This version of BIP! Finder aims to ease the exploration of COVID-19-related literature by enabling ranking articles based on various impact metrics.
Last Update: 18 - 01 - 2023 (628506 entries)
Popularity: Citation-based measure reflecting the current impact.
Influence: Citation-based measure reflecting the total impact.
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Social Media Attention: The number of recent tweets related to this article.
*More details on these impact measures can be found here.
Exceptional score (in top 0.01%).
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| Title | Venue | Year | Impact | Source | |
|---|---|---|---|---|---|
| 351 | The Safety and Immunogenicity of the mRNA-BNT162b2 SARS-CoV-2 Vaccine in Hemodialysis Patients BACKGROUND: Hemodialysis patients are at high risk for severe COVID-19. SARS-CoV-2 vaccination related safety and immunogenicity data in these patients are rare. METHODS: In this observational study SARS-CoV-2-seronegative hemodialysis patients were vaccinated with two doses of the Pfizer/BioNTech mRNA-BNT162b2 vaccine (COMIRNATY(®) 30 µg) and followed for 90 days. Local and systemic side effects were assessed at every dialysis session during the first post-vaccination week after the first and second vaccine dose. Immunogenicity was determined four weeks after vaccination by quantifying anti-SARS-CoV-2 spike protein IgG antibodies (LIAISON(®) SARS-CoV-2-TrimericS IgG chemiluminescent immunoassay) expressed in binding activity units per milliliter (BAU/mL) adapted to the WHO International standard. RESULTS: Fifty patients (32% women, 68% men) with a mean (SD) age of 67.6 (14.8) years were included. Mild local reactions occurred in 38% after the first injection, and in 29.2% with mild, in 2.1% with moderate and in 2.1% with severe degree after the second injection. Systemic reactive events occurred less often, with diarrhea (4% mild, 4% moderate) and fatigue (8% mild) being the most frequent ones. After the first injection 42% of the patients developed a positive response using the assay specific cut-off value of 33.8 binding activity units per milliliter (BAU/mL) with a median (Q1, Q3) anti-SARS-CoV-2 spike IgG concentration of 20.0 (11.7, 51.0) BAU/mL. After the second injection the percentage of seropositive patients increased to 97.9% with an anti-SARS-CoV-2 spike IgG concentration of 1075 (290.8, 1735) BAU/mL. Higher age and immunosuppression were associated with lower, calcitriol treatment and prior seroconversion to hepatitis B vaccination with significantly higher antibody concentration. CONCLUSIONS: The mRNA-BNT162b2 SARS-CoV-2 vaccine appears to be safe and well-tolerated and shows a high immunogenicity in hemodialysis patients. | Front Immunol | 2021 | LitCov and CORD-19 | |
| 352 | Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial BACKGROUND: People living with HIV are at an increased risk of fatal outcome when admitted to hospital for severe COVID-19 compared with HIV-negative individuals. We aimed to assess safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV and HIV-negative individuals in South Africa. METHODS: In this ongoing, double-blind, placebo-controlled, phase 1B/2A trial (COV005), people with HIV and HIV-negative participants aged 18–65 years were enrolled at seven South African locations and were randomly allocated (1:1) with full allocation concealment to receive a prime-boost regimen of ChAdOx1 nCoV-19, with two doses given 28 days apart. Eligibility criteria for people with HIV included being on antiretroviral therapy for at least 3 months, with a plasma HIV viral load of less than 1000 copies per mL. In this interim analysis, safety and reactogenicity was assessed in all individuals who received at least one dose of ChAdOx1 nCov 19 between enrolment and Jan 15, 2021. Primary immunogenicity analyses included participants who received two doses of trial intervention and were SARS-CoV-2 seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinicals Trials Registry, PACTR202006922165132. FINDINGS: Between June 24 and Nov 12, 2020, 104 people with HIV and 70 HIV-negative individuals were enrolled. 102 people with HIV (52 vaccine; 50 placebo) and 56 HIV-negative participants (28 vaccine; 28 placebo) received the priming dose, 100 people with HIV (51 vaccine; 49 placebo) and 46 HIV-negative participants (24 vaccine; 22 placebo) received two doses (priming and booster). In participants seronegative for SARS-CoV-2 at baseline, there were 164 adverse events in those with HIV (86 vaccine; 78 placebo) and 237 in HIV-negative participants (95 vaccine; 142 placebo). Of seven serious adverse events, one severe fever in a HIV-negative participant was definitely related to trial intervention and one severely elevated alanine aminotranferase in a participant with HIV was unlikely related; five others were deemed unrelated. One person with HIV died (unlikely related). People with HIV and HIV-negative participants showed vaccine-induced serum IgG responses against wild-type Wuhan-1 Asp614Gly (also known as D614G). For participants seronegative for SARS-CoV-2 antigens at baseline, full-length spike geometric mean concentration (GMC) at day 28 was 163·7 binding antibody units (BAU)/mL (95% CI 89·9–298·1) for people with HIV (n=36) and 112·3 BAU/mL (61·7–204·4) for HIV-negative participants (n=23), with a rising day 42 GMC booster response in both groups. Baseline SARS-CoV-2 seropositive people with HIV demonstrated higher antibody responses after each vaccine dose than did people with HIV who were seronegative at baseline. High-level binding antibody cross-reactivity for the full-length spike and receptor-binding domain of the beta variant (B.1.351) was seen regardless of HIV status. In people with HIV who developed high titre responses, predominantly those who were receptor-binding domain seropositive at enrolment, neutralising activity against beta was retained. INTERPRETATION: ChAdOx1 nCoV-19 was well tolerated, showing favourable safety and immunogenicity in people with HIV, including heightened immunogenicity in SARS-CoV-2 baseline-seropositive participants. People with HIV showed cross-reactive binding antibodies to the beta variant and Asp614Gly wild-type, and high responders retained neutralisation against beta. FUNDING: The Bill & Melinda Gates Foundation, South African Medical Research Council, UK Research and Innovation, UK National Institute for Health Research, and the South African Medical Research Council. | Lancet HIV | 2021 | LitCov and CORD-19 | |
| 353 | SARS-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 Spectr | 2022 | LitCov and CORD-19 | |
| 354 | Combination of a Sindbis-SARS-CoV-2 Spike Vaccine and alphaOX40 Antibody Elicits Protective Immunity Against SARS-CoV-2 Induced Disease and Potentiates Long-Term SARS-CoV-2-Specific Humoral and T-Cell Immunity The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 is a major global public threat. Currently, a worldwide effort has been mounted to generate billions of effective SARS-CoV-2 vaccine doses to immunize the world’s population at record speeds. However, there is still a demand for alternative effective vaccines that rapidly confer long-term protection and rely upon cost-effective, easily scaled-up manufacturing. Here, we present a Sindbis alphavirus vector (SV), transiently expressing the SARS-CoV-2 spike protein (SV.Spike), combined with the OX40 immunostimulatory antibody (αOX40) as a novel, highly effective vaccine approach. We show that SV.Spike plus αOX40 elicits long-lasting neutralizing antibodies and a vigorous T-cell response in mice. Protein binding, immunohistochemical, and cellular infection assays all show that vaccinated mice sera inhibits spike functions. Immunophenotyping, RNA Seq transcriptome profiles, and metabolic analysis indicate a reprogramming of T cells in vaccinated mice. Activated T cells were found to mobilize to lung tissue. Most importantly, SV.Spike plus αOX40 provided robust immune protection against infection with authentic coronavirus in transgenic mice expressing the human ACE2 receptor (hACE2-Tg). Finally, our immunization strategy induced strong effector memory response, potentiating protective immunity against re-exposure to SARS-CoV-2 spike protein. Our results show the potential of a new Sindbis virus-based vaccine platform to counteract waning immune response, which can be used as a new candidate to combat SARS-CoV-2. Given the T-cell responses elicited, our vaccine is likely to be effective against variants that are proving challenging, as well as serve as a platform to develop a broader spectrum pancoronavirus vaccine. Similarly, the vaccine approach is likely to be applicable to other pathogens. | Front Immunol | 2021 | LitCov and CORD-19 | |
| 355 | Immune Profile and Clinical Outcome of Breakthrough Cases After Vaccination With an Inactivated SARS-CoV-2 Vaccine Constant efforts to prevent infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are actively carried out around the world. Several vaccines are currently approved for emergency use in the population, while ongoing studies continue to provide information on their safety and effectiveness. CoronaVac is an inactivated SARS-CoV-2 vaccine with a good safety and immunogenicity profile as seen in phase 1, 2, and 3 clinical trials around the world, with an effectiveness of 65.9% for symptomatic cases. Although vaccination reduces the risk of disease, infections can still occur during or after completion of the vaccination schedule (breakthrough cases). This report describes the clinical and immunological profile of vaccine breakthrough cases reported in a clinical trial in progress in Chile that is evaluating the safety, immunogenicity, and efficacy of two vaccination schedules of CoronaVac (clinicaltrials.gov NCT04651790). Out of the 2,263 fully vaccinated subjects, at end of June 2021, 45 have reported symptomatic SARS-CoV-2 infection 14 or more days after the second dose (1.99% of fully vaccinated subjects). Of the 45 breakthrough cases, 96% developed mild disease; one case developed a moderate disease; and one developed a severe disease and required mechanical ventilation. Both cases that developed moderate and severe disease were adults over 60 years old and presented comorbidities. The immune response before and after SARS-CoV-2 infection was analyzed in nine vaccine breakthrough cases, revealing that six of them exhibited circulating anti-S1-RBD IgG antibodies with neutralizing capacities after immunization, which showed a significant increase 2 and 4 weeks after symptoms onset. Two cases exhibited low circulating anti-S1-RBD IgG and almost non-existing neutralizing capacity after either vaccination or infection, although they developed a mild disease. An increase in the number of interferon-γ-secreting T cells specific for SARS-CoV-2 was detected 2 weeks after the second dose in seven cases and after symptoms onset. In conclusion, breakthrough cases were mostly mild and did not necessarily correlate with a lack of vaccine-induced immunity, suggesting that other factors, to be defined in future studies, could lead to symptomatic infection after vaccination with CoronaVac. | Front Immunol | 2021 | LitCov and CORD-19 | |
| 356 | Enhanced Binding of SARS-CoV-2 Spike Protein to Receptor by Distal Polybasic Cleavage Sites [Image: see text] The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a crucial role in binding the human cell receptor ACE2 that is required for viral entry. Many studies have been conducted to target the structures of RBD–ACE2 binding and to design RBD-targeting vaccines and drugs. Nevertheless, mutations distal from the SARS-CoV-2 RBD also impact its transmissibility and antibody can target non-RBD regions, suggesting the incomplete role of the RBD region in the spike protein–ACE2 binding. Here, in order to elucidate distant binding mechanisms, we analyze complexes of ACE2 with the wild-type spike protein and with key mutants via large-scale all-atom explicit solvent molecular dynamics simulations. We find that though distributed approximately 10 nm away from the RBD, the SARS-CoV-2 polybasic cleavage sites enhance, via electrostatic interactions and hydration, the RBD–ACE2 binding affinity. A negatively charged tetrapeptide (GluGluLeuGlu) is then designed to neutralize the positively charged arginine on the polybasic cleavage sites. We find that the tetrapeptide GluGluLeuGlu binds to one of the three polybasic cleavage sites of the SARS-CoV-2 spike protein lessening by 34% the RBD–ACE2 binding strength. This significant binding energy reduction demonstrates the feasibility to neutralize RBD–ACE2 binding by targeting this specific polybasic cleavage site. Our work enhances understanding of the binding mechanism of SARS-CoV-2 to ACE2, which may aid the design of therapeutics for COVID-19 infection. | ACS Nano | 2020 | LitCov and CORD-19 | |
