\ BIP! Finder for COVID-19 - Impact-based ranking

BIP! Finder for COVID-19

This version of BIP! Finder aims to ease the exploration of COVID-19-related literature by enabling ranking articles based on various impact metrics.

Last Update: 18 - 01 - 2023 (628506 entries)

Provided impact measures:
Popularity: Citation-based measure reflecting the current impact.
Influence: Citation-based measure reflecting the total impact.
Reader Attention: The current number of Mendeley readers.
Social Media Attention: The number of recent tweets related to this article.
*More details on these impact measures can be found here.
Score interpretations:
Exceptional score (in top 0.01%).
Substantial score (in top 1%).
Average score (in bottom 99%).
Score not available.
Main data sources:
CORD-19 dataset(1) (list of papers)
LitCovid hub(2) (list of papers)
PMC & PubMed (citations)
Mendeley (number of readers)
COVID-19-TweetIDs(3) (tweets)

Use:  Impact  Relevance & Impact
TitleVenueYearImpactSource
5601Model for utilizing distance learning post-COVID-19 using (PACT)™ a cross sectional qualitative study  

BACKGROUND: COVID − 19 pandemic pressured medical schools globally to shift to Distance learning (DL) as an alternative way to ensure that the content delivered is satisfactory for student progression. AIM OF THE WORK: This work aims at mapping priorities for post-COVID planning for better balance between distance learning and face to face learning. METHODS: This qualitative study aimed to develop a model for utilizing DL using The Polarity Approach for Continuity and Transformation (PACT)™. A virtual mapping session was held with 79 faculty from 19 countries. They worked in small groups to determine upsides and downsides of face-to-face and DL subsequently. An initial polarity map was generated identifying five tension areas; Faculty, Students, Curriculum, Social aspects and Logistics. A 63-item assessment tool was generated based on this map, piloted and then distributed as a self-administered assessment. The outcomes of this assessment were utilized for another mapping session to discuss warning signs and action steps to maintain upsides and avoid downsides of each pole. RESULTS: Participants agreed that face-to-face teaching allows them to inspire students and have meaningful connections with them. They also agreed that DL provides a good environment for most students. However, students with financial challenges and special needs may not have equal opportunities to access technology. As regards social issues, participants agreed that face-to-face learning provides a better chance for professionalism through enhanced team-work. Cognitive, communication and clinical skills are best achieved in face-to-face. Participants agreed that logistics for conducting DL are much more complicated when compared to face-to-face learning. Participants identified around 10 warning signs for each method that need to be continuously monitored in order to minimize the drawbacks of over focusing on one pole at the expense of the other. Action steps were determined to ensure optimized use of in either method. CONCLUSION: In order to plan for the future, we need to understand the dynamics of education within the context of polarities. Educators need to understand that the choice of DL, although was imposed as a no-alternative solution during the COVID era, yet it has always existed as a possible alternative and will continue to exist after this era. The value of polarity mapping and leveraging allows us to maximize the benefit of each method and guide educators’ decisions to minimize the downsides for the good of the learning process.

BMC Med Educ2020       LitCov and CORD-19
5602Prediction of death status on the course of treatment in SARS-COV-2 patients with deep learning and machine learning methods  

BACKGROUND AND OBJECTIVE: The new type of Coronavirus (2019-nCov) epidemic spread rapidly, causing more than 250 thousand deaths worldwide. The virus, which first appeared as a sign of pneumonia, was later called the SARS-COV-2 with Severe Acute Respiratory Syndrome by the World Health Organization. The SARS-COV-2 virus is triggered by binding to the Angiotensin-Converting Enzyme 2 (ACE 2) inhibitor, which is vital in cardiovascular diseases and the immune system, especially in conditions such as cerebrovascular, hypertension, and diabetes. This study aims to evaluate the prediction performance of death status based on the demographic/clinical factors (including COVID-19 severity) by data mining methods. METHODS: The dataset consists of 1603 SARS-COV-2 patients and 13 variables obtained from an open-source web address. The current dataset contains age, gender, chronic disease (hypertension, diabetes, renal, cardiovascular, etc.), some enzymes (ACE, angiotensin II receptor blockers), and COVID-19 severity, which are used to predict death status using deep learning and machine learning approaches (random forest, k-nearest neighbor, extreme gradient boosting [XGBoost]). A grid search algorithm tunes hyperparameters of the models, and predictions are assessed through performance metrics. Steps of knowledge discovery in databases are applied to obtain the relevant information. RESULTS: The accuracy rate of deep learning (97.15%) was more successful than the accuracy rate based on classical machine learning (92.15% for RF and 93.4% for k-NN), but the ensemble classifier XGBoost method gave the highest accuracy (99.7%). While COVID-19 severity and age calculated from XGBoost were the two most important factors associated with death status, the most determining variables for death status estimated from deep learning were COVID-19 severity and hypertension. CONCLUSIONS: The proposed model (XGBoost) achieved the best prediction of death status based on the factors as compared to the other algorithms. The results of this study can guide patients with certain variables to take early measures and access preventive health care services before they become infected with the virus.

Comput Methods Programs Biomed2021       LitCov and CORD-19
5603Molecular insights into the binding variance of the SARS-CoV-2 spike with human, cat and dog ACE2 proteins  

N/A

Phys Chem Chem Phys2021       LitCov and CORD-19
5604Fear of the coronavirus: Predictors in an online study conducted in March 2020  

Fear is an adaptive response in the presence of danger. However, when threat is uncertain and continuous, as in the current coronavirus disease (COVID-19) pandemic, fear can become chronic and burdensome. To identify predictors of fear of the coronavirus, we conducted an online survey (N = 439) three days after the World Health Organization declared the coronavirus outbreak a pandemic (i.e., between March 14 and 17, 2020). Fear of the coronavirus was assessed with the newly developed Fear of the Coronavirus Questionnaire (FCQ) consisting of eight questions pertaining to different dimensions of fear (e.g., subjective worry, safety behaviors, preferential attention), and an open-ended question. The predictors included psychological vulnerability factors (i.e., intolerance of uncertainty, worry, and health anxiety), media exposure, and personal relevance (i.e., personal health, risk for loved ones, and risk control). We found four predictors for the FCQ in a simultaneous regression analysis: health anxiety, regular media use, social media use, and risks for loved ones (R(2) = .37). Furthermore, 16 different topics of concern were identified based participants’ open-ended responses, including the health of loved ones, health care systems overload, and economic consequences. We discuss the relevance of our findings for managing people’s fear of the coronavirus.

J Anxiety Disord2020       LitCov and CORD-19
5605Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients  

BACKGROUND: Due to the general susceptibility of new coronaviruses, the clinical characteristics and outcomes of elderly and young patients may be different. OBJECTIVE: To analyze the clinical characteristics of elderly patients with 2019 new-type coronavirus pneumonia (COVID-19). METHODS: This is a retrospective study of patients with new coronavirus pneumonia (COVID-19) who were hospitalized in Hainan Provincial People's Hospital from January 15, 2020 to February 18, 2020. Compare the clinical characteristics of elderly with Young and Middle-aged patients. RESULTS: A total of 56 patients were enrolled 18 elderly patients (32.14%), and 38 young and middle-aged patients (67.86%). The most common symptoms in both groups were fever, followed by cough and sputum. Four patients in the elderly group received negative pressure ICU for mechanical ventilation, and five patients in the young and middle-aged group. One patient died in the elderly group (5.56%), and two patients died in the young and middle-aged group (5.26%). The PSI score of the elderly group was higher than that of the young and middle-aged group (P < 0.001). The proportion of patients with PSI grades IV and V was significantly higher in the elderly group than in the young and middle-aged group (P < 0.05). The proportion of multiple lobe involvement in the elderly group was higher than that in the young and middle-aged group (P < 0.001), and there was no difference in single lobe lesions between the two groups. The proportion of lymphocytes in the elderly group was significantly lower than that in the young and middle-aged group (P < 0.001), and the C-reactive protein was significantly higher in the young group (P < 0.001). The Lopinavir and Ritonavir Tablets, Chinese medicine, oxygen therapy, and mechanical ventilation were statistically different in the elderly group and the young and middle-aged group, and the P values were all <0.05. INTERPRETATION: The mortality of elderly patients with COVID-19 is higher than that of young and middle-aged patients, and the proportion of patients with PSI grade IV and V is significantly higher than that of young and middle-aged patients. Elderly patients with COVID-19 are more likely to progress to severe disease.

J Infect2020       LitCov and CORD-19
5606Enhancing COVID-19 Vaccines Acceptance: Results from a Survey on Vaccine Hesitancy in Northern Italy  

In March 2021, the coronavirus disease 2019 (COVID-19) pandemic still poses a threat to the global population, and is a public health challenge that needs to be overcome. Now more than ever, action is needed to tackle vaccine hesitancy, especially in light of the availability of effective and safe vaccines. A cross-sectional online survey was carried out on a representative random sample of 1011 citizens from the Emilia-Romagna region, in Italy, in January 2021. The questionnaire collected information on socio-demographics, comorbidities, past vaccination refusal, COVID-19-related experiences, risk perception of infection, and likelihood to accept COVID-19 vaccination. Multiple logistic regression analyses and classification tree analyses were performed to identify significant predictors of vaccine hesitancy and to distinguish groups with different levels of hesitancy. Overall, 31.1% of the sample reported hesitancy. Past vaccination refusal was the key discriminating variable followed by perceived risk of infection. Other significant predictors of hesitancy were: ages between 35 and 54 years, female gender, low educational level, low income, and absence of comorbidities. The most common concerns about the COVID-19 vaccine involved safety (54%) and efficacy (27%). Studying the main determinants of vaccine hesitancy can help with targeting vaccination strategies, in order to gain widespread acceptance—a key path to ensure a rapid way out of the current pandemic emergency.

