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: 16 - 06 - 2022 (568924 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
301Towards the development of a vibrant, super-aged society: The future of medicine and society in Japan  

N/A

Geriatr Gerontol Int2021       CORD-19
302Comparison of SARS-CoV-2 Spike Protein Binding to ACE2 Receptors from Human, Pets, Farm Animals and Putative Intermediate Hosts  

The emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in a pandemic. Here, we used X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptors allows the definition of residues important for binding. From the 20 amino acids in ACE2 that contact S, up to 7 can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or acquisition of N-glycosylation sites located near the S interface. Of note, pigs and dogs, which are not infected or are not effectively infected and have only a few changes in the binding site, exhibit relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with that from bat coronavirus strain RaTG13 (Bat-CoV-RaTG13) and pangolin coronavirus (Pangolin-CoV) strain hCoV-19/pangolin/Guangdong/1/2019 revealed that the latter contains only one substitution, whereas Bat-CoV-RaTG13 exhibits five. However, ACE2 of pangolin exhibits seven changes relative to human ACE2, and a similar number of substitutions is present in ACE2 of bats, raccoon dogs, and civets, suggesting that SARS-CoV-2 may not be especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-CoV-2. IMPORTANCE SARS-CoV-2 is threatening people worldwide, and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear, and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes, indicating that the species barrier might be low. Exceptions are dogs and especially pigs, which revealed relatively low ACE2 expression levels in the respiratory tract. Monitoring of animals is necessary to prevent the generation of a new coronavirus reservoir. Finally, our analysis also showed that SARS-CoV-2 may not be specifically adapted to any of its putative intermediate hosts.

J Virol2020       LitCov and CORD-19
303Stressors faced by healthcare professionals and coping strategies during the early stage of the COVID-19 pandemic in Germany  

BACKGROUND: The COVID-19 pandemic has exerted great pressure on national health systems, which have aimed to ensure comprehensive healthcare at all times. Healthcare professionals working with COVID-19 patients are on the frontline and thereby confronted with enormous demands. Although early reports exist on the psychological impact of the pandemic on frontline medical staff working in Asia, little is known about its impact on healthcare professionals in other countries and across various work sectors. The present cross-sectional, online survey sought to investigate common work stressors among healthcare professionals, their psychological stress as well as coping resources during the pandemic. METHODS: A sample of 575 healthcare professionals (57% male) in three different sectors (hospital, prehospital emergency care, and outpatient service) reported their experiences concerning work and private stressors, psychological stress, and coping strategies between April 17, 2020 and June 5, 2020. To capture pandemic-specific answers, most of the items were adapted or newly developed. Exploratory factor analyses (EFA) were conducted to detect underlying latent factors relating to COVID-specific work stressors. In a next step, the effects of these latent stressors across various work sectors on psychological stress (perceived stress, fatigue, and mood) were examined by means of structural equation models (SEM). To add lived experience to the findings, responses to open-ended questions about healthcare professionals’ stressors, effective crisis measures and prevention, and individual coping strategies were coded inductively, and emergent themes were identified. RESULTS: The EFA revealed that the examined work stressors can be grouped into four latent factors: “fear of transmission”, “interference of workload with private life”, “uncertainty/lack of knowledge”, and “concerns about the team”. The SEM results showed that “interference of workload with private life” represented the pivotal predictor of psychological stress. “Concerns about the team” had stress-reducing effects. The latent stressors had an equal effect on psychological stress across work sectors. On average, psychological stress levels were moderate, yet differed significantly between sectors (all p < .001); the outpatient group experienced reduced calmness and more stress than the other two sectors, while the prehospital group reported lower fatigue than the other two sectors. The prehospital group reported significantly higher concerns about the team than the hospital group (p < .001). In their reports, healthcare professionals highlighted regulations such as social distancing and the use of compulsory masks, training, experience and knowledge exchange, and social support as effective coping strategies during the pandemic. The hospital group mainly mentioned organizational measures such as visiting bans as effective crisis measures, whereas the prehospital sector most frequently named governmental measures such as contact restrictions. CONCLUSION: The study demonstrated the need for sector-specific crisis measures to effectively address the specific work stressors faced by the outpatient sector in particular. The results on pandemic-specific work stressors reveal that healthcare professionals might benefit from coping strategies that facilitate the utilization of social support. At the workplace, team commitment and knowledge exchange might buffer against adverse psychological stress responses. Schedules during pandemics should give healthcare workers the opportunity to interact with families and friends in ways that facilitate social support outside work. Future studies should investigate cross-sector stressors using a longitudinal design to identify both sector- and time-specific measures. Ultimately, an international comparison of stressors and measures in different sectors of healthcare systems is desirable.

PLoS One2022       LitCov and CORD-19
304SARS-CoV-2 Virus-Like Particle Neutralizing Capacity in Blood Donors Depends on Serological Profile and Donor-Declared SARS-CoV-2 Vaccination History  

This study attempted to understand the levels of neutralizing titers and the breadth of antibody protection against wild-type and variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Canadian blood donors during the first 3 months of 2021. During this period, it is unlikely that many of the blood donors had received a second dose, since vaccine rollout had not yet ramped up, and less than 2% of the Canadian population had received a second dose of vaccine. A repeated cross-sectional design was used. A random cross-sectional sampling of all available Canadian Blood Services retention samples (n = 1,500/month) was drawn monthly for January, February, and March 2021. A tiered testing approach analyzed 4,500 Canadian blood donor specimens for potential evidence of a signal for anti-spike (anti-S), anti-receptor-binding domain (anti-RBD), and anti-nucleocapsid protein (anti-N). Specimens were stratified based on donor-declared vaccination history and then stratified on the presence or absence of anti-N as follows: (i) “vaccinated plus anti-N” (n = 5), (ii) “vaccinated and no anti-N” (n = 20), (iii) “unvaccinated plus anti-N” (n = 20), and (iv) “unvaccinated and no anti-N” (n = 20). Randomized specimens were then characterized for neutralizing capacity against wild-type as well as SARS-CoV-2 variants of concern (VOCs) (Alpha [B.1.1.7], Beta [B.1.351], Gamma [P.1], and Delta [B.1.617.2]) using S-pseudotyped virus-like particle (VLP) neutralization assays. There was no neutralizing capacity against wild-type and VOC VLPs within the “no vaccine and no anti-N” group. Neutralization of Beta VLPs was less than wild-type VLPs within “vaccinated plus anti-N,” “vaccinated and no anti-N”, and “unvaccinated plus anti-N” groups. IMPORTANCE In the first 3 months of 2021 as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination was in the initial stages of a mass rollout, Canadian blood donors had various levels of humoral protection against wild-type and variant of concern (VOC) SARS-CoV-2. Very few Canadians would have received a second dose of a SARS-CoV-2 vaccine. In this study, we identified elevated levels of neutralizing capacity, albeit with reduced neutralization capacity against one or more SARS-CoV-2 strains (wild type and VOCs) in vaccinated blood donors. This broad neutralizing response we present regardless of evidence of natural SARS-CoV-2 infection. Neutralizing capacity against wild type and VOCs varied significantly within the unvaccinated group, with one subset of unvaccinated plasma specimens (unvaccinated and no anti-N) having no measurable wild type- nor variant-neutralizing capacity. The study is important because it indicates that vaccination can be associated with a broad neutralizing antibody capacity of donor plasma against SARS-CoV-2 VOCs.

Microbiol Spectr2022       LitCov and CORD-19
305Investigating the Prevalence of Reactive Online Searching in the COVID-19 Pandemic: Infoveillance Study  

BACKGROUND: The ongoing pandemic has placed an unprecedented strain on global society, health care, governments, and mass media. Public dissemination of government policies, medical interventions, and misinformation has been remarkably rapid and largely unregulated during the COVID-19 pandemic, resulting in increased misinterpretations, miscommunication, and public panic. Being the first full-scale global pandemic of the digital age, COVID-19 has presented novel challenges pertinent to government advice, the spread of news and misinformation, and the trade-off between the accessibility of science and the premature public use of unproven medical interventions. OBJECTIVE: This study aims to assess the use of internet search terms relating to COVID-19 information and misinformation during the global pandemic, identify which were most used in six affected countries, investigate any temporal trends and the likely propagators of key search terms, and determine any correlation between the per capita cases and deaths with the adoption of these search terms in each of the six countries. METHODS: This study uses relative search volume data extracted from Google Trends for search terms linked to the COVID-19 pandemic alongside per capita case and mortality data extracted from the European Open Data Portal to identify the temporal dynamics of the spread of news and misinformation during the global pandemic in six affected countries (Australia, Germany, Italy, Spain, the United Kingdom, and the United States). A correlation analysis was carried out to ascertain any correlation between the temporal trends of search term use and the rise of per capita mortality and disease cases. RESULTS: Of the selected search terms, most were searched immediately following promotion by governments, public figures, or viral circulation of information, but also in relation to the publication of scientific resources, which were sometimes misinterpreted before further dissemination. Strong correlations were identified between the volume of these COVID-19–related search terms (overall mean Spearman rho 0.753, SD 0.158), and per capita mortality (mean per capita deaths Spearman rho 0.690, SD 0.168) and cases (mean per capita cases Spearman rho 0.800, SD 0.112). CONCLUSIONS: These findings illustrate the increased rate and volume of the public consumption of novel information during a global health care crisis. The positive correlation between mortality and online searching, particularly in countries with lower COVID-19 testing rates, may demonstrate the imperative to safeguard official communications and dispel misinformation in these countries. Online news, government briefings, and social media provide a powerful tool for the dissemination of important information to the public during pandemics, but their misuse and the presentation of misrepresented medical information should be monitored, minimized, and addressed to safeguard public safety. Ultimately, governments, public health authorities, and scientists have a moral imperative to safeguard the truth and maintain an accessible discourse with the public to limit fear.

J Med Internet Res2020       LitCov and CORD-19
306Risk Factors of Psychological Responses of Chinese University Students During the COVID-19 Outbreak: Cross-sectional Web-Based Survey Study  

BACKGROUND: COVID-19 is a highly contagious and highly pathogenic disease caused by a novel coronavirus, SARS-CoV-2, and it has become a pandemic. As a vulnerable population, university students are at high risk during the epidemic, as they have high mobility and often overlook the severity of the disease because they receive incomplete information about the epidemic. In addition to the risk of death from infection, the epidemic has placed substantial psychological pressure on the public. In this respect, university students are more prone to psychological problems induced by the epidemic compared to the general population because for most students, university life is their first time outside the structure of the family, and their mental development is still immature. Internal and external expectations and academic stress lead to excessive pressure on students, and unhealthy lifestyles also deteriorate their mental health. The outbreak of COVID-19 was a significant social event, and it could potentially have a great impact on the life and the mental health of university students. Therefore, it is of importance to investigate university students’ mental health status during the outbreak of COVID-19. OBJECTIVE: The principal objective of this study was to investigate the influencing factors of the psychological responses of Chinese university students during the COVID-19 outbreak. METHODS: This study used data from a survey conducted in China between February 21 and 24, 2020, and the data set contains demographic information and psychological measures including the Self-Rating Anxiety Scale, the Self-Rating Depression Scale, and the compulsive behaviors portion of the Yale-Brown Obsessive-Compulsive Scale. A total of 2284 questionnaires were returned, and 2270 of them were valid and were used for analysis. The Mann-Whitney U test for two independent samples and binary logistic regression models were used for statistical analysis. RESULTS: Our study surveyed 563 medical students and 1707 nonmedical students. Among them, 251/2270 students (11.06%) had mental health issues. The results showed that contact history of similar infectious disease (odds ratio [OR] 3.363, P=.02), past medical history (OR 3.282, P<.001), and compulsive behaviors (OR 3.525, P<.001) contributed to the risk of mental health issues. Older students (OR 0.928, P=.02), regular daily life during the epidemic outbreak (OR 0.410, P<.001), exercise during the epidemic outbreak (OR 0.456, P<.001), and concern related to COVID-19 (OR 0.638, P=.002) were protective factors for mental health issues. CONCLUSIONS: According to the study results, mental health issues have seriously affected university students, and our results are beneficial for identifying groups of university students who are at risk for possible mental health issues so that universities and families can prevent or intervene in the development of potential mental health issues at the early stage of their development.

