-2 N gene Ct value of 23·7, or RNA copy number of 3 × 10(6)/mL). Sensitivities of the LFDs on clinical samples ranged from 65·0% (55·2–73·6) to 89·0% (81·4–93·8). These sensitivities increased to greater than 90% for samples with Ct values of lower than 25 for all tests except the SureScreen fluorescence (SureScreen-F) test. Positive virus culture was identified in 57 (40·4%) of 141 samples; 54 (94·7%) of the positive cultures were from swabs with Ct values lower than 25. Among the three LFDs selected for detailed comparisons (the tests with highest sensitivity [Innova], highest specificity [Encode], and alternative technology [SureScreen-F]), sensitivity of the LFDs increased to at least 94·7% when only including samples with detected viral growth. Longitudinal studies of RT-rtPCR-positive samples (tested with Innova, Encode, and both SureScreen-F and the SureScreen visual [SureScreen-V] test) showed that most of the tests identified all infectious samples as positive. Test performance (assessed for Innova and SureScreen-V) was not affected when reassessed on swabs positive for the UK variant B.1.1.7. INTERPRETATION: In this comprehensive comparison of antigen LFDs and virus infectivity, we found a clear relationship between Ct values, quantitative culture of infectious virus, and antigen LFD positivity in clinical samples. Our data support regular testing of target groups with LFDs to supplement the current PCR testing capacity, which would help to rapidly identify infected individuals in situations in which they would otherwise go undetected. FUNDING: King's Together Rapid COVID-19, Medical Research Council, Wellcome Trust, Huo Family Foundation, UK Department of Health, National Institute for Health Research Comprehensive Biomedical Research Centre. | Lancet Microbe | 2021 | LitCov and CORD-19 | |
| 660 | How the public used face masks in China during the coronavirus disease pandemic: A survey study BACKGROUND: Universal face mask use was recommended owing to the growing pandemic of the coronavirus disease (COVID-19). However, little is known about the public's compliance with mask-wearing behaviours. OBJECTIVE: To evaluate the public's mask-wearing behaviours in the context of COVID-19. DESIGN: Cross-sectional study. SETTING: Online survey from 6 April 2020 to 5 May 2020 in China. PARTICIPANTS: This study included 10,165 persons who lived in China, understood Chinese, and were not health care providers. METHODS: Descriptive statistics were used to assess the public's mask-wearing behaviours. A binary logistic regression analysis was performed to identify the risk factors affecting the mask-wearing behaviours. RESULTS: Nearly all (99%) people wore a mask during the covid-19 pandemic, with most (73.3%) demonstrating good compliance with face mask use. However, 41.8% of the participants seldom cleaned their hands before putting on a face mask, and more than half (55.3%, 62.1%) of those who touched (n=8108, 79.8%) or adjusted (n=9356, 92.0%) their mask while using it failed to consistently wash their hands afterward. When removing a used mask, 7.6% of the participants discarded it into a garbage bin without a lid and 22.5% discarded it into a garbage bin in their reach regardless of presence of a lid. Participants reported wearing disposable medical masks (93.8%), followed by N95 respirators (26.2%), and cloth face masks (8.5%). Some participants wore multiple masks simultaneously (occasionally 26.5%, often 2.1%, always 1.5%). A total of 5,981 (58.8%) participants reported reusing disposable masks, with nearly two thirds (n=3923, 65.6%) indicating they would hang the used masks in well-ventilated places. More than one-third (37.6%) of the respondents did not replace mask when it had been used for more than 8 hours. Exposure to instructions on face mask use was the strongest predictor of good compliance (odds ratio=4.13, 95% confidential interval= 3.60-4.75, p=0.000). Other factors included specific situations, location, and gender. The influence of age needs further investigation. Most participants (76.4%) accessed information mainly via social media platforms. CONCLUSIONS: Nearly all people wore face mask and most of them used it properly during the COVID-19 pandemic. Hand hygiene before and during mask-wearing, choosing an appropriate type of face mask, reusing disposal face mask, and disposing of used face masks should be particularly emphasized in future evidence dissemination or behaviour-change interventions. Information on social media platforms for evidence dissemination and behaviour change may benefit the public the most, but this initiative requires further research to investigate its effectiveness. | Int J Nurs Stud | 2020 | LitCov and CORD-19 | |
| 661 | In silico validation of coumarin derivatives as potential inhibitors against Main Protease, NSP10/NSP16-Methyltransferase, Phosphatase and Endoribonuclease of SARS CoV-2 Coronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus was named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), (Coronavirus Disease 2019). Currently, there is no specific drug for the therapy of COVID-19. So, there is a need to develop or find out the new drug from the existing to cure the COVID-19. Identification of a potent inhibitor of Methyltransferase, Endoribonuclease, Phosphatase and Main Protease enzymes of SARS CoV-2 by coumarin derivatives using insilico approach. The in silico studies were performed on maestro 12.0 software (Schrodinger LLC 2019, USA). Two thousand seven hundred fifty-five biologically active coumarin derivative was docked with above receptor proteins of SARS CoV-2. The molecular dynamic simulation of the top one ligand of respected proteins was performed. Top five ligands of each protein were taken for study. Coumarin derivatives actively interact with taken receptors and showed good docking results for Methyltransferase, Endoribonuclease, Phosphatase and Main Protease and top five compounds of each have docking score from –9.00 to –7.97, –8.42 to –6.80, –8.63 to –7.48 and –7.30 to –6.01 kcal/mol, respectively. The docked compounds were showed RMSD and binding stability of simulated ligands are show the potency of ligands against the SARS CoV-2. Our study provides information on drugs that may be a potent inhibitor of COVID-19 infection. Drug repurposing of the available drugs would be great help in the treatment of COVID-19 infection. The combination therapy of the finding may improve inhibitory activity. Communicated by Ramaswamy H. Sarma HIGHLIGHTS: Coronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In silico virtual screening, docking, ADME, MM-GBSA and MD simulation analysis of coumarin derivatives against Methyltransferase (MTase), Endoribonuclease(endoU), ADP ribose Phosphatase and Main Protease enzyme of SARS CoV-2. All the analysis was performed on Maestro 12.0 Schrodinger software against respective receptors. Top five compounds of coumarin derivatives s docked at the active site of Methyltransferase (MTase), Endoribonuclease(endoU), ADP ribose Phosphatase and protease and top five compounds of each have docking score from –9.00 to –7.97, –8.42 to –6.80, –8.63 to –7.48 and –7.30 to –6.01 kcal/mol, respectively, of SARS CoV-2. These compounds were used to analysis of binding free energy by using the Prime MM-GBSA module. All the compounds showed drug-likeness properties. MD simulation of Proteins and ligands showed binding stability and good RMSD, radius of gyration of protein, coulomb-SR and LJ-SR energy. | J Biomol Struct Dyn | 2020 | LitCov and CORD-19 | |
| 662 | Exploring the behavioral determinants of COVID-19 vaccine acceptance among an urban population in Bangladesh: Implications for behavior change interventions BACKGROUND: While vaccines ensure individual protection against COVID-19 infection, delay in receipt or refusal of vaccines will have both individual and community impacts. The behavioral factors of vaccine hesitancy or refusal are a crucial dimension that need to be understood in order to design appropriate interventions. The aim of this study was to explore the behavioral determinants of COVID-19 vaccine acceptance and to provide recommendations to increase the acceptance and uptake of COVID-19 vaccines in Bangladesh. METHODS: We employed a Barrier Analysis (BA) approach to examine twelve potential behavioral determinants (drawn from the Health Belief Model [HBM] and Theory of Reasoned Action [TRA]) of intended vaccine acceptance. We conducted 45 interviews with those who intended to take the vaccine (Acceptors) and another 45 interviews with those who did not have that intention (Non-acceptors). We performed data analysis to find statistically significant differences and to identify which beliefs were most highly associated with acceptance and non-acceptance with COVID-19 vaccines. RESULTS: The behavioral determinants associated with COVID-19 vaccine acceptance in Dhaka included perceived social norms, perceived safety of COVID-19 vaccines and trust in them, perceived risk/susceptibility, perceived self-efficacy, perceived positive and negative consequences, perceived action efficacy, perceived severity of COVID-19, access, and perceived divine will. In line with the HBM, beliefs about the disease itself were highly predictive of vaccine acceptance, and some of the strongest statistically-significant (p<0.001) predictors of vaccine acceptance in this population are beliefs around both injunctive and descriptive social norms. Specifically, Acceptors were 3.2 times more likely to say they would be very likely to get a COVID-19 vaccine if a doctor or nurse recommended it, twice as likely to say that most people they know will get a vaccine, and 1.3 times more likely to say that most close family and friends will get a vaccine. The perceived safety of vaccines was found to be important since Non-acceptors were 1.8 times more likely to say that COVID-19 vaccines are “not safe at all”. Beliefs about one’s risk of getting COVID-19 disease and the severity of it were predictive of being a vaccine acceptor: Acceptors were 1.4 times more likely to say that it was very likely that someone in their household would get COVID-19, 1.3 times more likely to say that they were very concerned about getting COVID-19, and 1.3 times more likely to say that it would be very serious if someone in their household contracted COVID-19. Other responses of Acceptors on what makes immunization easier may be helpful in programming to boost acceptance, such as providing vaccination through government health facilities, schools, and kiosks, and having vaccinators maintain proper COVID-19 health and safety protocols. CONCLUSION: An effective behavior change strategy for COVID-19 vaccines uptake will need to address multiple beliefs and behavioral determinants, reducing barriers and leveraging enablers identified in this study. National plans for promoting COVID-19 vaccination should address the barriers, enablers, and behavioral determinants found in this study in order to maximize the impact on COVID-19 vaccination acceptance. | PLoS One | 2021 | LitCov and CORD-19 | |