| 357 | COVID-19-Related Mental Health Effects in the Workplace: A Narrative Review The Coronavirus Disease 2019 (COVID-19) pandemic has deeply altered social and working environments in several ways. Social distancing policies, mandatory lockdowns, isolation periods, and anxiety of getting sick, along with the suspension of productive activity, loss of income, and fear of the future, jointly influence the mental health of citizens and workers. Workplace aspects can play a crucial role on moderating or worsening mental health of people facing this pandemic scenario. The purpose of this literature review is to deepen the psychological aspects linked to workplace factors, following the epidemic rise of COVID-19, in order to address upcoming psychological critical issues in the workplaces. We performed a literature search using Google Scholar, PubMed, and Scopus, selecting papers focusing on workers’ psychological problems that can be related to the workplace during the pandemic. Thirty-five articles were included. Mental issues related to the health emergency, such as anxiety, depression, post-traumatic stress disorder (PTSD), and sleep disorders are more likely to affect healthcare workers, especially those on the frontline, migrant workers, and workers in contact with the public. Job insecurity, long periods of isolation, and uncertainty of the future worsen the psychological condition, especially in younger people and in those with a higher educational background. Multiple organizational and work-related interventions can mitigate this scenario, such as the improvement of workplace infrastructures, the adoption of correct and shared anti-contagion measures, including regular personal protective equipment (PPE) supply, and the implementation of resilience training programs. This review sets the basis for a better understanding of the psychological conditions of workers during the pandemic, integrating individual and social perspectives, and providing insight into possible individual, social, and occupational approaches to this “psychological pandemic”. | Int J Environ Res Public Healt | 2020 | LitCov and CORD-19 | |
| 358 | Association 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 Res | 2021 | LitCov and CORD-19 | |
| 359 | Sarilumab vs standard of care for the early treatment of COVID-19 pneumonia in hospitalized patients: SARTRE: a structured summary of a study protocol for a randomised controlled trial OBJECTIVES: In some patients, acute, life-threatening respiratory injury produced by viruses such as SARS-CoV and other viral pneumonia are associated with an over-exuberant cytokine release. Elevated levels of blood IL-6 had been identified as a one of the risk factors associated with severe COVID-19 disease. Anti-IL6 inhibitors are among the therapeutic armamentarium for preventing the fatal consequences of acute respiratory and multi organ failure in around 20% of the COVID-19 infected patients. At present, their use is prioritized to patients with severe interstitial pneumonia (Brescia-COVID Scale-COVID 2-3) with hyperinflammation as determined by the presence of elevated IL6 and/or d-dimer, or progressive d-dimer increase, in patients who otherwise are subsidiary to ICU admission. However, many uncertainties remain on the actual role of anti-IL6 inhibitors in this setting, and whether current use and timing is the right one. There is the hypothesis that the use of anti-IL6 inhibitors at an earlier state during the hyperinflammatory syndrome would be beneficial and may avoid progressing to ARDS. On the other hand, the standard of care has changed and nowadays the use of corticosteroids has become part of the SOC in the treatment of COVID-19 pneumonia. Our limited experience suggests that better treatment outcomes can be achieved when combining IL6-inhibitors (e.g. sarilumab) with corticosteroids. The aim of the present study is to evaluate if an earlier therapeutic intervention with sarilumab plus SOC (including corticosteroids) may be more effective than current standard of care alone, in preventing progression to respiratory failure in COVID-19 infected patients with interstitial pneumonia. This study will also provide supportive evidence to that provided by currently ongoing studies on the efficacy and safety of sarilumab in this clinical context. TRIAL DESIGN: A phase two multi-center randomised controlled trial (RCT) with two parallel arms (1:1 ratio). PARTICIPANTS: They will be hospitalized patients, of at least 18 years of age, with severe COVID-19 who have positive RT-PCR test and have radiographic evidence of pulmonary infiltrates by imaging or rales/crackles on exam and SpO2 ≤ 94% on room air that requires supplemental oxygen. Patients must present elevation of inflammatory parameters (IL-6 > 40 pg/mL or d-dimer >1.0 mcg/ml) or, alternatively, progressive worsening in at least two of these inflammatory parameters in the prior 24-48h: CRP, LDH, serum ferritin, lymphopenia, or d-dimer. Exclusion criteria: high oxygen requirements (including face mask with reservoir, non-invasive mechanical ventilation or high flow nasal cannula, or mechanical ventilation), admission to ICU, pregnancy or lactation, allergy or hypersensitivity to sarilumab or corticoesteroids, immunosuppressive antibody therapy within the past 5 months, AST/ALT values > 10 x ULN, neutropenia (< 0.5 x 109/L), severe thrombocytopenia (< 50 x 109/L), sepsis caused by an alternative pathogen, diverticulitis with risk of perforation or ongoing infectious dermatitis. The study will be conducted in several hospitals in Spain. INTERVENTION AND COMPARATOR: Patients randomised to the experimental arm will receive sarilumab + methylprednisolone plus SOC for COVID-19. Patients included in the control arm will receive methylprednisolone plus SOC for COVID-19. Corticosteroids will be given to all patients at a 1mg/kg/d of methylprednisolone for at least 3 days. Clinical follow-up visits will be performed at 3, 5, and 15 days after treatment randomization. Patients in the control group (SOC group without sarilumab) progressing to Brescia- COVID 2-3 plus inflammatory markers, will be given the option to be rescued with sarilumab at the same doses and, in that case, be included in an open-label phase and be followed up for additional weeks (with visits at 3, 7 and 15 days after sarilumab rescue administration). Patients randomly assigned to sarilumab therapy at baseline progressing to Brescia-COVID 2-3 will be rescued according to local clinical practice protocols. A final follow-up visit will be conducted for all patients at day 29 from randomization, regardless of initial treatment assignment. MAIN OUTCOMES: Primary end point is the proportion of patients progressing to either severe respiratory failure (Brescia-COVID ≥2), ICU admission, or death. RANDOMIZATION: Randomization codes were produced by means of the PROC PLAN of the SAS system, with a 1:1 assignment ratio, stratifying by centre and using blocks multiple of 2 elements. The randomization schedule will be managed through the eCRF in a concealed manner. BLINDING (MASKING): All study drugs will be administered as open label. No blinding methods will be used in this trial. NUMBERS TO BE RANDOMISED (SIMPLE SIZE): The target sample size will be 200 COVID-19 patients, who will be allocated randomly to control arm (100) and treatment arm (100). TRIAL STATUS: Protocol Code: SARTRE Protocol Date: May 05th 2020. Version: 2.0 The study has been approved by the Spanish Competent Authority (AEMPS) as a low intervention clinical trial. Start of recruitment: August, 2020 End of recruitment: May, 2021 TRIAL REGISTRATION: Identifier: EudraCT Number: 2020-002037-15; Registration date: 26 May 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). | Trials | 2020 | LitCov and CORD-19 | |
| 360 | Use of mRNA COVID-19 Vaccine After Reports of Myocarditis Among Vaccine Recipients: Update from the Advisory Committee on Immunization Practices-United States, June 2021 In December 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine and the Moderna COVID-19 (mRNA-1273) vaccine,† and the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for their use in persons aged ≥16 years and ≥18 years, respectively.§ In May 2021, FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12-15 years; ACIP recommends that all persons aged ≥12 years receive a COVID-19 vaccine. Both Pfizer-BioNTech and Moderna vaccines are mRNA vaccines encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Both mRNA vaccines were authorized and recommended as a 2-dose schedule, with second doses administered 21 days (Pfizer-BioNTech) or 28 days (Moderna) after the first dose. After reports of myocarditis and pericarditis in mRNA vaccine recipients,¶ which predominantly occurred in young males after the second dose, an ACIP meeting was rapidly convened to review reported cases of myocarditis and pericarditis and discuss the benefits and risks of mRNA COVID-19 vaccination in the United States. Myocarditis is an inflammation of the heart muscle; if it is accompanied by pericarditis, an inflammation of the thin tissue surrounding the heart (the pericardium), it is referred to as myopericarditis. Hereafter, myocarditis is used to refer to myocarditis, pericarditis, or myopericarditis. On June 23, 2021, after reviewing available evidence including that for risks of myocarditis, ACIP determined that the benefits of using mRNA COVID-19 vaccines under the FDA's EUA clearly outweigh the risks in all populations, including adolescents and young adults. The EUA has been modified to include information on myocarditis after receipt of mRNA COVID-19 vaccines. The EUA fact sheets should be provided before vaccination; in addition, CDC has developed patient and provider education materials about the possibility of myocarditis and symptoms of concern, to ensure prompt recognition and management of myocarditis. | MMWR Morb Mortal Wkly Rep | 2021 | LitCov and CORD-19 | |
| 361 | Conversations and Medical News Frames on Twitter: Infodemiological Study on COVID-19 in South Korea BACKGROUND: SARS-CoV-2 (severe acute respiratory coronavirus 2) was spreading rapidly in South Korea at the end of February 2020 following its initial outbreak in China, making Korea the new center of global attention. The role of social media amid the current coronavirus disease (COVID-19) pandemic has often been criticized, but little systematic research has been conducted on this issue. Social media functions as a convenient source of information in pandemic situations. OBJECTIVE: Few infodemiology studies have applied network analysis in conjunction with content analysis. This study investigates information transmission networks and news-sharing behaviors regarding COVID-19 on Twitter in Korea. The real time aggregation of social media data can serve as a starting point for designing strategic messages for health campaigns and establishing an effective communication system during this outbreak. METHODS: Korean COVID-19-related Twitter data were collected on February 29, 2020. Our final sample comprised of 43,832 users and 78,233 relationships on Twitter. We generated four networks in terms of key issues regarding COVID-19 in Korea. This study comparatively investigates how COVID-19-related issues have circulated on Twitter through network analysis. Next, we classified top news channels shared via tweets. Lastly, we conducted a content analysis of news frames used in the top-shared sources. RESULTS: The network analysis suggests that the spread of information was faster in the Coronavirus network than in the other networks (Corona19, Shincheon, and Daegu). People who used the word “Coronavirus” communicated more frequently with each other. The spread of information was faster, and the diameter value was lower than for those who used other terms. Many of the news items highlighted the positive roles being played by individuals and groups, directing readers’ attention to the crisis. Ethical issues such as deviant behavior among the population and an entertainment frame highlighting celebrity donations also emerged often. There was a significant difference in the use of nonportal (n=14) and portal news (n=26) sites between the four network types. The news frames used in the top sources were similar across the networks (P=.89, 95% CI 0.004-0.006). Tweets containing medically framed news articles (mean 7.571, SD 1.988) were found to be more popular than tweets that included news articles adopting nonmedical frames (mean 5.060, SD 2.904; N=40, P=.03, 95% CI 0.169-4.852). CONCLUSIONS: Most of the popular news on Twitter had nonmedical frames. Nevertheless, the spillover effect of the news articles that delivered medical information about COVID-19 was greater than that of news with nonmedical frames. Social media network analytics cannot replace the work of public health officials; however, monitoring public conversations and media news that propagates rapidly can assist public health professionals in their complex and fast-paced decision-making processes. | J Med Internet Res | 2020 | LitCov and CORD-19 | |