J Med Internet Res2021       LitCov and CORD-19
307Bell's palsy following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines: a case series and nested case-control study  

BACKGROUND: Bell's palsy is a rare adverse event reported in clinical trials of COVID-19 vaccines. However, to our knowledge no population-based study has assessed the association between the inactivated SARS-CoV-2 vaccines and Bell's palsy. The aim of this study was to evaluate the risk of Bell's palsy after BNT162b2 and CoronaVac vaccination. METHODS: In this case series and nested case-control study done in Hong Kong, we assessed the risk of Bell's palsy within 42 days following vaccination with BNT162b2 (Fosun–BioNTech [equivalent to Pfizer–BioNTech]) or CoronaVac (from Sinovac Biotech, Hong Kong) using data from voluntary surveillance reporting with the Hospital Authority, the COVID-19 Vaccine Adverse Event Online Reporting system for all health-care professionals, and the Hospital Authority's territory-wide electronic health records from the Clinical Data Analysis and Reporting System. We described reported cases of Bell's palsy among vaccine recipients (aged 18–110 years for CoronaVac and aged 16–110 years for BNT162b2). We compared the estimated age-standardised incidence of clinically confirmed cases among individuals who had received the CoronaVac or BNT162b2 vaccination (up to 42 days before presentation) with the background incidence in the population. A nested case-control study was also done using conditional logistic regression to estimate the odds ratio (OR) for risk of Bell's palsy and vaccination. Cases and controls were matched (1:4) by age, sex, admission setting, and admission date. FINDINGS: Between February 23 and May 4, 2021, 451 939 individuals received the first dose of CoronaVac and 537 205 individuals received the first dose of BNT162b2. 28 clinically confirmed cases of Bell's palsy were reported following CoronaVac and 16 cases were reported following BNT162b2. The age-standardised incidence of clinically confirmed Bell's palsy was 66·9 cases per 100 000 person-years (95% CI 37·2 to 96·6) following CoronaVac vaccination and 42·8 per 100 000 person-years (19·4 to 66·1) for BNT162b2 vaccination. The age-standardised difference for the incidence compared with the background population was 41·5 (95% CI 11·7 to 71·4) for CoronaVac and 17·0 (−6·6 to 40·6) for BNT162b2, equivalent to an additional 4·8 cases per 100 000 people vaccinated for CoronaVac and 2·0 cases per 100 000 people vaccinated for BNT162b2. In the nested case-control analysis, 298 cases were matched to 1181 controls, and the adjusted ORs were 2·385 (95% CI 1·415 to 4·022) for CoronaVac and 1·755 (0·886 to 3·477) for BNT162b2. INTERPRETATION: Our findings suggest an overall increased risk of Bell's palsy after CoronaVac vaccination. However, the beneficial and protective effects of the inactivated COVID-19 vaccine far outweigh the risk of this generally self-limiting adverse event. Additional studies are needed in other regions to confirm our findings. FUNDING: The Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Lancet Infect Dis2021       LitCov and CORD-19
308Multi-centre, three arm, randomized controlled trial on the use of methylprednisolone and unfractionated heparin in critically ill ventilated patients with pneumonia from SARS-CoV-2 infection: A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: To assess the hypothesis that an adjunctive therapy with methylprednisolone and unfractionated heparin (UFH) or with methylprednisolone and low molecular weight heparin (LMWH) are more effective in reducing any-cause mortality in critically-ill ventilated patients with pneumonia from SARS-CoV-2 infection compared to LMWH alone. TRIAL DESIGN: The study is designed as a multi-centre, interventional, parallel group, superiority, randomized, investigator sponsored, three arms study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the three treatment groups in a ratio 1:1:1. PARTICIPANTS: Inpatients will be recruited from 8 Italian Academic and non-Academic Intensive Care Units INCLUSION CRITERIA (ALL REQUIRED): 1. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) 2. Positive pressure ventilation (either non-invasive or invasive) from > 24 hours 3. Invasive mechanical ventilation from < 96 hours 4. PaO(2)/FiO(2) ratio lower than 150 mmHg 5. D-dimer level > 6 times the upper limit of normal reference range 6. C-reactive Protein > 6-fold upper the limit of normal reference range EXCLUSION CRITERIA: 1. Age < 18 years 2. On-going treatment with anticoagulant drugs 3. Platelet count < 100.000/mm(3) 4. History of heparin-induced thrombocytopenia 5. Allergy to sodium enoxaparin or other LMWH, UFH or methylprednisolone 6. Active bleeding or on-going clinical condition deemed at high risk of bleeding contraindicating anticoagulant treatment 7. Recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery 8. Chronic assumption or oral corticosteroids 9. Pregnancy or breastfeeding or positive pregnancy test. In childbearing age women, before inclusion, a pregnancy test will be performed if not available 10. Clinical decision to withhold life-sustaining treatment or “too sick to benefit” 11. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) 12. Lack or withdrawal of informed consent INTERVENTION AND COMPARATOR: • LMWH group: patients in this group will be administered enoxaparin at standard prophylactic dosage. • LMWH + steroid group: patients in this group will receive enoxaparin at standard prophylactic dosage and methylprednisolone. • UFH + steroid group: patients in this group will receive UFH at therapeutic dosages and methylprednisolone. UFH will be administered intravenously in UFH + steroid group at therapeutic doses. The infusion will be started at an infusion rate of 18 UI/kg/hour and then modified to obtain aPTT Ratio in between the range of 1.5-2.0. aPTT will be periodically checked at intervals no longer than 12 hours. The treatment with UFH will be administered up to ICU discharge. After ICU discharge anticoagulant therapy may be interrupted or switched to prophylaxis with LMWH in the destination ward up to clinical judgement of the attending physician. Enoxaparin will be administered in both LMWH group and LMWH + steroid group at standard prophylactic dose (i.e., 4000 UI once day, increased to 6000 UI once day for patients weighting more than 90 kg). The treatment will be administered subcutaneously once a day up to ICU discharge. After ICU discharge it may be continued or interrupted in the destination ward up to clinical judgement of the attending physician. Methylprednisolone will be administered in both LMWH + steroid group and UHF + steroid group intravenously with an initial bolus of 0,5 mg/kg followed by administration of 0,5 mg/kg 4 times daily for 7 days, 0,5 mg/kg 3 times daily from day 8 to day 10, 0,5 mg/kg 2 times daily at days 11 and 12 and 0,5 mg/kg once daily at days 13 and 14. MAIN OUTCOMES: Primary Efficacy Endpoint: All-cause mortality at day 28 Secondary Efficacy Endpoints: - Ventilation free days (VFDs) at day 28, defined as the total number of days that patient is alive and free of ventilation (either invasive or non-invasive) between randomization and day 28 (censored at hospital discharge). - Need of rescue administration of high-dose steroids or immune-modulatory drugs; - Occurrence of switch from non-invasive to invasive mechanical ventilation during ICU stay; - Delay from start of non-invasive ventilation to switch to invasive ventilation; - All-cause mortality at ICU discharge and hospital discharge; - ICU free days (IFDs) at day 28, defined as the total number of days between ICU discharge and day 28. - Occurrence of new infections from randomization to day 28; including infections by Candida, Aspergillus, Adenovirus, Herpes Virus e Cytomegalovirus - Occurrence of new organ dysfunction and grade of dysfunction during ICU stay. - Objectively confirmed venous thromboembolism, stroke or myocardial infarction; Safety endpoints: - Occurrence of major bleeding, defined as transfusion of 2 or more units of packed red blood cells in a day, bleeding that occurs in at least one of the following critical sites [intracranial, intra-spinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal], bleeding that necessitates surgical intervention and bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death); - Occurrence of clinically relevant non-major bleeding, defined ad acute clinically overt bleeding that does not meet the criteria for major and consists of any bleeding compromising hemodynamic; spontaneous hematoma larger than 25 cm(2), intramuscular hematoma documented by ultrasonography, haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures; haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention or any other bleeding requiring temporary cessation of a study drug. RANDOMIZATION: A block randomisation will be used with variable block sizes (block size 4-6-8), stratified by 3 factors: Centre, BMI (<30/≥30) and Age (<75/≥75). Central randomisation will be performed using a secure, web-based, randomisation system with an allocation ratio of 1:1:1. The allocation sequence will be generated by the study statistician using computer generated random numbers. BLINDING (MASKING): Participants to the study will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size is based on the hypothesis that the combined use of UHF and steroid versus the LMWH group will significantly reduce the risk of death at day 28. The overall sample size in this study is expected to be 210 with a randomization 1:1:1 and seventy patients in each group. Assuming an alpha of 2.5% (two tailed) and mortality rate in LMWH group of 50%, as indicated from initial studies of ICU patients, the study will have an 80% power to detect at least a 25 % absolute reduction in the risk of death between: a) LMHW + steroid group and LMWH group or b) UHF + steroid group and LMWH group. The study has not been sized to assess the difference between LMHW + steroid group and UHF + steroid group, therefore the results obtained from this comparison will need to be interpreted with caution and will need further adequately sized studies confirm the effect. On the basis of a conservative estimation, that 8 participating sites admit an average of 3 eligible patients per month per centre (24 patients/month). Assuming that 80 % of eligible patients are enrolled, recruitment of 210 participants will be completed in approximately 10 months. TRIAL STATUS: Protocol version 1.1 of April 26(th), 2020. Recruitment start (expected): September 1(st), 2020 Recruitment finish (expected): June 30(th), 2021 TRIAL REGISTRATION: EudraCT number 2020-001921-30, registered on April 15(th), 2020 AIFA approval on May 4(th), 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19
309COVID-19 Vaccine Hesitancy Among Chinese Population: A Large-Scale National Study  

Globally, vaccine hesitancy is a growing public health problem. It is detrimental to the consolidation of immunization program achievements and elimination of vaccine-targeted diseases. The objective of this study was to estimate the prevalence of COVID-19 vaccine hesitancy in China and explore its contributing factors. A national cross-sectional online survey among Chinese adults (≥18 years old) was conducted between August 6, 2021 and August 9 via a market research company. We collected sociodemographic information; lifestyle behavior; quality of life; the knowledge, awareness, and behavior of COVID-19; the knowledge, awareness, and behavior of COVID-19 vaccine; willingness of COVID-19 vaccination; accessibility of COVID-19 vaccination services; skepticism about COVID-19 and COVID-19 vaccine; doctor and vaccine developer scale; and so on. Odds ratios (OR) with 95% confidence intervals (CI) were used to estimate the associations by using logistic regression models. A total of 29,925 residents (48.64% men) were enrolled in our study with mean age of 30.99 years. We found an overall prevalence of COVID-19 vaccine hesitancy at 8.40% (95% CI, 8.09–8.72) in primary vaccination and 8.39% (95% CI, 8.07–8.70) in booster vaccination. In addition, after adjusting for potential confounders, we found that women, higher educational level, married residents, higher score of health condition, never smoked, increased washing hands, increased wearing mask, increased social distance, lower level of vaccine conspiracy beliefs, disease risks outweigh vaccine risk, higher level of convenient vaccination, and higher level of trust in doctor and developer were more willing to vaccinate than all others (all p < 0.05). Age, sex, educational level, marital status, chronic disease condition, smoking, healthy behaviors, the curability of COVID-19, the channel of accessing information of COVID-19 vaccine, endorsement of vaccine conspiracy beliefs, weigh risks of vaccination against risks of the disease, making a positive influence on the health of others around you, and lower trust in healthcare system may affect the variation of willingness to take a COVID-19 vaccine (all p < 0.05). The prevalence of COVID-19 vaccine hesitancy was modest in China, even with the slight resulting cascade of changing vaccination rates between the primary and booster vaccination. Urgent action to address vaccine hesitancy is needed in building trust in medical personnel and vaccine producers, promoting the convenience of vaccination services, and spreading reliable information of COVID-19 vaccination via the Internet and other media.