| 663 | Seroprevalence of and Risk Factors Associated With SARS-CoV-2 Infection in Healthcare Workers During the Early COVID-19 Pandemic in Italy IMPORTANCE: Identifying health care settings and professionals at increased risk of SARS-CoV-2 infection is crucial to defining appropriate strategies, resource allocation, and protocols to protect health care workers (HCWs) and patients. Moreover, such information is crucial to decrease the risk that HCWs and health care facilities become amplifiers for SARS-CoV-2 transmission in the community. OBJECTIVE: To assess the association of different health care professional categories and operational units, including in-hospital wards, outpatient facilities, and territorial care departments, with seroprevalence and odds of SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted using IgG serological tests collected from April 1 through May 26, 2020, in the Lombardy region in Italy. Voluntary serological screening was offered to all clinical and nonclinical staff providing any health care services or support to health care services in the region. Data were analyzed from June 2020 through April 2021. EXPOSURES: Employment in the health care sector. MAIN OUTCOMES AND MEASURES: Seroprevalence of positive IgG antibody tests for SARS-CoV-2 was collected, and odds ratios of experiencing infection were calculated. RESULTS: A total of 140 782 professionals employed in the health sector were invited to participate in IgG serological screening, among whom 82 961 individuals (59.0% response rate) were tested for SARS-CoV-2 antibodies, with median (interquartile range [IQR]; range) age, 50 (40-56; 19-83) years and 59 839 (72.1%) women. Among these individuals, 10 115 HCWs (12.2%; 95% CI, 12.0%-12.4%) had positive results (median [IQR; range] age, 50 [39-55; 20-80] years; 7298 [72.2%] women). Statistically significantly higher odds of infection were found among health assistants (adjusted odds ratio [aOR], 1.48; 95% CI, 1.33-1.65) and nurses (aOR, 1.28; 95% CI, 1.17-1.41) compared with administrative staff and among workers employed in internal medicine (aOR, 2.24; 95% CI, 1.87-2.68), palliative care (aOR, 1.84; 95% CI, 1.38-2.44), rehabilitation (aOR, 1.59; 95% CI, 1.33-1.91), and emergency departments (aOR, 1.56; 95% CI, 1.29-1.89) compared with those working as telephone operators. Statistically significantly lower odds of infection were found among individuals working in forensic medicine (aOR, 0.40; 95% CI, 0.19-0.88), histology and anatomical pathology (aOR, 0.71; 95% CI, 0.52-0.97), and medical device sterilization (aOR, 0.54; 95% CI, 0.35-0.84) compared with those working as telephone operators. The odds of infection for physicians and laboratory personnel were not statistically significantly different from those found among administrative staff. The odds of infection for workers employed in intensive care units and infectious disease wards were not statistically significantly different from those of telephone operators. CONCLUSIONS AND RELEVANCE: These findings suggest that professionals partially accustomed to managing infectious diseases had higher odds of SARS-CoV-2 infection. The findings further suggest that adequate organization of clinical wards and personnel, appropriate personal protective equipment supply, and training of all workers directly and repeatedly exposed to patients with clinical or subclinical COVID-19 should be prioritized to decrease the risk of infection in health care settings. | JAMA Netw Open | 2021 | LitCov and CORD-19 | |
| 664 | Norwegian COVID-19 (NO COVID-19) Pragmatic Open label Study to assess early use of hydroxychloroquine sulphate in moderately severe hospitalised patients with COVID-19: A structured summary of a study protocol for a randomised controlled trial OBJECTIVES: The hypothesis of the study is that treatment with hydroxychloroquine sulphate in hospitalised patients with coronavirus disease 2019 (Covid-19) is safe and will accelerate the virological clearance rate for patients with moderately severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when compared to standard care. Furthermore, we hypothesize that early treatment with hydroxychloroquine sulphate is associated with more rapid resolve of clinical symptoms as assessed by the National Early Warning Score 2 (NEWS2), decreased admission rate to intensive care units and mortality, and improvement in protein biomarker profiles (C-reactive protein, markers of renal and hepatic injury, and established cardiac biomarkers like cardiac troponin and B-type natriuretic peptide). TRIAL DESIGN: The study is a two-arm, open label, pragmatic randomised controlled group sequential adaptive trial designed to assess the effect on viral loads and clinical outcome of hydroxychloroquine sulphate therapy in addition to standard care compared to standard care alone in patients with established Covid-19. By utilizing resources already paid for by the hospitals (physicians and nurses in daily clinical practice), this pragmatic trial can include a larger number of patients over a short period of time and at a lower cost than studies utilizing traditional randomized controlled trial designs with an external study organization. The pragmatic approach will enable swift initiation of randomisation and allocation to treatment. PARTICIPANTS: Patients will be recruited from all inpatients at Akershus University Hospital, Lørenskog, Norway. Electronic real-time surveillance of laboratory reports from the Department of Microbiology will be examined regularly for SARS-CoV-2 positive subjects. All of the following conditions must apply to the prospective patient at screening prior to inclusion: (1) Hospitalisation; (2) Adults 18 years or older; (3) Moderately severe Covid-19 disease (NEWS2 of 6 or less); (4) SARS-CoV-2 positive nasopharyngeal swab; (5) Expected time of hospitalisation > 48 hours; and (6) Signed informed consent must be obtained and documented according to Good Clinical Practice guidelines of the International Conference on Harmonization, and national/local regulations. Patients will be excluded from participation in the study if they meet any of the following criteria: (1) Requiring intensive care unit admission at screening; (2) History of psoriasis; (3) Known adverse reaction to hydroxychloroquine sulphate; (4) Pregnancy; or (5) Prolonged corrected QT interval (>450 ms). Clinical data, including standard hospital biochemistry, medical therapy, vital signs, NEWS2, and microbiology results (including blood culture results and reverse transcriptase polymerase chain reaction [RT-PCR] for other upper airway viruses), will be automatically extracted from the hospital electronic records and merged with the study specific database. INTERVENTION AND COMPARATOR: Included patients will be randomised in a 1:1 ratio to (1) standard care with the addition of 400 mg hydroxychloroquine sulphate (Plaquenil(TM)) twice daily for seven days or (2) standard care alone. MAIN OUTCOMES: The primary endpoint of the study is the rate of decline in SARS-CoV-2 viral load in oropharyngeal samples as assessed by RT-PCR in samples collected at baseline, 48 and 96 hours after randomization and administration of drug for the intervention arm. Secondary endpoints include change in NEWS2 at 96 hours after randomisation, admission to intensive care unit, mortality (in-hospital, and at 30 and 90 days), duration of hospital admission, clinical status on a 7-point ordinal scale 14 days after randomization ([1] Death [2] Hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation [3] Hospitalised, on non-invasive ventilation or high flow oxygen devices [4] Hospitalized, requiring supplemental oxygen [5] Hospitalised, not requiring supplemental oxygen [6] Not hospitalized, but unable to resume normal activities [7] Not hospitalised, with resumption of normal activities), and improvement in protein biomarker profiles (C-reactive protein, markers of renal and hepatic injury, and established cardiac biomarkers like cardiac troponin and B-type natriuretic peptide) at 96 hours after randomization. RANDOMISATION: Eligible patients will be allocated in a 1:1 ratio, using a computer randomisation procedure. The allocation sequence has been prepared by an independent statistician. BLINDING (MASKING): Open label randomised controlled pragmatic trial without blinding, no active or placebo control. The virologist assessing viral load in the oropharyngeal samples and the statistician responsible for analysis of the data will be blinded to the treatment allocation for the statistical analyses. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): This is a group sequential adaptive trial where analyses are planned after 51, 101, 151 and 202 completed patients, with a maximum sample size of 202 patients (101 patients allocated to intervention and standard care and 101 patients allocated to standard care alone). TRIAL STATUS: Protocol version 1.3 (March 26, 2020). Recruitment of first patient on March 26, 2020, and 51 patients were included as per April 28, 2020. Study recruitment is anticipated to be completed by July 2020. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04316377. Trial registered March 20, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. | Trials | 2020 | LitCov and CORD-19 | |