| 362 | The impact of the COVID-19 pandemic on maternal and perinatal health: a scoping review INTRODUCTION: The Covid-19 pandemic affects maternal health both directly and indirectly, and direct and indirect effects are intertwined. To provide a comprehensive overview on this broad topic in a rapid format behooving an emergent pandemic we conducted a scoping review. METHODS: A scoping review was conducted to compile evidence on direct and indirect impacts of the pandemic on maternal health and provide an overview of the most significant outcomes thus far. Working papers and news articles were considered appropriate evidence along with peer-reviewed publications in order to capture rapidly evolving updates. Literature in English published from January 1st to September 11 2020 was included if it pertained to the direct or indirect effects of the COVID-19 pandemic on the physical, mental, economic, or social health and wellbeing of pregnant people. Narrative descriptions were written about subject areas for which the authors found the most evidence. RESULTS: The search yielded 396 publications, of which 95 were included. Pregnant individuals were found to be at a heightened risk of more severe symptoms than people who are not pregnant. Intrauterine, vertical, and breastmilk transmission were unlikely. Labor, delivery, and breastfeeding guidelines for COVID-19 positive patients varied. Severe increases in maternal mental health issues, such as clinically relevant anxiety and depression, were reported. Domestic violence appeared to spike. Prenatal care visits decreased, healthcare infrastructure was strained, and potentially harmful policies implemented with little evidence. Women were more likely to lose their income due to the pandemic than men, and working mothers struggled with increased childcare demands. CONCLUSION: Pregnant women and mothers were not found to be at higher risk for COVID-19 infection than people who are not pregnant, however pregnant people with symptomatic COVID-19 may experience more adverse outcomes compared to non-pregnant people and seem to face disproportionate adverse socio-economic consequences. High income and low- and middle-income countries alike faced significant struggles. Further resources should be directed towards quality epidemiological studies. PLAIN ENGLISH SUMMARY: The Covid-19 pandemic impacts reproductive and perinatal health both directly through infection itself but also indirectly as a consequence of changes in health care, social policy, or social and economic circumstances. The direct and indirect consequences of COVID-19 on maternal health are intertwined. To provide a comprehensive overview on this broad topic we conducted a scoping review. Pregnant women who have symptomatic COVID-19 may experience more severe outcomes than people who are not pregnant. Intrauterine and breastmilk transmission, and the passage of the virus from mother to baby during delivery are unlikely. The guidelines for labor, delivery, and breastfeeding for COVID-19 positive patients vary, and this variability could create uncertainty and unnecessary harm. Prenatal care visits decreased, healthcare infrastructure was strained, and potentially harmful policies are implemented with little evidence in high and low/middle income countries. The social and economic impact of COVID-19 on maternal health is marked. A high frequency of maternal mental health problems, such as clinically relevant anxiety and depression, during the epidemic are reported in many countries. This likely reflects an increase in problems, but studies demonstrating a true change are lacking. Domestic violence appeared to spike. Women were more vulnerable to losing their income due to the pandemic than men, and working mothers struggled with increased childcare demands. We make several recommendations: more resources should be directed to epidemiological studies, health and social services for pregnant women and mothers should not be diminished, and more focus on maternal mental health during the epidemic is needed. | Reprod Health | 2021 | LitCov and CORD-19 | |
| 363 | How the COVID-19 Pandemic Impacted Medical Education during the Last Year of Medical School: A Class Survey The novel coronavirus disease 2019 (COVID-19) pandemic has changed the medical education platform for students in the United States of America (USA). In that light, medical schools had to rapidly rearrange the dynamics of their educational curricula from the traditional platforms, to incorporate telemedicine. The telemedicine platform is supported in many specialties, allowing students various options to continue their education without interruption during the COVID-19 pandemic, and beyond. Telemedicine platforms are projected to grow exponentially due to the COVID-19 pandemic, allowing a segue for medical schools to modify their curricula by incorporating telemedicine programs. These distant-, e-learning (tele-education) programs align with the recommendations and guidelines for practicing social distancing. In this article, we surveyed fourth-year medical students to better understand their views on multiple aspects of e-learning, and its impact on their medical education during the COVID-19 pandemic. We assessed the medical students’ experiences, satisfaction, insight and knowledge with e-learning, tele-education, telehealth, and their related modalities during COVID-19. We provide an organized overview and analysis of the main factors that influence medical education during the COVID-19 pandemic, while bringing forth the main challenges, limitations, and emerging approaches in the field of telemedicine and its application as it relates to medical education and e-learning across medical specialties. We outline the main themes and ideas that the medical students voiced, as to how their medical education is being impacted by the COVID-19 pandemic and how they will incorporate telemedicine and tele-education in their future career. A cross-sectional, mixed-method survey was developed and distributed via Google Surveys to 181 University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, United States of America, 4th year medical students, in December 2020. Results were compiled and analyzed after a 6-day open period for responses to be submitted. The survey instrument consisted of questions that inquire about the students’ perspectives as it relates to their rapid switch from their traditional method of learning to the on-line version of medical education during the COVID-19 pandemic. A total of 65 students responded to the survey, of which 63 completed the survey. More than half of the students (n = 63, 57%) indicated that both their specialty of interest, and (n = 21, 33%) their sub-internships were impacted by the temporary lockdown, due to the COVID-19 pandemic. Students also indicated that the top three specialties that were affected included surgery, internal medicine and obstetrics and gynecology. When the students were asked if they were satisfied with the use of aquifer for their health care e-learning, only 35% of the students were satisfied. The students expressed that the school’s administration team did a good job in developing the new tele-education curriculum for those in clinical training. In addition, responses indicated that students were open to case-based video learning and readings, when combined with the abbreviated clinical exposure during the make-up “clinical immersions periods” allowed for adequate learning. Overall, the survey responses show that more than half, approximately 54% of the medical students utilized telemedicine platforms during their clerkships that were impacted by COVID-19. The 4th-year medical students did not find tele-education and e-learning to be as effective as traditional medical education that combines in-person didactic classroom instructions and in-person face-to-face in hospital clerkships. Students felt that the telemedicine program that was rapidly set up due to the COVID-19 ‘lockdown’ was fragmented, since it was not a formal integration of a telemedicine E-learning program. Students would have preferred more ‘real’ cases to follow, instead of the ready-made, aquifer type of cases. Telemedicine has significant potential to address many of the challenges facing the medical education environment today. We believe now that people have become comfortable with this method of teaching, that even after the pandemic ends, we will continue to see tele-education used as a platform for medical education. | Life (Basel) | 2021 | LitCov and CORD-19 | |
| 364 | Effectiveness of mRNA vaccines and waning of protection against SARS-CoV-2 infection and severe covid-19 during predominant circulation of the delta variant in Italy: retrospective cohort study OBJECTIVES: To estimate the effectiveness of mRNA vaccines against SARS-CoV-2 infection and severe covid-19 at different time after vaccination. DESIGN: Retrospective cohort study. SETTING: Italy, 27 December 2020 to 7 November 2021. PARTICIPANTS: 33 250 344 people aged ≥16 years who received a first dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine and did not have a previous diagnosis of SARS-CoV-2 infection. MAIN OUTCOME MEASURES: SARS-CoV-2 infection and severe covid-19 (admission to hospital or death). Data were divided by weekly time intervals after vaccination. Incidence rate ratios at different time intervals were estimated by multilevel negative binomial models with robust variance estimator. Sex, age group, brand of vaccine, priority risk category, and regional weekly incidence in the general population were included as covariates. Geographic region was included as a random effect. Adjusted vaccine effectiveness was calculated as (1−IRR)×100, where IRR=incidence rate ratio, with the time interval 0-14 days after the first dose of vaccine as the reference. RESULTS: During the epidemic phase when the delta variant was the predominant strain of the SARS-CoV-2 virus, vaccine effectiveness against SARS-CoV-2 infection significantly decreased (P<0.001) from 82% (95% confidence interval 80% to 84%) at 3-4 weeks after the second dose of vaccine to 33% (27% to 39%) at 27-30 weeks after the second dose. In the same time intervals, vaccine effectiveness against severe covid-19 also decreased (P<0.001), although to a lesser extent, from 96% (95% to 97%) to 80% (76% to 83%). High risk people (vaccine effectiveness −6%, −28% to 12%), those aged ≥80 years (11%, −15% to 31%), and those aged 60-79 years (2%, −11% to 14%) did not seem to be protected against infection at 27-30 weeks after the second dose of vaccine. CONCLUSIONS: The results support the vaccination campaigns targeting high risk people, those aged ≥60 years, and healthcare workers to receive a booster dose of vaccine six months after the primary vaccination cycle. The results also suggest that timing the booster dose earlier than six months after the primary vaccination cycle and extending the offer of the booster dose to the wider eligible population might be warranted. | BMJ | 2022 | LitCov and CORD-19 | |
| 365 | Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season This report updates the 2020–21 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2020;69[No. RR-8]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. ACIP makes no preferential recommendation for a specific vaccine when more than one licensed, recommended, and age-appropriate vaccine is available. During the 2021–22 influenza season, the following types of vaccines are expected to be available: inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4). The 2021–22 influenza season is expected to coincide with continued circulation of SARS-CoV-2, the virus that causes COVID-19. Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient visits, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html. Recommendations for the use of COVID-19 vaccines are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html, and additional clinical guidance is available at https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html. Updates described in this report reflect discussions during public meetings of ACIP that were held on October 28, 2020; February 25, 2021; and June 24, 2021. Primary updates to this report include the following six items. First, all seasonal influenza vaccines available in the United States for the 2021–22 season are expected to be quadrivalent. Second, the composition of 2021–22 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09 and influenza A(H3N2) components. U.S.-licensed influenza vaccines will contain hemagglutinin derived from an influenza A/Victoria/2570/2019 (H1N1)pdm09-like virus (for egg-based vaccines) or an influenza A/Wisconsin/588/2019 (H1N1)pdm09-like virus (for cell culture–based and recombinant vaccines), an influenza A/Cambodia/e0826360/2020 (H3N2)-like virus, an influenza B/Washington/02/2019 (Victoria lineage)-like virus, and an influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus. Third, the approved age indication for the cell culture–based inactivated influenza vaccine, Flucelvax Quadrivalent (ccIIV4), has been expanded from ages ≥4 years to ages ≥2 years. Fourth, discussion of administration of influenza vaccines with other vaccines includes considerations for coadministration of influenza vaccines and COVID-19 vaccines. Providers should also consult current ACIP COVID-19 vaccine recommendations and CDC guidance concerning coadministration of these vaccines with influenza vaccines. Vaccines that are given at the same time should be administered in separate anatomic sites. Fifth, guidance concerning timing of influenza vaccination now states that vaccination soon after vaccine becomes available can be considered for pregnant women in the third trimester. As previously recommended, children who need 2 doses (children aged 6 months through 8 years who have never received influenza vaccine or who have not previously received a lifetime total of ≥2 doses) should receive their first dose as soon as possible after vaccine becomes available to allow the second dose (which must be administered ≥4 weeks later) to be received by the end of October. For nonpregnant adults, vaccination in July and August should be avoided unless there is concern that later vaccination might not be possible. Sixth, contraindications and precautions to the use of ccIIV4 and RIV4 have been modified, specifically with regard to persons with a history of severe allergic reaction (e.g., anaphylaxis) to an influenza vaccine. A history of a severe allergic reaction to a previous dose of any egg-based IIV, LAIV, or RIV of any valency is a precaution to use of ccIIV4. A history of a severe allergic reaction to a previous dose of any egg-based IIV, ccIIV, or LAIV of any valency is a precaution to use of RIV4. Use of ccIIV4 and RIV4 in such instances should occur in an inpatient or outpatient medical setting under supervision of a provider who can recognize and manage a severe allergic reaction; providers can also consider consulting with an allergist to help identify the vaccine component responsible for the reaction. For ccIIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any ccIIV of any valency or any component of ccIIV4 is a contraindication to future use of ccIIV4. For RIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any RIV of any valency or any component of RIV4 is a contraindication to future use of RIV4. This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2021–22 influenza season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used according to Food and Drug Administration–licensed indications. Updates and other information are available from CDC’s influenza website (https://www.cdc.gov/flu); vaccination and health care providers should check this site periodically for additional information. | MMWR Recomm Rep | 2021 | LitCov and CORD-19 | |