Vaccines (Basel)2021       LitCov and CORD-19
5607Ultra-sensitive and high-throughput CRISPR-p owered COVID-19 diagnosis  

Recent research suggests that SARS-CoV-2-infected individuals can be highly infectious while asymptomatic or pre-symptomatic, and that an infected person may infect 5.6 other individuals on average. This situation highlights the need for rapid, sensitive SARS-CoV-2 diagnostic assays capable of high-throughput operation that can preferably utilize existing equipment to facilitate broad, large-scale screening efforts. We have developed a CRISPR-based assay that can meet all these criteria. This assay utilizes a custom CRISPR Cas12a/gRNA complex and a fluorescent probe to amplify target amplicons produced by standard RT-PCR or isothermal recombinase polymerase amplification (RPA), to allow sensitive detection at sites not equipped with real-time PCR systems required for qPCR diagnostics. We found this approach allowed sensitive and robust detection of SARS-CoV-2 positive samples, with a sample-to-answer time of ∼50 min, and a limit of detection of 2 copies per sample. CRISPR assay diagnostic results obtained nasal swab samples of individuals with suspected COVID-19 cases were comparable to paired results from a CDC-approved qPCR assay performed in a state testing lab, and superior to those produced by same assay in a clinical lab, where the qPCR assay exhibited multiple invalid or inconclusive results. Our assay also demonstrated greater analytical sensitivity and more robust diagnostic performance than other recently reported CRISPR-based assays. Based on these findings, we believe that a CRISPR-based fluorescent application has potential to improve current COVID-19 screening efforts.

Biosens Bioelectron2020       LitCov and CORD-19
5608Mental Health Outcomes in Australian Healthcare and Aged-Care Workers during the Second Year of the COVID-19 Pandemic  

Objective: the COVID-19 pandemic has incurred psychological risks for healthcare workers (HCWs). We established a Victorian HCW cohort (the Coronavirus in Victorian Healthcare and Aged-Care Workers (COVIC-HA) cohort study) to examine COVID-19 impacts on HCWs and assess organisational responses over time. Methods: mixed-methods cohort study, with baseline data collected via an online survey (7 May–18 July 2021) across four healthcare settings: ambulance, hospitals, primary care, and residential aged-care. Outcomes included self-reported symptoms of depression, anxiety, post-traumatic stress (PTS), wellbeing, burnout, and resilience, measured using validated tools. Work and home-related COVID-19 impacts and perceptions of workplace responses were also captured. Results: among 984 HCWs, symptoms of clinically significant depression, anxiety, and PTS were reported by 22.5%, 14.0%, and 20.4%, respectively, highest among paramedics and nurses. Emotional exhaustion reflecting moderate–severe burnout was reported by 65.1%. Concerns about contracting COVID-19 at work and transmitting COVID-19 were common, but 91.2% felt well-informed on workplace changes and 78.3% reported that support services were available. Conclusions: Australian HCWs employed during 2021 experienced adverse mental health outcomes, with prevalence differences observed according to occupation. Longitudinal evidence is needed to inform workplace strategies that support the physical and mental wellbeing of HCWs at organisational and state policy levels.

Int J Environ Res Public Healt2022       LitCov and CORD-19
5609Ethnic/racial minorities' and migrants' access to COVID-19 vaccines: A systematic review of barriers and facilitators  

BACKGROUND: There are widespread concerns that ethnic minorities and migrants may have inadequate access to COVID-19 vaccines. . Improving vaccine uptake among these vulnerable groups is important towards controlling the spread of COVID-19 and reducing unnecessary mortality. Here we perform a systematic review of ethnic minorities’ and migrants’ access to and acceptance of COVID-19 vaccines. METHODS: We searched PubMed and Web of Science databases for papers published between 1 January 2020 and 7 October 2021. Studies were included if they were peer-reviewed articles; written in English, included data or estimates of ethnic minorities’ or migrants’ access to vaccines; and employed either qualitative or quantitative methods. Of a total of 248 studies screened, 33 met these criteria and included in the final sample. Risk of bias in the included studies was assessed using Newcastle Ottawa Scale and Critical Appraisal Skills Program tools. We conducted a Synthesis Without Meta-analysis for quantitative studies and a Framework synthesis for qualitative studies. RESULTS: 31 of the included studies were conducted in high-income countries, including in the US (n = 17 studies), UK (n = 10), Qatar (n = 2), Israel (n = 1) and France (n = 1). One study was in an upper middle-income country -China (n=1) and another covered multiple countries (n = 1). 26 studies reported outcomes for ethnic minorities while 9 studies reported on migrants. Most of the studies were quantitative -cross sectional studies (n=24) and ecological (n=4). The remaining were qualitative (n=4) and mixed methods (n=1). There was consistent evidence of elevated levels of COVID-19 vaccine hesitancy among Black/Afro-Caribbean groups in the US and UK, while studies of Hispanic/Latino populations in the US and Asian populations in the UK provided mixed pictures, with levels higher, lower, or the same as their White counterparts. Asians in the US had the highest COVID-19 vaccine acceptance compared to other ethnic groups. There was higher vaccine acceptance among migrant groups in Qatar and China than in the general population. However, migrants to the UK experienced barriers to vaccine access, mainly attributed to language and communication issues. Lack of confidence, mainly due to mistrust of government and health systems coupled with poor communication were the main barriers to uptake among Black ethnic minorities and migrants. CONCLUSIONS: Our study found that low confidence in COVID-19 vaccines among Black ethnic minorities driven by mistrust and safety concerns led to high vaccine hesitancy in this group. Such vaccine hesitancy rates constitute a major barrier to COVID-19 vaccine uptake among this ethnic minority. For migrants, convenience factors such as language barriers, fear of deportation and reduced physical access reduced access to COVID-19 vaccines. Building trust, reducing physical barriers and improving communication and transparency about vaccine development through healthcare workers, religious and community leaders can improve access and facilitate uptake of COVID-19 vaccines among ethnic minority and migrant communities.

J Migr Health2022       LitCov and CORD-19
5610Distribution of SARS-CoV-2 Variants in a Large Integrated Healthcare System-California, March-July 2021  

Data from observational studies demonstrate that variants of SARS-CoV-2, the virus that causes COVID-19, have evolved rapidly across many countries (1,2). The SARS-CoV-2 B.1.617.2 (Delta) variant of concern is more transmissible than previously identified variants,* and as of September 2021, is the predominant variant in the United States.† Studies characterizing the distribution and severity of illness caused by SARS-CoV-2 variants, particularly the Delta variant, are limited in the United States (3), and are subject to limitations related to study setting, specimen collection, study population, or study period (4-7). This study used whole genome sequencing (WGS) data on SARS-CoV-2-positive specimens collected across Kaiser Permanente Southern California (KPSC), a large integrated health care system, to describe the distribution and risk of hospitalization associated with SARS-CoV-2 variants during March 4-July 21, 2021, by patient vaccination status. Among 13,039 SARS-CoV-2-positive specimens identified from KPSC patients during this period, 6,798 (52%) were sequenced and included in this report. Of these, 5,994 (88%) were collected from unvaccinated persons, 648 (10%) from fully vaccinated persons, and 156 (2%) from partially vaccinated persons. Among all sequenced specimens, the weekly percentage of B.1.1.7 (Alpha) variant infections increased from 20% to 67% during March 4-May 19, 2021. During April 15-July 21, 2021, the weekly percentage of Delta variant infections increased from 0% to 95%. During March 4-July 21, 2021, the weekly percentage of variants was similar among fully vaccinated and unvaccinated persons, but the Delta variant was more commonly identified among vaccinated persons then unvaccinated persons overall, relative to other variants. The Delta variant was more prevalent among younger persons, with the highest percentage (55%) identified among persons aged 18-44 years. Infections attributed to the Delta variant were also more commonly identified among non-Hispanic Black persons, relative to other variants. These findings reinforce the importance of continued monitoring of SARS-CoV-2 variants and implementing multiple COVID-19 prevention strategies, particularly during the current period in which Delta is the predominant variant circulating in the United States.

MMWR Morb Mortal Wkly Rep2021       LitCov and CORD-19
5611Inequalities in excess premature mortality in England during the COVID-19 pandemic: a cross-sectional analysis of cumulative excess mortality by area deprivation and ethnicity  

OBJECTIVES: To examine magnitude of the impact of the COVID-19 pandemic on inequalities in premature mortality in England by deprivation and ethnicity. DESIGN: A statistical model to estimate increased mortality in population subgroups during the COVID-19 pandemic by comparing observed with expected mortality in each group based on trends over the previous 5 years. SETTING: Information on deaths registered in England since 2015 was used, including age, sex, area of residence and cause of death. Ethnicity was obtained from Hospital Episode Statistics records linked to death data. PARTICIPANTS: Population study of England, including all 569 824 deaths from all causes registered between 21 March 2020 and 26 February 2021. MAIN OUTCOME MEASURES: Excess mortality in each subgroup over and above the number expected based on trends in mortality in that group over the previous 5 years. RESULTS: The gradient in excess mortality by area deprivation was greater in the under 75s (the most deprived areas had 1.25 times as many deaths as expected, least deprived 1.14) than in all ages (most deprived had 1.24 times as many deaths as expected, least deprived 1.20). Among the black and Asian groups, all area deprivation quintiles had significantly larger excesses than white groups in the most deprived quintiles and there were no clear gradients across quintiles. Among the white group, only those in the most deprived quintile had more excess deaths than deaths directly involving COVID-19. CONCLUSION: The COVID-19 pandemic has widened inequalities in premature mortality by area deprivation. Among those under 75, the direct and indirect effects of the pandemic on deaths have disproportionately impacted ethnic minority groups irrespective of area deprivation, and the white group the most deprived areas. Statistics limited to deaths directly involving COVID-19 understate the pandemic’s impact on inequalities by area deprivation and ethnic group at younger ages.