Front Immunol2021       LitCov and CORD-19
310Distance learning in clinical medical education amid COVID-19 pandemic in Jordan: current situation, challenges and perspectives  

BACKGROUND: As COVID-19 has been declared as a pandemic disease by the WHO on March 11th, 2020, the global incidence of COVID-19 disease increased dramatically. In response to the COVID-19 situation, Jordan announced the emergency state on the 19th of March, followed by the curfew on 21 March. All educational institutions have been closed as well as educational activities including clinical medical education have been suspended on the 15th of March. As a result, Distance E-learning emerged as a new method of teaching to maintain the continuity of medical education during the COVID-19 pandemic related closure of educational institutions. Distance E-Learning is defined as using computer technology to deliver training, including technology-supported learning either online, offline, or both. Before this period, distance learning was not considered in Jordanian universities as a modality for education. This study aims to explore the situation of distance E-learning among medical students during their clinical years and to identify possible challenges, limitations, satisfaction as well as perspectives for this approach to learning. METHODS: This cross-sectional study is based on a questionnaire that was designed and delivered to medical students in their clinical years. For this study, the estimated sample size (n = 588) is derived from the online Raosoft sample size calculator. RESULTS: A total of 652 students have completed the questionnaire, among them, 538 students (82.5%) have participated in distance learning in their medical schools amid COVID-19 pandemic. The overall satisfaction rate in medical distance learning was 26.8%, and it was significantly higher in students with previous experience in distance learning in their medical schools as well as when instructors were actively participating in learning sessions, using multimedia and devoting adequate time for their sessions. The delivery of educational material using synchronous live streaming sessions represented the major modality of teaching and Internet streaming quality and coverage was the main challenge that was reported by 69.1% of students. CONCLUSION: With advances in technologies and social media, distance learning is a new and rapidly growing approach for undergraduate, postgraduate, and health care providers. It may represent an optimal solution to maintain learning processes in exceptional and emergency situations such as COVID-19 pandemic. Technical and infrastructural resources reported as a major challenge for implementing distance learning, so understanding technological, financial, institutional, educators, and student barriers are essential for the successful implementation of distance learning in medical education.

BMC Med Educ2020       LitCov and CORD-19
311Factors associated with COVID-19-related death using OpenSAFELY  

COVID-19 has rapidly impacted on mortality worldwide.(1) There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19 related deaths. COVID-19 related death was associated with: being male (hazard ratio 1.59, 95%CI 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared to people with white ethnicity, black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.29-1.69 and 1.45, 1.32-1.58 respectively). We have quantified a range of clinical risk factors for COVID-19 related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly.

Nature2020       LitCov and CORD-19
312Ivermectin for preventing and treating COVID-19  

BACKGROUND: Ivermectin, an antiparasitic agent used to treat parasitic infestations, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral mode of action suggests an inhibitory effect on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) replication in the early stages of infection. Currently, evidence on efficacy and safety of ivermectin for prevention of SARS‐CoV‐2 infection and COVID‐19 treatment is conflicting. OBJECTIVES: To assess the efficacy and safety of ivermectin compared to no treatment, standard of care, placebo, or any other proven intervention for people with COVID‐19 receiving treatment as inpatients or outpatients, and for prevention of an infection with SARS‐CoV‐2 (postexposure prophylaxis). SEARCH METHODS: We searched the Cochrane COVID‐19 Study Register, Web of Science (Emerging Citation Index and Science Citation Index), medRxiv, and Research Square, identifying completed and ongoing studies without language restrictions to 26 May 2021. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing ivermectin to no treatment, standard of care, placebo, or another proven intervention for treatment of people with confirmed COVID‐19 diagnosis, irrespective of disease severity, treated in inpatient or outpatient settings, and for prevention of SARS‐CoV‐2 infection. Co‐interventions had to be the same in both study arms. We excluded studies comparing ivermectin to other pharmacological interventions with unproven efficacy. DATA COLLECTION AND ANALYSIS: We assessed RCTs for bias, using the Cochrane risk of bias 2 tool. The primary analysis excluded studies with high risk of bias. We used GRADE to rate the certainty of evidence for the following outcomes 1. to treat inpatients with moderate‐to‐severe COVID‐19: mortality, clinical worsening or improvement, adverse events, quality of life, duration of hospitalization, and viral clearance; 2. to treat outpatients with mild COVID‐19: mortality, clinical worsening or improvement, admission to hospital, adverse events, quality of life, and viral clearance; (3) to prevent SARS‐CoV‐2 infection: SARS‐CoV‐2 infection, development of COVID‐19 symptoms, adverse events, mortality, admission to hospital, and quality of life. MAIN RESULTS: We found 14 studies with 1678 participants investigating ivermectin compared to no treatment, placebo, or standard of care. No study compared ivermectin to an intervention with proven efficacy. There were nine studies treating participants with moderate COVID‐19 in inpatient settings and four treating mild COVID‐19 cases in outpatient settings. One study investigated ivermectin for prevention of SARS‐CoV‐2 infection. Eight studies had an open‐label design, six were double‐blind and placebo‐controlled. Of the 41 study results contributed by included studies, about one third were at overall high risk of bias. Ivermectin doses and treatment duration varied among included studies. We identified 31 ongoing and 18 studies awaiting classification until publication of results or clarification of inconsistencies. Ivermectin compared to placebo or standard of care for inpatient COVID‐19 treatment We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.14 to 2.51; 2 studies, 185 participants; very low‐certainty evidence) and clinical worsening up to day 28 assessed as need for invasive mechanical ventilation (IMV) (RR 0.55, 95% CI 0.11 to 2.59; 2 studies, 185 participants; very low‐certainty evidence) or need for supplemental oxygen (0 participants required supplemental oxygen; 1 study, 45 participants; very low‐certainty evidence), adverse events within 28 days (RR 1.21, 95% CI 0.50 to 2.97; 1 study, 152 participants; very low‐certainty evidence), and viral clearance at day seven (RR 1.82, 95% CI 0.51 to 6.48; 2 studies, 159 participants; very low‐certainty evidence). Ivermectin may have little or no effect compared to placebo or standard of care on clinical improvement up to 28 days (RR 1.03, 95% CI 0.78 to 1.35; 1 study; 73 participants; low‐certainty evidence) and duration of hospitalization (mean difference (MD) −0.10 days, 95% CI −2.43 to 2.23; 1 study; 45 participants; low‐certainty evidence). No study reported quality of life up to 28 days. Ivermectin compared to placebo or standard of care for outpatient COVID‐19 treatment We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality up to 28 days (RR 0.33, 95% CI 0.01 to 8.05; 2 studies, 422 participants; very low‐certainty evidence) and clinical worsening up to 14 days assessed as need for IMV (RR 2.97, 95% CI 0.12 to 72.47; 1 study, 398 participants; very low‐certainty evidence) or non‐IMV or high flow oxygen requirement (0 participants required non‐IMV or high flow; 1 study, 398 participants; very low‐certainty evidence). We are uncertain whether ivermectin compared to placebo reduces or increases viral clearance at seven days (RR 3.00, 95% CI 0.13 to 67.06; 1 study, 24 participants; low‐certainty evidence). Ivermectin may have little or no effect compared to placebo or standard of care on the number of participants with symptoms resolved up to 14 days (RR 1.04, 95% CI 0.89 to 1.21; 1 study, 398 participants; low‐certainty evidence) and adverse events within 28 days (RR 0.95, 95% CI 0.86 to 1.05; 2 studies, 422 participants; low‐certainty evidence). None of the studies reporting duration of symptoms were eligible for primary analysis. No study reported hospital admission or quality of life up to 14 days. Ivermectin compared to no treatment for prevention of SARS‐CoV‐2 infection We found one study. Mortality up to 28 days was the only outcome eligible for primary analysis. We are uncertain whether ivermectin reduces or increases mortality compared to no treatment (0 participants died; 1 study, 304 participants; very low‐certainty evidence). The study reported results for development of COVID‐19 symptoms and adverse events up to 14 days that were included in a secondary analysis due to high risk of bias. No study reported SARS‐CoV‐2 infection, hospital admission, and quality of life up to 14 days. AUTHORS' CONCLUSIONS: Based on the current very low‐ to low‐certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent COVID‐19. The completed studies are small and few are considered high quality. Several studies are underway that may produce clearer answers in review updates. Overall, the reliable evidence available does not support the use ivermectin for treatment or prevention of COVID‐19 outside of well‐designed randomized trials.

Cochrane Database Syst Rev2021       LitCov and CORD-19
3136-month consequences of COVID-19 in patients discharged from hospital: a cohort study  

BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5–6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0–65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0–199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5–6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5–6, and median CT scores were 3·0 (IQR 2·0–5·0) for severity scale 3, 4·0 (3·0–5·0) for scale 4, and 5·0 (4·0–6·0) for scale 5–6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80–3·25) for scale 4 versus scale 3 and 4·60 (1·85–11·48) for scale 5–6 versus scale 3 for diffusion impairment; OR 0·88 (0·66–1·17) for scale 4 versus scale 3 and OR 1·77 (1·05–2·97) for scale 5–6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58–0·96) for scale 4 versus scale 3 and 2·69 (1·46–4·96) for scale 5–6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m(2) or more at acute phase had eGFR less than 90 mL/min per 1·73 m(2) at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

Lancet2021       LitCov and CORD-19
314New York Inner City Hospital COVID-19 Experience and Current Data: Retrospective Analysis at the Epicenter of the American Coronavirus Outbreak  

BACKGROUND: In the midst of the coronavirus disease pandemic, emerging clinical data across the world has equipped frontline health care workers, policy makers, and researchers to better understand and combat the illness. OBJECTIVE: The aim of this study is to report the correlation of clinical and laboratory parameters with patients requiring mechanical ventilation and the mortality in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We did a review of patients with SARS-CoV-2 confirmed infection admitted and managed by our institution during the last month. Patients were grouped into intubated and nonintubated, and subgrouped to alive and deceased. A comprehensive analysis using the following parameters were performed: age, sex, ethnicity, BMI, comorbidities, inflammatory markers, laboratory values, cardiac and renal function, electrocardiogram (EKG), chest x-ray findings, temperature, treatment groups, and hospital-acquired patients with SARS-CoV-2. RESULTS: A total of 184 patients were included in our study with ages ranging from 28-97 years (mean 64.72 years) and including 73 females (39.67%) and 111 males (60.33%) with a mean BMI of 29.10. We had 114 African Americans (61.96%), 58 Hispanics (31.52%), 11 Asians (5.98%), and 1 Caucasian (0.54%), with a mean of 1.70 comorbidities. Overall, the mortality rate was 17.39% (n=32), 16.30% (n=30) of our patients required mechanical ventilation, and 11.41% (n=21) had hospital-acquired SARS-CoV-2 infection. Pertinent and statistically significant results were found in the intubated versus nonintubated patients with confirmed SARS-CoV-2 for the following parameters: age (P=.01), BMI (P=.07), African American ethnicity (P<.001), Hispanic ethnicity (P=.02), diabetes mellitus (P=.001), creatinine (P=.29), blood urea nitrogen (BUN; P=.001), procalcitonin (P=.03), C-reactive protein (CRP; P=.007), lactate dehydrogenase (LDH; P=.001), glucose (P=.01), temperature (P=.004), bilateral pulmonary infiltrates in chest x-rays (P<.001), and bilateral patchy opacity (P=.02). The results between the living and deceased subgroups of patients with confirmed SARS-CoV-2 (linking to or against mortality) were BMI (P=.04), length of stay (P<.001), hypertension (P=.02), multiple comorbidity (P=.045), BUN (P=.04), and EKG findings with arrhythmias or blocks (P=.02). CONCLUSIONS: We arrived at the following conclusions based on a comprehensive review of our study group, data collection, and statistical analysis. Parameters that were strongly correlated with the need for mechanical ventilation were younger age group, overweight, Hispanic ethnicity, higher core body temperature, EKG findings with sinus tachycardia, and bilateral diffuse pulmonary infiltrates on the chest x-rays. Those intubated exhibited increased disease severity with significantly elevated levels of serum procalcitonin, CRP, LDH, mean glucose, creatinine, and BUN. Mortality was strongly correlated with BMI, African American ethnicity, hypertension, presence of multiple comorbidities (with a mean of 2.32), worsening renal function with acute kidney injury or acute chronic kidney injury, and EKG findings of arrhythmias and heart blocks.