| 366 | Self-Reported Compliance With Personal Preventive Measures Among Chinese Factory Workers at the Beginning of Work Resumption Following the COVID-19 Outbreak: Cross-Sectional Survey Study BACKGROUND: Maintaining compliance with personal preventive measures is important to achieve a balance of COVID-19 pandemic control and work resumption. OBJECTIVE: The aim of this study was to investigate self-reported compliance with four personal measures to prevent COVID-19 among a sample of factory workers in Shenzhen, China, at the beginning of work resumption in China following the COVID-19 outbreak. These preventive measures included consistent wearing of face masks in public spaces (the workplace and other public settings); sanitizing hands using soap, liquid soap, or alcohol-based hand sanitizer after returning from public spaces or touching public installations and equipment; avoiding social and meal gatherings; and avoiding crowded places. METHODS: The participants were adult factory workers who had resumed work in Shenzhen, China. A stratified two-stage cluster sampling design was used. We randomly selected 14 factories that had resumed work. All full-time employees aged ≥18 years who had resumed work in these factories were invited to complete a web-based survey. Out of 4158 workers who had resumed work in these factories, 3035 (73.0%) completed the web-based survey from March 1 to 14, 2020. Multilevel logistic regression models were fitted. RESULTS: Among the 3035 participants, 2938 (96.8%) and 2996 (98.7%) reported always wearing a face mask in the workplace and in other public settings, respectively, in the past month. However, frequencies of self-reported sanitizing hands (2152/3035, 70.9%), avoiding social and meal gatherings (2225/3035, 73.3%), and avoiding crowded places (1997/3035, 65.8%) were relatively low. At the individual level, knowledge about COVID-19 (adjusted odds ratios [AORs] from 1.16, CI 1.10-1.24, to 1.29, CI 1.21-1.37), perceived risk (AORs from 0.58, CI 0.50-0.68, to 0.85, CI 0.72-0.99) and severity (AOR 1.05, CI 1.01-1.09, and AOR 1.07, CI 1.03-1.11) of COVID-19, perceived effectiveness of preventive measures by the individual (AORs from 1.05, CI 1.00-1.10, to 1.09, CI 1.04-1.13), organization (AOR 1.30, CI 1.20-1.41), and government (AORs from 1.14, CI 1.04-1.25, to 1.21, CI 1.02-1.42), perceived preparedness for a potential outbreak after work resumption (AORs from 1.10, CI 1.00-1.21, to 1.50, CI 1.36-1.64), and depressive symptoms (AORs from 0.93, CI 0.91-0.94, to 0.96, CI 0.92-0.99) were associated with self-reported compliance with at least one personal preventive measure. At the interpersonal level, exposure to COVID-19–specific information through official media channels (AOR 1.08, CI 1.04-1.11) and face-to-face communication (AOR 0.90, CI 0.83-0.98) were associated with self-reported sanitizing of hands. The number of preventive measures implemented in the workplace was positively associated with self-reported compliance with all four preventive measures (AORs from 1.30, CI 1.08-1.57, to 1.63, CI 1.45-1.84). CONCLUSIONS: Measures are needed to strengthen hand hygiene and physical distancing among factory workers to reduce transmission following work resumption. Future programs in workplaces should address these factors at multiple levels. | J Med Internet Res | 2020 | LitCov and CORD-19 | |
| 367 | The 2020 Pandemic: Current SARS-CoV-2 Vaccine Development Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome infecting animals and humans. Coronaviruses have been described more than 70 years ago and contain many species. Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are lethal species caused by human coronaviruses (HCoVs). Currently, a novel strain of HCoVs, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (Covid-19). SARS-CoV-2 was first identified in December 2019 in Wuhan, the capital city of the Hubei province of China, and has since spread worldwide causing an outbreak in more than 200 countries. The SARS-CoV-2 outbreak was declared a pandemic on March 11th, 2020 and a public health emergency of international concern (PHEIC) in late January 2020 by the World Health Organization (WHO). SARS-CoV-2 infects the respiratory tract causing flu-like symptoms and, in some, may cause severe illness like pneumonia and multi-organ failure leading to death. Today, Covid-19 cases almost reaching 9 million, with more than 450 thousand deaths. There is an urgent demand for developing a vaccine since no effective therapies or vaccines have been approved to this day to prevent or minimize the spread of the infection. In this review, we summarized the furthest vaccines in the clinical pipeline. | Front Immunol | 2020 | LitCov and CORD-19 | |
| 368 | Real Asymptomatic SARS-CoV-2 Infection Might Be Rare: Importance of Careful Interviews and Follow-up BACKGROUND: There is limited information on the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) who are asymptomatic or have mild symptoms. METHODS: We performed a retrospective case series of patients with COVID-19 enrolled from February 22 to March 26, 2020. Forty cases of COVID-19 were confirmed using real-time reverse-transcription polymerase chain reaction among patients who underwent screening tests and were consecutively hospitalized at Ulsan University Hospital, Ulsan, Korea. The final follow-up date was May 19, 2020. All COVID-19 cases in Ulsan were included. Demographic and epidemiological information, comorbidities, clinical signs and symptoms, laboratory and radiologic findings, medications, treatments, outcomes, and main durations of patients with COVID-19 were compared according to supplemental oxygen requirement. RESULTS: Forty patients were included (median age, 30 years; interquartile range [IQR], 25–57 years; 58% female). Six (15%) patients required supplemental oxygen. The prevalence of asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection was 5% and that of presymptomatic infection was 13%. Cough, fever, myalgia, rhinorrhea or nasal congestion, and diarrhea were the screening criteria for diagnosing symptomatic and presymptomatic SARS-CoV-2 infections. Sputum production, chest discomfort, a large number of symptoms, abnormal procalcitonin and C-reactive protein levels, and abnormal chest X-ray or chest computed tomography findings were more common in patients requiring supplemental oxygen than in those not requiring supplemental oxygen. Overall mortality rate was 3% (1/40). Four patients (10%) were readmitted after testing positive by reverse-transcription polymerase chain reaction again. Incubation period was 5 days (IQR, 4–6 days), and the duration of viral shedding was 21 days (IQR, 14–28 days; maximum, 51 days). CONCLUSION: The prevalence of asymptomatic SARS-CoV-2 infection was 5%, which is much lower than that previously reported. This finding suggests that careful interviews and follow-ups should be performed to identify SARS-CoV-2 infections. Cough, fever, myalgia, rhinorrhea or nasal congestion, and diarrhea are adequate screening criteria for covering all symptoms of SARS-CoV-2 infection. Further evaluation is required to create representative screening criteria for COVID-19. | J Korean Med Sci | 2020 | LitCov and CORD-19 | |
| 369 | Impact of COVID-19 pandemic on mental health among general Bangladeshi population: a cross-sectional study OBJECTIVES: Mental health problems significantly increased worldwide during the coronavirus (COVID-19) pandemic. At the early stage of the outbreak, the government of Bangladesh imposed lockdown and quarantine approaches to prevent the spread of the virus, which impacted people’s daily life and health. The COVID-19 pandemic has also affected people’s economic status, healthcare facilities and other lifestyle factors in Bangladesh. We aimed to assess the impact of the COVID-19 pandemic on mental health among the Bangladeshi population. METHODS: We conducted an online cross-sectional survey among 672 Bangladeshi people aged between 15 and 65 years all over the country from 15 April to 10 May 2020. After obtaining electronic consent, we conducted a survey assessing people’s sociodemographic profiles and psychometric measures. We used The University of California, Los Angeles (UCLA) Loneliness Scale-8, Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-Item Scale and Pittsburgh Sleep Quality Index to assess loneliness, depression, anxiety and sleep disturbance, respectively. RESULTS: The prevalence of loneliness, depression, anxiety and sleep disturbance was estimated at 71% (mild: 32%, moderate: 29%, severe: 10%), 38% (mild: 24%, moderate: 11%, severe: 3%), 64% (mild: 30%, moderate: 17%, severe: 17%) and 73% (mild: 50%, moderate: 18%, severe: 5%), respectively. In Bangladesh, the key factors associated with poor mental health during COVID-19 were female sex, unemployment, being a student, obesity and living without a family. The present study also identified statistically significant interrelationships among the measured mental health issues. CONCLUSIONS: A large portion of respondents reported mental health problems during the COVID-19 pandemic in Bangladesh. The present study suggests longitudinal assessments of mental health among Bangladeshi people to determine the gravity of this issue during and after the pandemic. Appropriate supportive programmes and interventional approaches would address mental health problems in Bangladesh during the COVID-19 pandemic. | BMJ Open | 2021 | LitCov and CORD-19 | |
| 370 | Characteristics of SARS-CoV-2 and COVID-19 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19), which threatens human health and public safety. In this Review, we describe the basic virology of SARS-CoV-2, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses. We summarize current knowledge of clinical, epidemiological and pathological features of COVID-19, as well as recent progress in animal models and antiviral treatment approaches for SARS-CoV-2 infection. We also discuss the potential wildlife hosts and zoonotic origin of this emerging virus in detail. | Nat Rev Microbiol | 2020 | LitCov and CORD-19 | |
| 371 | Barriers and facilitators of adherence to social distancing recommendations during COVID-19 among a large international sample of adults BACKGROUND: Social distancing measures (e.g., avoiding travel, limiting physical contact with people outside of one’s household, and maintaining a 1 or 2-metre distance between self and others when in public, depending on the country) are the primary strategies used to prevent transmission of the SARS-Cov-2 virus that causes COVID-19. Given that there is no effective treatment or vaccine for COVID-19, it is important to identify barriers and facilitators to adherence to social distancing to inform ongoing and future public health campaigns. METHOD: This cross-sectional study was conducted online with a convenience sample of English-speaking adults. The survey was administered over the course of three weeks (March 30 –April 16, 2020) when social distancing measures were well-enforced in North America and Europe. Participants were asked to complete measures assessing socio-demographic characteristics, psychological constructs, including motivations to engage in social distancing, prosocial attitudes, distress, and social distancing behaviors. Descriptive (mean, standard deviation, percentage) and inferential statistics (logistic regression) were used to describes endorsement rates for various motivations, rates of adherence to social distancing recommendations, and predictors of adherence. RESULTS: Data were collected from 2013 adults living primarily in North America and Europe. Most frequently endorsed motivations to engage in social distancing (or facilitators) included “I want to protect others” (86%), “I want to protect myself” (84%), and I feel a sense of responsibility to protect our community” (84%). Most frequently endorsed motivations against social distancing (or barriers) included “There are many people walking on the streets in my area” (31%), “I have friends or family who need me to run errands for them” (25%), “I don’t trust the messages my government provides about the pandemic” (13%), and “I feel stressed when I am alone or in isolation” (13%). Adherence to social distancing recommendations ranged from 45% for “working from home or remotely” to 90% for “avoiding crowded places/non-essential travel”, with men and younger individuals (18–24 years) showing lower adherence compared to women and older individuals. CONCLUSION: This study found that adherence to social distancing recommendations vary depending on the behaviour, with none of the surveyed behaviours showing perfect adherence. Strongest facilitators included wanting to protect the self, feeling a responsibility to protect the community, and being able to work/study remotely; strongest barriers included having friends or family who needed help with running errands and socializing in order to avoid feeling lonely. Future interventions to improve adherence to social distancing measures should couple individual-level strategies targeting key barriers to social distancing identified herein, with effective institutional measures and public health interventions. Public health campaigns should continue to highlight compassionate attitudes towards social distancing. | PLoS One | 2020 | LitCov and CORD-19 | |