| 665 | Haplotype distribution of SARS-CoV-2 variants in low and high vaccination rate countries during ongoing global COVID-19 pandemic in early 2021 The widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuously impacts our economic and public health. The potential of emerging variants to increase transmissibility and evade vaccine-induced immunity lets us put more effort to research on viral mutations and explore the pathogenic haplotypes. In this study, we characterized the haplotype and sub-haplotype diversity of SARS-CoV-2 global variants in January–March and the areas with low and high COVID19 vaccination rates in May 2021 by analyzing viral proteome of complete genome sequences published. Phylogenetic tree analysis of the proteomes of SARS-CoV-2 variants with Neighbor-Joining and Maximum Parsimony methods indicated that haplotype 2 variant with nsp12 P323L and Spike D614G was dominant (98.81%), including new sub-haplotypes 2A_1 to 2A_3, 2B_1 to 2B_3, and 2C_1 to 2C_2 emerged post-one-year COVID-19 outbreak. In addition, the profiling of sub-haplotypes indicated that sub-haplotype 2A_1 with the mutations at N501Y, A570D, D614G, P681H, T716I, S982A, and D118H in Spike was over 58% in May 2021 in the high partly vaccinated rate group (US, Canada, and Germany). Meanwhile, the new haplotype 2C_3 bearing the mutations at EFR156-158del, T19R, A222V, L452R, T478K, and D614G in Spike occupied over 54.8% in May 2021 in the low partly vaccinated rate group (India, Malaysia, Taiwan, and Vietnam). Sub-haplotypes 2A_1 and 2C_3 had a meaningful alternation of ACE2-specific recognition site, neutralization epitopes, and furin cleavage site in SARS-CoV-2 Spike protein. The results discovered the haplotype diversity and new sub-haplotypes of SARS-CoV-2 variants post one-year pandemic in January–March 2021, showing the profiles of sub-haplotypes in the groups with low and high partly vaccinated rates in May 2021. The study reports the emergence of new SARS-CoV-2 sub-haplotypes during ongoing pandemic and vaccination in early 2021, which might help inform the response to vaccination strategies. | Infect Genet Evol | 2021 | LitCov and CORD-19 | |
| 666 | Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults BACKGROUND: Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age. METHODS: We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart. RESULTS: Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-μg dose, the anti–S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells. CONCLUSIONS: In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-μg dose induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100-μg dose in a phase 3 vaccine trial. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 Study ClinicalTrials.gov number, NCT04283461.) | N Engl J Med | 2020 | LitCov and CORD-19 | |
| 667 | Origin and evolution of pathogenic coronaviruses Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs. | Nat Rev Microbiol | 2018 | CORD-19 | |
| 668 | Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone N/A | Int J Mol Sci | 2022 | LitCov | |
| 669 | Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift N/A | Nature | 2022 | LitCov and CORD-19 | |
| 670 | Clinical Evaluation of Self-Collected Saliva by Quantitative Reverse Transcription-PCR (RT-qPCR), Direct RT-qPCR, Reverse Transcription-Loop-Mediated Isothermal Amplification and a Rapid Antigen Test To Diagnose COVID-19 The clinical performances of six molecular diagnostic tests and a rapid antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were clinically evaluated for the diagnosis of coronavirus disease 2019 (COVID-19) in self-collected saliva. Saliva samples from 103 patients with laboratory-confirmed COVID-19 (15 asymptomatic and 88 symptomatic) were collected on the day of hospital admission. SARS-CoV-2 RNA in saliva was detected using a quantitative reverse transcription-PCR (RT-qPCR) laboratory-developed test (LDT), a cobas SARS-CoV-2 high-throughput system, three direct RT-qPCR kits, and reverse transcription–loop-mediated isothermal amplification (RT-LAMP). The viral antigen was detected by a rapid antigen immunochromatographic assay. Of the 103 samples, viral RNA was detected in 50.5 to 81.6% of the specimens by molecular diagnostic tests, and an antigen was detected in 11.7% of the specimens by the rapid antigen test. Viral RNA was detected at significantly higher percentages (65.6 to 93.4%) in specimens collected within 9 days of symptom onset than in specimens collected after at least 10 days of symptoms (22.2 to 66.7%) and in specimens collected from asymptomatic patients (40.0 to 66.7%). Self-collected saliva is an alternative specimen option for diagnosing COVID-19. The RT-qPCR LDT, a cobas SARS-CoV-2 high-throughput system, direct RT-qPCR kits (except for one commercial kit), and RT-LAMP showed sufficient sensitivities in clinical use to be selectively used in clinical settings and facilities. The rapid antigen test alone is not recommended for an initial COVID-19 diagnosis because of its low sensitivity. | J Clin Microbiol | 2020 | LitCov and CORD-19 | |
| 671 | Prevalence and correlates of depression and anxiety among Chinese international students in US colleges during the COVID-19 pandemic: A cross-sectional study BACKGROUND: Previous studies showed that the COVID-19 outbreak increased the levels of depression and anxiety in heterogeneous populations. However, none has explored the prevalence and correlates of depression and anxiety among Chinese international students studying in US colleges during the pandemic. OBJECTIVE: This study examines the prevalence of depression and anxiety among Chinese international students enrolled in US universities during the COVID-19 pandemic and identifies the associated factors, including habits, social and psychological support, sleep quality, and remote learning. METHODS: Between June and July 2020, we conducted a cross-sectional study through Wenjuanxing, a web-based survey platform. Participants were recruited with snowball sampling through 21 Chinese international student associations in US universities. The survey consisted of demographic questions, the Social Support Rating Scale (SSRS), the Insomnia Severity Index (ISI), the Patient Health Questionnaire-9 (PHQ-9), the General Anxiety Disorder-7 (GAD-7), and self-constructed questions on academic performance, financial concerns, use of social media, physical exercise, and psychological support. Cut-off scores of 10 were used for both PHQ-9 and GAD-7 to determine the binary outcomes of depression and anxiety, respectively. Bivariant analyses and multivariable logistic regression analyses were performed to identify the associated factors. RESULTS: Among 1881 participants, we found a prevalence of depression (PHQ-9 score⩾ 10) at 24.5% and that of anxiety (GAD-7 score⩾ 10) at 20.7%. A higher risk of depression was associated with recent exposure to traumatic events, agreement to pandemic’s negative impacts on financial status, agreement and strong agreement to the negative impacts of remote learning on personal relationships, and a higher ISI score. A lower risk of depression was associated with disagreement to the negative impacts of remote learning on academic performance and future careers, strong willingness to seek professional help with emotional issues, and a higher SSRS score. In addition, a higher risk of anxiety was associated with recent exposure to traumatic events, a lot of workloads, often staying up for online classes, agreement and strong agreement to the negative impacts of remote learning on personal relationships, and a higher ISI score. A lower risk of anxiety was associated with the willingness and strong willingness to seek professional help with emotional issues, and a higher SSRS score. CONCLUSION: This study showed a high prevalence of depression and anxiety among Chinese international students studying in US colleges during the COVID-19 pandemic. Multiple correlates—including recent exposure to traumatic events, pandemic-related financial concerns, workload, social support, remote learning, willingness to seek professional help, and sleep quality—were identified. It is critical for future studies to further investigate this student population and for universities to provide more flexible learning options and more access to psychological services. | PLoS One | 2022 | LitCov and CORD-19 | |
| 672 | Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy N/A | JAMA | 2020 | LitCov and CORD-19 | |
| 673 | Perception towards E-learning and COVID-19 on the mental health status of university students in Malaysia N/A | Sci Prog | 2021 | LitCov and CORD-19 | |
| 674 | Therapeutic respiratory and functional rehabilitation protocol for intensive care unit patients affected by COVID-19: a structured summary of a study protocol for a randomised controlled trial OBJECTIVES: The primary objective of the presented study is to analyze the respiratory and functional effects of a rehabilitation program in patients affected by hospitalization in Intensive Care Unit (ICU) due to COVID-19, in comparison with the group treated with standard of care, at discharge endpoint. The secondary objectives of the presented study are to evaluate different outcomes of the rehabilitation program in comparison to standard of care regarding: functional performance at 4-week and 12-week post- discharge mark; health-related quality of life, the impact on the health services (namely days of hospitalization), the cost-effectiveness of the intervention proposed. TRIAL DESIGN: This is a randomized, controlled, double-blind, double-arm clinical trial of treatment, with an allocation ratio 1:1 and framework of superiority. PARTICIPANTS: The study will be conducted at Centro Hospitalar Entre Douro e Vouga, Santa Maria da Feira, Portugal. Potential participants will be adult patients (≥18 years old) hospitalized in ICU with respiratory insufficiency due to COVID-19, who are referred to respiratory and functional rehabilitation. Only patients approved by physical rehabilitation doctors to perform respiratory and functional rehabilitation will be considered potential participants. To be eligible for inclusion participants must have been independent in their activities of daily living before the onset of critical illness (verbal statement by their proxy) and have to meet the safety criteria defined by the Portuguese Society of Physical Rehabilitation Medicine. INTERVENTION AND COMPARATOR: Both groups will receive usual medical and nursing care in the ICU, which involves assessment and treatment of the respiratory system and may include positioning, hyperinflation techniques and suctioning. The physical function of the patient is assessed, and active bed exercises and mobility are encouraged as soon as possible and may include sitting out of bed. The intervention group will receive a functional and respiratory multidisciplinary rehabilitation protocol (that includes medical, nursing, physiotherapy and occupational therapy interventions) during their entire hospital stay. After