J Med Internet Res2020       LitCov and CORD-19
315SARS-CoV-2 mRNA Vaccines Elicit Different Responses in Immunologically Naïve and Pre-Immune Humans  

As the COVID-19 pandemic continues, the authorization of vaccines for emergency use has been crucial in slowing down the rate of infection and transmission of the SARS-CoV-2 virus that causes COVID-19. In order to investigate the longitudinal serological responses to SARS-CoV-2 natural infection and vaccination, a large-scale, multi-year serosurveillance program entitled SPARTA (SARS SeroPrevalence and Respiratory Tract Assessment) was initiated at 4 locations in the U.S. The serological assay presented here measuring IgG binding to the SARS-CoV-2 receptor binding domain (RBD) detected antibodies elicited by SARS-CoV-2 infection or vaccination with a 95.5% sensitivity and a 95.9% specificity. We used this assay to screen more than 3100 participants and selected 20 previously infected pre-immune and 32 immunologically naïve participants to analyze their antibody binding to RBD and viral neutralization (VN) responses following vaccination with two doses of either the Pfizer-BioNTech BNT162b2 or the Moderna mRNA-1273 vaccine. Vaccination not only elicited a more robust immune reaction than natural infection, but the level of neutralizing and anti-RBD antibody binding after vaccination is also significantly higher in pre-immune participants compared to immunologically naïve participants (p<0.0033). Furthermore, the administration of the second vaccination did not further increase the neutralizing or binding antibody levels in pre-immune participants (p=0.69). However, ~46% of the immunologically naïve participants required both vaccinations to seroconvert.

Front Immunol2021       LitCov and CORD-19
316COVID-19 CG enables SARS-CoV-2 mutation and lineage tracking by locations and dates of interest  

COVID-19 CG (covidcg.org) is an open resource for tracking SARS-CoV-2 single-nucleotide variations (SNVs), lineages, and clades using the virus genomes on the GISAID database while filtering by location, date, gene, and mutation of interest. COVID-19 CG provides significant time, labor, and cost-saving utility to projects on SARS-CoV-2 transmission, evolution, diagnostics, therapeutics, vaccines, and intervention tracking. Here, we describe case studies in which users can interrogate (1) SNVs in the SARS-CoV-2 spike receptor binding domain (RBD) across different geographical regions to inform the design and testing of therapeutics, (2) SNVs that may impact the sensitivity of commonly used diagnostic primers, and (3) the emergence of a dominant lineage harboring an S477N RBD mutation in Australia in 2020. To accelerate COVID-19 efforts, COVID-19 CG will be upgraded with new features for users to rapidly pinpoint mutations as the virus evolves throughout the pandemic and in response to therapeutic and public health interventions.

Elife2021       LitCov and CORD-19
317Comparative Effectiveness and Antibody Responses to Moderna and Pfizer-BioNTech COVID-19 Vaccines among Hospitalized Veterans-Five Veterans Affairs Medical Centers, United States, February 1-September 30, 2021  

The mRNA COVID-19 vaccines (Moderna and Pfizer-BioNTech) provide strong protection against severe COVID-19, including hospitalization, for at least several months after receipt of the second dose (1,2). However, studies examining immune responses and differences in protection against COVID-19-associated hospitalization in real-world settings, including by vaccine product, are limited. To understand how vaccine effectiveness (VE) might change with time, CDC and collaborators assessed the comparative effectiveness of Moderna and Pfizer-BioNTech vaccines in preventing COVID-19-associated hospitalization at two periods (14-119 days and ≥120 days) after receipt of the second vaccine dose among 1,896 U.S. veterans at five Veterans Affairs medical centers (VAMCs) during February 1-September 30, 2021. Among 234 U.S. veterans fully vaccinated with an mRNA COVID-19 vaccine and without evidence of current or prior SARS-CoV-2 infection, serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2 were also compared. Adjusted VE 14-119 days following second Moderna vaccine dose was 89.6% (95% CI = 80.1%-94.5%) and after the second Pfizer-BioNTech dose was 86.0% (95% CI = 77.6%-91.3%); at ≥120 days VE was 86.1% (95% CI = 77.7%-91.3%) for Moderna and 75.1% (95% CI = 64.6%-82.4%) for Pfizer-BioNTech. Antibody levels were significantly higher among Moderna recipients than Pfizer-BioNTech recipients across all age groups and periods since vaccination; however, antibody levels among recipients of both products declined between 14-119 days and ≥120 days. These findings from a cohort of older, hospitalized veterans with high prevalences of underlying conditions suggest the importance of booster doses to help maintain long-term protection against severe COVID-19.†.

MMWR Morb Mortal Wkly Rep2021       LitCov and CORD-19
318Seroresponse to SARS-CoV-2 Vaccines among Maintenance Dialysis Patients over 6 Months  

N/A

Clin J Am Soc Nephrol2022       LitCov and CORD-19
319SARS-CoV-2 B.1.1.529 (Omicron) Variant-United States, December 1-8, 2021  

A new variant of SARS-CoV-2 (the virus that causes COVID-19), B.1.1.529 (Omicron) (1), was first reported to the World Health Organization (WHO) by South Africa on November 24, 2021. Omicron has numerous mutations with potential to increase transmissibility, confer resistance to therapeutics, or partially escape infection- or vaccine-induced immunity (2). On November 26, WHO designated B.1.1.529 as a variant of concern (3), as did the U.S. SARS-CoV-2 Interagency Group (SIG)* on November 30. On December 1, the first case of COVID-19 attributed to the Omicron variant was reported in the United States. As of December 8, a total of 22 states had identified at least one Omicron variant case, including some that indicate community transmission. Among 43 cases with initial follow-up, one hospitalization and no deaths were reported. This report summarizes U.S. surveillance for SARS-CoV-2 variants, characteristics of the initial persons investigated with COVID-19 attributed to the Omicron variant and public health measures implemented to slow the spread of Omicron in the United States. Implementation of concurrent prevention strategies, including vaccination, masking, increasing ventilation, testing, quarantine, and isolation, are recommended to slow transmission of SARS-CoV-2, including variants such as Omicron, and to protect against severe illness and death from COVID-19.

MMWR Morb Mortal Wkly Rep2021       LitCov and CORD-19
320Factors Influencing COVID-19 Vaccination Intentions Among College Students: A Cross-Sectional Study in India  

Background: Students act as messengers in delivering effective messages for better uptake of health-promoting behavior. Understanding their knowledge about coronavirus disease 2019 (COVID-19), intentions to use the COVID-19 vaccine, and its associated factors will help develop promising strategies in vaccine promotion concerning the current COVID-19 pandemic. Methods: A cross-sectional online survey was carried out among students in the healthcare and non-healthcare sectors to assess their intentions to get vaccinated against the COVID-19. A non-probability snowball sampling technique was used to recruit study participants (N = 655) through social media platforms and emails. Study participants were recruited across the country, including six major geographical regions (Eastern, Western, Northern, Southern, North-east, and Central) in India between November 2020 and January 2021 before the introduction of the COVID-19 vaccine. Descriptive statistics were used to present the sociodemographic, and vaccine-related behaviors of the study participants. Key determinants that likely predict vaccine acceptance among students were modeled using logistic regression analysis. For each analysis, p < 0.05 was considered significant. Results: A total of 655 students were recruited, 323 from healthcare and 332 from non-healthcare sectors, to assess their intentions to receive the COVID-19 vaccine. Of the 655 students, 63.8% expressed intentions to receive the COVID-19 vaccine. The acceptance was higher among non-healthcare students (54.07 vs. 45.93%). At the time of the study, 27.8% of the students indicated that they had been exposed to a confirmed COVID-19 patient. A vast majority (93.4%) of the students knew about the COVID-19 virus, and most (89.3%) of them were aware of the development of a COVID-19 vaccine. The history of vaccine hesitancy was found to be low (17.1%). Only one-third (33.4%) of the students showed concern about contracting COVID-19. Trust in the healthcare system [adjusted odds ratio (aOR): 4.13; (95% CI: 2.83–6.04), p < 0.00] and trust in domestic vaccines [aOR: 1.46; (95% CI: 1.02–2.08), p < 0.05] emerged as the significant predictors of student's intention to get vaccinated. Higher acceptance for vaccine was observed among students in the non-healthcare [aOR: 1.982; 95% CI: 1.334–2.946, p < 0.00]. Conclusion: This study shows that the Indian college students had relatively high levels of positive intentions to receive COVID-19 vaccines, although about one-third were not sure or unwilling to receive the vaccine, highlighting possible vaccine hesitancy. Informational campaigns and other strategies to address vaccine hesitancy are needed to promote uptake of COVID-19 vaccines.

Front Public Health2021       LitCov and CORD-19
321Pathological findings of COVID-19 associated with acute respiratory distress syndrome  

Lancet Respir Med2020       LitCov and CORD-19
322Association of Age With Likelihood of Developing Symptoms and Critical Disease Among Close Contacts Exposed to Patients With Confirmed SARS-CoV-2 Infection in Italy  

We quantified the probability of developing symptoms (respiratory or fever geq 37.5 {deg}C) and critical disease (requiring intensive care or resulting in death) of SARS-CoV-2 positive subjects. 5,484 contacts of SARS-CoV-2 index cases detected in Lombardy, Italy were analyzed, and positive subjects were ascertained via nasal swabs and serological assays. 73.9% of all infected individuals aged less than 60 years did not develop symptoms (95% confidence interval: 71.8-75.9%). The risk of symptoms increased with age. 6.6% of infected subjects older than 60 years had critical disease, with males at significantly higher risk.

JAMA Netw Open2021       LitCov and CORD-19
323How has COVID-19 affected mental health nurses and the delivery of mental health nursing care in the UK? Results of a mixed-methods study  

WHAT IS KNOWN ON THE SUBJECT? During the COVID‐19 pandemic, there has been research considering the impact on medical healthcare professionals and the mental health needs of the general population. However, limited focus has been placed on mental health services or mental health staff providing care in the community and in hospitals. While nurses make up the largest section of the mental health workforce in the UK, the impact that this pandemic has had on their work has been largely ignored. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE? This paper provides a unique insight into the experiences and impact that the COVID‐19 pandemic has had on mental health nurses across a range of community and inpatient settings to understand what has changed in their work and the care they can and do provide during this crisis. This includes exploring how services have changed, the move to remote working, the impact of the protective equipment crisis on nurses and the difficult working conditions facing those in inpatient settings where there is minimal guidance provided. WHAT ARE THE IMPLICATIONS FOR PRACTICE? By understanding the impact the pandemic has had on mental health nursing care, we can understand the gaps in guidance that exist, the challenges being faced and the impact the crisis has had on care for mental health service users. By doing so, we can plan for the ongoing nature of this pandemic and the aftermath that the crisis may leave for our service users and workforce alike. ABSTRACT: INTRODUCTION: While evidence has emerged concerning the impact of COVID‐19 on the general population and the challenges facing health services, much less is known regarding how the pandemic has directly affected the delivery of mental health nursing care. AIM: This paper aimed to explore how COVID‐19 has affected the ability of mental health nurses to deliver care in community and inpatient mental health services in the UK. METHOD: We investigated staff reports regarding the impact of the COVID‐19 pandemic on mental healthcare and mental health service users in the UK, using a mixed‐methods online survey. A total of 897 nurses across a range of inpatient and community settings participated. DISCUSSION: Key themes within the data explore the following: new ways of working; remote working; risks of infection/infection control challenges; and the impact on service users. Targeted guidelines are required to support mental health nurses providing care and support during a pandemic to people in severe mental distress, often in unsuitable environments. IMPLICATIONS FOR PRACTICE: Service developments need to occur alongside tailored guidance and support for staff welfare supported by clear leadership. These findings identify areas requiring attention and investment to prepare for future crises and the consequences of the pandemic.