| 372 | Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 N/A | Nature | 2021 | LitCov and CORD-19 | |
| 373 | Age-Dependent Reduction in Neutralization against Alpha and Beta Variants of BNT162b2 SARS-CoV-2 Vaccine induced Immunity Vaccines against severe acute respiratory syndrome coronavirus-2 have been introduced. To investigate the relationship between vaccine-induced humoral immunity and patient age, we measured antibody levels and neutralization in vaccinated sera. Sera from 13 to 17 days after the second dose of the BNT162b2 vaccine were collected from health care workers at the University of Toyama (n = 740). Antibody levels were measured by the anti-receptor binding domain antibody test (anti-RBD test), and neutralization against wild-type (WT), α- and β-variant pseudotyped viruses were assayed using a high-throughput chemiluminescent reduction neutralizing test (htCRNT; positivity cutoff, 50% neutralization at serum dilution 1:100). Basic clinical characteristics were obtained from questionnaires. Antibodies were confirmed in all participants in both the anti-RBD test (median, 2,112 U/ml; interquartile range [IQR], 1,275 to 3,390 U/ml) and the htCRNT against WT (median % inhibition, >99.9; IQR, >99.9 to >99.9). For randomly selected sera (n = 61), 100.0% had positive htCRNT values against the α- and β-derived variants. Among those who answered the questionnaire (n = 237), the values of the anti-RBD test were negatively correlated with age in females (P < 0.01). An age-dependent decline in neutralization was observed against the variants but not against the wild-type virus (wild type, P = 0.09; α, P < 0.01; β, P < 0.01). The neutralizing activity induced by BNT162b2 was obtained not only against the wild-type virus, but also against the variants; however, there was an age-dependent decrease in the latter. Age-related heterogeneity of vaccine-acquired immunity is a concern in preventive strategies in the era dominated by variants. IMPORTANCE Since mRNA vaccines utilize wild-type SARS-CoV-2 spike protein as an antigen, there are potential concerns about acquiring immunity to variants of this virus. The neutralizing activity in BNT162b2-vaccinated individuals was higher against the wild-type virus than against its variants; this effect was more apparent in older age groups. This finding suggests that one of the weaknesses of the mRNA vaccine is the high risk of variant infection in the elderly population. Because the elderly are at a higher risk of SARS-CoV-2 infection, the age-dependent decline of neutralization against viral variants should be considered while planning vaccination programs that include boosters. | Microbiol Spectr | 2021 | LitCov and CORD-19 | |
| 374 | Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military N/A | JAMA Cardiol | 2021 | LitCov and CORD-19 | |
| 375 | The Long Road Towards COVID-19 Herd Immunity: Vaccine Platform Technologies and Mass Immunization Strategies There is an urgent need for effective countermeasures against the current emergence and accelerating expansion of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Induction of herd immunity by mass vaccination has been a very successful strategy for preventing the spread of many infectious diseases, hence protecting the most vulnerable population groups unable to develop immunity, for example individuals with immunodeficiencies or a weakened immune system due to underlying medical or debilitating conditions. Therefore, vaccination represents one of the most promising counter-pandemic measures to COVID-19. However, to date, no licensed vaccine exists, neither for SARS-CoV-2 nor for the closely related SARS-CoV or Middle East respiratory syndrome-CoV. In addition, a few vaccine candidates have only recently entered human clinical trials, which hampers the progress in tackling COVID-19 infection. Here, we discuss potential prophylactic interventions for SARS-CoV-2 with a focus on the challenges existing for vaccine development, and we review pre-clinical progress and ongoing human clinical trials of COVID-19 vaccine candidates. Although COVID-19 vaccine development is currently accelerated via so-called fast-track programs, vaccines may not be timely available to have an impact on the first wave of the ongoing COVID-19 pandemic. Nevertheless, COVID-19 vaccines will be essential in the future for reducing morbidity and mortality and inducing herd immunity, if SARS-CoV-2 becomes established in the population like for example influenza virus. | Front Immunol | 2020 | LitCov and CORD-19 | |
| 376 | Humoral and Cellular Immune Responses to Vector, Mix-and-Match, or mRNA Vaccines against SARS-CoV-2 and the Relationship between the Two Immune Responses N/A | Microbiol Spectr | 2022 | LitCov | |
| 377 | Diagnostic Performance of Self-Collected Saliva Versus Nasopharyngeal Swab for the Molecular Detection of SARS-CoV-2 in the Clinical Setting Coronavirus disease 19 (COVID-19)—caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—has spread rapidly around the world. The global shortage of equipment and health care professionals, diagnostic cost, and difficulty in collecting nasopharyngeal swabs (NPSs) necessitate the use of an alternative specimen type for SARS-CoV-2 diagnosis. In this study, we investigated the use of saliva as an alternative specimen type for SARS-CoV-2 detection. Participants presenting COVID-19 symptoms and their contacts were enrolled at the COVID-19 Screening Unit of Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), from July to November 2020. Paired NPS and saliva specimens were collected from each participant. Reverse transcription-quantitative PCR (RT-qPCR) was performed to detect SARS-CoV-2. Of the 596 suspected COVID-19-positive participants, 231 (38.7%) were detected as COVID-19 positive by RT-qPCR from at least 1 specimen type. Among the positive cases, 184 (79.6%) patients were identified to be positive for SARS-CoV-2 based on NPS and saliva samples, whereas 45 (19.65%) patients were positive for SARS-CoV-2 based on NPS samples but negative for SARS-CoV-2 based on the saliva samples. Two (0.5%) patients were positive for SARS-CoV-2 based on saliva samples but negative for SARS-CoV-2 based on NPS samples. The sensitivity and specificity of the saliva samples were 80.3% and 99.4%, respectively. SARS-CoV-2 detection was higher in saliva (85.1%) among the patients who visited the clinic after 1 to 5 days of symptom onset. A lower median cycle threshold (C(T)) value indicated a higher SARS-CoV-2 viral load in NPS than that in saliva for target genes among the positive specimens. The study findings suggest that saliva can be used accurately for diagnosis of SARS-CoV-2 early after symptom onset in clinical and community settings. IMPORTANCE As the COVID-19 pandemic erupted, the WHO recommended the use of nasopharyngeal or throat swabs for the detection of SARS-CoV-2 etiology of COVID-19. The collection of NPS causes discomfort because of its invasive collection procedure. There are considerable risks to health care workers during the collection of these specimens. Therefore, an alternative, noninvasive, reliable, and self-collected specimen was explored in this study. This study investigated the feasibility and suitability of saliva versus NPS for the detection of SARS-CoV-2. Here, we showed that the sensitivity of saliva specimens was 80.35%, which meets the WHO criteria. Saliva is an easy-to-get, convenient, and low-cost specimen that yields better results if it is collected within the first 5 days of symptom onset. Our study findings suggest that saliva can be used in low-resource countries, community settings, and vulnerable groups, such as children and elderly people. | Microbiol Spectr | 2021 | LitCov and CORD-19 | |
| 378 | COVID-19 Cases and Hospitalizations by COVID-19 Vaccination Status and Previous COVID-19 Diagnosis-California and New York, May-November 2021 N/A | MMWR Morb Mortal Wkly Rep | 2022 | LitCov and CORD-19 | |
| 379 | Antibody Responses to BNT162b2 Vaccination in Japan: Monitoring Vaccine Efficacy by Measuring IgG Antibodies against the Receptor-Binding Domain of SARS-CoV-2 To fight severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), mass vaccination has begun in many countries. To investigate the usefulness of a serological assay to predict vaccine efficacy, we analyzed the levels of IgG, IgM, and IgA against the receptor-binding domain (RBD) of SARS-CoV-2 in the sera from BNT162b2 vaccinated individuals in Japan. This study included 219 individuals who received two doses of BNT162b2. The levels of IgG, IgM, and IgA against RBD were measured by enzyme-linked immunosorbent assay before and after the first and second vaccination, respectively. The relationship between antibody levels and several factors, including age, gender, and hypertension were analyzed. Virus-neutralizing activity in sera was measured to determine the correlation with the levels of antibodies. A chemiluminescent enzyme immunoassay (CLEIA) method to measure IgG against RBD was developed and validated for the clinical setting. The levels of all antibody isotypes were increased after vaccination. Among them, RBD-IgG was dramatically increased after the second vaccination. The IgG levels in females were significantly higher than in males. There was a negative correlation between age and IgG levels in males. The IgG levels significantly correlated with the neutralizing activity. The CLEIA assay measuring IgG against RBD showed a reliable performance and a high correlation with neutralizing activity. Monitoring of IgG against RBD is a powerful tool to predict the efficacy of SARS-CoV-2 vaccination and provides useful information in considering a personalized vaccination strategy for COVID-19. IMPORTANCE Mass vaccination campaigns using mRNA vaccines against SARS-CoV-2 have begun in many countries. Serological assays to detect antibody production may be a useful tool to monitor the efficacy of SARS-CoV-2 vaccination in individuals. Here, we reported the induction of antibody isotype responses after the first and second dose of the BNT162b2 vaccine in a well-defined cohort of employees in Japan. We also reported that age, gender, and hypertension are associated with differences in antibody response after vaccination. This study not only provides valuable information with respect to antibody responses after BNT162b2 vaccination in the Japanese population but also the usefulness of serological assays for monitoring vaccine efficacy in clinical laboratories to determine a personalized vaccination strategy for COVID-19. | Microbiol Spectr | 2022 | LitCov and CORD-19 | |
| 380 | Influenza vaccine uptake, COVID-19 vaccination intention and vaccine hesitancy among nurses: A survey BACKGROUND: A healthy healthcare system requires healthy healthcare workers. Protecting healthcare workers including nurses against COVID-19 is crucial, and vaccination could be a viable future option. However, vaccine hesitancy remains a global challenge. Nurses, as a trustworthy and creditable source of vaccine-related information, may build public confidence in vaccination. Hence, research on vaccine hesitancy among nurses is warranted. OBJECTIVES: This study estimated nurses’ influenza vaccination behaviors and intention to receive COVID-19 vaccine when available, and examined their corresponding 5C psychological antecedents (confidence, complacency, constraints, calculation, and collective responsibility). To investigate the impact of COVID-19-related work demands, the mediation effects of work stress on the association between work demands and COVID-19 vaccination intention were also examined. DESIGN: Cross-sectional online survey SETTINGS: Nurses were invited to participate via the promotion of a professional nursing organization and by personal referrals during the COVID-19 outbreak in Hong Kong between mid-March and late April 2020. PARTICIPANTS: 1,205 eligible nurses (mean age = 40.79, SD = 10.47; 90% being female) were included in the analyses. METHODS: Demographics, influenza vaccination, intention to have COVID-19 vaccine, the 5C vaccine hesitancy components, work stress and COVID-19-related work demands (insufficient supply of personal protective equipment, involvement in isolation rooms, and unfavorable attitudes towards workplace infection control policies) were reported in the survey. RESULTS: The influenza vaccine uptake rate and the proportion intending to take COVID-19 vaccine were 49% and 63%, respectively. Influenza vaccination was associated with working in public hospitals and all 5C constructs (more confidence, more collective responsibility and less complacency, constraints, and calculation), whereas stronger COVID-19 vaccination intention was associated with younger age, more confidence, less complacency and more collective responsibility. COVID-19-related demands were associated with greater work stress, and hence stronger COVID-19 vaccination intention. CONCLUSION: The potential uptake rate of COVID-19 vaccine among nurses was suboptimal to achieve herd immunity. The 5C constructs were useful in predicting influenza vaccination and, to a lesser extent, the intention to take COVID-19 vaccine. The uncertain attributes such as effectiveness, side effects, and effective duration of the COVID-19 vaccine may contribute to this discrepancy. With less work stress among nurses in the post-pandemic period, the intention to take COVID-19 vaccine will likely drop. The 5C constructs should be infused in vaccination campaigns. While a COVID-19 vaccine could be ready soon, the nursing profession may not be ready to accept it. More research work is needed to boost the uptake rate. TWEETABLE ABSTRACT: Less than two-third of nurses intended to take COVID-19 vaccine when available. While a COVID-19 vaccine could be ready soon, nursing profession is not ready to accept it. | Int J Nurs Stud | 2020 | LitCov and CORD-19 | |