reassurance that the patients fulfil the safety criteria, they will initiate the rehabilitation protocol, individualized to each patient based on the clinical status. The rehabilitation interventions and exercises implemented will be consistent with recommendations from the Portuguese Society of Physical Rehabilitation Medicine. The intervention will occur 6 days per week (Monday to Saturday), fifteen minutes, twice per day for each participant. Throughout all activities, progression will be increased successively, depending on the individual’s tolerance and stability. After discharge, the intervention group will continue with rehabilitation exercises, prescribed by physical rehabilitation doctors. These exercises are designed for the patient to do at home, and then report their execution to rehabilitation nurses through teleconsultation, until 12 weeks after ICU discharge. MAIN OUTCOMES: Baseline descriptive data collection will include age, sex, comorbidities and date of admission to ICU. The need of mechanical ventilation and length of use, as well as the need for oxygen therapy, length of ICU stay (days/hours), incidence of ICU readmission, discharge destination and survival will also be recorded. Prior to intervention, every two days and at discharge, participants will be evaluated using the following scales: Glasgow Coma Scale, Richmond Agitation Sedation Scale, Chelsea Critical Care Physical Assessment, 5 standardized questions for cooperation, Medical Research Council Sum-Score, Handgrip strength test and Medical Research Council dyspnea scale. At discharge, Borg Rating of Perceived Exertion will be evaluated. The primary outcome measure will be functional capacity using the 6-Minute Walk Test, and it will be measured at discharge and at the 4-week and 12-week mark. Medical Research Council Sum-Score, Handgrip strength test, Medical Research Council dyspnea scale and Borg Rating of Perceived Exertion will also be re-evaluated at the 4-week and 12-week mark. The health related quality of life will also be used as an outcome measure, using the 12-Item Short Form Survey, at 12 weeks of follow-up. RANDOMISATION: Participants will be divided into two groups, standard care and intervention, by means of balanced randomization at a 1:1 ratio using blocks of 10 participants. The randomization sequence is going to be created using a free software (http://www.randomized.org/). In order to ensure the confidentiality of the randomisation sequence, this process will be conducted by an assessor external to the study. BLINDING (MASKING): The evaluators in the study will be blinded during the entire process. The evaluators will be unaware of the study objectives and the randomized distribution of patients to study groups and will not have access to the randomization sequence. Although blinding for patients will not be possible to achieve completely, subjects will be unaware of other treatment modalities, and they will not know if they belong to the intervention or standard group. As for the treating physiotherapists and ICU staff, blinding will not be possible to achieve, but they will not be responsible for assessing outcomes. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We plan to randomise 40 participants to each group. 80 participants in total. TRIAL STATUS: This is the second and definitive protocol version, dated from 26th February 2021. Recruitment started on 8(th) March 2021. Participants will be recruited between March 8, 2021, and June 8, 2021. Study completion is expected to be October 2021. TRIAL REGISTRATION: ReBEC RBR-7rvhpq9. Registry name: The effect of rehabilitation in hospitalized COVID-19 patients. Registered on 17 March 2021.Retrospectively registered. FULL PROTOCOL: “The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol”. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05210-y. | Trials | 2021 | LitCov and CORD-19 | |
| 675 | Association between medical students' prior experiences and perceptions of formal online education developed in response to COVID-19: a cross-sectional study in China OBJECTIVES: (1) Understanding the characteristics of online learning experiences of Chinese undergraduate medical students; (2) Investigating students’ perceptions of ongoing online education developed in response to COVID-19 and (3) Exploring how prior online learning experiences are associated with students’ perceptions. DESIGN: Students’ familiarity with online learning modes and corresponding perceived usefulness (PU) according to their previous experiences were investigated using an online survey. The survey also collected data on students’ perceptions through their evaluation of and satisfaction with current online learning. SETTING: In response to the educational challenges created by COVID-19, medical schools in China have adopted formal online courses for students. PARTICIPANTS: The questionnaire was sent to 225 329 students, of whom 52.38% (118 080/225 329) replied, with valid data available for 44.18% (99 559/225 329). METHODS: Pearson correlations and t-tests were used to examine the relationship between familiarity and PU. Multiple linear regression and logistic regression analyses were used to determine the impact of prior learning experiences and its interactions with gender, area, learning phase and academic performance on students’ perceptions. RESULTS: Students’ PU had a significant positive correlation with their familiarity with online learning modes (p<0.01). Students’ evaluation of and satisfaction with their current online education were positively associated with their familiarity (β=0.46, 95% CI 0.45 to 0.48, p<0.01; OR 1.14, 95% CI 1.13 to 1.14, p<0.01) with and PU (β=3.11, 95% CI 2.92 to 3.30, p<0.01; OR 2.55, 95% CI 2.37 to 2.75, p<0.01) of online learning. Moreover, the higher the students’ learning phases, the lower the associations between PU and students’ evaluation of and satisfaction with ongoing online education. CONCLUSIONS: Medical students in China have experiences with various online learning modes. Prior learning experiences are positively associated with students’ evaluation of and satisfaction with current online education. Higher learning phases, in which clinical practices are crucial, and high academic performance led to lower evaluation and satisfaction scores. | BMJ Open | 2020 | LitCov and CORD-19 | |
| 676 | Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in September 2020 and is rapidly spreading toward fixation. Using a variety of statistical and dynamic modeling approaches, we estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine rollout, COVID-19 hospitalizations and deaths across England in the first 6 months of 2021 were projected to exceed those in 2020. VOC 202012/01 has spread globally and exhibits a similar transmission increase (59 to 74%) in Denmark, Switzerland, and the United States. | Science | 2021 | LitCov and CORD-19 | |
| 677 | Pregnancy Outcomes Among Women With and Without SARS-CoV-2 Infection IMPORTANCE: Published data suggest that there are increased hospitalizations, placental abnormalities, and rare neonatal transmission among pregnant women with coronavirus disease 2019 (COVID-19). OBJECTIVES: To evaluate adverse outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy and to describe clinical management, disease progression, hospital admission, placental abnormalities, and neonatal outcomes. DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study of maternal and neonatal outcomes among delivered women with and without SARS-CoV-2 during pregnancy was conducted from March 18 through August 22, 2020, at Parkland Health and Hospital System (Dallas, Texas), a high-volume prenatal clinic system and public maternity hospital with widespread access to SARS-CoV-2 testing in outpatient, emergency department, and inpatient settings. Women were included if they were tested for SARS-CoV-2 during pregnancy and delivered. For placental analysis, the pathologist was blinded to illness severity. EXPOSURES: SARS-CoV-2 infection during pregnancy. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of preterm birth, preeclampsia with severe features, or cesarean delivery for abnormal fetal heart rate among women delivered after 20 weeks of gestation. Maternal illness severity, neonatal infection, and placental abnormalities were described. RESULTS: From March 18 through August 22, 2020, 3374 pregnant women (mean [SD] age, 27.6 [6] years) tested for SARS-CoV-2 were delivered, including 252 who tested positive for SARS-CoV-2 and 3122 who tested negative. The cohort included 2520 Hispanic (75%), 619 Black (18%), and 125 White (4%) women. There were no differences in age, parity, body mass index, or diabetes among women with or without SARS-CoV-2. SARS-CoV-2 positivity was more common among Hispanic women (230 [91%] positive vs 2290 [73%] negative; difference, 17.9%; 95% CI, 12.3%-23.5%; P < .001). There was no difference in the composite primary outcome (52 women [21%] vs 684 women [23%]; relative risk, 0.94; 95% CI, 0.73-1.21; P = .64). Early neonatal SARS-CoV-2 infection occurred in 6 of 188 tested infants (3%), primarily born to asymptomatic or mildly symptomatic women. There were no placental pathologic differences by illness severity. Maternal illness at initial presentation was asymptomatic or mild in 239 women (95%), and 6 of those women (3%) developed severe or critical illness. Fourteen women (6%) were hospitalized for the indication of COVID-19. CONCLUSIONS AND RELEVANCE: In a large, single-institution cohort study, SARS-CoV-2 infection during pregnancy was not associated with adverse pregnancy outcomes. Neonatal infection may be as high as 3% and may occur predominantly among asymptomatic or mildly symptomatic women. Placental abnormalities were not associated with disease severity, and hospitalization frequency was similar to rates among nonpregnant women. | JAMA Netw Open | 2020 | LitCov and CORD-19 | |