J Psychiatr Ment Health Nurs2021       LitCov and CORD-19
324Seroprevalence of Unidentified SARS-CoV-2 Infection in Hong Kong During 3 Pandemic Waves  

IMPORTANCE: Seroprevalence studies inform the extent of infection and assist evaluation of mitigation strategies for the COVID-19 pandemic. OBJECTIVE: To estimate the prevalence of unidentified SARS-CoV-2 infection in the general population of Hong Kong. DESIGN, SETTING, AND PARTICIPANTS: A prospective cross-sectional study was conducted in Hong Kong after each major wave of the COVID-19 pandemic (April 21 to July 7, 2020; September 29 to November 23, 2020; and January 15 to April 18, 2021). Adults (age ≥18 years) who had not been diagnosed with COVID-19 were recruited during each period, and their sociodemographic information, symptoms, travel, contact, quarantine, and COVID-19 testing history were collected. MAIN OUTCOMES AND MEASURES: The main outcome was prevalence of SARS-CoV-2 infection. SARS-CoV-2 IgG antibodies were detected by an enzyme-linked immunosorbent assay based on spike (S1/S2) protein, followed by confirmation with a commercial electrochemiluminescence immunoassay based on the receptor binding domain of spike protein. RESULTS: The study enrolled 4198 participants (2539 [60%] female; median age, 50 years [IQR, 25 years]), including 903 (22%), 1046 (25%), and 2249 (53%) during April 21 to July 7, 2020; during September 29 to November 23, 2020; and during January 15 to April 18, 2021, respectively. The numbers of participants aged 18 to 39 years, 40 to 59 years, and 60 years or older were 1328 (32%), 1645 (39%), and 1225 (29%), respectively. Among the participants, 2444 (58%) stayed in Hong Kong since November 2019 and 2094 (50%) had negative SARS-CoV-2 RNA test results. Only 170 (4%) reported ever having contact with individuals with confirmed cases, and 5% had been isolated or quarantined. Most (2803 [67%]) did not recall any illnesses, whereas 737 (18%), 212 (5%), and 385 (9%) had experienced respiratory symptoms, gastrointestinal symptoms, or both, respectively, before testing. Six participants were confirmed to be positive for anti-SARS-CoV-2 IgG; the adjusted prevalence of unidentified infection was 0.15% (95% CI, 0.06%-0.32%). Extrapolating these findings to the whole population, there were fewer than 1.9 unidentified infections for every recorded confirmed case. The overall prevalence of SARS-CoV-2 infection in Hong Kong before the roll out of vaccination was less than 0.45%. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of participants from the general public in Hong Kong, the prevalence of unidentified SARS-CoV-2 infection was low after 3 major waves of the pandemic, suggesting the success of the pandemic mitigation by stringent isolation and quarantine policies even without complete city lockdown. More than 99.5% of the general population of Hong Kong remain naive to SARS-CoV-2, highlighting the urgent need to achieve high vaccine coverage.

JAMA Netw Open2021       LitCov and CORD-19
325Vaccine effectiveness against SARS-CoV-2 infection, hospitalization and death when combining a first dose ChAdOx1 vaccine with a subsequent mRNA vaccine in Denmark: A nationwide population-based cohort study  

BACKGROUND: The recommendations in several countries to stop using the ChAdOx1 vaccine has led to vaccine programs combining different Coronavirus Disease 2019 (COVID-19) vaccine types, which necessitates knowledge on vaccine effectiveness (VE) of heterologous vaccine schedules. The aim of this Danish nationwide population-based cohort study was therefore to estimate the VE against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and COVID-19–related hospitalization and death following the first dose of the ChAdOx1 vaccine and the combination of the ChAdOx1/mRNA vaccines. METHODS AND FINDINGS: All individuals alive in or immigrating to Denmark from 9 February 2021 to 23 June 2021 were identified in the Danish Civil Registration System. Information on exposure, outcomes, and covariates was obtained from Danish national registries. Poisson and Cox regression models were used to calculate crude and adjusted VE, respectively, along with 95% confidence intervals (CIs) against SARS-CoV-2 infection and COVID-19–related hospitalization or death comparing vaccinated versus unvaccinated individuals. The VE estimates were adjusted for calendar time as underlying time and for sex, age, comorbidity, country of origin, and hospital admission. The analyses included 5,542,079 individuals (97.6% of the total Danish population). A total of 144,360 individuals were vaccinated with the ChAdOx1 vaccine as the first dose, and of these, 136,551 individuals received an mRNA vaccine as the second dose. A total of 1,691,464 person-years and 83,034 SARS-CoV-2 infections were included. The individuals vaccinated with the first dose of the ChAdOx1 vaccine dose had a median age of 45 years. The study population was characterized by an equal distribution of males and females; 6.7% and 9.2% originated from high-income and other countries, respectively. The VE against SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine was 88% (95% CI: 83; 92) 14 days after the second dose and onwards. There were no COVID-19–related hospitalizations or deaths among the individuals vaccinated with the combined vaccine schedule during the study period. Study limitations including unmeasured confounders such as risk behavior and increasing overall vaccine coverage in the general population creating herd immunity are important to take into consideration when interpreting the results. CONCLUSIONS: In this study, we observed a large reduction in the risk of SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine, compared with unvaccinated individuals.

PLoS Med2021       LitCov and CORD-19
326Exploring the use and challenges of implementing virtual visits during COVID-19 in primary care and lessons for sustained use  

BACKGROUND: The COVID-19 pandemic has rapidly transformed how healthcare is delivered to limit the transmission of the virus. This descriptive cross-sectional study explored the current use of virtual visits in providing care among primary care providers in southwestern Ontario during the first wave of the COVID-19 pandemic and the anticipated level of utilization post-pandemic. It also explored clinicians’ perceptions of the available support tools and resources and challenges to incorporating virtual visits within primary care practices. METHODS: Primary care physicians and nurse practitioners currently practicing in the southwestern part of Ontario were invited to participate in an online survey. The survey invite was distributed via email, different social media platforms, and newsletters. The survey questions gathered clinicians’ demographic information and assessed their experience with virtual visits, including the proportion of visits conducted virtually (before, during the pandemic, and expected volume post-pandemic), overall satisfaction and comfort level with offering virtual visits using modalities, challenges experienced, as well as useful resources and tools to support them in using virtual visits in their practice. RESULTS: We received 207 responses, with 96.6% of respondents offering virtual visits in their practice. Participants used different modalities to conduct virtual visits, with the vast majority offering visits via phone calls (99.5%). Since the COVID-19 pandemic, clinicians who offered virtual visits have conducted an average of 66.4% of their visits virtually, compared to an average of 6.5% pre-pandemic. Participants anticipated continuing use of virtual visits with an average of 43.9% post-pandemic. Overall, 74.5% of participants were satisfied with their experience using virtual visits, and 88% believed they could incorporate virtual visits well within the usual workflow. Participants highlighted some challenges in offering virtual care. For example, 58% were concerned about patients’ limited access to technology, 55% about patients’ knowledge of technology, and 41% about the lack of integration with their current EMR, the increase in demand over time, and the connectivity issues such as inconsistent Wi-Fi/Internet connection. There were significant differences in perception of some challenges between clinicians in urban vs, rural areas. Clinicians in rural areas were more likely to consider the inconsistent Wi-Fi and limited connectivity as barriers to incorporating virtual visits within the practice setting (58.8% vs. 40.2%, P = 0.030). In comparison, clinicians in urban areas were significantly more concerned about patients overusing virtual care services (39.4% vs. 21.6%, P = 0.024). As for support tools, 47% of clinicians advocated for virtual care standards outlined by their profession’s college. About 32% identified change management support and technical training as supportive tools. Moreover, 39% and 28% thought local colleagues and in-house organizational support are helpful resources, respectively. CONCLUSION: Our study shows that the adoption of virtual visits has exponentially increased during the pandemic, with a significant interest in continuing to use virtual care options in the delivery of primary care post-pandemic. The study sheds light on tools and resources that could enhance operational efficiencies in adopting virtual visits in primary care settings and highlights challenges that, when addressed, can expand the health system capacity and sustained use of virtual care.

PLoS One2021       LitCov and CORD-19
327The outbreak of the novel SARS-CoV-2: A review of the current global status  

There is currently an ongoing worldwide pandemic of a novel virus belonging to the family of Coronaviruses (CoVs) which are large, enveloped, plus-stranded RNA viruses. Coronaviruses belong to the order of Nidovirales, family of Coronavirinae and are divided into four genera: alphacoronavirus, betacoronavirus, gammacoronavirus and deltacoronavirus. CoVs cause diseases in a wide variety of birds and mammals and have been found in humans since 1960. To date, seven human CoVs were identified including the alpha-CoVs HCoVs-NL63 and HCoVs-229E and the beta-CoVs HCoVs-OC43, HCoVs-HKU1, the severe acute respiratory syndrome-CoV (SARS-CoV), the Middle East respiratory syndrome-CoV (MERS-CoV) and the novel virus that first appeared in December 2019 in Wuhan, China, and rapidly spread to 213 countries as of the writing this paper. It was officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the international committee on taxonomy of viruses (ICTV) and the disease’s name is COVID-19 for coronavirus disease 2019. SARS-CoV-2 is very contagious and is capable of spreading from human to human. Infection routes include droplet and contact, and aerosol transmission is currently under investigation. It is associated with a respiratory illness that may cause severe pneumonia and acute respiratory distress syndrome (ARDS). SARS-CoV-2 became an emergency of international concern. As of July 12, 2020, the virus has been responsible for 12,698,995 confirmed cases and 564,924 deaths worldwide and the number is still increasing. Up until now, no specific treatment has yet been proven effective against SARS-CoV-2. Since the beginning of this outbreak, several interesting papers on SARS-CoV-2 and COVID-19 have been published to report on the phylogenetic evolution, epidemiology, pathogenesis, transmission as well as clinical characteristics of COVID-19 and possible treatments agents. This paper is a systematic review of the available literature on SARS-CoV-2. It was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and aims to help readers access the latest knowledge surrounding this new infectious disease and to provide a reference for future studies.

J Infect Public Health2020       LitCov and CORD-19
328Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection  

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Nat Med2021       LitCov and CORD-19
329A longitudinal study on the mental health of general population during the COVID-19 epidemic in China  

Abstract In addition to being a public physical health emergency, Coronavirus disease 2019 (COVID-19) affected global mental health, as evidenced by panic-buying worldwide as cases soared. Little is known about changes in levels of psychological impact, stress, anxiety and depression during this pandemic. This longitudinal study surveyed the general population twice - during the initial outbreak, and the epidemic's peak four weeks later, surveying demographics, symptoms, knowledge, concerns, and precautionary measures against COVID-19. There were 1738 respondents from 190 Chinese cities (1210 first-survey respondents, 861 second-survey respondents; 333 respondents participated in both). Psychological impact and mental health status were assessed by the Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety and Stress Scale (DASS-21), respectively. IES-R measures PTSD symptoms in survivorship after an event. DASS -21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. This study found that there was a statistically significant longitudinal reduction in mean IES-R scores (from 32.98 to 30.76, p<0.01) after 4 weeks. Nevertheless, the mean IES-R score of the first- and second-survey respondents were above the cut-off scores (>24) for PTSD symptoms, suggesting that the reduction in scores was not clinically significant. During the initial evaluation, moderate-to-severe stress, anxiety and depression were noted in 8.1%, 28.8% and 16.5%, respectively and there were no significant longitudinal changes in stress, anxiety and depression levels (p>0.05). Protective factors included high level of confidence in doctors, perceived survival likelihood and low risk of contracting COVID-19, satisfaction with health information, personal precautionary measures. As countries around the world brace for an escalation in cases, Governments should focus on effective methods of disseminating unbiased COVID-19 knowledge, teaching correct containment methods, ensuring availability of essential services/commodities, and providing sufficient financial support.

Brain Behav Immun2020       LitCov and CORD-19
330Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR  

BACKGROUND: The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. AIM: We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. METHODS: Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. RESULTS: The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. CONCLUSION: The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.

Euro Surveill2020       LitCov and CORD-19
331Update on SARS-CoV-2 Omicron Variant of Concern and Its Peculiar Mutational Profile  

The process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversification is still ongoing and has very recently led to the emergence of a new variant of concern (VOC), defined as Omicron or B.1.1.529. Omicron VOC is the most divergent variant identified so far and has generated immediate concern for its potential capability to increase SARS-CoV-2 transmissibility and, more worryingly, to escape therapeutic and vaccine-induced antibodies. Nevertheless, a clear definition of the Omicron VOC mutational spectrum is still missing. Herein, we provide a comprehensive definition and functional characterization (in terms of infectivity and/or antigenicity) of mutations characterizing the Omicron VOC. In particular, 887,475 SARS-CoV-2 Omicron VOC whole-genome sequences were retrieved from the GISAID database and used to precisely define its specific patterns of mutations across the different viral proteins. In addition, the functional characterization of Omicron VOC spike mutations was finely discussed according to published manuscripts. Lastly, residues characterizing the Omicron VOC and the previous four VOCs (Alpha, Beta, Gamma, and Delta) were mapped on the three-dimensional structure of the SARS-CoV-2 spike protein to assess their localization in the different spike domains. Overall, our study will assist with deciphering the Omicron VOC mutational profile and will shed more light on its clinical implications. This is critical considering that Omicron VOC is currently the predominant variant worldwide. IMPORTANCE The Omicron variant of concern (VOC) has a peculiar spectrum of mutations characterized by the acquisition of mutations or deletions rarely detected in previously identified variants, particularly in the spike glycoprotein. Such mutations, mostly residing in the receptor-binding domain, could play a pivotal role in enhancing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity (by increasing binding affinity for ACE2), jeopardizing spike recognition by therapeutic and vaccine-induced antibodies and causing diagnostic assay failure. To our knowledge, this is one of the first exhaustive descriptions of newly emerged mutations underlying the Omicron VOC and its biological and clinical implications.