| 381 | Characterization of the novel SARS-CoV-2 Omicron (B.1.1.529) variant of concern and its global perspective N/A | J Med Virol | 2022 | LitCov and CORD-19 | |
| 382 | Clinical severity of and effectiveness of mRNA vaccines against, covid-19 from omicron, delta and alpha SARS-CoV-2 variants in the United States: prospective observational study OBJECTIVES: To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. DESIGN: Case-control study. SETTING: 21 hospitals across the United States. PARTICIPANTS: 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022). MAIN OUTCOME MEASURES: Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization’s clinical progression scale was compared among variants using proportional odds regression. RESULTS: Effectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85). CONCLUSIONS: mRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants. | BMJ | 2022 | LitCov and CORD-19 | |
| 383 | Self-Reported Symptoms of SARS-CoV-2 Infection in a Nonhospitalized Population in Italy: Cross-Sectional Study of the EPICOVID-19 Web-Based Survey BACKGROUND: Understanding the occurrence of symptoms resembling those of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large nonhospitalized population at the peak of the epidemic in Italy is of paramount importance; however, data are currently scarce. OBJECTIVE: The aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test results in nonhospitalized individuals and to estimate the occurrence of symptoms associated with coronavirus disease (COVID-19) in a larger nontested population. METHODS: EPICOVID19 is a self-administered cross-sectional voluntary web-based survey of adults throughout Italy who completed an anonymous questionnaire in the period of April 13 to 21, 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios (aORs) with 95% CIs by multiple logistic regression analysis controlling for age, sex, education, smoking habits, and number of comorbidities. Thereafter, for each symptom and for combinations of the symptoms, we calculated the sensitivity, specificity, accuracy, and areas under the curve (AUCs) in a receiver operating characteristic (ROC) analysis to estimate the occurrence of COVID-19–like infection in the nontested population. RESULTS: A total of 171,310 people responded to the survey, of whom 102,543 (59.9%) were women; mean age 47.4 years. Out of the 4785 respondents with known NPS test results, 4392 were not hospitalized. Among the 4392 nonhospitalized respondents, those with positive NPS tests (856, 19.5%) most frequently reported myalgia (527, 61.6%), olfactory and taste disorders (507, 59.2%), cough (466, 54.4%), and fever (444, 51.9%), whereas 7.7% were asymptomatic. Multiple regression analysis showed that olfactory and taste disorders (aOR 10.3, 95% CI 8.4-12.7), fever (aOR 2.5, 95% CI 2.0-3.1), myalgia (aOR 1.5, 95% CI 1.2-1.8), and cough (aOR 1.3, 95% CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95% CI 5.6-9.7) to 35.5 (95% CI 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95% CI 0.795-0.825) in classifying positive NPS test results and then was applied to the nonhospitalized and nontested sample (n=165,782). We found that 7739 to 20,103 of these 165,782 respondents (4.4% to 12.1%) had experienced symptoms suggestive of COVID-19 infection. CONCLUSIONS: Our results suggest that self-reported symptoms are reliable indicators of SARS-CoV-2 infection in a pandemic context. A nonnegligible number of symptomatic respondents (up to 12.1%) were undiagnosed and potentially contributed to the spread of the infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701 | JMIR Public Health Surveill | 2020 | LitCov and CORD-19 | |
| 384 | Maternal depressive and anxiety symptoms before and during the COVID-19 pandemic in Canada: a longitudinal analysis BACKGROUND: Parents have faced substantial social and economic challenges during the COVID-19 pandemic. Preliminary cross-sectional research has demonstrated increases in mental health problems in mothers during the COVID-19 pandemic compared with pre-pandemic estimates. We aimed to study an existing longitudinal cohort of mothers to assess changes in the prevalence of maternal depression and anxiety symptoms as a result of the COVID-19 pandemic over time and at the individual level. METHODS: In this longitudinal observational study, women who took part in the All Our Families pregnancy cohort in Canada were invited to complete a COVID-19 impact survey between May 20 and July 15, 2020. Women who had not agreed to additional research, had discontinued, were lost to follow-up, or who were not contactable via email were excluded. Maternal depression and anxiety symptoms during the COVID-19 pandemic were compared with three previous estimates collected at 3, 5, and 8-year timepoints (between April, 2012, and October, 2019). Depression symptoms were assessed using the 10-item Center for Epidemiological Studies Depression scale and anxiety symptoms were assessed using the short form of the Spielberger State-Trait Anxiety Inventory. Repeated cross-sectional analyses were done to assess temporal trends and fixed-effects regression models were fitted to assess within-person change over time. FINDINGS: Of the 3387 women included in the All Our Families study, 2445 women were eligible and were invited to participate in the COVID-19 impact study, of whom 1333 consented to participate, and 1301 were included in the longitudinal analysis. At the COVID-19 impact survey timepoint, a higher proportion of mothers had clinically significant depression (35·21%, 95% CI 32·48–38·04) and anxiety symptoms (31·39%, 28·76–34·15) than at all previous data collection timepoints. The mean depression score (8·31, 95% CI 7·97–8·65) and anxiety score (11·90, 11·66–12·13) at the COVID-19 pandemic timepoint were higher than previous data collection waves at the 3-year timepoint (mean depression score 5·05, 4·85–5·25; mean anxiety score 9·51, 9·35–9·66), 5-year timepoint (mean depression score 5·43, 5·20–5·66; mean anxiety score 9·49, 9·33–9·65), and 8-year timepoint (mean depression score 5·79, 5·55–6·02; mean anxiety score 10·26, 10·10–10·42). For the within-person comparisons, depression scores were a mean of 2·30 points (95% CI 1·95–2·65) higher and anxiety scores were a mean of 1·04 points (0·65–1·43) higher at the COVID-19 pandemic timepoint, after controlling for time trends. Larger increases in depression and anxiety symptoms were observed for women who had income disruptions, difficulty balancing home schooling with work responsibilities, and those with difficulty obtaining childcare. White mothers had greater increases in anxiety scores than non-white mothers and health-care workers had smaller increases in depressive symptoms than non-health-care workers. INTERPRETATION: Compared with previous estimates, the prevalence of maternal depression and anxiety among mothers in a Canadian cohort increased during the COVID-19 pandemic. Financial support, childcare provision, and avoiding the closure of schools, might be key priorities for preventing future increases in maternal psychological distress. FUNDING: Alberta Innovates Health Solutions Interdisciplinary Team, Canadian Institutes of Health Research, Alberta Innovates, and Alberta Children's Hospital Foundation. | Lancet Psychiatry | 2021 | LitCov and CORD-19 | |
| 385 | Mental health status among family members of Healthcare workers in Ningbo, China, during the COVID-19 outbreak: a cross-sectional study BACKGROUND: To date, the psychological impact of COVID-19 epidemic among family members of health care workers (HCWs) in China has been neglected. This cross-sectional study investigates the mental health status and related factors in families of HCWs employed in designated hospitals in Ningbo, China. METHODS: Family members of HCWs in five designated hospitals in Ningbo, China, were recruited in February, 2020 for this study. Demographic variables, COVID-19-related events in the lives of the participants, knowledge of COVID-19, and the working status of family members (that is, HCWs) were collected using online self-administered questionnaires. Mental health status was assessed using the Chinese versions of the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression analyses were performed to identify the main factors associated with the mental health conditions. RESULTS: In total, 845 participants completed the questionnaires correctly (95.80% response rate). The prevalence of anxiety and depression symptoms were respectively 33.73% (95% CI: 30.53–36.92%) and 29.35% (95% CI: 26.27–32.43%) when a cut-off score of 5 was used for GAD-7 and PHQ-9. Risk factors for anxiety symptoms included more time (hours) spent thinking about the COVID-19, and whether or not family members (that is, HCWs) had direct contact with confirmed or suspected COVID-19 patients while high participants’ self-reported safety scores for HCW’s protective equipment was a protective factor. More time (hours) spent thinking about COVID-19, longer average working time per week worked by family members (that is, HCWs), and being parents and other next of kin of HCWs were risk factors for depressive symptoms. Compared to participants who were HCWs, participants who were private sector workers were more likely to develop depressive symptoms, while government or institutional employees were less likely to suffer from depressive symptoms. CONCLUSIONS: Psychological responses to COVID-19 have been dramatic among family members of HCWs during the rising phase of the outbreak. Our findings provide strong evidence to examine and attend to the mental health of this population during the COVID-19 epidemic. | BMC Psychiatry | 2020 | LitCov and CORD-19 | |
| 386 | Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China N/A | Allergy | 2020 | LitCov and CORD-19 | |
| 387 | Prevalence, Psychological Responses and Associated Correlates of Depression, Anxiety and Stress in a Global Population, During the COVID-19 Pandemic Uncertainty and isolation have been linked to mental health problems. Uncertainty surrounding the COVID-19 pandemic has the potential to trigger mental health problems, which include anxiety, stress, and depression. This paper evaluates the prevalence, psychological responses, and associated correlates of depression, anxiety, and stress in a global population during the Coronavirus Disease (COVID-19) pandemic. A cross-sectional study design was adopted. 678 completed forms were collected during the COVID-19 quarantine/lockdown. An online questionnaire was designed and DASS-21 was used as the screening tool. A non-probability sampling technique strategy was applied. 50.9% of participants showed traits of anxiety, 57.4% showed signs of stress, and 58.6% exhibited depression. Stress, anxiety, and depression are overwhelmingly prevalent across the globe during this COVID-19 pandemic, and multiple factors can influence the rates of these mental health conditions. Our factorial analysis showed notable associations and manifestations of stress, anxiety, and depressive symptoms. People aged 18–24, females, and people in non-marital relationships experienced stress, anxiety, and depression. Separated individuals experienced stress and anxiety. Married people experienced anxiety. Single and divorced people experienced depression. Unemployed individuals experienced stress and depression. Students experienced anxiety and depression. Canada, the UK, and Pakistan are all countries that are experiencing stress and depression as a whole. An extended number of days in quarantine was associated with increased stress, anxiety, and depression. Family presence yielded lower levels of stress, anxiety, and depression. Lastly, lack of exercise was associated with increased stress, anxiety, and depression. | Community Ment Health J | 2020 | LitCov and CORD-19 | |
| 388 | Evaluation of the Rapid Antigen Detection Kit with the PCR for Detection of SARS-CoV-2 in Respiratory Samples N/A | Mikrobiyol Bul | 2022 | LitCov and CORD-19 | |