| 678 | The Differential Effects of Social Media on Depressive Symptoms and Suicidal Ideation Among the Younger and Older Adult Population in Hong Kong During the COVID-19 Pandemic: Population-Based Cross-sectional Survey Study BACKGROUND: Social media has become a ubiquitous part of daily life during the COVID-19 pandemic isolation. However, the role of social media use in depression and suicidal ideation of the general public remains unclear. Related empirical studies were limited and reported inconsistent findings. Little is known about the potential underlying mechanisms that may illustrate the relationship between social media use and depression and suicidal ideation during the COVID-19 pandemic. OBJECTIVE: This study tested the mediation effects of social loneliness and posttraumatic stress disorder (PTSD) symptoms on the relationship between social media use and depressive symptoms and suicidal ideation, as well as the moderation effect of age on the mediation models. METHODS: We administered a population-based random telephone survey in May and June 2020, when infection control measures were being vigorously implemented in Hong Kong. A total of 1070 adults (658 social media users and 412 nonusers) completed the survey. Structural equation modeling (SEM) and multigroup SEM were conducted to test the mediation and moderation effects. RESULTS: The weighted prevalence of probable depression was 11.6%; 1.6% had suicidal ideation in the past 2 weeks. Both moderated mediation models of depressive symptoms (χ(2)(62)=335.3; P<.05; comparative fit index [CFI]=0.94; nonnormed fit index [NNFI]=0.92; root mean square error of approximation [RMSEA]=0.06) and suicidal ideation (χ(2)(34)=50.8; P<.05; CFI=0.99; NNFI=0.99; RMSEA=0.02) showed acceptable model fit. There was a significantly negative direct effect of social media use on depressive symptoms among older people (β=–.07; P=.04) but not among younger people (β=.04; P=.55). The indirect effect via PTSD symptoms was significantly positive among both younger people (β=.09; P=.02) and older people (β=.10; P=.01). The indirect effect via social loneliness was significant among older people (β=–.01; P=.04) but not among younger people (β=.01; P=.31). The direct effect of social media use on suicidal ideation was not statistically significant in either age group (P>.05). The indirect effects via PTSD symptoms were statistically significant among younger people (β=.02; P=.04) and older people (β=.03; P=.01). Social loneliness was not a significant mediator between social media use and suicidal ideation among either age group (P>.05). CONCLUSIONS: Social media may be a “double-edged sword” for psychosocial well-being during the COVID-19 pandemic, and its roles vary across age groups. The mediators identified in this study can be addressed by psychological interventions to prevent severe mental health problems during and after the COVID-19 pandemic. | JMIR Public Health Surveill | 2021 | LitCov and CORD-19 | |
| 679 | Self-reported psychological problems and coping strategies: a web-based study in Peruvian population during COVID-19 pandemic BACKGROUND: The Coronavirus pandemic has disrupted health systems across the world and led to major shifts in individual behavior by forcing people into isolation in home settings. Its rapid spread has overwhelmed populations in all corners of Latin-American countries resulting in individual psychological reactions that may aggravate the health crisis. This study reports on demographics, self-reported psychological disturbances and associated coping styles during the COVID-19 pandemic for the Peruvian population. METHODS: This cross-sectional study uses an online survey with snowball sampling that was conducted after the state of emergency was declared in Perú (on April 2nd). The General Health Questionnaire (GHQ-28) was used to identify somatic symptoms, incidence of anxiety/ insomnia, social dysfunction and depression and the Coping Strategy Questionnaire (COPE-28) mapped personal strategies to address recent stress. RESULTS: 434 self-selected participants ranging in age from 18 to 68 years old (Mean age = 33.87) completed the survey. The majority of participants were women (61.30%), aged between 18 and 28 (41.70%), well-educated (> = 85.00%), Peruvian (94.20%), employed (57.40%) and single (71.20%). 40.8% reported psychological distress, expressing fear of coronavirus infection (71.43%). Regression analysis shows that men had lower somatic-related symptom (β = − 1.87, 95%, CI: − 2.75 to −.99) and anxiety/insomnia symptom (β = − 1.91, 95% CI: − 2.98 to 0.84) compared to women. The risk for depression and social dysfunction are less likely with increasing age. Educational status was protective against developing psychological conditions (p < 0.05). While active responses (acceptance and social support) are scarcely used by individuals with psychological distress; passive strategies (such as denial, self-distraction, self-blame, disconnection, and venting) are more commonly reported. CONCLUSION: This study provides a better understanding of the psychological health impact occurring during the COVID-19 pandemic on the Peruvian population. About half of the respondents reported psychological distress and poor coping responses. This evidence informs the need for broader promotional health policies focused on strengthening individual’s active strategies aiming at improving emotional health and preventing psychiatric conditions, during and after the COVID-19 pandemic. | BMC Psychiatry | 2021 | LitCov and CORD-19 | |
| 680 | COVID-19 in Africa: care and protection for frontline healthcare workers Medical staff caring for COVID-19 patients face mental stress, physical exhaustion, separation from families, stigma, and the pain of losing patients and colleagues. Many of them have acquired SARS-CoV-2 and some have died. In Africa, where the pandemic is escalating, there are major gaps in response capacity, especially in human resources and protective equipment. We examine these challenges and propose interventions to protect healthcare workers on the continent, drawing on articles identified on Medline (Pubmed) in a search on 24 March 2020. Global jostling means that supplies of personal protective equipment are limited in Africa. Even low-cost interventions such as facemasks for patients with a cough and water supplies for handwashing may be challenging, as is ‘physical distancing’ in overcrowded primary health care clinics. Without adequate protection, COVID-19 mortality may be high among healthcare workers and their family in Africa given limited critical care beds and difficulties in transporting ill healthcare workers from rural to urban care centres. Much can be done to protect healthcare workers, however. The continent has learnt invaluable lessons from Ebola and HIV control. HIV counselors and community healthcare workers are key resources, and could promote social distancing and related interventions, dispel myths, support healthcare workers, perform symptom screening and trace contacts. Staff motivation and retention may be enhanced through carefully managed risk ‘allowances’ or compensation. International support with personnel and protective equipment, especially from China, could turn the pandemic’s trajectory in Africa around. Telemedicine holds promise as it rationalises human resources and reduces patient contact and thus infection risks. Importantly, healthcare workers, using their authoritative voice, can promote effective COVID-19 policies and prioritization of their safety. Prioritizing healthcare workers for SARS-CoV-2 testing, hospital beds and targeted research, as well as ensuring that public figures and the population acknowledge the commitment of healthcare workers may help to maintain morale. Clearly there are multiple ways that international support and national commitment could help safeguard healthcare workers in Africa, essential for limiting the pandemic’s potentially devastating heath, socio-economic and security impacts on the continent. | Global Health | 2020 | LitCov and CORD-19 | |
| 681 | Considerable escape of SARS-CoV-2 Omicron to antibody neutralization N/A | Nature | 2022 | LitCov and CORD-19 | |
| 682 | Cell entry mechanisms of SARS-CoV-2 A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is causing the global coronavirus disease 2019 (COVID-19) pandemic. Understanding how SARS-CoV-2 enters human cells is a high priority for deciphering its mystery and curbing its spread. A virus surface spike protein mediates SARS-CoV-2 entry into cells. To fulfill its function, SARS-CoV-2 spike binds to its receptor human ACE2 (hACE2) through its receptor-binding domain (RBD) and is proteolytically activated by human proteases. Here we investigated receptor binding and protease activation of SARS-CoV-2 spike using biochemical and pseudovirus entry assays. Our findings have identified key cell entry mechanisms of SARS-CoV-2. First, SARS-CoV-2 RBD has higher hACE2 binding affinity than SARS-CoV RBD, supporting efficient cell entry. Second, paradoxically, the hACE2 binding affinity of the entire SARS-CoV-2 spike is comparable to or lower than that of SARS-CoV spike, suggesting that SARS-CoV-2 RBD, albeit more potent, is less exposed than SARS-CoV RBD. Third, unlike SARS-CoV, cell entry of SARS-CoV-2 is preactivated by proprotein convertase furin, reducing its dependence on target cell proteases for entry. The high hACE2 binding affinity of the RBD, furin preactivation of the spike, and hidden RBD in the spike potentially allow SARS-CoV-2 to maintain efficient cell entry while evading immune surveillance. These features may contribute to the wide spread of the virus. Successful intervention strategies must target both the potency of SARS-CoV-2 and its evasiveness. | Proc Natl Acad Sci U S A | 2020 | LitCov and CORD-19 | |
| 683 | Seroprevalence of anti-SARS-CoV-2 IgG/IgM antibodies in Borgosesia (Piedmont Region, Northern Italy) population: a surveillance strategy in post-lockdown period? N/A | Epidemiol Prev | 2020 | LitCov and CORD-19 | |
| 684 | The SARS-CoV-2 Spike Glycoprotein as a Drug and Vaccine Target: Structural Insights into Its Complexes with ACE2 and Antibodies Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the Coronavirus disease (COVID-19) pandemic, has so far resulted in more than 1.1 M deaths and 40 M cases worldwide with no confirmed remedy yet available. Since the first outbreak in Wuhan, China in December 2019, researchers across the globe have been in a race to develop therapies and vaccines against the disease. SARS-CoV-2, similar to other previously identified Coronaviridae family members, encodes several structural proteins, such as spike, envelope, membrane, and nucleocapsid, that are responsible for host penetration, binding, recycling, and pathogenesis. Structural biology has been a key player in understanding the viral infection mechanism and in developing intervention strategies against the new coronavirus. The spike glycoprotein has drawn considerable attention as a means to block viral entry owing to its interactions with the human angiotensin-converting enzyme 2 (ACE2), which acts as a receptor. Here, we review the current knowledge of SARS-CoV-2 and its interactions with ACE2 and antibodies. Structural information of SARS-CoV-2 spike glycoprotein and its complexes with ACE2 and antibodies can provide key input for the development of therapies and vaccines against the new coronavirus. | Cells | 2020 | LitCov and CORD-19 | |
