| Title | Venue | Year | Impact | Source |
3951 | How to make an alternative plastic gown during the personal protective equipment shortage due to the COVID-19 pandemic | Endoscopy | 2020 | | LitCov and CORD-19 |
3952 | The role of vitamin D in the prevention of COVID-19 infection and mortality WHO declared SARS-CoV-2 a global pandemic. The present aim was to propose an hypothesis that there is a potential association between mean levels of vitamin D in various countries with cases and mortality caused by COVID-19. The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were acquired. Negative correlations between mean levels of vitamin D (average 56 mmol/L, STDEV 10.61) in each country and the number of COVID-19 cases/1 M (mean 295.95, STDEV 298.7, and mortality/1 M (mean 5.96, STDEV 15.13) were observed. Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity. | Aging Clin Exp Res | 2020 | | LitCov and CORD-19 |
3953 | Political casualties of the COVID-19 pandemic | Lancet Infect Dis | 2020 | | LitCov and CORD-19 |
3954 | Heterogeneity of infectious bronchitis virus grown in eggs Egg-grown infectious bronchitis virus, strain Beaudette, was concentrated and centrifuged on sucrose density gradients to separate the virus into five peaks with densities of 1.144, 1.160, 1.172, 1.191 and 1.218 g/cm(3). All peaks retained infectivity, complement fixation activity and were labelled with(3)H-uridine. Morphologically the densest peak consisted of very large virus particles and amorphous material, the other peaks consisted of mainly intact particles although small differences in size and pleomorphism were seen. Polyacrylamide gel electrophoresis of material from the density gradient peaks revealed four major polypeptides and at least 10 minor polypeptides. The proportions of the polypeptides were approximately similar for all peaks with the exception of the densest peak in which the major polypeptides were greatly reduced. The four major polypeptides had approximate molecular weights of 1. 52,000, 2. 45,000, 3. 34,000, 4. 32,000. The major polypeptides 1 and 4 were shown to be glycosylated as were two of the minor polypeptides. | Arch Virol | 1976 | | CORD-19 |
3955 | Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome N/A | J Virol | 2007 | | CORD-19 |
3956 | A qualitative study on the psychological experience of caregivers of COVID-19 patients BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading rapidly, bringing pressure and challenges to nursing staff. OBJECTIVE: To explore the psychology of nurses caring for COVID-19 patients. METHOD: Using a phenomenological approach, we enrolled 20 nurses who provided care for COVID-19 patients in the First Affiliated Hospital of Henan University of Science and Technology from 20 January to 10 February 2020. The interviews were conducted face-to-face or by telephone and were analysed by Colaizzi's 7-step method. RESULTS: The psychological experience of nurses caring for COVID-19 patients can be summarized into four themes. Firstly, negative emotions present in early stage consisting of fatigue, discomfort, and helplessness was caused by high-intensity work, fear and anxiety, and concern for patients and family members. Secondly, self-coping styles included psychological and life adjustment, altruistic acts, team support, and rational cognition. Thirdly, we found growth under pressure, which included increased affection and gratefulness, development of professional responsibility, and self-reflection. Finally, we showed that positive emotions occurred simultaneously with negative emotions. CONCLUSIONS: During an epidemic outbreak, positive and negative emotions of the front-line nurses interweaved and coexisted. In the early stage, negative emotions were dominant and positive emotions appeared gradually. Self-coping styles and psychological growth played an important role in maintaining mental health of nurses. | Am J Infect Control | 2020 | | LitCov and CORD-19 |