| 389 | Risk factors for mental health symptoms during the COVID-19 pandemic in ophthalmic personnel and students in USA (& Canada): a cross-sectional survey study BACKGROUND: The COVID-19 pandemic poses mental health challenges to frontline healthcare workers. Eye care professionals may be especially susceptible to mental health problems due to high-risk exposures to patients. Yet, no prior research has studied mental health issues among eye care professionals during the COVID-19 pandemic. OBJECTIVE: The purpose of this study was to identify risk factors for mental health problems during the COVID-19 pandemic among eye care professionals. METHODS: We conducted a cross-sectional survey study among eye care professionals and students in the United States and Canada from June 23 to July 8, 2020 during the COVID-19 pandemic. A total of 8505 eye care professionals and students received email invitations to the survey and 2134 participated. We measured mental health outcomes including symptoms of depression, anxiety, and stress using validated scales, as well as potential risk factors including demographic characteristics, state-level COVID-19 case counts, participants’ patient interactions, childcare responsibilities, and pre-pandemic stress levels. Linear multiple regression and logistic regression analyses were used to determine relationships between risk factors and mental health outcomes. RESULTS: We found that 38.4% of eyecare professional participants in the survey met screening threshold as probable cases of anxiety, depression, or both during the COVID-19 pandemic. Controlling for self-reported pre-pandemic stress level and state COVID-19 case daily cases, significant risk factors for depression, anxiety, and psychological stress during the COVID-19 pandemic included: being female, younger age, and being Black or Asian. Interestingly, we found two somewhat surprising protective factors against depression symptoms: more frequent interactions with patients and having a greater proportion of childcare responsibilities at home. CONCLUSIONS: This study showed a high prevalence of mental health problems and revealed disparities in mental health among eye care personnel and students: Female, younger, Black, and Asian populations are particularly vulnerable to mental health issues. These results indicate that it is critical to identify mental health issues more effectively and develop interventions among this population to address this significant and growing public health issue. The strategies and policies should be reflective of the demographic disparities in this vulnerable population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-021-03535-1. | BMC Psychiatry | 2021 | LitCov and CORD-19 | |
| 390 | Comparative 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 Rep | 2021 | LitCov and CORD-19 | |
| 391 | The Incubation Period of COVID-19 From Publicly Reported Confirmed Cases: Estimation and Application BACKGROUND: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. OBJECTIVE: To estimate the length of the incubation period of COVID-19 and describe its public health implications. DESIGN: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. SETTING: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. PARTICIPANTS: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. MEASUREMENTS: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. RESULTS: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. LIMITATION: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. CONCLUSION: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases. PRIMARY FUNDING SOURCE: U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation. | Ann Intern Med | 2020 | LitCov and CORD-19 | |
| 392 | Counseling in maternal-fetal medicine: SARS-CoV-2 infection in pregnancy Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a zoonotic coronavirus that crossed species to infect humans, causing coronavirus disease 2019 (COVID‐19). Despite a potentially higher risk of pregnant women acquiring SARS‐CoV‐2 infection compared with the non‐pregnant population (particularly in some ethnic minorities), no additional specific recommendations to avoid exposure are needed in pregnancy. The most common clinical symptoms and laboratory signs of SARS‐CoV‐2 infection in pregnancy are fever, cough, lymphopenia and elevated C‐reactive protein levels. Pregnancy is associated with a higher risk of severe SARS‐CoV‐2 infection compared with the non‐pregnant population, including pneumonia, admission to the intensive care unit and death, even after adjusting for potential risk factors for severe outcomes. The risk of miscarriage does not appear to be increased in women with SARS‐CoV‐2 infection. Evidence with regards to preterm birth and perinatal mortality is conflicting, but these risks are generally higher only in symptomatic, hospitalized women. The risk of vertical transmission, defined as the transmission of SARS‐CoV‐2 from the mother to the fetus or the newborn, is generally low. Fetal invasive procedures are considered to be generally safe in pregnant women with SARS‐CoV‐2 infection, although the evidence is still limited. In pregnant women with COVID‐19, use of steroids should not be avoided if clinically indicated; the preferred regimen is a 2‐day course of dexamethasone followed by an 8‐day course of methylprednisolone. Non‐steroidal anti‐inflammatory drugs may be used if there are no contraindications. Hospitalized pregnant women with severe COVID‐19 should undergo thromboprophylaxis throughout the duration of hospitalization and at least until discharge, preferably with low molecular weight heparin. Hospitalized women who have recovered from a period of serious or critical illness with COVID‐19 should be offered a fetal growth scan about 14 days after recovery from their illness. In asymptomatic or mildly symptomatic women who have tested positive for SARS‐CoV‐2 infection at full term (i.e. ≥ 39 weeks of gestation), induction of labor might be reasonable. To date, there is no clear consensus on the optimal timing of delivery for critically ill women. In women with no or few symptoms, management of labor should follow routine evidence‐based guidelines. Regardless of COVID‐19 status, mothers and their infants should remain together and breastfeeding, skin‐to‐skin contact, kangaroo mother care and rooming‐in throughout the day and night should be practiced, while applying necessary infection prevention and control measures. Many pregnant women have already undergone vaccination, mostly in the USA where the first reports show no significant difference in pregnancy outcomes in pregnant women receiving SARS‐CoV‐2 vaccination during pregnancy compared with the background risk. Vaccine‐generated antibodies were present in the umbilical cord blood and breast milk samples of pregnant and lactating women who received the mRNA COVID‐19 vaccine. Based on the available limited data on the safety of the COVID‐19 vaccine in pregnancy, it seems reasonable to offer the option of vaccination to pregnant women after accurate counseling on the potential risk of a severe course of the disease and the unknown risk of fetal exposure to the vaccine. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. | Ultrasound Obstet Gynecol | 2021 | LitCov and CORD-19 | |
| 393 | Effects of Internet Hospital Consultations on Psychological Burdens and Disease Knowledge During the Early Outbreak of COVID-19 in China: Cross-Sectional Survey Study BACKGROUND: Coronavirus disease (COVID-19) has become a global threat to human health. Internet hospitals have emerged as a critical technology to bring epidemic-related web-based services and medical support to the public. However, only a few very recent scientific literature reports have explored the effects of internet hospitals on psychological burden and disease knowledge in major public health emergencies such as the COVID-19 pandemic. OBJECTIVE: The aim of this study was to explore the role of internet hospitals in relieving psychological burden and increasing disease knowledge during the early outbreak of the COVID-19 pandemic. METHODS: This survey was conducted from January 26 to February 1, 2020, during the early outbreak of COVID-19 in China. The platform used for the consultation was the WeChat public account of our hospital. To participate in the study, the patient was required to answer a list of questions to exclude the possibility of COVID-19 infection and confirm their willingness to participate voluntarily. Next, the participant was directed to complete the self-report questionnaire. After the internet consultation, the participant was directed to complete the self-report questionnaire again. The questionnaire included sections on general information, the General Health Questionnaire-28 (GHQ-28), and the participant’s worries, disease knowledge, and need for hospital treatment. RESULTS: The total number of internet consultations was 4120. The consultation topics mainly included respiratory symptoms such as cough, expectoration, and fever (2489/4120, 60.4%) and disease knowledge, anxiety, and fear (1023/4120, 24.8%). A total of 1530 people filled out the questionnaires before and after the internet consultation. Of these people, 1398/1530 (91.4%) experienced psychological stress before the internet consultation, which significantly decreased after consultation (260/1530, 17.0%) (χ(2)(1)=1704.8, P<.001). There was no significant difference in the number of people who expressed concern about the COVID-19 pandemic before and after the internet consultation (χ(2)(1)=0.7, P=.43). However, the degree of concern after the internet consultation was significantly alleviated (t(2699)=90.638, P<.001). The main worries before and after consultation were the dangers posed by the disease and the risk of infection of family members. The scores of the self-assessment risk after the internet consultation were significantly lower than those before consultation (t(3058)=95.694, P<.001). After the consultation, the participants’ knowledge of the symptoms, transmission routes, and preventive measures of COVID-19 was significantly higher than before the consultation (t(3058)=–106.105, –80.456, and –152.605, respectively; all P<.001). The hospital treatment need score after the internet consultation decreased from 3.3 (SD 1.2) to 1.6 (SD 0.8), and the difference was statistically significant (t(3058)=45.765, P<.001). CONCLUSIONS: During the early outbreak of COVID-19, internet hospitals could help relieve psychological burdens and increase disease awareness through timely and rapid spread of knowledge regarding COVID-19 prevention and control. Internet hospitals should be an important aspect of a new medical model in public health emergency systems. | J Med Internet Res | 2020 | LitCov and CORD-19 | |
| 394 | Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia BACKGROUND: In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern. OBJECTIVES: To describe the coagulation feature of patients with NCP. METHODS: Conventional coagulation results and outcomes of 183 consecutive patients with confirmed NCP in Tongji hospital were retrospectively analyzed. RESULTS: The overall mortality was 11.5%, the non‐survivors revealed significantly higher D‐dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P < .05); 71.4% of non‐survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay. CONCLUSIONS: The present study shows that abnormal coagulation results, especially markedly elevated D‐dimer and FDP are common in deaths with NCP. | J Thromb Haemost | 2020 | LitCov and CORD-19 | |
| 395 | Effects of Spike Mutations in SARS-CoV-2 Variants of Concern on Human or Animal ACE2-Mediated Virus Entry and Neutralization N/A | Microbiol Spectr | 2022 | LitCov | |
| 396 | Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome–coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B(0)AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B(0)AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection. | Science | 2020 | LitCov and CORD-19 | |
| 397 | A prospective, randomised, double blind placebo-controlled trial to evaluate the efficacy and safety of tocilizumab in patients with severe COVID-19 pneumonia (TOC-COVID): A structured summary of a study protocol for a randomised controlled trial OBJECTIVES: SARS-CoV2 infection leads to a concomitant pulmonary inflammation. This inflammation is supposed to be the main driver in the pathogenesis of lung failure (Acute Respiratory Distress Syndrome) in COVID-19. Objective of this study is to evaluate the efficacy and safety of a single dose treatment with Tocilizumab in patients with severe COVID-19. We hypothesize that Tocilizumab slows down the progression of SARS-CoV-2 induced pneumonia and inflammation. We expect an improvement in pulmonary function compared to placebo-treated patients. Desirable outcomes would be that tocilizumab reduces the number of days that patients are dependent on mechanical ventilation and reduces the invasiveness of breathing assistance. Furthermore, this treatment might result in fewer admissions to intensive care units. Next to these efficacy parameters, safety of a therapy with Tocilizumab in COVID-19 patients has to be monitored closely, since immunosuppression could lead to an increased rate of bacterial infections, which could negatively influence the patient’s outcome. TRIAL DESIGN: Multicentre, prospective, 2-arm randomised (ratio 1:1), double blind, placebo-controlled trial with parallel group design. PARTICIPANTS: : 1. Proof of SARS-CoV2 (Symptoms and positive polymerase chain reaction (PCR)). 2. a. Ambient air SpO(2) ≤ 92% or b. Need of ≥ 6l O2/min or c. NIV (non-invasive ventilation) or d. IMV (invasive mechanical ventilation). 3. Age ≥ 18 years. : 1. Non-invasive or invasive mechanical ventilation ≥ 48 hours. 2. Pregnancy or breast feeding. 3. Liver injury or failure (AST/ALT ≥ 5x ULN). 4. Leukocytes < 2 × 10(3)/μl. 5. Thrombocytes < 50 × 10(3)/μl. 6. Severe bacterial infection (PCT > 3ng/ml). 7. Acute or chronic diverticulitis. 8. Immunosuppressive therapy (e.g. mycophenolate, azathioprine, methotrexate, biologicals, prednisolone >10mg/d; exceptions are: prednisolone ≤ 10mg/d, sulfasalazine or hydroxychloroquine). 9. Known active or chronic tuberculosis. 10. Known active or chronic viral hepatitis. 11. Known allergic reactions to tocilizumab or its ingredients. 12. Life expectation of less than 1 year (independent of COVID-19). 