| 685 | Temporal dynamics in viral shedding and transmissibility of COVID-19 N/A | Nat Med | 2020 | LitCov and CORD-19 | |
| 686 | Intention to get vaccinations against COVID-19 in French healthcare workers during the first pandemic wave: a cross-sectional survey INTRODUCTION: Healthcare workers (HCWs) are at the frontline of the COVID-19 pandemic and identified as a priority target group for COVID-19 vaccines. We aimed to determine COVID-19 vaccine acceptance rate in HCWs people in France. METHODS: We conducted an anonymous survey from the March 26(th) to July 2(nd) 2020. Primary endpoint was the intention to get vaccinated against COVID-19 if a vaccine was available. RESULTS: Two thousand and forty-seven HCWs answered the survey; women accounted for 74% of respondents. Among respondents, 1.554 (76.9%, 95 %CI 75.1-78.9) would accept a COVID-19 vaccine. Older age, male gender, fear about COVID-19, individual perceived risk and flu vaccination during previous season were associated with hypothetic COVID-19 vaccine acceptance. Nurses and assistant nurses were less prone to get vaccinated against COVID-19 than physicians. Vaccine hesitancy was associated with a decrease in COVID-19 vaccine acceptance. Flu vaccine rate was 57.3 % during the previous season, and 54.6 % of the respondents had intention to get flu vaccine during the next season. CONCLUSIONS: Intention to get vaccinated against COVID-19 reached 75% in HCWs with discrepancies between occupational categories. COVID-19 pandemic had no positive effect on flu vaccine acceptance rate. | J Hosp Infect | 2020 | LitCov and CORD-19 | |
| 687 | The Impact of COVID-19 Management Policies Tailored to Airborne SARS-CoV-2 Transmission: Policy Analysis BACKGROUND: Daily new COVID-19 cases from January to April 2020 demonstrate varying patterns of SARS-CoV-2 transmission across different geographical regions. Constant infection rates were observed in some countries, whereas China and South Korea had a very low number of daily new cases. In fact, China and South Korea successfully and quickly flattened their COVID-19 curve. To understand why this was the case, this paper investigated possible aerosol-forming patterns in the atmosphere and their relationship to the policy measures adopted by select countries. OBJECTIVE: The main research objective was to compare the outcomes of policies adopted by countries between January and April 2020. Policies included physical distancing measures that in some cases were associated with mask use and city disinfection. We investigated whether the type of social distancing framework adopted by some countries (ie, without mask use and city disinfection) led to the continual dissemination of SARS-CoV-2 (daily new cases) in the community during the study period. METHODS: We examined the policies used as a preventive framework for virus community transmission in some countries and compared them to the policies adopted by China and South Korea. Countries that used a policy of social distancing by 1-2 m were divided into two groups. The first group consisted of countries that implemented social distancing (1-2 m) only, and the second comprised China and South Korea, which implemented distancing with additional transmission/isolation measures using masks and city disinfection. Global daily case maps from Johns Hopkins University were used to provide time-series data for the analysis. RESULTS: The results showed that virus transmission was reduced due to policies affecting SARS-CoV-2 propagation over time. Remarkably, China and South Korea obtained substantially better results than other countries at the beginning of the epidemic due to their adoption of social distancing (1-2 m) with the additional use of masks and sanitization (city disinfection). These measures proved to be effective due to the atmosphere carrier potential of SARS-CoV-2 transmission. CONCLUSIONS: Our findings confirm that social distancing by 1-2 m with mask use and city disinfection yields positive outcomes. These strategies should be incorporated into prevention and control policies and be adopted both globally and by individuals as a method to fight the COVID-19 pandemic. | JMIR Public Health Surveill | 2021 | LitCov and CORD-19 | |
| 688 | Thoracic imaging tests for the diagnosis of COVID-19 N/A | Cochrane Database Syst Rev | 2020 | LitCov and CORD-19 | |
| 689 | Early antiviral treatment in outpatients with COVID-19 (FLARE): a structured summary of a study protocol for a randomised controlled trial OBJECTIVES: The objective of this trial is to assess whether early antiviral therapy in outpatients with COVID-19 with either favipiravir plus lopinavir/ritonavir, lopinavir/ritonavir alone, or favipiravir alone, is associated with a decrease in viral load of SARS-CoV-2 compared with placebo. TRIAL DESIGN: FLARE is a phase IIA randomised, double-blind, 2x2 factorial placebo-controlled, interventional trial. PARTICIPANTS: This trial is being conducted in the United Kingdom, with Royal Free Hospital, London as the lead site. Participants are non-hospitalised adults with highly suspected COVID-19 within the first 5 days of symptom onset, or who have tested positive with SARS-CoV-2 causing COVID-19 within the first 7 days of symptom onset, or who are asymptomatic but tested positive for SARS-CoV-2 for the first time within the last 48 hours. Inclusion criteria are as follows: 1. Any adult with the following: Symptoms compatible with COVID-19 disease (Fever >37.8°C on at least one occasion AND either cough and/ or anosmia) within the first 5 days of symptom onset (date/time of enrolment must be within the first 5 days of symptom onset). OR ANY symptoms compatible with COVID-19 disease (may include, but are not limited to fever, cough, shortness of breath, malaise, myalgia, headache, coryza) and tested positive for SARS-CoV-2 within the first 7 days of symptom onset) (date/time of enrolment must be within the first 7 days of symptom onset). OR no symptoms but tested positive for SARS-CoV-2 within the last 48 hours (date/time of test must be within 48 hours of enrolment): 2. Male or female aged 18 years to 70 years old inclusive at screening; 3. Willing and able to take daily saliva samples; 4. Able to provide full informed consent and willing to comply with trial-related procedures. 1. Known hypersensitivity to any of the active ingredients or excipients in favipiravir and matched placebo, and in lopinavir/ritonavir and matched placebo (See Appendix 2). 2. Chronic liver disease at screening (known cirrhosis of any aetiology, chronic hepatitis (e.g. autoimmune, viral, steatohepatitis), cholangitis or any known elevation of liver aminotransferases with AST or ALT > 3 X ULN)*. 3. Chronic kidney disease (stage 3 or beyond) at screening: eGFR < 60 ml/min/1.73m(2) *. 4. HIV infection, if untreated, detectable viral load or on protease inhibitor therapy. 5. Any clinical condition which the investigator considers would make the participant unsuitable for the trial. 6. Concomitant medications known to interact with favipiravir and matched placebo, and with lopinavir/ritonavir and matched placebo, and carry risk of toxicity for the participant. 7. Current severe illness requiring hospitalisation. 8. Pregnancy and/ or breastfeeding. 9. Eligible female participants of childbearing potential and male participants with a partner of childbearing potential not willing to use highly effective contraceptive measures during the trial and within the time point specified following last trial treatment dose. 10. Participants enrolled in any other interventional drug or vaccine trial (co-enrolment in observational studies is acceptable). 11. Participants who have received the COVID-19 vaccine; *Considering the importance of early treatment of COVID-19 to impact viral load, the absence of known chronic liver/ kidney disease will be confirmed verbally by the participant during pre-screening and Screening/Baseline visit. Safety blood samples will be collected at Screening/Baseline visit (Day 1) and test results will be examined as soon as they become available and within 24 hours. INTERVENTION AND COMPARATOR: Arm 1: Favipiravir + Lopinavir/ritonavir. Arm 2: Favipiravir + Lopinavir/ritonavir placebo. Arm 3: Favipiravir placebo + Lopinavir/ritonavir. Arm 4: Favipiravir placebo + Lopinavir/ritonavir placebo. Oral favipiravir matched placebo at 1800mg twice daily on Day 1, followed by 400mg four (4) times daily from Day 2 to Day 7 PLUS lopinavir/ritonavir matched placebo at 400mg/100mg twice daily on Day 1, followed by 200mg/50mg four (4) times daily from Day 2 to Day 7. MAIN OUTCOMES: The primary outcome is upper respiratory tract viral load at Day 5. Percentage of participants with undetectable upper respiratory tract viral load after 5 days of therapy. Proportion of participants with undetectable stool viral load after 7 days of therapy. Rate of decrease in upper respiratory tract viral load during 7 days of therapy. Duration of fever following commencement of trial medications. Proportion of participants with hepatotoxicity after 7 days of therapy. Proportion of participants with other medication-related toxicity after 7 days of therapy and 14 days post-randomisation. Proportion of participants admitted to hospital with COVID-19 related illness. Proportion of participants admitted to ICU with COVID-19 related illness. Proportion of participants who have died with COVID-19 related illness. Pharmacokinetic and pharmacodynamic analysis of favipiravir. Exploratory: Proportion of participants with deleterious or resistance-conferring mutations in SARS-CoV-2. RANDOMISATION: Participants will be randomised 1:1:1:1 using a concealed online minimisation process, with the following factors: trial site, age (≤ 55 vs > 55 years old), gender, obesity (BMI <30 vs ≥30), symptomatic or asymptomatic, current smoking status (Yes = current smoker, No = ex-smoker, never smoker), ethnicity (Caucasian, other) and presence or absence of comorbidity (defined as diabetes, hypertension, ischaemic heart disease (including previous myocardial infarction), other heart disease (arrhythmia and valvular heart disease), asthma, COPD, other chronic respiratory disease). BLINDING (MASKING): Participants and investigators will both be blinded to treatment allocation (double-blind). NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 240 participants, 60 in each arm. TRIAL STATUS: Protocol version 4.0 dated 7(th) January 2021. Date of first enrolment: October 2020. Recruitment is ongoing, with anticipated finish date of 31(st) March 2021. TRIAL REGISTRATION: The FLARE trial is registered with Clinicaltrials.gov, trial identifying number NCT04499677, date of registration 4(th) August 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05139-2. | Trials | 2021 | LitCov and CORD-19 | |