BMJ Open2021       LitCov and CORD-19
5612Humoral and cellular response to SARS-CoV-2 BNT162b2 mRNA vaccine in hemodialysis patients  

BACKGROUND: Hemodialysis (HD) patients have an increased risk of acquiring infections due to many health care contacts and may, in addition, have a suboptimal response to vaccination and a high mortality from Covid-19 infection. METHODS: In 50 HD patients (mean age 69.4 years, 62% men) administration of SARS-CoV-2BNT162b2 mRNA vaccine began in Dec 2020 and the immune response was evaluated 7–15 weeks after the last dose. Levels of Covid-19 (SARS-CoV-2) IgG antibody against the nucleocapsid antigen (anti-N) and the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using ELISPOT technology were evaluated. RESULTS: Out of 50 patients, anti-S IgG antibodies indicating a vaccine effect or previous Covid-19 infection, were detected in 37 (74%), 5 (10%) had a borderline response and 8 (16%) were negative after two doses of vaccine. T-cell responses were detected in 29 (58%). Of the 37 patients with anti-S antibodies, 25 (68%) had a measurable T-cell response. 2 (40%) out of 5 patients with borderline anti-S and 2 (25%) without anti-S had a concomitant T-cell response. Twenty-seven (54%) had both an antibody and T-cell response. IgG antibodies to anti-N indicating a previous Covid-19 disease were detected in 7 (14%) patients. CONCLUSIONS: Most HD patients develop a B- and/or T-cell response after vaccination against Covid-19 but approx. 20% had a limited immunological response. T-cell reactivity against Covid-19 was only present in a few of the anti-S antibody negative patients.

BMC Immunol2021       LitCov and CORD-19
5613Cross-sectional study on COVID-19 vaccine hesitancy and determinants in healthcare students: interdisciplinary trainings on vaccination are needed  

BACKGROUND: To ensure the success of COVID-19 vaccination, public authorities need to have the support of the entire population and build vaccine confidence. Identifying and understanding the determinants of vaccine acceptance is essential for conducting vaccine strategy. The aim was to estimate vaccine hesitancy among healthcare students in France and to investigate the associated factors. METHODS: A web-based cross-sectional study was conducted in a large French University in greater Paris area, among 4927 healthcare students from the different training courses such as medicine studies, midwifery studies, physiotherapy studies, nurse studies and others health studies. The study was conducted between January 21 and February 8, 2021 based on a questionnaire including 25 single or multiple-choice questions, made using the free software Limesurvey. The link of the questionnaire was distributed to the students by the teachers and the student associations. The SAGE group definition of vaccine hesitancy was used. All estimates were weighted using the gender and training courses category of all healthcare students registered for the 2020–2021 year. Crude and adjusted weighted odds ratio (wOR) and 95% confidence interval (95%CI) were estimated using logistic regression. RESULTS: A total of 1465 healthcare students answered. A proportion of 44.5% (95%CI = [41.7–47.3]) of them were considered as hesitant. Women were more hesitant (50.9, 95%CI = [48.0–53.9]) than men (21.6, 95%CI = [15.2–28.0]). Vaccine hesitancy was significantly associated with gender (wOR = 0.27, 95%CI = [0.18–0.39]) and training courses: medical students were less likely to be hesitant than students in the common and first year of several health studies (wOR = 0.48, 95%CI = [0.33–0.70]) while nursing students were more than 5 times more likely to be hesitant (wOR = 5.20, 95%CI = [3.71–7.28]). Students who did an internship during the epidemic (wOR = 0.53, 95%CI = [0.41–0.69]) and who downloaded the mobile contact-tracing mobile app “TousAntiCovid” (wOR = 0.34, 95%CI = [0.26–0.44]) were significantly less likely to be hesitant. CONCLUSIONS: Overall vaccine hesitancy among healthcare students was high, substantial differences were found between training courses. To reduce these disparities, interdisciplinary lectures on vaccines for all healthcare students may be implemented and evaluated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12909-022-03343-5.

BMC Med Educ2022       LitCov and CORD-19
5614The effects of the COVID-19 pandemic on the physical activity of the Thai population: Evidence from Thailand's Surveillance on Physical Activity 2020  

BACKGROUND: The coronavirus disease (COVID-19) pandemic has undoubtedly disrupted the physical activity (PA) of the Thai population. This study examined the effect of the COVID-19 pandemic on moderate-to-vigorous PA (MVPA) of Thai adults and assessed the effects of the national curfew policy and health promotion campaigns in influencing PA during the pandemic. METHODS: Thailand's Surveillance on Physical Activity (SPA) 2019 and 2020 datasets were employed to compare the PA level of Thai adults aged 18–64 years before and during the COVID-19 pandemic. Samples of 4460 respondents from SPA 2019 and 4482 respondents from SPA 2020 were included in the analysis. Global Physical Activity Questionnaires (GPAQ) Version 2.0 was used to measure PA in both periods. Sufficient MVPA for adults was defined based on the recommendation of 75 min of vigorous PA or a combination of 150 min of MVPA per week. RESULTS: The proportion of Thai adults who had sufficient MVPA declined from 74.6% before the pandemic to 54.7% during the pandemic, and that decline was accompanied by a reduction in the cumulative minutes of MVPA from 580 to 420. During the COVID-19 pandemic, male and middle-aged individuals were 1.3 and 1.1 times more likely to have sufficient MVPA, respectively. Those who were unemployed, resided in an urban area, and/or had chronic disease(s) were 27%, 13%, and 29% less likely to meet the recommended level of PA during the pandemic, respectively. Those who were exposed to the Fit from Home (FFH) campaign were 1.4 times more likely to have sufficient MVPA. CONCLUSION: The pandemic measures imposed by the government have reduced the cumulative minutes of work-related PA, transportation PA, and recreational PA and have slowed Thailand's progress toward its PA goals. Although the FFH campaign has probably contributed to a slight increase in MVPA, it will take some time for Thais to return to the pre-COVID-19 level of PA. Health promotion messages need to be continuously delivered to reduce irrational fear of infection and to boost the PA level of the Thai population as a health-promoting intervention.

J Sport Health Sci2020       LitCov and CORD-19
5615Understanding the Driving Forces That Trigger Mutations in SARS-CoV-2: Mutational Energetics and the Role of Arginine Blockers in COVID-19 Therapy  

SARS-CoV-2 is a global challenge due to its ability to mutate into variants that spread more rapidly than the wild-type virus. Because the molecular biology of this virus has been studied in such great detail, it represents an archetypal paradigm for research into new antiviral drug therapies. The rapid evolution of SARS-CoV-2 in the human population is driven, in part, by mutations in the receptor-binding domain (RBD) of the spike (S-) protein, some of which enable tighter binding to angiotensin-converting enzyme (ACE2). More stable RBD-ACE2 association is coupled with accelerated hydrolysis of furin and 3CLpro cleavage sites that augment infection. Non-RBD and non-interfacial mutations assist the S-protein in adopting thermodynamically favorable conformations for stronger binding. The driving forces of key mutations for Alpha, Beta, Gamma, Delta, Kappa, Lambda and Omicron variants, which stabilize the RBD-ACE2 complex, are investigated by free-energy computational approaches, as well as equilibrium and steered molecular dynamic simulations. Considered also are the structural hydropathy traits of the residues in the interface between SARS-CoV-2 RBD and ACE2 protein. Salt bridges and π-π interactions are critical forces that create stronger complexes between the RBD and ACE2. The trend of mutations is the replacement of non-polar hydrophobic interactions with polar hydrophilic interactions, which enhance binding of RBD with ACE2. However, this is not always the case, as conformational landscapes also contribute to a stronger binding. Arginine, the most polar and hydrophilic among the natural amino acids, is the most aggressive mutant amino acid for stronger binding. Arginine blockers, such as traditional sartans that bear anionic tetrazoles and carboxylates, may be ideal candidate drugs for retarding viral infection by weakening S-protein RBD binding to ACE2 and discouraging hydrolysis of cleavage sites. Based on our computational results it is suggested that a new generation of “supersartans”, called “bisartans”, bearing two anionic biphenyl-tetrazole pharmacophores, are superior to carboxylates in terms of their interactions with viral targets, suggesting their potential as drugs in the treatment of COVID-19. In Brief: This in silico study reviews our understanding of molecular driving forces that trigger mutations in the SARS-CoV-2 virus. It also reports further studies on a new class of “supersartans” referred to herein as “bisartans”, bearing two anionic biphenyltetrazole moieties that show potential in models for blocking critical amino acids of mutants, such as arginine, in the Delta variant. Bisartans may also act at other targets essential for viral infection and replication (i.e., ACE2, furin cleavage site and 3CLpro), rendering them potential new drugs for additional experimentation and translation to human clinical trials.

Viruses2022       LitCov and CORD-19
5616Microglia Do Not Restrict SARS-CoV-2 Replication following Infection of the Central Nervous System of K18-Human ACE2 Transgenic Mice  

Unlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not exhibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited antiviral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, ∼50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine (Cxcl9, Cxcl10, Ccl2, Ccl5 and Ccl19) and cytokine (Ifn-λ and Tnf-α) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Microglia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work demonstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease. IMPORTANCE Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the role of microglia in aiding in host defense following experimental infection of the central nervous system (CNS) of K18-hACE2 with SARS-CoV-2, the causative agent of COVID-19. Neurologic symptoms that range in severity are common in COVID-19 patients and understanding immune responses that contribute to restricting neurologic disease can provide important insight into better understanding consequences associated with SARS-CoV-2 infection of the CNS.