Microbiol Spectr2022       LitCov and CORD-19
332Attitudes and Intentions of US Veterans Regarding COVID-19 Vaccination  

IMPORTANCE: Compared with the general population, veterans are at high risk for COVID-19 and have a complex relationship with the government. This potentially affects their attitudes toward receiving COVID-19 vaccines. OBJECTIVE: To assess veterans’ attitudes toward and intentions to receive COVID-19 vaccines. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional web-based survey study used data from the Department of Veterans Affairs (VA) Survey of Healthcare Experiences of Patients’ Veterans Insight Panel, fielded between March 12 and 28, 2021. Of 3420 veterans who were sent a link to complete a 58-item web-based survey, 1178 veterans (34%) completed the survey. Data were analyzed from April 1 to August 25, 2021. EXPOSURES: Veterans eligible for COVID-19 vaccines. MAIN OUTCOMES AND MEASURES: The outcomes of interest were veterans’ experiences with COVID-19, vaccination status and intention groups, reasons for receiving or not receiving a vaccine, self-reported health status, and trusted and preferred sources of information about COVID-19 vaccines. Reasons for not getting vaccinated were classified into categories of vaccine deliberation, dissent, distrust, indifference, skepticism, and policy and processes. RESULTS: Among 1178 respondents, 974 (83%) were men, 130 (11%) were women, and 141 (12%) were transgender or nonbinary; 58 respondents (5%) were Black, 54 veterans (5%) were Hispanic or Latino, and 987 veterans (84%) were non-Hispanic White. The mean (SD) age of respondents was 66.7 (10.1) years. A total of 817 respondents (71%) self-reported being vaccinated against COVID-19. Of 339 respondents (29%) who were not vaccinated, those unsure of getting vaccinated were more likely to report fair or poor overall health (32 respondents [43%]) and mental health (33 respondents [44%]) than other nonvaccinated groups (overall health: range, 20%-32%; mental health: range, 18%-40%). Top reasons for not being vaccinated were skepticism (120 respondents [36%] were concerned about side effects; 65 respondents [20%] preferred using few medications; 63 respondents [19%] preferred gaining natural immunity), deliberation (74 respondents [22%] preferred to wait because vaccine is new), and distrust (61 respondents [18%] did not trust the health care system). Among respondents who were vaccinated, preventing oneself from getting sick (462 respondents [57%]) and contributing to the end of the COVID-19 pandemic (453 respondents [56%]) were top reasons for getting vaccinated. All veterans reported the VA as 1 of their top trusted sources of information. The proportion of respondents trusting their VA health care practitioner as a source of vaccine information was higher among those unsure about vaccination compared with those who indicated they would definitely not or probably not get vaccinated (18 respondents [26%] vs 15 respondents [15%]). There were no significant associations between vaccine intention groups and age (χ(2)(4) = 5.90; P = .21) or gender (χ(2)(2) = 3.99; P = .14). CONCLUSIONS AND RELEVANCE: These findings provide information needed to develop trusted messages used in conversations between VA health care practitioners and veterans addressing specific vaccine hesitancy reasons, as well as those in worse health. Conversations need to emphasize societal reasons for getting vaccinated and benefits to one’s own health.

JAMA Netw Open2021       LitCov and CORD-19
333Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection  

BACKGROUND: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. METHODS: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. FINDINGS: A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11–13 of 283 days (95% CI 231–349) for anti-N and 725 days (95% CI 623–921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42–1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. INTERPRETATION: Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants.

EBioMedicine2021       LitCov and CORD-19
334Digital contact tracing technologies in epidemics: a rapid review  

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Cochrane Database Syst Rev2020       LitCov and CORD-19
335Association Between What People Learned About COVID-19 Using Web Searches and Their Behavior Towards Public Health Guidelines: Empirical Infodemiology Study  

BACKGROUND: The use of the internet and web-based platforms to obtain public health information and manage health-related issues has become widespread in this digital age. The practice is so pervasive that the first reaction to obtaining health information is to “Google it.” As SARS-CoV-2 broke out in Wuhan, China, in December 2019 and quickly spread worldwide, people flocked to the internet to learn about the novel coronavirus and the disease, COVID-19. Lagging responses by governments and public health agencies to prioritize the dissemination of information about the coronavirus outbreak through the internet and the World Wide Web and to build trust gave room for others to quickly populate social media, online blogs, news outlets, and websites with misinformation and conspiracy theories about the COVID-19 pandemic, resulting in people’s deviant behaviors toward public health safety measures. OBJECTIVE: The goals of this study were to determine what people learned about the COVID-19 pandemic through web searches, examine any association between what people learned about COVID-19 and behavior toward public health guidelines, and analyze the impact of misinformation and conspiracy theories about the COVID-19 pandemic on people’s behavior toward public health measures. METHODS: This infodemiology study used Google Trends’ worldwide search index, covering the first 6 months after the SARS-CoV-2 outbreak (January 1 to June 30, 2020) when the public scrambled for information about the pandemic. Data analysis employed statistical trends, correlation and regression, principal component analysis (PCA), and predictive models. RESULTS: The PCA identified two latent variables comprising past coronavirus epidemics (pastCoVepidemics: keywords that address previous epidemics) and the ongoing COVID-19 pandemic (presCoVpandemic: keywords that explain the ongoing pandemic). Both principal components were used significantly to learn about SARS-CoV-2 and COVID-19 and explained 88.78% of the variability. Three principal components fuelled misinformation about COVID-19: misinformation (keywords “biological weapon,” “virus hoax,” “common cold,” “COVID-19 hoax,” and “China virus”), conspiracy theory 1 (ConspTheory1; keyword “5G” or “@5G”), and conspiracy theory 2 (ConspTheory2; keyword “ingest bleach”). These principal components explained 84.85% of the variability. The principal components represent two measurements of public health safety guidelines—public health measures 1 (PubHealthMes1; keywords “social distancing,” “wash hands,” “isolation,” and “quarantine”) and public health measures 2 (PubHealthMes2; keyword “wear mask”)—which explained 84.7% of the variability. Based on the PCA results and the log-linear and predictive models, ConspTheory1 (keyword “@5G”) was identified as a predictor of people’s behavior toward public health measures (PubHealthMes2). Although correlations of misinformation (keywords “COVID-19,” “hoax,” “virus hoax,” “common cold,” and more) and ConspTheory2 (keyword “ingest bleach”) with PubHealthMes1 (keywords “social distancing,” “hand wash,” “isolation,” and more) were r=0.83 and r=–0.11, respectively, neither was statistically significant (P=.27 and P=.13, respectively). CONCLUSIONS: Several studies focused on the impacts of social media and related platforms on the spreading of misinformation and conspiracy theories. This study provides the first empirical evidence to the mainly anecdotal discourse on the use of web searches to learn about SARS-CoV-2 and COVID-19.

J Med Internet Res2021       LitCov and CORD-19
336Prevalence and Related Factors of Depression, Anxiety, Acute Stress and Insomnia Symptoms Among Medical Staffs Experiencing the Second Wave of COVID-19 Pandemic in Xinjiang, China  

The prevalence and related factors of mental health impact among medical staffs who experienced the second wave of the COVID-19 pandemic in China is unknown. Therefore, this survey was conducted to investigate the prevalence and related factors of depressive, anxiety, acute stress, and insomnia symptoms in medical staffs in Kashi, Xinjiang, China during the second wave of the COVID-19 pandemic. A cross-sectional online survey was conducted among medical staffs working in First People's Hospital of Kashi, Xinjiang. The questionnaire collected demographic data and self-design questions related to the COVID-19 pandemic. The Impact of Events Scale-6, the Insomnia Severity Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder Scale-7, the Perceived Social Support Scale, the Chinese Big Five Personality Inventory-15, and the Trait Coping Style Questionnaire were used to measure psychological symptoms or characteristics. Binary logistic regression was carried out to examine the associations between socio-demographic factors and symptoms of depression, anxiety, stress, and insomnia. In total, data from 123 participants were finally included, among which the prevalence rate of depressive, anxiety, acute stress, and insomnia symptoms is 60.2, 49.6, 43.1, and 41.1%, respectively. The regression model revealed that minority ethnicity, being worried about infection, spending more time on following pandemic information, and neurotic personality were positively associated with the mental health symptoms, while extraversion personality, higher education level, and better social support were negatively associated. In our study, the prevalence of mental health impact was high among medical staffs in Kashi, China who experienced the second wave of the COVID-19 pandemic. Several factors were found to be associated with mental health conditions. These findings could help identify medical staffs at risk for mental health problems and be helpful for making precise mental health intervention policies during the resurgence. Our study may pave way for more research into Xinjiang during the COVID-19 pandemic.

Front Public Health2021       LitCov and CORD-19
337Psychosocial factors associated with postpartum psychological distress during the Covid-19 pandemic: a cross-sectional study  

BACKGROUND: Trauma, natural and man-made catastrophic events can be predictors of postpartum psychological distress. In a public health response due to coronavirus disease 2019 outbreak, the Italian government imposed a lockdown from March 9 to May 3. This extraordinary situation may have been challenging for maternal psychological health. The aim of this study was to investigate the prevalence of depressive and post-traumatic stress symptoms in women giving birth during the Covid-19 pandemic and its associations with quarantine measures, obstetrical factors, and relational attachment style. METHODS: Women who gave birth in a high-volume obstetric/gynaecological medical centre located in an epidemic area during the Covid-19 pandemic (March 8 to June 15) were asked to complete an online survey about their childbirth experience and the perceived effect of the pandemic. The Edinburgh Postnatal Depression Scale (EPDS), the Impact of Event Scale-Revised (IES-R), and the Relationship Questionnaire (RQ) were administered to assess levels of postpartum depressive and post-traumatic stress symptoms (PTSS) and relational style of attachment, respectively. Multivariate analysis was applied to identify associations between quarantine measures, childbirth experience, attachment style, and EPDS and IES-R scores. RESULTS: The survey was completed by 163 women (response rate 60.8%). The prevalence of depressive symptoms was 44.2% (EPDS cut-off score ≥ 11) and the PTSS rate was 42.9% (IES-R cut-off score ≥ 24). Dismissive and fearful avoidant attachment styles were significantly associated with the risk of depression and PTSS, respectively. Perceived pain during birth was a risk factor for postpartum depression. Perceived support provided by healthcare staff was a protective factor against depression and PTSS. Another protective factor against PTSS was quiet on the ward due to the absence of hospital visitors. CONCLUSION: This study reports a high prevalence of postpartum depressive and PTSS in women who gave birth during the Covid-19 pandemic. Postnatal psychological distress seemed to be associated more with the prenatal experience and other individual factors than with the pandemic hospital restrictions. Early detection during pregnancy of an insecure attachment style is fundamental to provide targeted preventive and therapeutic psychological interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-020-03399-5.