| 690 | The impact of the COVID-19 pandemic on stress and other psychological factors in pregnant women giving birth during the first wave of the pandemic N/A | Reprod Health | 2022 | LitCov | |
| 691 | A Multiplex and Colorimetric Reverse Transcription Loop-Mediated Isothermal Amplification Assay for Sensitive and Rapid Detection of Novel SARS-CoV-2 Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major threat to public health. Rapid molecular testing for convenient and timely diagnosis of SARS-CoV-2 infections represents a challenge that could help to control the current pandemic and prevent future outbreaks. We aimed to develop and validate a multiplex and colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using lyophilized LAMP reagents for sensitive and rapid detection of SARS-CoV-2. LAMP primers were designed for a set of gene targets identified by a genome-wide comparison of viruses. Primer sets that showed optimal features were combined into a multiplex RT-LAMP assay. Analytical validation included assessment of the limit of detection (LoD), intra- and inter-assay precision, and cross-reaction with other respiratory pathogens. Clinical performance compared to that of real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was assessed using 278 clinical RNA samples isolated from swabs collected from individuals tested for COVID-19. The RT-LAMP assay targeting the RNA-dependent RNA polymerase (RdRp), membrane (M), and ORF1ab genes achieved a comparable LoD (0.65 PFU/mL, CT=34.12) to RT-qPCR and was 10-fold more sensitive than RT-qPCR at detecting viral RNA in clinical samples. Cross-reactivity to other respiratory pathogens was not observed. The multiplex RT-LAMP assay demonstrated a strong robustness and acceptable intra- and inter-assay precision (mean coefficient of variation, 4.75% and 8.30%). Diagnostic sensitivity and specificity values were 100.0% (95% CI: 97.4–100.0%) and 98.6% (95% CI: 94.9–99.8%), respectively, showing high consistency (Cohen’s kappa, 0.986; 95% CI: 0.966–1.000; p<0.0001) compared to RT-qPCR. The novel one-step multiplex RT-LAMP assay is storable at room temperature and showed similar diagnostic accuracy to conventional RT-qPCR, while being faster (<45 min), simpler, and cheaper. The new assay could allow reliable and early diagnosis of SARS-CoV-2 infections in primary health care. It may aid large-scale testing in resource-limited settings, especially if it is integrated into a point-of-care diagnostic device. | Front Cell Infect Microbiol | 2021 | LitCov and CORD-19 | |
| 692 | Comparative Effectiveness of Moderna, Pfizer-BioNTech and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions-United States, March-August 2021 Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization. | MMWR Morb Mortal Wkly Rep | 2021 | LitCov and CORD-19 | |
| 693 | Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening(1,2) to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A–F)—a grouping that is highly concordant with knowledge-based structural classifications(3–5). Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, neutralizing antibodies in groups A–D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and Q493R. Antibodies in group E (for example, S309)(6) and group F (for example, CR3022)(7), which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes. In total, over 85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 and BRII-196 was greatly undermined by Omicron, whereas VIR-7831 and DXP-604 still functioned at a reduced efficacy. Together, our data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus conserved region will remain most effective. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants. | Nature | 2021 | LitCov and CORD-19 | |
| 694 | Disparities in Outpatient and Telehealth Visits During the COVID-19 Pandemic in a Large Integrated Healthcare Organization: Retrospective Cohort Study BACKGROUND: Dramatic decreases in outpatient visits and sudden increases in telehealth visits were observed during the COVID-19 pandemic, but it was unclear whether these changes differed by patient demographics and socioeconomic status. OBJECTIVE: This study aimed to assess the impact of the pandemic on in-person outpatient and telehealth visits (telephone and video) by demographic characteristics and household income in a diverse population. METHODS: We calculated weekly rates of outpatient and telehealth visits by age, sex, race/ethnicity, and neighborhood-level median household income among members of Kaiser Permanente Southern California (KPSC) from January 5, 2020, to October 31, 2020, and the corresponding period in 2019. We estimated the percentage change in visit rates during the early pandemic period (March 22 to April 25, 2020) and the late pandemic period (October 4 to October 31, 2020) from the prepandemic period (January 5 to March 7, 2020) in Poisson regression models for each subgroup while adjusting for seasonality using 2019 data. We examined if the changes in visit rates differed by subgroups statistically by comparing their 95% CIs. RESULTS: Among 4.56 million KPSC members enrolled in January 2020, 15.0% (n=682,947) were ≥65 years old, 51.5% (n=2,345,020) were female, 39.4% (n=1,795,994) were Hispanic, and 7.7% (n=350,721) lived in an area of median household income | J Med Internet Res | 2021 | LitCov and CORD-19 | |
| 695 | The Prevalence of COVID-19 Vaccination and Vaccine Hesitancy in Pregnant Women: An Internet-based Cross-sectional Study in Japan BACKGROUND: Reluctance of people to receive recommended vaccines is a growing concern, as distribution of vaccines is considered critical to ending the COVID-19 pandemic. There is little information regarding pregnant women’s views toward coronavirus vaccination in Japan. Therefore, we investigated the vaccination rate and reasons for vaccination and vaccine hesitancy among pregnant women in Japan. METHODS: We conducted a cross-sectional study involving 1,791 pregnant women using data from the Japan “COVID-19 and Society” Internet Survey, conducted from July to August 2021, and valid response from 1,621 respondents were analyzed. We defined participants with vaccine hesitancy as those who identified with the statement “I do not want to be vaccinated” or “I want to ‘wait and see’ before getting vaccinated.” Multivariate Poisson regression analysis was used to investigate the factors contributing to vaccine hesitancy. RESULTS: The prevalence of vaccination and vaccine hesitancy among pregnant women was 13.4% (n = 217) and 50.9% (n = 825), respectively. The main reasons for hesitancy were concerns about adverse reactions and negative effects on the fetus and breastfeeding. Vaccine hesitancy was significantly associated with the lack of trust in the government (adjusted prevalence ratio, 1.26; 95% confidence interval, 1.03–1.54). Other factors, such as age, educational attainment, and state of emergency declaration, were not associated with vaccine hesitancy. CONCLUSIONS: COVID-19 vaccination is not widespread among pregnant women in Japan, although many vaccines have been shown to be safe in pregnancy. Accurate information dissemination and boosting trust in the government may be important to address vaccine hesitancy among pregnant women. | J Epidemiol | 2022 | LitCov and CORD-19 | |
| 696 | Dynamic IgG seropositivity after rollout of CoronaVac and BNT162b2 COVID-19 vaccines in Chile: a sentinel surveillance study BACKGROUND: By July 14, 2021, 81·3 % of adults (aged ≥18 years) in Chile had received a first SARS-CoV-2 vaccine and 72·3% had received a second SARS-CoV-2 vaccine, with the majority of people given Sinovac's inactivated CoronaVac vaccine (75·3% of vaccines dispensed) or Pfizer–BioNTech's mRNA BNT162b2 vaccine (20·9% of vaccines dispensed). Due to the absence of simultaneous real-world data for these vaccines, we aimed to compare SARS-CoV-2 IgG positivity between vaccines using a dynamic national monitoring strategy. METHODS: From March 12, 2021, 28 testing stations for SARS-CoV-2 IgG detection were installed in hotspots based on cellular-phone mobility tracking within the most populated cities in Chile. Individuals voluntarily approaching the testing stations were invited to do a lateral flow test by finger prick and respond to a questionnaire on sociodemographic characteristics, vaccination status (including type of vaccine if one was received), variables associated with SARS-CoV-2 exposure, and comorbidities. We compared the proportion of individuals testing positive for anti-SARS-CoV-2 IgG across sites by week since vaccination between recipients of CoronaVac and BNT162b2. Unvaccinated participants served as a control population and were matched to vaccinated individuals on the basis of date of presentation to the testing station, gender, and age group. Individuals were excluded from the analysis if they were younger than 18 years, had no declared gender, had an invalid IgG test result, had previously tested positive for SARS-CoV-2 infection on PCR, could not recall their vaccination status, or had been immunised against COVID-19 with vaccines other than CoronaVac or BNT162b2. Here, we report data collected up to July 2, 2021. FINDINGS: Of 64 813 individuals enrolled, 56 261 were included in the final analysis, of whom 33 533 (59·6%) had received at least one dose of the CoronaVac vaccine, 8947 (15·9%) had received at least one dose of the BNT162b2 vaccine, and 13 781 (24·5%) had not received a vaccine. SARS-CoV-2 IgG positivity during week 4 after the first dose of CoronaVac was 28·1% (95% CI 25·0–31·2; 220 of 783 individuals), reaching a peak of 77·4% (75·5–79·3; 1473 of 1902 individuals) during week 3 after the second dose. SARS-CoV-2 IgG positivity during week 4 after the first dose of the BNT162b2 vaccine was 79·4% (75·7–83·1; 367 of 462 individuals), increasing to 96·5% (94·9–98·1; 497 of 515 individuals) during week 3 after the second dose and remaining above 92% until the end of the study. For unvaccinated individuals, IgG seropositivity ranged from 6·0% (4·4–7·6; 49 of 810 individuals) to 18·7% (12·5–24·9; 28 of 150 individuals) during the 5 month period. Regression analyses showed that IgG seropositivity was significantly lower in men than women and in people with diabetes or chronic diseases for CoronaVac vaccine recipients (p<0·0001), and for individuals aged 60 years and older compared with people aged 18–39 years for both vaccines (p<0·0001), 3–16 weeks after the second dose. INTERPRETATION: IgG seropositivity was lower after CoronaVac than after BNT162b2 and declined over time since vaccination for CoronaVac recipients but not BNT162b2 recipients. Prolonged IgG monitoring will allow further evaluation of seropositivity overtime, providing data, in conjunction with effectiveness studies, for possible future re-assessment of vaccination strategies. FUNDING: Instituto Sistemas Complejos de Ingeniería and Ministerio de Salud Chile. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section. | Lancet Infect Dis | 2021 | LitCov and CORD-19 | |