J Virol2022       LitCov and CORD-19
5617The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach  

[Image: see text] SARS-CoV-2 has caused the largest pandemic of the twenty-first century (COVID-19), threatening the life and economy of all countries in the world. The identification of novel therapies and vaccines that can mitigate or control this global health threat is among the most important challenges facing biomedical sciences. To construct a long-term strategy to fight both SARS-CoV-2 and other possible future threats from coronaviruses, it is critical to understand the molecular mechanisms underlying the virus action. The viral entry and associated infectivity stems from the formation of the SARS-CoV-2 spike protein complex with angiotensin-converting enzyme 2 (ACE2). The detection of putative allosteric sites on the viral spike protein molecule can be used to elucidate the molecular pathways that can be targeted with allosteric drugs to weaken the spike-ACE2 interaction and, thus, reduce viral infectivity. In this study, we present the results of the application of different computational methods aimed at detecting allosteric sites on the SARS-CoV-2 spike protein. The adopted tools consisted of the protein contact networks (PCNs), SEPAS (Affinity by Flexibility), and perturbation response scanning (PRS) based on elastic network modes. All of these methods were applied to the ACE2 complex with both the SARS-CoV2 and SARS-CoV spike proteins. All of the adopted analyses converged toward a specific region (allosteric modulation region [AMR]), present in both complexes and predicted to act as an allosteric site modulating the binding of the spike protein with ACE2. Preliminary results on hepcidin (a molecule with strong structural and sequence with AMR) indicated an inhibitory effect on the binding affinity of the spike protein toward the ACE2 protein.

J Proteome Res2020       LitCov and CORD-19
5618Application of Big Data Technology for COVID-19 Prevention and Control in China: Lessons and Recommendations  

BACKGROUND: In the prevention and control of infectious diseases, previous research on the application of big data technology has mainly focused on the early warning and early monitoring of infectious diseases. Although the application of big data technology for COVID-19 warning and monitoring remain important tasks, prevention of the disease’s rapid spread and reduction of its impact on society are currently the most pressing challenges for the application of big data technology during the COVID-19 pandemic. After the outbreak of COVID-19 in Wuhan, the Chinese government and nongovernmental organizations actively used big data technology to prevent, contain, and control the spread of COVID-19. OBJECTIVE: The aim of this study is to discuss the application of big data technology to prevent, contain, and control COVID-19 in China; draw lessons; and make recommendations. METHODS: We discuss the data collection methods and key data information that existed in China before the outbreak of COVID-19 and how these data contributed to the prevention and control of COVID-19. Next, we discuss China’s new data collection methods and new information assembled after the outbreak of COVID-19. Based on the data and information collected in China, we analyzed the application of big data technology from the perspectives of data sources, data application logic, data application level, and application results. In addition, we analyzed the issues, challenges, and responses encountered by China in the application of big data technology from four perspectives: data access, data use, data sharing, and data protection. Suggestions for improvements are made for data collection, data circulation, data innovation, and data security to help understand China’s response to the epidemic and to provide lessons for other countries’ prevention and control of COVID-19. RESULTS: In the process of the prevention and control of COVID-19 in China, big data technology has played an important role in personal tracking, surveillance and early warning, tracking of the virus’s sources, drug screening, medical treatment, resource allocation, and production recovery. The data used included location and travel data, medical and health data, news media data, government data, online consumption data, data collected by intelligent equipment, and epidemic prevention data. We identified a number of big data problems including low efficiency of data collection, difficulty in guaranteeing data quality, low efficiency of data use, lack of timely data sharing, and data privacy protection issues. To address these problems, we suggest unified data collection standards, innovative use of data, accelerated exchange and circulation of data, and a detailed and rigorous data protection system. CONCLUSIONS: China has used big data technology to prevent and control COVID-19 in a timely manner. To prevent and control infectious diseases, countries must collect, clean, and integrate data from a wide range of sources; use big data technology to analyze a wide range of big data; create platforms for data analyses and sharing; and address privacy issues in the collection and use of big data.

J Med Internet Res2020       LitCov and CORD-19
5619A mixed-methods sequential explanatory design comparison between COVID-19 infection control guidelines' applicability and their protective value as perceived by Israeli healthcare workers and healthcare executives' response  

BACKGROUND: Healthcare workers (HCWs) are on the front line of the COVID-19 outbreak, and their constant exposure to infected patients and contaminated surfaces puts them at risk of acquiring and transmitting the infection. Therefore, they must employ protective measures. In practice, HCWs in Israel were not fully prepared for this sudden COVID-19 outbreak. This research aimed to identify and compare: (1) Israeli HCWs’ perceptions regarding the official COVID-19 guidelines’ applicability and their protective value, and (2) HCWs executives’ response to HWCs’ concern regarding personal protective equipment (PPE) shortage. METHODS: A mixed-methods sequential explanatory design consists of: (1) An online survey of 242 HCWs about the application of the guidelines and PPE, and (2) Personal interviews of 15 HCWs executives regarding PPE shortage and the measures they are taking to address it. RESULTS: A significant difference between the perceived applicability and protective value was found for most of the guidelines. Some of the guidelines were perceived as more applicable than protective (hand hygiene, signage at entrance, alcohol rub sanitizers at entrance, and mask for contact with symptomatic patients). Other were perceived as less applicable than protective (prohibited gathering of over 10 people, maintaining a distance of 2 m’, and remote services). CONCLUSIONS: HCWs need the support of the healthcare authorities not only to provide missing equipment, but also to communicate the risk to them. Conveying the information with full transparency, while addressing the uncertainty element and engaging the HCWs in evaluating the guidelines, are critical for establishing trust.

Antimicrob Resist Infect Contr2020       LitCov and CORD-19
5620Performance and Implementation Evaluation of the Abbott BinaxNOW Rapid Antigen Test in a High-Throughput Drive-Through Community Testing Site in Massachusetts  

N/A

J Clin Microbiol2021       LitCov and CORD-19
5621Acute myocarditis following a third dose of COVID-19 mRNA vaccination in adults  

N/A

Int J Cardiol2022       LitCov
5622BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully vaccinated hospitalized COVID-19 patients in Israel  

OBJECTIVES: mRNA COVID-19 vaccines have shown high effectiveness in the prevention of symptomatic COVID-19, hospitalization, severe disease, and death. Nevertheless, a minority of vaccinated individuals might get infected and suffer significant morbidity. Characteristics of vaccine breakthrough infections have not been studied. We sought to portray the population of Israeli patients, who were hospitalized with COVID-19 despite full vaccination. METHODS: A retrospective multicenter cohort study of 17 hospitals included Pfizer/BioNTech's BNT162b2 fully-vaccinated patients who developed COVID-19 more than 7 days after the second vaccine dose and required hospitalization. The risk for poor outcome, defined as a composite of mechanical ventilation or death, was assessed. RESULTS: 152 patients were included, accounting for half of hospitalized fully-vaccinated patients in Israel. Poor outcome was noted in 38 patients and mortality rate reached 22% (34/152). Notable, the cohort was characterized by a high rate of comorbidities predisposing to severe COVID-19, including hypertension (108, 71%), diabetes (73, 48%), CHF (41, 27%), chronic kidney and lung diseases (37, 24% each), dementia (29, 19%), and cancer (36, 24%), and only 6 (%) had no comorbidities. Sixty (40%) of the patients were immunocompromised. Higher SARS-CoV-2 viral-load was associated with a significant risk for poor outcome. Risk also appeared higher in patients receiving anti-CD20 treatment and in patients with low titers of anti-spike IgG, but these differences did not reach statistical significance. CONCLUSIONS: We found that severe COVID-19 infection, associated with a high mortality rate, might develop in a minority of fully-vaccinated individuals with multiple comorbidities. Our patients had a higher rate of comorbidities and immunosuppression compared to previously reported non-vaccinated hospitalized COVID-19 patients. Further characterization of this vulnerable population may help to develop guidance to augment their protection, either by continued social-distancing, or by additional active or passive vaccinations.

Clin Microbiol Infect2021       LitCov and CORD-19
5623Prevalence of antibodies to SARS-CoV-2 in Irish hospital healthcare workers  

Hospital healthcare workers (HCWs) are at increased risk of contracting COVID-19 infection. We aimed to determine the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in HCWs in Ireland. Two tertiary referral hospitals in Irish cities with diverging community incidence and seroprevalence were identified; COVID-19 had been diagnosed in 10.2% and 1.8% of staff respectively by the time of the study (October 2020). All staff of both hospitals (N = 9038) were invited to participate in an online questionnaire and blood sampling for SARS-CoV-2 antibody testing. Frequencies and percentages for positive SARS-CoV-2 antibody were calculated and adjusted relative risks (aRR) for participant characteristics were calculated using multivariable regression analysis. In total, 5788 HCWs participated (64% response rate). Seroprevalence of antibodies to SARS-CoV-2 was 15% and 4.1% in hospitals 1 and 2, respectively. Thirty-nine percent of infections were previously undiagnosed. Risk for seropositivity was higher for healthcare assistants (aRR 2.0, 95% confidence interval (CI) 1.4–3.0), nurses (aRR: 1.6, 95% CI 1.1–2.2), daily exposure to patients with COVID-19 (aRR: 1.6, 95% CI 1.2–2.1), age 18–29 years (aRR: 1.4, 95% CI 1.1–1.9), living with other HCWs (aRR: 1.3, 95% CI 1.1–1.5), Asian background (aRR: 1.3, 95% CI 1.0–1.6) and male sex (aRR: 1.2, 95% CI 1.0–1.4). The HCW seroprevalence was six times higher than community seroprevalence. Risk was higher for those with close patient contact. The proportion of undiagnosed infections call for robust infection control guidance, easy access to testing and consideration of screening in asymptomatic HCWs. With emerging evidence of reduction in transmission from vaccinated individuals, the authors strongly endorse rapid vaccination of all HCWs.