BMC Pregnancy Childbirth2020       LitCov and CORD-19
338SARS-CoV-2 Neutralization in Convalescent Plasma and Commercial Lots of Plasma-Derived Immunoglobulin  

INTRODUCTION: Patients with primary or secondary immunodeficiency (PID or SID) face increased insecurity and discomfort in the light of the COVID-19 pandemic, not knowing if and to what extent their comorbidities may impact the course of a potential SARS-CoV-2 infection. Furthermore, recently available vaccination options might not be amenable or effective for all patients in this heterogeneous population. Therefore, these patients often rely on passive immunization with plasma-derived, intravenous or subcutaneous immunoglobulin (IVIG/SCIG). Whether the ongoing COVID-19 pandemic and/or the progress in vaccination programs lead to increased and potentially protective titers in plasma-derived immunoglobulins (Ig) indicated (e.g., for humoral immunodeficiency) remains a pressing question for this patient population. PURPOSE: We investigated SARS-CoV-2 reactivity of US plasma-derived IVIG/SCIG products from the end of 2020 until June 2021 as well as in convalescent plasma (CP) from May 2020 to August 2020 to determine whether potentially neutralizing antibody titers may be present. METHODS: Final containers of IVIG/SCIG and CP donations were analyzed by commercial ELISA for anti-SARS-CoV-2 S1-receptor binding domain (RBD) IgG as well as microneutralization assay using a patient-derived SARS-CoV-2 (D614G) isolate. Neutralization capacities of 313 single plasma donations and 119 plasma-derived IVIG/SCIG lots were determined. Results obtained from both analytical methods were normalized against the WHO International Standard. Finally, based on dense pharmacokinetic profiles of an IVIG preparation from previously published investigations, possible steady-state plasma levels of SARS-CoV-2 neutralization capacities were approximated based on currently measured anti-SARS-CoV-2 potencies in IVIG/SCIG preparations. RESULTS: CP donations presented with high variability with regards to anti-SARS-CoV-2 reactivity in ELISA as well as in neutralization testing. While approximately 50% of convalescent donations were not/low neutralizing, approximately 10% were at or above 600 IU/mL. IVIG/SCIG lots derived from pre-pandemic plasma donations did not show neutralizing capacities for SARS-CoV-2. Lots produced between December 2020 and June 2021 entailing plasma donations after the emergence of SARS-CoV-2 showed a rapid and constant increase in anti-SARS-CoV-2 reactivity and neutralization capacity over time. While lot-to-lot variability was substantial, neutralization capacity increased from a mean of 21 IU/mL in December 2020 to 506 IU/mL in June 2021 with a maximum of 864 IU/mL for the most recent lots. Pharmacokinetic extrapolations, based on non-compartmental superposition principles using steady-state reference profiles from previously published pharmacokinetic investigations on IVIG in PID, yielded potential steady-state trough plasma levels of 16 IU/mL of neutralizing SARS-CoV-2 IgG based on the average final container concentration from May 2021 of 216 IU/mL. Maximum extrapolated trough levels could reach 64 IU/mL based on the latest maximal final container potency tested in June 2021. CONCLUSIONS: SARS-CoV-2 reactivity and neutralization capacity in IVIG/SCIG produced from US plasma rapidly and in part exponentially increased in the first half of 2021. The observed increase of final container potencies is likely trailing the serological status of the US donor population in terms of COVID-19 convalescence and vaccination by at least 5 months due to production lead times and should in principle continue at least until Fall 2021. In summary, the data support rapidly increasing levels of anti-SARS-CoV-2 antibodies in IVIG/SCIG products, implicating that a certain level of protection could be possible against COVID-19 for regularly substituted PID/SID patients. Nevertheless, more research is still needed to confirm which plasma levels are needed to provide protection against SARS-CoV-2 infection in immune-compromised patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40259-021-00511-9.

BioDrugs2021       LitCov and CORD-19
339Psychological impact of COVID-19 pandemic in the Philippines  

BACKGROUND: : The 2019 coronavirus disease (COVID-19) pandemic poses a threat to societies’ mental health. This study examined the prevalence of psychiatric symptoms and identified the factors contributing to psychological impact in the Philippines. METHODS: : A total of 1879 completed online surveys were gathered from March 28-April 12, 2020. Collected data included socio-demographics, health status, contact history, COVID-19 knowledge and concerns, precautionary measures, information needs, the Depression, Anxiety and Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) ratings. RESULTS: : The IES-R mean score was 19.57 (SD=13.12) while the DASS-21 mean score was 25.94 (SD=20.59). In total, 16.3% of respondents rated the psychological impact of the outbreak as moderate-to-severe; 16.9% reported moderate-to-severe depressive symptoms; 28.8% had moderate-to-severe anxiety levels; and 13.4% had moderate-to-severe stress levels. Female gender; youth age; single status; students; specific symptoms; recent imposed quarantine; prolonged home-stay; and reports of poor health status, unnecessary worry, concerns for family members, and discrimination were significantly associated with greater psychological impact of the pandemic and higher levels of stress, anxiety and depression (p<0.05). Adequate health information, having grown-up children, perception of good health status and confidence in doctors’ abilities were significantly associated with lesser psychological impact of the pandemic and lower levels of stress, anxiety and depression (p<0.05). LIMITATIONS: : An English online survey was used. CONCLUSION: : During the early phase of the pandemic in the Philippines, one-fourth of respondents reported moderate-to-severe anxiety and one-sixth reported moderate-to-severe depression and psychological impact. The factors identified can be used to devise effective psychological support strategies.

J Affect Disord2020       LitCov and CORD-19
340Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration  

The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated. The impact of this post-translational modification on viral entry is yet unestablished. We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus. We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding. However, these carbohydrates played a major role in regulating viral entry. Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells. Blocking O-glycan elaboration also partially blocked viral entry. Mechanistic studies suggest multiple roles for glycans during viral entry. Among them, inhibition of N-glycan biosynthesis enhanced Spike-protein proteolysis. This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry. Overall, chemical inhibitors of glycosylation may be evaluated for COVID-19.

Elife2020       LitCov and CORD-19
341The origin, transmission and clinical therapies on COVID-19 outbreak-an update on the status  

An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

Mil Med Res2020       LitCov and CORD-19
342Pre-exposure prophylaxis with hydroxychloroquine for high-risk healthcare workers during the COVID-19 pandemic: A structured summary of a study protocol for a multicentre, double-blind randomized controlled trial  

OBJECTIVES: The aim of this study is to assess the efficacy of the use of pre-exposure prophylaxis (PrEP) with hydroxychloroquine against placebo in healthcare workers with high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in reducing their risk of coronavirus disease 2019 (COVID-19) disease during an epidemic period. As secondary objectives, we would like to: i) assess the efficacy of the use of PrEP with hydroxychloroquine against placebo in healthcare workers with high risk of SARS-CoV-2 infection in reducing their risk of exposure to SARS-CoV-2 (defined by seroconversion) during an epidemic period, ii) evaluate the safety of PrEP with hydroxychloroquine in adults, iii) describe the incidence of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 infection, iv) identify clinical, analytical and microbiological predictors of COVID-19 among healthcare workers at high risk of SARS-CoV-2 infection, v) set up a repository of serum samples obtained from healthcare workers at high risk of SARS-CoV-2 infection for future research on blood markers to predict SARS-CoV-2 infection. TRIAL DESIGN: Multicentre double-blind parallel design (ratio 1:1) randomized controlled clinical trial. PARTICIPANTS: Approximately 440 healthcare workers of four Spanish hospitals (Hospital Clínic of Barcelona, Hospital de la Santa Creu i Sant Pau of Barcelona, Hospital Plató of Barcelona, Hospital General de Granollers, Barcelona) will be recruited. Participants are considered to be at high-risk of SARS-CoV-2 infection due to their frequent contact with suspected and confirmed cases of COVID-19. For eligibility, healthcare workers with 18 years old or older working at least 3 days a week in a hospital with both negative SARS-CoV-2 polymerase chain reaction (PCR) assays and serological COVID-19 rapid diagnostic tests (RDT) are invited to participate. Participants with any of the following conditions are excluded: pregnancy, breastfeeding, ongoing antiviral, antiretroviral or corticosteroids treatment, chloroquine or hydroxychloroquine uptake the last month or any contraindication to hydroxychloroquine treatment. INTERVENTION AND COMPARATOR: Intervention group (PrEP): participants will receive the standard of care and will take 400mg of hydroxychloroquine (2 tablets of 200 mg per Dolquine® tablet) daily the first four consecutive days, followed by 400 mg weekly for a period of 6 months. Control group: participants will receive placebo tablets with identical physical appearance to hydroxychloroquine 200 mg (Dolquine®) tablets following the same treatment schedule of the intervention group. Both groups will be encouraged to use the personal protection equipment (PPE) for COVID-19 prevention according to current hospital guidelines. MAIN OUTCOMES: The primary endpoint will be the number of confirmed cases of a COVID-19 (defined by a positive PCR for SARS-CoV-2 or symptoms compatible with COVID-19 with seroconversion) in the PrEP group compared to the placebo group at any time during the 6 months of the follow-up in healthcare workers with negative SARS-CoV-2 PCR and serology at day 0. As secondary endpoints, we will obtain: i) the SARS-CoV-2 seroconversion in the PrEP group compared to placebo during the 6 months of follow-up in healthcare workers with negative serology at day 0; ii) the occurrence of any adverse event related with hydroxychloroquine treatment; iii) the incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers in the non-PrEP group, among the total of healthcare workers included in the non-PrEP group during the study period; iv) the risk ratio for the different clinical, analytical and microbiological conditions to develop COVID-19; v) a repository of serum samples obtained from healthcare workers confirmed COVID-19 cases for future research on blood markers to predict SARS-CoV-2 infection. RANDOMISATION: Participants meeting all eligibility requirements will be allocated to one of the two study arms (PrEP with hydroxychloroquine or non-PrEP control group) in a 1:1 ratio using simple randomisation with computer generated random numbers. BLINDING (MASKING): Participants, doctors and nurses caring for participants, and investigators assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Each intervention group will have 220 participants, giving a total of 440 participants. TRIAL STATUS: The current protocol version is 1.5, 2(nd) of June 2020. Two hundred and seventy-fiveparticipants were recruited and completed first month follow-up until date. The estimated sample size could not be reached yet due to the declining national epidemic curve. Thus, 275 is the total number of participants included until date. The study has been suspended (26(th) of June) until new epidemic curve occurs. TRIAL REGISTRATION: This trial was registered on April 2(nd) 2020 at clinicaltrials.gov with the number NCT04331834. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19
343Social Media Insights Into US Mental Health During the COVID-19 Pandemic: Longitudinal Analysis of Twitter Data  

BACKGROUND: The COVID-19 pandemic led to unprecedented mitigation efforts that disrupted the daily lives of millions. Beyond the general health repercussions of the pandemic itself, these measures also present a challenge to the world’s mental health and health care systems. Considering that traditional survey methods are time-consuming and expensive, we need timely and proactive data sources to respond to the rapidly evolving effects of health policy on our population’s mental health. Many people in the United States now use social media platforms such as Twitter to express the most minute details of their daily lives and social relations. This behavior is expected to increase during the COVID-19 pandemic, rendering social media data a rich field to understand personal well-being. OBJECTIVE: This study aims to answer three research questions: (1) What themes emerge from a corpus of US tweets about COVID-19? (2) To what extent did social media use increase during the onset of the COVID-19 pandemic? and (3) Does sentiment change in response to the COVID-19 pandemic? METHODS: We analyzed 86,581,237 public domain English language US tweets collected from an open-access public repository in three steps. First, we characterized the evolution of hashtags over time using latent Dirichlet allocation (LDA) topic modeling. Second, we increased the granularity of this analysis by downloading Twitter timelines of a large cohort of individuals (n=354,738) in 20 major US cities to assess changes in social media use. Finally, using this timeline data, we examined collective shifts in public mood in relation to evolving pandemic news cycles by analyzing the average daily sentiment of all timeline tweets with the Valence Aware Dictionary and Sentiment Reasoner (VADER) tool. RESULTS: LDA topics generated in the early months of the data set corresponded to major COVID-19–specific events. However, as state and municipal governments began issuing stay-at-home orders, latent themes shifted toward US-related lifestyle changes rather than global pandemic-related events. Social media volume also increased significantly, peaking during stay-at-home mandates. Finally, VADER sentiment analysis scores of user timelines were initially high and stable but decreased significantly, and continuously, by late March. CONCLUSIONS: Our findings underscore the negative effects of the pandemic on overall population sentiment. Increased use rates suggest that, for some, social media may be a coping mechanism to combat feelings of isolation related to long-term social distancing. However, in light of the documented negative effect of heavy social media use on mental health, social media may further exacerbate negative feelings in the long-term for many individuals. Thus, considering the overburdened US mental health care structure, these findings have important implications for ongoing mitigation efforts.