13. Participation in any other interventional clinical trial within the last 30 days before the start of this trial. 14. Simultaneous participation in other interventional trials (except for participation in COVID-19 trials) which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed. 15. Failure to use one of the following safe methods of contraception: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception. The data collection of the primary follow up (28 days after randomisation) takes place during the hospital stay. Subsequently, a telephone interview on the quality of life is conducted after 6 and 12 months. Participants will be recruited from inpatients at ten medical centres in Germany. INTERVENTION AND COMPARATOR: Intervention arm: Application of 8mg/kg body weight (BW) Tocilizumab i.v. once immediately after randomisation (12 mg/kg for patients with <30kg BW; total dose should not exceed 800 mg) AND conventional treatment. Control arm: Placebo (NaCl) i.v. once immediately after randomisation AND conventional treatment. MAIN OUTCOMES: Primary endpoint is the number of ventilator free days (d) (VFD) in the first 28 days after randomisation. Non-invasive ventilation (NIV), Invasive mechanical ventilation (IMV) and extracorporeal membrane oxygenation (ECMO) are defined as ventilator days. VFD’s are counted as zero if the patient dies within the first 28 days. RANDOMISATION: The randomisation code will be generated by the CTU (Clinical Trials Unit, ZKS Freiburg) using the following procedure to ensure that treatment assignment is unbiased and concealed from patients and investigator staff. Randomisation will be stratified by centre and will be performed in blocks of variable length in a ratio of 1:1 within each centre. The block lengths will be documented separately and will not be disclosed to the investigators. The randomisation code will be produced by validated programs based on the Statistical Analysis System (SAS). BLINDING (MASKING): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 100 participants will be randomised to each group (thus 200 participants in total). TRIAL STATUS: Protocol Version: V 1.2, 16.04.2020. Recruitment began 27th April 2020 and is anticipated to be completed by December 2020. TRIAL REGISTRATION: The trial was registered before trial start in trial registries (EudraCT: No. 2020-001408-41, registered 21st April 2020, and DRKS: No. DRKS00021238, registered 22nd April 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. | Trials | 2020 | LitCov and CORD-19 | |
| 398 | A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared with Best Supportive Care in Patients with COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome: A structured summary of a study p OBJECTIVES: Primary Objective • To evaluate the effect of ravulizumab, a long-acting complement (C5) inhibitor plus best supportive care (BSC) compared with BSC alone on the survival of patients with COVID-19. Secondary Objectives • Number of days free of mechanical ventilation at Day 29 • Duration of intensive care unit stay at Day 29 • Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 29 • Change from baseline in peripheral capillary oxygen saturation/ fraction of inspired oxygen (SpO2 /FiO2) at Day 29 • Duration of hospitalization at Day 29 • Survival (based on all-cause mortality) at Day 60 and Day 90 Safety • Incidence of treatment-emergent adverse events and treatment-emergent serious adverse events. PK/PD/Immunogenicity • Change in serum ravulizumab concentrations over time • Change in serum free and total C5 concentrations over time • Incidence and titer of anti-ALXN1210 antibodies Biomarkers • Change in absolute level of soluble biomarkers in blood associated with complement activation, inflammatory processes, and hypercoagulable states over time Exploratory • Incidence of progression to renal failure requiring dialysis at Day 29 • Time to clinical improvement (based on a modified 6-point ordinal scale) over 29 days • SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores at Day 29 (or discharge), Day 60, and Day 90 • EuroQol 5-dimension 5-level (EQ-5D-5L) scores at Day 29 (or discharge), Day 60, and Day 90 TRIAL DESIGN: This is a multicenter Phase 3, open-label, randomized, controlled, study. The study is being conducted in acute care hospital settings in the United States, United Kingdom, Spain, France, Germany, and Japan. PARTICIPANTS: Male or female patients at least 18 years of age, weighing ≥ 40 kg, admitted to a designated hospital facility for treatment will be screened for eligibility in this study. Key Inclusion criteria • Confirmed diagnosis of SARS-CoV-2 infection (eg, via polymerase chain reaction [PCR] and/or antibody test) presenting as severe COVID-19 requiring hospitalization • Severe pneumonia, acute lung injury, or ARDS confirmed by computed tomography (CT) or X-ray at Screening or within the 3 days prior to Screening, as part of the patient’s routine clinical care • Respiratory distress requiring mechanical ventilation, which can be either invasive (requiring endotracheal intubation) or non-invasive (with continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]) Key Exclusion criteria • Patient is not expected to survive for more than 24 hours • Patient is on invasive mechanical ventilation with intubation for more than 48 hours prior to Screening • Severe pre-existing cardiac disease (ie, NYHA Class 3 or Class 4, acute coronary syndrome, or persistent ventricular tachyarrhythmias) • Patient has an unresolved Neisseria meningitidis infection Excluded medications and therapies • Current treatment with a complement inhibitor • Intravenous immunoglobulin (IVIg) within 4 weeks prior to randomization on Day 1 Excluded prior/concurrent clinical study experience • Treatment with investigational therapy in a clinical study within 30 days before randomization, or within 5 half-lives of that investigational therapy, whichever is greater • Exceptions a. Investigational therapies will be allowed if received as part of best supportive care through an expanded access protocol or emergency approval for the treatment of COVID-19. b. Investigational antiviral therapies (such as remdesivir) will be allowed even if received as part of a clinical study. INTERVENTION AND COMPARATOR: The study consists of a Screening Period of up to 3 days, a Primary Evaluation Period of 4 weeks, a final assessment at Day 29, and a Follow-up Period of 8 weeks. For patients randomized to ravulizumab plus BSC, a weight-based dose of ravulizumab (≥40 to < 60 kg/2400 mg, 60 to < 100 kg/2700 mg, ≥ 100 kg/3000 mg) will be administered on Day 1. On Day 5 and Day 10, additional doses of 600 mg (≥40 to <60 kg) or 900 mg (>60 kg) ravulizumab will be administered and on Day 15 patients will receive 900 mg ravulizumab. There is no active or placebo comparator in this open-label clinical trial. The total duration of each patient’s participation is anticipated to be approximately 3 months. MAIN OUTCOMES: The primary efficacy outcome of this study is survival (based on all-cause mortality) at Day 29. RANDOMISATION: Patients will be randomized in a 2:1 ratio (ravulizumab plus BSC:BSC alone). Randomization will be stratified by intubated or not intubated on Day 1. Computer-generated randomization lists will be prepared by a third party under the direction of the sponsor. Investigators, or designees, will enrol patients and then obtain randomization codes using an interactive voice/web response system. The block size will be kept concealed so that investigators cannot select patients for a particular treatment assignment. Blinding (masking): This is an open-label study. Numbers to be randomised (sample size): Approximately 270 patients will be randomly assigned in a 2:1 ratio to ravulizumab plus BSC (n=180) or BSC alone (n=90). TRIAL STATUS: Protocol Number: ALXN1210-COV-305 Original Protocol: 09 Apr 2020 Protocol Amendment 1 (Global): 13 Apr 2020 Protocol Amendment 2 (Global): 17 Apr 2020 Protocol Amendment 3 (Global): 09 Jun 2020 Recruitment is currently ongoing. Recruitment was initiated on 11 May 2020. We expect recruitment to be completed by 30 Nov 2020. TRIAL REGISTRATION: Clinicaltrials.gov: Protocol Registry Number: NCT04369469; First posted; 30 Apr 2020 EU Clinical Trials Register: EudraCT Number: https://www.clinicaltrialsregister.eu/ctr-search/search?query=ALXN1210-COV-305, Start date: 07 May 2020 FULL PROTOCOL: The full redacted protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. | Trials | 2020 | LitCov and CORD-19 | |
| 399 | Eating habits and lifestyle changes during COVID-19 lockdown: an Italian survey BACKGROUND: On December 12th 2019, a new coronavirus (SARS-Cov2) emerged in Wuhan, China, sparking a pandemic of acute respiratory syndrome in humans (COVID-19). On the 24th of April 2020, the number of COVID-19 deaths in the world, according to the COVID-Case Tracker by Johns Hopkins University, was 195,313, and the number of COVID-19 confirmed cases was 2,783,512. The COVID-19 pandemic represents a massive impact on human health, causing sudden lifestyle changes, through social distancing and isolation at home, with social and economic consequences. Optimizing public health during this pandemic requires not only knowledge from the medical and biological sciences, but also of all human sciences related to lifestyle, social and behavioural studies, including dietary habits and lifestyle. METHODS: Our study aimed to investigate the immediate impact of the COVID-19 pandemic on eating habits and lifestyle changes among the Italian population aged ≥ 12 years. The study comprised a structured questionnaire packet that inquired demographic information (age, gender, place of residence, current employment); anthropometric data (reported weight and height); dietary habits information (adherence to the Mediterranean diet, daily intake of certain foods, food frequency, and number of meals/day); lifestyle habits information (grocery shopping, habit of smoking, sleep quality and physical activity). The survey was conducted from the 5th to the 24th of April 2020. RESULTS: A total of 3533 respondents have been included in the study, aged between 12 and 86 years (76.1% females). The perception of weight gain was observed in 48.6% of the population; 3.3% of smokers decided to quit smoking; a slight increased physical activity has been reported, especially for bodyweight training, in 38.3% of respondents; the population group aged 18–30 years resulted in having a higher adherence to the Mediterranean diet when compared to the younger and the elderly population (p < 0.001; p < 0.001, respectively); 15% of respondents turned to farmers or organic, purchasing fruits and vegetables, especially in the North and Center of Italy, where BMI values were lower. CONCLUSIONS: In this study, we have provided for the first time data on the Italian population lifestyle, eating habits and adherence to the Mediterranean Diet pattern during the COVID-19 lockdown. However, as the COVID-19 pandemic is ongoing, our data need to be confirmed and investigated in future more extensive population studies. | J Transl Med | 2020 | LitCov and CORD-19 | |
| 400 | Using BCG vaccine to enhance non-specific protection of Healthcare workers during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial in Denmark Objectives: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism. The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. Hypothesis: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. Trial design: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. Participants: The trial will recruit 1,500 HCW at Danish hospitals. To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week. Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration. Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis); or other mycobacterial species. Previous confirmed COVID-19. Fever (>38 C) within the past 24 hours. Suspicion of active viral or bacterial infection. Pregnancy. Breastfeeding. Vaccination with other live attenuated vaccine within the last 4 weeks. Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1); b) subjects with solid organ transplantation; c) subjects with bone marrow transplantation; d) subjects under chemotherapy; e) subjects with primary immunodeficiency; f) subjects under treatment with any anti-cytokine therapy within the last year; g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months; h) Active solid or non-solid malignancy or lymphoma within the prior two years. Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial. Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. Main outcomes: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation. Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation. Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1. Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference. The physicians administering the treatment are not blinded. Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group. Trial Status: Current protocol version 5.1, from July 6, 2020. Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. Trial registration: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291. 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. Keywords: COVID-19, Randomised controlled trial, Protocol, BCG vaccine, NSEs/Non-specific effects of vaccines, Heterologous effects of vaccines, Health care workers, Pandemic, Immune training. | Trials | 2020 | 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
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(3) Currently tweets of June 23rd to June 29th 2022 have been considered.