Epidemiol Infect2021       LitCov and CORD-19
5624At-home testing to mitigate community transmission of SARS-CoV-2: protocol for a public health intervention with a nested prospective cohort study  

BACKGROUND: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve as a global health crisis. Although highly effective vaccines have been developed, non-pharmaceutical interventions remain critical to controlling disease transmission. One such intervention—rapid, at-home antigen self-testing—can ease the burden associated with facility-based testing programs and improve testing access in high-risk communities. However, its impact on SARS-CoV-2 community transmission has yet to be definitively evaluated, and the socio-behavioral aspects of testing in underserved populations remain unknown. METHODS: As part of the Rapid Acceleration of Diagnostics–Underserved Populations (RADx-UP) program funded by the National Institutes of Health, we are implementing a public health intervention titled “Say Yes! COVID Test” (SYCT) involving at-home self-testing using a SARS-CoV-2 rapid antigen assay in North Carolina (Greenville, Pitt County) and Tennessee (Chattanooga City, Hamilton County). The intervention is supported by a multifaceted communication and community engagement strategy to ensure widespread awareness and uptake, particularly in marginalized communities. Participants receive test kits either through online orders or via local community distribution partners. To assess the impact of this intervention on SARS-CoV-2 transmission, we will conduct a non-randomized, ecological study using community-level outcomes. Specifically, we will evaluate trends in SARS-CoV-2 cases and hospitalizations, SARS-CoV-2 viral load in wastewater, and population mobility in each community before, during, and after the SYCT intervention. Individuals who choose to participate in SYCT will also have the option to enroll in an embedded prospective cohort substudy gathering participant-level data to evaluate behavioral determinants of at-home self-testing and socio-behavioral mechanisms of SARS-CoV-2 community transmission. DISCUSSION: This is the first large-scale, public health intervention implementing rapid, at-home SARS-CoV-2 self-testing in the United States. The program consists of a novel combination of an at-home testing program, a broad communications and community engagement strategy, an ecological study to assess impact, and a research substudy of the behavioral aspects of testing. The findings from the SYCT project will provide insights into innovative methods to mitigate viral transmission, advance the science of public health communications and community engagement, and evaluate emerging, novel assessments of community transmission of disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-12007-w.

BMC Public Health2021       LitCov and CORD-19
5625The Impact of Sheltering in Place During the COVID-19 Pandemic on Older Adults' Social and Mental Well-Being  

OBJECTIVES: We examined whether social isolation due to the COVID-19 shelter-in-place orders was associated with greater loneliness and depression for older adults, and, if so, whether declines in social engagement or relationship strength moderated that relationship. METHODS: Between April 21 and May 21, 2020, 93 older adults in the United States who had completed measures characterizing their personal social networks, subjective loneliness, and depression 6–9 months prior to the pandemic completed the same measures via phone interview, as well as questions about the impact of the pandemic on their social relationships. RESULTS: Older adults reported higher depression and greater loneliness following the onset of the pandemic. Loneliness positively predicted depression. Perceived relationship strength, but not social engagement, moderated this relationship such that loneliness only predicted depression for individuals who became closer to their networks during the pandemic. For those who felt less close, depression was higher irrespective of loneliness. DISCUSSION: The COVID-19 pandemic negatively affected older adults’ mental health and social well-being in the short term. Potential long-term impacts are considered.

J Gerontol B Psychol Sci Soc S2020       LitCov and CORD-19
5626Prevalence of IgG antibodies against SARS-CoV-2 among healthcare workers in a tertiary pediatric hospital in Poland  

Data on the prevalence of the SARS-CoV-2 antibody in healthcare workers (HCWs) is scarce, especially in pediatric settings. The purpose of this study was to evaluate SARS-CoV-2 IgG-positivity among HCWs of a tertiary pediatric hospital. In addition, follow-up of the serological response in the subgroup of seropositive HCWs was analysed, to gain some insight on the persistence of IgG antibodies to SARS-CoV-2. We performed a retrospective analysis of voluntary SARS-CoV-2 IgG testing, which was made available free of charge to HCWs of the Children’s Memorial Health Institute in Warsaw (Poland). Plasma samples were collected between July 1 and August 9, 2020, and tested using the Abbott SARS-CoV-2 IgG assay. Of 2,282 eligible participants, 1,879 (82.3%) HCWs volunteered to undergo testing. Sixteen HCWs tested positive for SARS-CoV-2 IgG, corresponding to a seroprevalence of 0.85%. Among seropositive HCWs, three HCWs had confirmed COVID-19. Nine (56.3%) of the seropositive HCWs reported neither symptoms nor unprotected contact with confirmed SARS-CoV-2 cases in the previous months. A decline in the IgG index was observed at a median time of 86.5 days (range:84‒128 days) after symptom onset or RT-PCR testing. Further studies are necessary to elucidate the duration of persistence of anti-SARS-CoV-2 antibodies, as well as the correlation between seropositivity and protective immunity against reinfection. Regardless of the persistence of antibodies and their protective properties, such low prevalence indicates that this population is vulnerable to a second wave of the COVID-19 pandemic.

PLoS One2021       LitCov and CORD-19
5627Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study  

BACKGROUND: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. METHODS: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine’s registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. RESULTS: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. CONCLUSIONS: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s12916-020-01832-2.

BMC Med2020       LitCov and CORD-19
5628Examining K-12 teachers' feelings, experiences and perspectives regarding online teaching during the early stage of the COVID-19 pandemic  

This mixed-methods study explored K-12 teachers’ feelings, experiences, and perspectives regarding online teaching during the COVID-19 pandemic. The study also examined teachers’ perspectives of the “new normal” after COVID-19 and of what should be done to better prepare teachers for future emergencies. Both quantitative and qualitative data were collected from an online survey and follow-up interviews. A total of 107 teachers from 25 different states in the United States completed the online survey, and 13 teachers from 10 different states participated in the follow-up interviews. The results revealed teachers’ feelings about online teaching and various strategies and tools they used during the early stage of the COVID-19 pandemic. The major challenges faced by teachers during the pandemic included lack of student participation and engagement (or lack of parental support), students without access to technology, concerns about students’ well-being, no face-to-face interactions with students, no work-life balance, and learning new technology. Four major themes emerged regarding how to better prepare teachers for future emergencies: (1) professional development for online learning, (2) technology access, (3) technology training for both teachers and students, and (4) action plans and communication. Regarding teachers’ perspectives of the “new normal,” five major themes emerged: (1) more online or blended learning, (2) rethinking normal, (3) hygiene and social distancing, (4) smaller classes and different school schedules, and (5) uncertainty and concerns about the “new normal.”

Educ Technol Res Dev2021       LitCov and CORD-19
5629At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data  

BACKGROUND: Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. METHODS: We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. RESULTS: Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from − 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. CONCLUSIONS: RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated.

BMC Med2020       LitCov and CORD-19
5630An analysis of the domestic resumption of social production and life under the COVID-19 epidemic  

Population migration and urban traffic are two important aspects of the socioeconomic system. We analyze the trends of social production and resumption of life after the coronavirus disease 2019 (COVID-19)-influenced Spring Festival in 2020 with statistics on reported cases of COVID-19 from China’s National Health Commission and big data from Baidu Migration (a platform collecting population migration data). We find that (1) the distribution of COVID-19 cases throughout mainland China has a specific spatial pattern. Provinces in eastern China have more reported cases than those in western China, and provinces adjacent to Hubei have more confirmed COVID-19 cases than nonadjacent provinces. Densely populated regions with well-developed economies and transportation are more likely to have cluster infection incidents. (2) The COVID-19 epidemic severely impacts the return of the migrant population in the Spring Festival travel rush, as demonstrated by the significant reduction in the return scale, along with the extended timespan and uncertainty regarding the end of the travel rush. Among 33 provinces, special administrative regions, autonomous regions and municipalities, 23 of them (approximately 70%) have a return rate below 60%. Hubei, Hong Kong, Xinjiang, and Inner Mongolia have the lowest return rates (below 5%), whereas the return rates in Hainan and Shandong, 272.72% and 97.35%, respectively, indicate the best trend of resumption. Due to government regulations, the population return in densely populated and well-developed regions shows a positive trend. (3) The resumption of urban traffic is slow and varies greatly in different regions. The urban traffic conditions in 22 provinces and municipalities have a more than 60% level of resumption. Guizhou and Yunnan have the highest level of resumption of urban traffic, whereas Xinjiang, Hubei, and Heilongjiang have the lowest (29.37%, 35.76%, and 37.90%, respectively). However, provinces and municipalities with well-developed intercity traffic have a lower level of resumption, mainly because of regulatory methods such as lockdowns and traffic restrictions. The increased public awareness of epidemic prevention and the decreased frequency of outdoor activities are also two positive factors slowing the spread of the epidemic. (4) Time will be necessary to fully resume social production and life throughout China. Xining and Jinan have the highest levels of resumption, 82.14% and 71.51%, respectively. Urumqi and Wuhan are the cities with the lowest levels of resumption, only 0.11% and 0.61%, respectively. Currently, 12 of 33 provinces and municipalities have levels of resumption of more than 80%; among them, Guizhou, Yunnan, and Gansu have with the highest levels of resumption and have nearly resumed the 2019 levels of work and life, whereas Xinjiang and Hubei have the lowest resumption rates, only 0.09% and 7.57%, respectively. Thus, relevant government departments should focus more on densely populated and well-developed provinces and cities when applying epidemic prevention and work resumption methods. We reveal the general conditions of the epidemic and the population return scale across China, along with urban traffic conditions and the resumption of social production and life under COVID-19, providing a scientific basis for local governments to make further decisions on work resumption.