J Med Internet Res2020       LitCov and CORD-19
344Endothelial cell infection and endotheliitis in COVID-19  

Lancet2020       LitCov and CORD-19
345Investigating Mental Health of US College Students During the COVID-19 Pandemic: Cross-Sectional Survey Study  

BACKGROUND: Evidence suggests that the COVID-19 pandemic has generally increased levels of stress and depression among the public. However, the impact on college students in the United States has not been well-documented. OBJECTIVE: This paper surveys the mental health status and severity of depression and anxiety of college students in a large university system in the United States during the COVID-19 pandemic. METHODS: An online survey was conducted among undergraduate and graduate students recruited from Texas A&M University via email. The survey consisted of two standardized scales—the Patient Health Questionnaire-9 and the General Anxiety Disorder-7—for depression and anxiety, and additional multiple-choice and open-ended questions regarding stressors and coping mechanisms specific to COVID-19. RESULTS: Among the 2031 participants, 48.14% (n=960) showed a moderate-to-severe level of depression, 38.48% (n=775) showed a moderate-to-severe level of anxiety, and 18.04% (n=366) had suicidal thoughts. A majority of participants (n=1443, 71.26%) indicated that their stress/anxiety levels had increased during the pandemic. Less than half of the participants (n=882, 43.25%) indicated that they were able to cope adequately with the stress related to the current situation. CONCLUSIONS: The proportion of respondents showing depression, anxiety, and/or suicidal thoughts is alarming. Respondents reported academic-, health-, and lifestyle-related concerns caused by the pandemic. Given the unexpected length and severity of the outbreak, these concerns need to be further understood and addressed.

J Med Internet Res2020       LitCov and CORD-19
346Concerns Expressed by Chinese Social Media Users During the COVID-19 Pandemic: Content Analysis of Sina Weibo Microblogging Data  

BACKGROUND: The COVID-19 pandemic has created a global health crisis that is affecting economies and societies worldwide. During times of uncertainty and unexpected change, people have turned to social media platforms as communication tools and primary information sources. Platforms such as Twitter and Sina Weibo have allowed communities to share discussion and emotional support; they also play important roles for individuals, governments, and organizations in exchanging information and expressing opinions. However, research that studies the main concerns expressed by social media users during the pandemic is limited. OBJECTIVE: The aim of this study was to examine the main concerns raised and discussed by citizens on Sina Weibo, the largest social media platform in China, during the COVID-19 pandemic. METHODS: We used a web crawler tool and a set of predefined search terms (New Coronavirus Pneumonia, New Coronavirus, and COVID-19) to investigate concerns raised by Sina Weibo users. Textual information and metadata (number of likes, comments, retweets, publishing time, and publishing location) of microblog posts published between December 1, 2019, and July 32, 2020, were collected. After segmenting the words of the collected text, we used a topic modeling technique, latent Dirichlet allocation (LDA), to identify the most common topics posted by users. We analyzed the emotional tendencies of the topics, calculated the proportional distribution of the topics, performed user behavior analysis on the topics using data collected from the number of likes, comments, and retweets, and studied the changes in user concerns and differences in participation between citizens living in different regions of mainland China. RESULTS: Based on the 203,191 eligible microblog posts collected, we identified 17 topics and grouped them into 8 themes. These topics were pandemic statistics, domestic epidemic, epidemics in other countries worldwide, COVID-19 treatments, medical resources, economic shock, quarantine and investigation, patients’ outcry for help, work and production resumption, psychological influence, joint prevention and control, material donation, epidemics in neighboring countries, vaccine development, fueling and saluting antiepidemic action, detection, and study resumption. The mean sentiment was positive for 11 topics and negative for 6 topics. The topic with the highest mean of retweets was domestic epidemic, while the topic with the highest mean of likes was quarantine and investigation. CONCLUSIONS: Concerns expressed by social media users are highly correlated with the evolution of the global pandemic. During the COVID-19 pandemic, social media has provided a platform for Chinese government departments and organizations to better understand public concerns and demands. Similarly, social media has provided channels to disseminate information about epidemic prevention and has influenced public attitudes and behaviors. Government departments, especially those related to health, can create appropriate policies in a timely manner through monitoring social media platforms to guide public opinion and behavior during epidemics.

J Med Internet Res2020       LitCov and CORD-19
347Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics  

The interaction between the SARS-CoV-2 virus Spike protein receptor binding domain (RBD) and the ACE2 cell surface protein is required for viral infection of cells. Mutations in the RBD are present in SARS-CoV-2 variants of concern that have emerged independently worldwide. For example, the B.1.1.7 lineage has a mutation (N501Y) in its Spike RBD that enhances binding to ACE2. There are also ACE2 alleles in humans with mutations in the RBD binding site. Here we perform a detailed affinity and kinetics analysis of the effect of five common RBD mutations (K417N, K417T, N501Y, E484K, and S477N) and two common ACE2 mutations (S19P and K26R) on the RBD/ACE2 interaction. We analysed the effects of individual RBD mutations and combinations found in new SARS-CoV-2 Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P1) variants. Most of these mutations increased the affinity of the RBD/ACE2 interaction. The exceptions were mutations K417N/T, which decreased the affinity. Taken together with other studies, our results suggest that the N501Y and S477N mutations enhance transmission primarily by enhancing binding, the K417N/T mutations facilitate immune escape, and the E484K mutation enhances binding and immune escape.

Elife2021       LitCov and CORD-19
348Understanding perception and acceptance of Sinopharm vaccine and vaccination against COVID-19 in the UAE  

BACKGROUND: In the current COVID-19 pandemic, the world has reached an important milestone where vaccinations are discovered and are proven to be effective against SARS-COV-2 infections. Though vaccines against COVID-19 are now available, around the globe there is some hesitancy in getting the vaccine. This hesitancy to get vaccinated against COVID-19 is a complex phenomenon with various factors playing a role. This study aims at understanding the perception and expectations of the people about COVID-19 vaccine and the factors influencing the vaccine acceptance. This information is crucial to challenge vaccine hesitancy and to win the combat against the COVID-19 Pandemic through voluntary vaccine efforts. METHODS: A cross-sectional survey among the residents of the UAE to understand the expectations and perception on vaccination against COVID-19. The survey was conducted online, and the survey design included participant samples to be representative of UAE’s demographics. The results of the survey were analysed with various demographical variables of interest. RESULTS: The survey showed that people were more likely to get vaccinated when vaccines are (i) endorsed by trusted government health authorities, (ii) recommended by physicians and family doctors, and (iii) the merits are effectively communicated through government websites and trusted news channels. Availability of vaccines at multiple sites and providing vaccines free of charges are likely to improve the rate of vaccination. The perceptions, expectations and the motivational factors needed for people to get vaccinated differed with age, gender, marital status, income level, and employment status. CONCLUSION: To attain herd immunity against COVID-19, a large proportion of the population needs to be vaccinated and to achieve this the vaccination campaigns should target on specific expectations and motivational factors pertaining to each target group to successfully overcome the challenge of vaccine hesitancy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-11620-z.

BMC Public Health2021       LitCov and CORD-19
349Application of telemedicine video visits in a maternal-fetal medicine practice at the epicenter of the COVID-19 pandemic  

BACKGROUND: Telemedicine in obstetrics has mostly been described in the rural areas that have limited access to subspecialties. During the COVID-19 pandemic, health systems rapidly expanded telemedicine services for urgent and nonurgent healthcare delivery, even in urban settings. The New York University health system implemented a prompt systemwide expansion of video-enabled telemedicine visits, increasing telemedicine to >8000 visits daily within 6 weeks of the beginning of the pandemic. There are limited studies that explore patient and provider satisfaction of telemedicine visits in obstetrical patients during the COVID-19 epidemic, particularly in the United States. OBJECTIVE: This study aimed to evaluate both the patients’ and the providers’ satisfaction with the administration of maternal-fetal medicine services through telemedicine and to identify the factors that drive the patients’ desire for future obstetrical telemedicine services. STUDY DESIGN: A cross-sectional survey was administered to patients who completed a telemedicine video visit with the Division of Maternal-Fetal Medicine at the New York University Langone Hospital—Long Island from March 19, 2020, to May 26, 2020. A 10-question survey assessing the patients’ digital experience and desire for future use was either administered by telephone or self-administered by the patients via a link after obtaining verbal consent. The survey responses were scored from 1—strongly disagree to 5—strongly agree. We analyzed the demographics and survey responses of the patients who agreed to vs those who answered neutral or disagree to the question “I would like telehealth to be an option for future obstetric visits.” The providers also answered a similar 10-question survey. The median scores were compared using appropriate tests. A P value of <.05 was considered significant. RESULTS: A total of 253 patients participated in 433 telemedicine visits, and 165 patients completed the survey, resulting in a 65% survey response rate. Overall, there were high rates of patient satisfaction in all areas assessed. Those who desired future telemedicine had significantly greater agreeability that they were able to see and hear their provider easily (5 [4.5, 5] vs 5 [4, 5]; P=.014) and that the lack of physical activity was not an issue (5 [4, 5] vs 5 [4, 5]; P=.032). They were also more likely to agree that the telemedicine visits were as good as in-person visits (4 [3, 5] vs 3 [2, 3]; P<.001) and that telehealth made it easier for them to see doctors or specialists (5 [4, 5] vs 3 [2, 3]; P<.001). The patients seeking consults for poor obstetrical history were more likely to desire future telemedicine compared with other visit types (19 (90%) vs 2 (10%); P=.05). Provider survey responses also demonstrated high levels of satisfaction, with 83% agreeing that they would like telemedicine to be an option for future obstetrical visits. CONCLUSION: We demonstrated that maternal-fetal medicine obstetrical patients and providers were highly satisfied with the implementation of telemedicine during the initial wave of the COVID-19 pandemic and a majority of them desire telemedicine as an option for future visits. A patient's desire for future telemedicine visits was significantly affected by their digital experience, the perception of a lack of need for physical contact, perceived time saved on travel, and access to healthcare providers. Health systems need to continue to improve healthcare delivery and invest in innovative solutions to conduct physical examinations remotely.

Am J Obstet Gynecol MFM2021       LitCov and CORD-19
350Staff SARS-CoV-2 Seroprevalence and Mental Health as Key Factors in University Response to COVID-19 Pandemic  

Background: In response to rapid global spread of the newly emerged coronavirus disease 2019 (COVID-19), universities transitioned to online learning and telework to decrease risks of inter-person contact. To help administrators respond to the COVID-19 pandemic and better understand its impacts, we surveyed SARS-CoV-2 seroprevalence among NOVA University employees and assessed community mental health. Methods: Data were collected from voluntary participants at six NOVA University locations, in the Lisbon metropolitan area, from June 15–30, 2020. All subjects provided written informed consent. Of 1,627 recruited participants (mean age 42.0 ± 12.3 years), 1,624 were tested. Prior to blood collection, participants completed a questionnaire that assessed: COVID-19 symptoms during the previous 14 days, chronic non-communicable diseases, chronic medication, anxiety, and depression symptoms. SARS-CoV-2 serology tests were then performed, and results communicated approximately 4 days after blood draw. Participants with positive serology tests were contacted to assess COVID-19 symptoms since February. Results: Estimated prevalence of SARS-CoV-2 IgG antibodies was 3.1% (n = 50), of which 43.5% reported symptoms in the previous 4 months. The Medical School had the highest seroprevalence (6.2%). Participants reported having at least one chronic disease (63.7%), depression-like symptoms (2.1%), and anxiety symptoms (8.1%). Rates of depression and anxiety symptoms were significantly higher in women, with sleep hours and occasional alcohol consumption negatively associated with depression. Male gender, older age, and sleep hours negatively associated with anxiety symptoms. School of employment and presence of comorbidities positively associated with anxiety. Conclusion: By measuring seroprevalence of SARS-CoV-2 antibodies among NOVA employees and assessing subjects' mental health, we aim to help administrators at European public universities in urban areas, such as Lisbon, Portugal, better understand the needs of their communities. This study resulted in implementation of a stricter contingency plan in the Medical School, while other schools continued to follow Government mitigation guidelines. These findings may also guide the development of tailored strategies to ensure physical and mental health of the academic community during this pandemic crisis. We conclude that, together with COVID-19 contingency plans, psychological support services and facilities to help people effectively face pandemic-associated challenges and minimise anxiety and depression should be implemented.

Front Public Health2021       LitCov and CORD-19

(1) COVID-19 Open Research Dataset (CORD-19). 2020. Version 2022-06-02. Retrieved from https://ai2-semanticscholar-cord-19.s3-us-west-2.amazonaws.com/historical_releases.html. Accessed 2022-06-05. doi:10.5281/zenodo.3715506
(2) Chen Q, Allot A, & Lu Z. (2020) Keep up with the latest coronavirus research, Nature 579:193 and Chen Q, Allot A, Lu Z. LitCovid: an open database of COVID-19 literature. Nucleic Acids Research. 2020. (version 2022-06-06)
(3) Currently tweets of May 15th to May 21st 2022 have been considered.

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