3957 | Antigenic Relationship between Human Coronavirus Strain DC 43 and Hemagglutinating Encephalomyelitis Virus Strain 67N of Swine: Antibody Responses in Human and Animal Sera Hemagglutinating encephalomyelitis virus of swine (HEV) was adapted to growth in suckling mouse brain. Electron micrographs of HEV-infected suckling mouse brain, prepared by negative staining and thin-section techniques, exhibited typical morphological characteristics shared with other members of the Coronaviridae. The adaptation of HEV to suckling mouse brain facilitated serologic testing by the use of common host reagents and compatible animal systems. With hemagglutination inhibition, complement-fixation, and neutralization tests, an antigenic relationship was demonstrated between human coronavirus OC 43 and HEV in specific immune and hyperimmune animal sera. Children and adults with seroconversion to OC 43 antigen had diagnostic rises in titer of antibody to HEV antigens. Individuals with seroconversion to human coronaviruses 229E and B814 demonstrated antibody to HEV but not diagnostic rises in titer. Swine with titers of antibody to HEV had lower or no detectable titers of antibody to coronavirus OC 43. Although the prevalence and geometric mean titer of antibody to DC 43 were higher than the titer of antibody to HEV in every group of normal humans tested, significant differences in antibody response to coronavirus DC 43 and HEV were seen between populations that did or did not have possible contact with swine. The evidence suggested that antibody to HEV in humans probably represented a heterologous response to infection with coronavirus DC 43. However, a heterotypic response to unknown or uncharacterized strains of coronavirus cannot be excluded. | J Infect Dis | 1977 | | CORD-19 |
3958 | Discovery and Evaluation of Entry Inhibitors for SARS-CoV-2 and Its Emerging Variants The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 19 (COVID-19) pandemic. Despite unprecedented research and developmental efforts, SARS-CoV-2-specific antivirals are still unavailable for the treatment of COVID-19. In most instances, SARS-CoV-2 infection initiates with the binding of Spike glycoprotein to the host cell ACE2 receptor. Utilizing the crystal structure of the ACE2/Spike receptor-binding domain (S-RBD) complex (PDB file 6M0J) in a computer-aided drug design approach, we identified and validated five potential inhibitors of S-RBD and ACE-2 interaction. Two of the five compounds, MU-UNMC-1 and MU-UNMC-2, blocked the entry of pseudovirus particles expressing SARS-CoV-2 Spike glycoprotein. In live SARS-CoV-2 infection assays, both compounds showed antiviral activity with IC(50) values in the micromolar range (MU-UNMC-1: IC(50) = 0.67 μM and MU-UNMC-2: IC(50) = 1.72 μM) in human bronchial epithelial cells. Furthermore, MU-UNMC-1 and MU-UNMC-2 effectively blocked the replication of rapidly transmitting variants of concern: South African variant B.1.351 (IC(50) = 9.27 and 3.00 μM) and Scotland variant B.1.222 (IC(50) = 2.64 and 1.39 μM), respectively. Following these assays, we conducted “induced-fit (flexible) docking” to understand the binding mode of MU-UNMC-1/MU-UNMC-2 at the S-RBD/ACE2 interface. Our data showed that mutation N501Y (present in B.1.351 variant) alters the binding mode of MU-UNMC-2 such that it is partially exposed to the solvent and has reduced polar contacts. Finally, MU-UNMC-2 displayed high synergy with remdesivir, the only approved drug for treating hospitalized COVID-19 patients. IMPORTANCE The ongoing coronavirus infectious disease 2019 (COVID-19) pandemic is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More than 207 million people have been infected globally, and 4.3 million have died due to this viral outbreak. While a few vaccines have been deployed, a SARS-CoV-2-specific antiviral for the treatment of COVID-19 is yet to be approved. As the interaction of SARS-CoV-2 Spike protein with ACE2 is critical for cellular entry, using a combination of a computer-aided drug design (CADD) approach and cell-based in vitro assays, we report the identification of five potential SARS-CoV-2 entry inhibitors. Out of the five, two compounds (MU-UNMC-1 and MU-UNMC-2) have antiviral activity against ancestral SARS-CoV-2 and emerging variants from South Africa and Scotland. Furthermore, MU-UNMC-2 acts synergistically with remdesivir (RDV), suggesting that RDV and MU-UNMC-2 can be developed as a combination therapy to treat COVID-19 patients. | J Virol | 2021 | | LitCov and CORD-19 |
3959 | SARS-CoV-2, which induces COVID-19, causes kawasaki-like disease in children: role of pro-inflammatory and anti-inflammatory cytokines N/A | J Biol Regul Homeost Agents | 2020 | | LitCov and CORD-19 |