PLoS One2020       LitCov and CORD-19
5631Artificial Intelligence in the Fight Against COVID-19: Scoping Review  

BACKGROUND: In December 2019, COVID-19 broke out in Wuhan, China, leading to national and international disruptions in health care, business, education, transportation, and nearly every aspect of our daily lives. Artificial intelligence (AI) has been leveraged amid the COVID-19 pandemic; however, little is known about its use for supporting public health efforts. OBJECTIVE: This scoping review aims to explore how AI technology is being used during the COVID-19 pandemic, as reported in the literature. Thus, it is the first review that describes and summarizes features of the identified AI techniques and data sets used for their development and validation. METHODS: A scoping review was conducted following the guidelines of PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews). We searched the most commonly used electronic databases (eg, MEDLINE, EMBASE, and PsycInfo) between April 10 and 12, 2020. These terms were selected based on the target intervention (ie, AI) and the target disease (ie, COVID-19). Two reviewers independently conducted study selection and data extraction. A narrative approach was used to synthesize the extracted data. RESULTS: We considered 82 studies out of the 435 retrieved studies. The most common use of AI was diagnosing COVID-19 cases based on various indicators. AI was also employed in drug and vaccine discovery or repurposing and for assessing their safety. Further, the included studies used AI for forecasting the epidemic development of COVID-19 and predicting its potential hosts and reservoirs. Researchers used AI for patient outcome–related tasks such as assessing the severity of COVID-19, predicting mortality risk, its associated factors, and the length of hospital stay. AI was used for infodemiology to raise awareness to use water, sanitation, and hygiene. The most prominent AI technique used was convolutional neural network, followed by support vector machine. CONCLUSIONS: The included studies showed that AI has the potential to fight against COVID-19. However, many of the proposed methods are not yet clinically accepted. Thus, the most rewarding research will be on methods promising value beyond COVID-19. More efforts are needed for developing standardized reporting protocols or guidelines for studies on AI.

J Med Internet Res2020       LitCov and CORD-19
5632Boceprevir, GC-376 and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease  

A new coronavirus SARS-CoV-2, also called novel coronavirus 2019 (2019-nCoV), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.35% as of May 26, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (M(pro)). Using the FRET-based enzymatic assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC(50) values in the enzymatic assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC(50) values ranging from 0.49 to 3.37 µM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known substrate-based peptidomimetic M(pro) inhibitors. A complex crystal structure of SARS-CoV-2 M(pro) with GC-376, determined at 2.15 Å resolution with three protomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by M(pro). Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.

Cell Res2020       LitCov and CORD-19
5633Heterologous ChAdOx1/BNT162b2 vaccination induces stronger immune response than homologous ChAdOx1 vaccination: The pragmatic, multi-center, three-arm, partially randomized HEVACC trial  

BACKGROUND: Several COVID-19 vaccines have been approved. The mRNA vaccine from Pfizer/BioNTech (Comirnaty, BNT162b2; BNT) and the vector vaccine from AstraZeneca (Vaxzevria, ChAdOx1; AZ) have been widely used. mRNA vaccines induce high antibody and T cell responses, also to SARS-CoV-2 variants, but are costlier and less stable than the slightly less effective vector vaccines. For vector vaccines, heterologous vaccination schedules have generally proven more effective than homologous schedules. METHODS: In the HEVACC three-arm, single-blinded, adaptive design study (ClinicalTrials.gov Identifier: NCT04907331), participants between 18 and 65 years with no prior history of SARS-CoV-2 infection and a first dose of AZ or BNT were included. The AZ/AZ and the AZ/BNT arms were randomized (in a 1:1 ratio stratified by sex and trial site) and single-blinded, the third arm (BNT/BNT) was observational. We compared the reactogenicity between the study arms and hypothesized that immunogenicity was higher for the heterologous AZ/BNT compared to the homologous AZ/AZ regimen using neutralizing antibody titers as primary endpoint. FINDINGS: This interim analysis was conducted after 234 participants had been randomized and 254 immunized (N=109 AZ/AZ, N=115 AZ/BNZ, N=30 BNT/BNT). Heterologous AZ/BNT vaccination was well tolerated without study-related severe adverse events. Neutralizing antibody titers on day 30 were statistically significant higher in the AZ/BNT and the BNT/BNT groups than in the AZ/AZ group, for B.1.617.2 (Delta) AZ/AZ median reciprocal titer 75.9 (99.9% CI 58.0 - 132.5), AZ/BNT 571.5 (99.9% CI 396.6 - 733.1), and BNT/BNT 404.5 (99.9% CI 68.3 - 1024). Similarly, the frequency and multifunctionality of spike-specific T cell responses was comparable between the AZ/BNT and the BNT/BNT groups, but lower in the AZ/AZ vaccinees. INTERPRETATION: This study clearly shows the immunogenicity and safety of heterologous AZ/BNT vaccination and encourages further studies on heterologous vaccination schedules. FUNDING: This work was supported by the Medical University of Innsbruck, and partially funded by NIAID contracts No. 75N9301900065, 75N93021C00016, and 75N93019C00051.

EBioMedicine2022       LitCov and CORD-19
5634Performance Evaluation of Serial SARS-CoV-2 Rapid Antigen Testing During a Nursing Home Outbreak  

BACKGROUND: To address high COVID-19 burden in U.S. nursing homes, rapid SARS-CoV-2 antigen tests have been widely distributed in those facilities. However, performance data are lacking, especially in asymptomatic people. OBJECTIVE: To evaluate the performance of SARS-CoV-2 antigen testing when used for facility-wide testing during a nursing home outbreak. DESIGN: A prospective evaluation involving 3 facility-wide rounds of testing where paired respiratory specimens were collected to evaluate the performance of the BinaxNOW antigen test compared with virus culture and real-time reverse transcription polymerase chain reaction (RT-PCR). Early and late infection were defined using changes in RT-PCR cycle threshold values and prior test results. SETTING: A nursing home with an ongoing SARS-CoV-2 outbreak. PARTICIPANTS: 532 paired specimens collected from 234 available residents and staff. MEASUREMENTS: Percentage of positive agreement (PPA) and percentage of negative agreement (PNA) for BinaxNOW compared with RT-PCR and virus culture. RESULTS: BinaxNOW PPA with virus culture, used for detection of replication-competent virus, was 95%. However, the overall PPA of antigen testing with RT-PCR was 69%, and PNA was 98%. When only the first positive test result was analyzed for each participant, PPA of antigen testing with RT-PCR was 82% among 45 symptomatic people and 52% among 343 asymptomatic people. Compared with RT-PCR and virus culture, the BinaxNOW test performed well in early infection (86% and 95%, respectively) and poorly in late infection (51% and no recovered virus, respectively). LIMITATION: Accurate symptom ascertainment was challenging in nursing home residents; test performance may not be representative of testing done by nonlaboratory staff. CONCLUSION: Despite lower positive agreement compared with RT-PCR, antigen test positivity had higher agreement with shedding of replication-competent virus. These results suggest that antigen testing could be a useful tool to rapidly identify contagious people at risk for transmitting SARS-CoV-2 during nascent outbreaks and help reduce COVID-19 burden in nursing homes. PRIMARY FUNDING SOURCE: None.

Ann Intern Med2021       LitCov and CORD-19
5635Qualitative exploration of medical student experiences during the Covid-19 pandemic: implications for medical education  

BACKGROUND: During the Covid-19 pandemic medical students were offered paid roles as medical student healthcare assistants. Anecdotal reports suggested that students found this experience rich for learning. Previous studies have explored alternative models of student service, however this defined medical student support role is novel. METHODS: Individual semi-structured interviews were recorded with 20 medical students at a UK medical school exploring their experiences of placement learning and experiences of working as healthcare assistants. Responses were analysed qualitatively using a framework approach. The framework was developed into a model describing key findings and their relationships. RESULTS: Interviews yielded data that broadly covered aspects of (1) Medical students’ experiences of clinical placement learning (2) Medical students’ experiences of working as medical student healthcare assistants (3) Learning resulting from working as a healthcare assistant (4) Hierarchies and professional barriers in the clinical environment (5) Influences on professional identity. Participants described barriers and facilitators of clinical learning and how assuming a healthcare assistant role impacted on learning and socialisation within the multidisciplinary team. Students became increasingly socialised within the healthcare team, contributing directly to patient care; the resulting social capital opened new opportunities for learning, team working and enhanced students’ interprofessional identity. Students described the impact of these experiences on their aspirations for their future practice. CONCLUSIONS: Changes to work patterns in healthcare and delivery models of medical education have eroded opportunities for students to contribute to healthcare delivery and be embedded within a team. This is impacting negatively on student learning and socialisation and we suggest that medical curricula have much to learn from nursing and allied health professional training. Longitudinal embedment with a multidisciplinary team, where students have a defined role and work directly with patients may not only add value to clinical service, but also overcome current barriers to effective placement learning and interprofessional identity formation for medical students. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12909-021-02726-4.

BMC Med Educ2021       LitCov and CORD-19
5636Impact of Social Isolation Due to COVID-19 on Health in Older People: Mental and Physical Effects and Recommendations  

OBJECTIVES: To review the impact of social isolation during COVID-19 pandemic on mental and physical health of older people and the recommendations for patients, caregivers and health professionals. DESIGN: Narrative review. SETTING: Non-institutionalized community-living people. PARTICIPANTS: 20.069 individuals from ten descriptive cross-sectional papers. MEASUREMENTS: Articles since 2019 to 2020 published on Pubmed, Scielo and Google Scholar databases with the following MeSh terms (‘COVID-19’, ‘coronavirus’, ‘aging’, ‘older people’, ‘elderly’, ‘social isolation’ and ‘quarantine’) in English, Spanish or Portuguese were included. The studies not including people over 60 were excluded. Guidelines, recommendations, and update documents from different international organizations related to mental and physical activity were also analysed. RESULTS: 41 documents have been included in this narrative review, involving a total of 20.069 individuals (58% women), from Asia, Europe and America. 31 articles included recommendations and 10 addressed the impact of social distancing on mental or physical health. The main outcomes reported were anxiety, depression, poor sleep quality and physical inactivity during the isolation period. Cognitive strategies and increasing physical activity levels using apps, online videos, telehealth, are the main international recommendations. CONCLUSION: Mental and physical health in older people are negatively affected during the social distancing for COVID-19. Therefore, a multicomponent program with exercise and psychological strategies are highly recommended for this population during the confinement. Future investigations are necessary in this field.