| 697 | Sex Differences in Lung Imaging and SARS-CoV-2 Antibody Responses in a COVID-19 Golden Syrian Hamster Model In the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more severe outcomes are reported in males than in females, including hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of SARS-CoV-2. Adult male and female golden Syrian hamsters (8 to 10 weeks of age) were inoculated intranasally with 10(5) 50% tissue culture infective dose (TCID(50)) of SARS-CoV-2/USA-WA1/2020 and euthanized at several time points during the acute (i.e., virus actively replicating) and recovery (i.e., after the infectious virus has been cleared) phases of infection. There was no mortality, but infected male hamsters experienced greater morbidity, losing a greater percentage of body mass, developed more extensive pneumonia as noted on chest computed tomography, and recovered more slowly than females. Treatment of male hamsters with estradiol did not alter pulmonary damage. Virus titers in respiratory tissues, including nasal turbinates, trachea, and lungs, and pulmonary cytokine concentrations, including interferon-β (IFN-β) and tumor necrosis factor-α (TNF-α), were comparable between the sexes. However, during the recovery phase of infection, females mounted 2-fold greater IgM, IgG, and IgA responses against the receptor-binding domain of the spike protein (S-RBD) in both plasma and respiratory tissues. Female hamsters also had significantly greater IgG antibodies against whole-inactivated SARS-CoV-2 and mutant S-RBDs as well as virus-neutralizing antibodies in plasma. The development of an animal model to study COVID-19 sex differences will allow for a greater mechanistic understanding of the SARS-CoV-2-associated sex differences seen in the human population. | mBio | 2021 | LitCov and CORD-19 | |
| 698 | COVID-19 Pneumonia Diagnosis Using a Simple 2D Deep Learning Framework With a Single Chest CT Image: Model Development and Validation BACKGROUND: Coronavirus disease (COVID-19) has spread explosively worldwide since the beginning of 2020. According to a multinational consensus statement from the Fleischner Society, computed tomography (CT) is a relevant screening tool due to its higher sensitivity for detecting early pneumonic changes. However, physicians are extremely occupied fighting COVID-19 in this era of worldwide crisis. Thus, it is crucial to accelerate the development of an artificial intelligence (AI) diagnostic tool to support physicians. OBJECTIVE: We aimed to rapidly develop an AI technique to diagnose COVID-19 pneumonia in CT images and differentiate it from non–COVID-19 pneumonia and nonpneumonia diseases. METHODS: A simple 2D deep learning framework, named the fast-track COVID-19 classification network (FCONet), was developed to diagnose COVID-19 pneumonia based on a single chest CT image. FCONet was developed by transfer learning using one of four state-of-the-art pretrained deep learning models (VGG16, ResNet-50, Inception-v3, or Xception) as a backbone. For training and testing of FCONet, we collected 3993 chest CT images of patients with COVID-19 pneumonia, other pneumonia, and nonpneumonia diseases from Wonkwang University Hospital, Chonnam National University Hospital, and the Italian Society of Medical and Interventional Radiology public database. These CT images were split into a training set and a testing set at a ratio of 8:2. For the testing data set, the diagnostic performance of the four pretrained FCONet models to diagnose COVID-19 pneumonia was compared. In addition, we tested the FCONet models on an external testing data set extracted from embedded low-quality chest CT images of COVID-19 pneumonia in recently published papers. RESULTS: Among the four pretrained models of FCONet, ResNet-50 showed excellent diagnostic performance (sensitivity 99.58%, specificity 100.00%, and accuracy 99.87%) and outperformed the other three pretrained models in the testing data set. In the additional external testing data set using low-quality CT images, the detection accuracy of the ResNet-50 model was the highest (96.97%), followed by Xception, Inception-v3, and VGG16 (90.71%, 89.38%, and 87.12%, respectively). CONCLUSIONS: FCONet, a simple 2D deep learning framework based on a single chest CT image, provides excellent diagnostic performance in detecting COVID-19 pneumonia. Based on our testing data set, the FCONet model based on ResNet-50 appears to be the best model, as it outperformed other FCONet models based on VGG16, Xception, and Inception-v3. | J Med Internet Res | 2020 | LitCov and CORD-19 | |
| 699 | Interaction of SARS-CoV-2 and Other Coronavirus With ACE (Angiotensin-Converting Enzyme)-2 as Their Main Receptor: Therapeutic Implications Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 originated from Wuhan, China, in December 2019 and rapidly spread to other areas worldwide. Since then, coronavirus disease 2019 (COVID-19) has reached pandemic proportions with >570 000 deaths globally by mid-July 2020. The magnitude of the outbreak and the potentially severe clinical course of COVID-19 has led to a burst of scientific research on this novel coronavirus and its host receptor ACE (angiotensin-converting enzyme)-2. ACE2 is a homolog of the ACE that acts on several substrates in the renin-Ang (angiotensin) system. With unprecedented speed, scientific research has solved the structure of SARS-CoV-2 and imaged its binding with the ACE2 receptor. In SARS-CoV-2 infection, the viral S (spike) protein receptor-binding domain binds to ACE2 to enter the host cell. ACE2 expression in the lungs is relatively low, but it is present in type II pneumocytes—a cell type also endowed with TMPRSS2 (transmembrane protease serine 2). This protease is critical for priming the SARS-CoV-2 S protein to complex with ACE2 and enter the cells. Herein, we review the current understanding of the interaction of SARS-CoV-2 with ACE2 as it has rapidly unfolded over the last months. While it should not be assumed that we have a complete picture of SARS-CoV-2 mechanism of infection and its interaction with ACE2, much has been learned with clear therapeutic implications. Potential therapies aimed at intercepting SARS-CoV-2 from reaching the full-length membrane-bound ACE2 receptor using soluble ACE2 protein and other potential approaches are briefly discussed as well. | Hypertension | 2020 | LitCov and CORD-19 | |
| 700 | Broad respiratory testing to identify SARS-CoV-2 viral co-circulation and inform diagnostic stewardship in the COVID-19 pandemic BACKGROUND: SARS-CoV-2 infection can present with a broad clinical differential that includes many other respiratory viruses; therefore, accurate tests are crucial to distinguish true COVID-19 cases from pathogens that do not require urgent public health interventions. Co-circulation of other respiratory viruses is largely unknown during the COVID-19 pandemic but would inform strategies to rapidly and accurately test patients with respiratory symptoms. METHODS: This study retrospectively examined 298,415 respiratory specimens collected from symptomatic patients for SARS-CoV-2 testing in the three months since COVID-19 was initially documented in the province of Alberta, Canada (March-May, 2020). By focusing on 52,285 specimens that were also tested with the Luminex Respiratory Pathogen Panel for 17 other pathogens, this study examines the prevalence of 18 potentially co-circulating pathogens and their relative rates in prior years versus since COVID-19 emerged, including four endemic coronaviruses. RESULTS: SARS-CoV-2 was identified in 2.2% of all specimens. Parallel broad multiplex testing detected additional pathogens in only 3.4% of these SARS-CoV-2-positive specimens: significantly less than in SARS-CoV-2-negative specimens (p < 0.0001), suggesting very low rates of SARS-CoV-2 co-infection. Furthermore, the overall co-infection rate was significantly lower among specimens with SARS-CoV-2 detected (p < 0.0001). Finally, less than 0.005% of all specimens tested positive for both SARS-CoV-2 and any of the four endemic coronaviruses tested, strongly suggesting neither co-infection nor cross-reactivity between these coronaviruses. CONCLUSIONS: Broad respiratory pathogen testing rarely detected additional pathogens in SARS-CoV-2-positive specimens. While helpful to understand co-circulation of respiratory viruses causing similar symptoms as COVID-19, ultimately these broad tests were resource-intensive and inflexible in a time when clinical laboratories face unprecedented demand for respiratory virus testing, with further increases expected during influenza season. A transition from broad, multiplex tests toward streamlined diagnostic algorithms targeting respiratory pathogens of public health concern could simultaneously reduce the overall burden on clinical laboratories while prioritizing testing of pathogens of public health importance. This is particularly valuable with ongoing strains on testing resources, exacerbated during influenza seasons. | Virol J | 2021 | LitCov and CORD-19 |
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(3) Currently tweets of June 23rd to June 29th 2022 have been considered.