J Nutr Health Aging2020       LitCov and CORD-19
5637Safety of systemic anti-cancer treatment in oncology patients with nonsevere COVID-19: a cohort study  

BACKGROUND: The viral pandemic coronavirus disease 2019 (COVID-19) has disrupted cancer patient management around the world. Most reported data relate to incidence, risk factors, and outcome of severe COVID-19. The safety of systemic anti-cancer therapy in oncology patients with non-severe COVID-19 is an important matter in daily practice. METHODS: ONCOSARS-1 was a single-center, academic observational study. Adult patients with solid tumors treated in the oncology day unit with systemic anti-cancer therapy during the initial phase of the COVID-19 pandemic in Belgium were prospectively included. All patients (n = 363) underwent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serological testing after the first peak of the pandemic in Belgium. Additionally, 141 of these patients also had a SARS-CoV-2 RT-PCR test during the pandemic. The main objective was to retrospectively determine the safety of systemic cancer treatment, measured by the rate of adverse events according to the Common Terminology Criteria for Adverse Events, in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative patients. RESULTS: Twenty-two (6%) of the 363 eligible patients were positive for SARS-CoV-2 by RT-PCR and/or serology. Of these, three required transient oxygen supplementation, but none required admission to the intensive care unit. Hematotoxicity was the only adverse event more frequently observed in SARS-CoV-2 -positive patients than in SARS-CoV-2-negative patients: 73% vs 35% (P < 0.001). This association remained significant (odds ratio (OR) 4.1, P = 0.009) even after adjusting for performance status and type of systemic treatment. Hematological adverse events led to more treatment delays for the SARS-CoV-2-positive group: 55% vs 20% (P < 0.001). Median duration of treatment interruption was similar between the two groups: 14 and 11 days, respectively. Febrile neutropenia, infections unrelated to COVID-19, and bleeding events occurred at a low rate in the SARS-CoV-2-positive patients. CONCLUSION: Systemic anti-cancer therapy appeared safe in ambulatory oncology patients treated during the COVID-19 pandemic. There were, however, more treatment delays in the SARS-CoV-2-positive population, mainly due to a higher rate of hematological adverse events. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08349-8.

BMC Cancer2021       LitCov and CORD-19
5638Coronavirus infections and immune responses  

Coronaviruses (CoVs) are by far the largest group of known positive‐sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV‐induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.

J Med Virol2020       LitCov and CORD-19
5639Efficacy of SARS-CoV-2 Vaccine in Patients With Thoracic Cancer: A Prospective Study Supporting a Third Dose in Patients With Minimal Serologic Response After Two Vaccine Doses  

Hypothesis Coronavirus disease 2019 (COVID-19) resulted in a 30% mortality rate in thoracic cancer patients. Given that cancer patients were excluded from serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine registration trials, it is still unknown whether they would develop a protective anti-spike antibody response following vaccination. This prospective vaccine monitoring study primarily aimed to assess humoral responses to SARS-CoV2 vaccine in thoracic cancer patients. Methods SARS-CoV2-spike antibodies were measured using Abbot ARCHITECT SARS-CoV-2 IgG immunoassay, prior to first injection of BNT162b2 mRNA vaccine, as well as at Week 4, and two-to-sixteen weeks after second vaccine dose. The factors associated with antibody response were analyzed. Results Overall, 306 patients, with a median age of 67.0 years (IQR=58-74), were vaccinated. Of these, 283 patients received two vaccine doses at 28-day intervals. After 6.7-month median follow-up, eight patients (2.6%) contracted proven symptomatic SARS-CoV-2 infection, with rapid favorable evolution. Of 269 serological results available beyond Day 14 post-second vaccine dose, 17 (6.3%) were still negative (<50 AU/mL) (arbitrary units/mL), while 34 (11%) were <300 AU/mL (12.5th percentile). In multivariate analysis, only age and chronic corticosteroid treatment were significantly associated with a lack of immunization. Thirty patients received a third vaccine dose, with only three patients showing persistent negative serology thereafter, whereas the others demonstrated clear seroconversion. Conclusion SARS-CoV2 vaccines were shown to be efficient in thoracic cancer patients, most of them being immunized after two doses. A third shot given to 1% of patients with persistent low antibody titers resulted in a 88% immunization rate.

J Thorac Oncol2021       LitCov and CORD-19
5640Ethnic and regional variations in hospital mortality from COVID-19 in Brazil: a cross-sectional observational study  

BACKGROUND: Brazil ranks second worldwide in total number of COVID-19 cases and deaths. Understanding the possible socioeconomic and ethnic health inequities is particularly important given the diverse population and fragile political and economic situation. We aimed to characterise the COVID-19 pandemic in Brazil and assess variations in mortality according to region, ethnicity, comorbidities, and symptoms. METHODS: We conducted a cross-sectional observational study of COVID-19 hospital mortality using data from the SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe) dataset to characterise the COVID-19 pandemic in Brazil. In the study, we included hospitalised patients who had a positive RT-PCR test for severe acute respiratory syndrome coronavirus 2 and who had ethnicity information in the dataset. Ethnicity of participants was classified according to the five categories used by the Brazilian Institute of Geography and Statistics: Branco (White), Preto (Black), Amarelo (East Asian), Indígeno (Indigenous), or Pardo (mixed ethnicity). We assessed regional variations in patients with COVID-19 admitted to hospital by state and by two socioeconomically grouped regions (north and central-south). We used mixed-effects Cox regression survival analysis to estimate the effects of ethnicity and comorbidity at an individual level in the context of regional variation. FINDINGS: Of 99 557 patients in the SIVEP-Gripe dataset, we included 11 321 patients in our study. 9278 (82·0%) of these patients were from the central-south region, and 2043 (18·0%) were from the north region. Compared with White Brazilians, Pardo and Black Brazilians with COVID-19 who were admitted to hospital had significantly higher risk of mortality (hazard ratio [HR] 1·45, 95% CI 1·33–1·58 for Pardo Brazilians; 1·32, 1·15–1·52 for Black Brazilians). Pardo ethnicity was the second most important risk factor (after age) for death. Comorbidities were more common in Brazilians admitted to hospital in the north region than in the central-south, with similar proportions between the various ethnic groups. States in the north had higher HRs compared with those of the central-south, except for Rio de Janeiro, which had a much higher HR than that of the other central-south states. INTERPRETATION: We found evidence of two distinct but associated effects: increased mortality in the north region (regional effect) and in the Pardo and Black populations (ethnicity effect). We speculate that the regional effect is driven by increasing comorbidity burden in regions with lower levels of socioeconomic development. The ethnicity effect might be related to differences in susceptibility to COVID-19 and access to health care (including intensive care) across ethnicities. Our analysis supports an urgent effort on the part of Brazilian authorities to consider how the national response to COVID-19 can better protect Pardo and Black Brazilians, as well as the population of poorer states, from their higher risk of dying of COVID-19. FUNDING: None.

Lancet Glob Health2020       LitCov and CORD-19
5641Global reports of myocarditis following COVID-19 vaccination: A systematic review and meta-analysis  

N/A

Diabetes Metab Syndr2022       LitCov and CORD-19
5642Risk of nosocomial transmission of COVID-19: an experience in a general ward setting in Hong Kong  

BACKGROUND: Coronavirus disease 2019 (COVID-19) was first reported in Wuhan in December 2019 and has rapidly spread across different cities within and outside China. Hong Kong started to prepare for COVID-19 on 31(st) December 2019 and infection control measures in public hospitals were tightened to limit nosocomial transmission within healthcare facilities. However, the recommendations on the transmission-based precautions required for COVID-19 in hospital settings vary from droplet and contact precautions, to contact and airborne precautions with placement of patients in airborne infection isolation rooms. AIM: To describe an outbreak investigation of a patient with COVID-19 who was nursed in an open cubicle of a general ward before the diagnosis was made. METHOD: Contacts were identified and risk categorized as ‘close’ or ‘casual’ for decisions on quarantine and/or medical surveillance. Respiratory specimens were collected from contacts who developed fever, and/or respiratory symptoms during the surveillance period and were tested for SARS-CoV-2. FINDINGS: A total of 71 staff and 49 patients were identified from contact tracing, seven staff and 10 patients fulfilled the criteria of ‘close contact’. At the end of 28-day surveillance, 76 tests were performed on 52 contacts and all were negative, including all patient close contacts and six of the seven staff close contacts. The remaining contacts were asymptomatic throughout the surveillance period. CONCLUSION: Our findings suggest that SARS-CoV-2 is not spread by an airborne route, and nosocomial transmissions can be prevented through vigilant basic infection control measures, including wearing of surgical masks, hand and environmental hygiene.

J Hosp Infect2020       LitCov and CORD-19
5643Neutralizing monoclonal antibodies for treatment of COVID-19  

Several neutralizing monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and are now under evaluation in clinical trials. With the US Food and Drug Administration recently granting emergency use authorizations for neutralizing mAbs in non-hospitalized patients with mild-to-moderate COVID-19, there is an urgent need to discuss the broader potential of these novel therapies and to develop strategies to deploy them effectively in clinical practice, given limited initial availability. Here, we review the precedent for passive immunization and lessons learned from using antibody therapies for viral infections such as respiratory syncytial virus, Ebola virus and SARS-CoV infections. We then focus on the deployment of convalescent plasma and neutralizing mAbs for treatment of SARS-CoV-2. We review specific clinical questions, including the rationale for stratification of patients, potential biomarkers, known risk factors and temporal considerations for optimal clinical use. To answer these questions, there is a need to understand factors such as the kinetics of viral load and its correlation with clinical outcomes, endogenous antibody responses, pharmacokinetic properties of neutralizing mAbs and the potential benefit of combining antibodies to defend against emerging viral variants.

Nat Rev Immunol2021       LitCov and CORD-19
5644A Case of Guillain-Barré Syndrome Associated With COVID-19  

A novel member of human RNA coronavirus, which is an enveloped betacoronavirus, has been termed severe acute respiratory syndrome coronavirus-2 (SARS COV-2). The illness caused by SARS COV-2 is referred to as the coronavirus disease 2019 (COVID-19). It is a highly contagious disease that has resulted in a global pandemic. The clinical spectrum of COVID-19 ranges from asymptomatic illness to acute respiratory distress syndrome, septic shock, multi-organ dysfunction, and death. The most common symptoms include fever, fatigue, dry cough, dyspnea, and diarrhea. Neurological manifestations have also been reported. However, the data on the association of Guillain-Barré syndrome (GBS) with COVID-19 are scarce. We report a rare case of a COVID-19-positive 36-year-old immunocompromised male who presented with clinical features of GBS. His clinical examination showed generalized weakness and hyporeflexia. The cerebrospinal fluid (CSF) analysis showed albuminocytological dissociation. Intravenous immunoglobulin (IVIG) was administered based on the high clinical suspicion of GBS. The patient’s neurological condition worsened with progression to bulbar weakness and ultimately neuromuscular respiratory failure requiring mechanical ventilation. His nerve conduction studies were consistent with demyelinating polyneuropathy. He received five plasma exchange treatments and was successfully weaned from mechanical ventilation. A brain and cervical spine magnetic resonance imaging was obtained to rule out other causes, which was normal. COVID-19 is believed to cause a dysregulated immune system, which likely plays an important role in the neuropathogenesis of GBS.

J Investig Med High Impact Cas2020       LitCov and CORD-19
5645Virtual screening, ADMET prediction and dynamics simulation of potential compounds targeting the main protease of SARS-CoV-2  

The coronavirus disease-2019 caused by a novel SARS CoV-2 virus has emerged as a global threat. Still, no drugs are available for its treatment. The main protease is the most conserved structure responsible for the posttranslational processing of non-structural polyproteins of this virus. Therefore, it can be the potential target for drug discovery against SARS CoV-2. Twenty-one thousand two hundred and seven chemical compounds used for sequential virtual screening studies including coronavirus screening compounds (Life Chemical database) and antiviral compounds (Asinex database). The Schrodinger suite 2019 employed for high throughput screening, molecular docking and MM-GBSA through the Glide module. Subsequently, 23 compounds were selected in the phase first selection criteria for re-docking with AutoDock and iDock followed by ADMET prediction. The drug-likeness predicted through Lipinski’s rule of five, Veber’s rule and Muegge’s rule. Finally, three ligands were selected for molecular dynamics simulation studies over 150 ns against the main protease of the SARS CoV-2. They showed promising docking scores on Glide, iDock and AutoDock Vina algorithms (ligand F2679-0163: −10.75, −10.29 and −9.2; ligand F6355-0442: −9.38, −8.61 and −7.6; ligand 8250: −9.795, −7.94 and −7.5), respectively. The RMSD parameter remained stable at 2.5 Å for all the three ligands for 150 ns. The high RMSF fluctuations, RoG of around 22 Å and the binding free energy were favorable in each case. The hydrogen bond interactions of 8250, F6355-0442 and F2679-0163 were six, five and three, respectively. These compounds can be further explored for in vitro experimental validation against SARS-CoV-2. Communicated by Ramaswamy H. Sarma

J Biomol Struct Dyn2020       LitCov and CORD-19
5646Averting an Outbreak of SARS-CoV-2 in a University Residence Hall through Wastewater Surveillance  

A wastewater surveillance program targeting a university residence hall was implemented during the spring semester 2021 as a proactive measure to avoid an outbreak of COVID-19 on campus. Over a period of 7 weeks from early February through late March 2021, wastewater originating from the residence hall was collected as grab samples 3 times per week. During this time, there was no detection of SARS-CoV-2 by reverse transcriptase quantitative PCR (RT-qPCR) in the residence hall wastewater stream. Aiming to obtain a sample more representative of the residence hall community, a decision was made to use passive samplers beginning in late March onwards. Adopting a Moore swab approach, SARS-CoV-2 was detected in wastewater samples just 2 days after passive samplers were deployed. These samples also tested positive for the B.1.1.7 (Alpha) variant of concern (VOC) using RT-qPCR. The positive result triggered a public health case-finding response, including a mobile testing unit deployed to the residence hall the following day, with testing of nearly 200 students and staff, which identified two laboratory-confirmed cases of Alpha variant COVID-19. These individuals were relocated to a separate quarantine facility, averting an outbreak on campus. Aggregating wastewater and clinical data, the campus wastewater surveillance program has yielded the first estimates of fecal shedding rates of the Alpha VOC of SARS-CoV-2 in individuals from a nonclinical setting. IMPORTANCE Among early adopters of wastewater monitoring for SARS-CoV-2 have been colleges and universities throughout North America, many of whom are using this approach to monitor congregate living facilities for early evidence of COVID-19 infection as an integral component of campus screening programs. Yet, while there have been numerous examples where wastewater monitoring on a university campus has detected evidence for infection among community members, there are few examples where this monitoring triggered a public health response that may have averted an actual outbreak. This report details a wastewater-testing program targeting a residence hall on a university campus during spring 2021, when there was mounting concern globally over the emergence of SARS-CoV-2 variants of concern, reported to be more transmissible than the wild-type Wuhan strain. In this communication, we present a clear example of how wastewater monitoring resulted in actionable responses by university administration and public health, which averted an outbreak of COVID-19 on a university campus.

Microbiol Spectr2021       LitCov and CORD-19
5647Neutralizing Activity of BNT162b2-Elicited Serum  

N Engl J Med2021       LitCov and CORD-19
5648College Campuses and COVID-19 Mitigation: Clinical and Economic Value  

BACKGROUND: Colleges in the United States are determining how to operate safely amid the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To examine the clinical outcomes, cost, and cost-effectiveness of COVID-19 mitigation strategies on college campuses. DESIGN: The Clinical and Economic Analysis of COVID-19 interventions (CEACOV) model, a dynamic microsimulation model, was used to examine alternative mitigation strategies. The CEACOV model tracks infections accrued by students and faculty, accounting for community transmissions. DATA SOURCES: Data from published literature were used to obtain parameters related to COVID-19 and contact-hours. TARGET POPULATION: Undergraduate students and faculty at U.S. colleges. TIME HORIZON: One semester (105 days). PERSPECTIVE: Modified societal. INTERVENTION: COVID-19 mitigation strategies, including social distancing, masks, and routine laboratory screening. OUTCOME MEASURES: Infections among students and faculty per 5000 students and per 1000 faculty, isolation days, tests, costs, cost per infection prevented, and cost per quality-adjusted life-year (QALY). RESULTS OF BASE-CASE ANALYSIS: Among students, mitigation strategies reduced COVID-19 cases from 3746 with no mitigation to 493 with extensive social distancing and masks, and further to 151 when laboratory testing was added among asymptomatic persons every 3 days. Among faculty, these values were 164, 28, and 25 cases, respectively. Costs ranged from about $0.4 million for minimal social distancing to about $0.9 million to $2.1 million for strategies involving laboratory testing ($10 per test), depending on testing frequency. Extensive social distancing with masks cost $170 per infection prevented ($49 200 per QALY) compared with masks alone. Adding routine laboratory testing increased cost per infection prevented to between $2010 and $17 210 (cost per QALY gained, $811 400 to $2 804 600). RESULTS OF SENSITIVITY ANALYSIS: Results were most sensitive to test costs. LIMITATION: Data are from multiple sources. CONCLUSION: Extensive social distancing with a mandatory mask-wearing policy can prevent most COVID-19 cases on college campuses and is very cost-effective. Routine laboratory testing would prevent 96% of infections and require low-cost tests to be economically attractive. PRIMARY FUNDING SOURCE: National Institutes of Health.

Ann Intern Med2020       LitCov and CORD-19
5649Repurposing of FDA-approved drugs as potential inhibitors of the SARS-CoV-2 main protease: Molecular insights into improved therapeutic discovery  

With numerous infections and fatalities, COVID-19 has wreaked havoc around the globe. The main protease (Mpro), which cleaves the polyprotein to form non-structural proteins, thereby helping in the replication of SARS-CoV-2, appears as an attractive target for antiviral therapeutics. As FDA-approved drugs have shown effectiveness in targeting Mpro in previous SARS-CoV(s), molecular docking and virtual screening of existing antiviral, antimalarial, and protease inhibitor drugs were carried out against SARS-CoV-2 Mpro. Among 53 shortlisted drugs with binding energies lower than that of the crystal-bound inhibitor α-ketoamide 13 b (−6.7 kcal/mol), velpatasvir, glecaprevir, grazoprevir, baloxavir marboxil, danoprevir, nelfinavir, and indinavir (−9.1 to −7.5 kcal/mol) were the most significant on the list (hereafter referred to as the 53-list). Molecular dynamics (MD) simulations confirmed the stability of their Mpro complexes, with the MMPBSA binding free energy (ΔG(bind)) ranging between −124 kJ/mol (glecaprevir) and −28.2 kJ/mol (velpatasvir). Despite having the lowest initial binding energy, velpatasvir exhibited the highest ΔG(bind) value for escaping the catalytic site during the MD simulations, indicating its reduced efficacy, as observed experimentally. Available inhibition assay data adequately substantiated the computational forecast. Glecaprevir and nelfinavir (ΔG(bind) = −95.4 kJ/mol) appear to be the most effective antiviral drugs against Mpro. Furthermore, the remaining FDA drugs on the 53-list can be worth considering, since some have already demonstrated antiviral activity against SARS-CoV-2. Hence, theoretical pK(i) (K(i) = inhibitor constant) values for all 53 drugs were provided. Notably, ΔG(bind) directly correlates with the average distance of the drugs from the His41–Cys145 catalytic dyad of Mpro, providing a roadmap for rapid screening and improving the inhibitor design against SARS-CoV-2 Mpro.

Comput Biol Med2021       LitCov and CORD-19
5650COVID-19 and the consequences of isolating the elderly  

Lancet Public Health2020       LitCov and CORD-19

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

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