3960 | Evaluation of Protection Level, Respiratory Safety and Practical Aspects of Commercially Available Snorkel Masks as Personal Protection Devices Against Aerosolized Contaminants and SARS-CoV-2 Introduction: The “Severe Acute Respiratory Syndrome Coronavirus 2″ (SARS-CoV2) pandemic has led to a worldwide shortage of personal protection devices (PPD) for medical and paramedical personnel. Adaptation of commercially available snorkel masks to serve as full face masks has been proposed. Even not formally approved as PPD, they are publicized on social media as suitable for this use. Concerns about actual protection levels and risk of carbon dioxide (CO(2)) accumulation while wearing them for extended periods made us perform a systematic testing of various brands, in order to verify whether they are as safe and effective as claimed. Methods: A ‘fit’ test was performed, analogous to gas mask testing. Respiratory safety was evaluated by measuring end-tidal CO(2) and oxygen saturation while wearing the masks in rest and during physical exercise. Masks were tested with 3D adaptors to mount regular bacterial-viral ventilator filters when available, or with snorkel openings covered with N95/FFP2 cloth. Results: Modified masks performed reasonably well on the fit test, comparable to regular N95/FFP2 masks. Not all ventilator filters are equally protective. For all masks, a small initial increase in end-tidal CO(2) was noted, remaining within physiological limits. 3D printed adaptors are safer, have more flexibility and reliability than makeshift adaptations. Conclusions: These masks can offer benefit as a substitute for complete protective gear as they are easier to don and remove and offer full-face protection. They may be more comfortable to wear for extended periods. Proper selection of mask size, fit testing, quality of 3D printed parts, and choice of filter are important. | Int J Environ Res Public Healt | 2020 | | LitCov and CORD-19 |
3961 | Lessons unfolding from pediatric cases of COVID-19 disease caused by SARS-CoV-2 infection | Pediatr Pulmonol | 2020 | | LitCov and CORD-19 |
3962 | Diarrhea During COVID-19 Infection: Pathogenesis, Epidemiology, Prevention and Management Abstract Background and aims The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 / COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. Methods We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechansism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Results Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Conclusion Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research. | Clin Gastroenterol Hepatol | 2020 | | LitCov and CORD-19 |
3963 | Immunogenicity of a first dose of mRNA- or vector-based SARS-CoV-2 vaccination in dialysis patients: a multicenter prospective observational pilot study BACKGROUND: Dialysis patients are at risk for lower SARS-CoV-2-vaccine immunogenicity than the normal population. We assessed immunogenicity to a first mRNA- or vector-based SARS-CoV-2-vaccination dose in dialysis patients. METHODS: In a multicenter observational pilot study, 2 weeks after a first vaccination (BNT162b2/Pfizer-BioNTech [Comirnaty] or ChAdOx1 nCoV-19/Oxford-Astra-Zeneca [Vaxzevria]), hemodialysis patients (N = 23), peritoneal dialysis patients (N = 4) and healthy staff (N = 14) were tested for SARS-CoV-2-spike IgG/IgM, Nucleocapsid-protein-IgG-antibodies and plasma ACE2-receptor-binding-inhibition capacity. Hemodialysis patients who had had prior COVID-19 infection (N = 18) served as controls. Both response to first SARS-CoV-2 vaccination and IgG spike-positivity following prior COVID-19 infection were defined as SARS-CoV-2 spike IgG levels ≥ 50 AU/mL. RESULTS: Vaccination responder rates were 17.4% (4/23) in hemodialysis patients, 100% (4/4) in peritoneal dialysis patients and 57.1% (8/14) in staff (HD vs. PD: p = 0.004, HD vs. staff: p = 0.027). Among hemodialysis patients, type of vaccine (Comirnaty N = 11, Vaxzevria N = 12, 2 responders each) did not appear to influence antibody levels (IgG spike: Comirnaty median 0.0 [1.–3. quartile 0.0–3.8] versus Vaxzevria 4.3 [1.6–20.1] AU/mL, p = 0.079). Of responders to the first dose of SARS-CoV-2 vaccination among hemodialysis patients (N = 4/23), median IgG spike levels and ACE2-receptor-binding-inhibition capacity were lower than that of IgG spike-positive hemodialysis patients with prior COVID-19 infection (13/18, 72.2%): IgG spike: median 222.0, 1.–3. quartile 104.1–721.9 versus median 3794.6, 1.–3. quartile 793.4–9357.9 AU/mL, p = 0.015; ACE2-receptor-binding-inhibition capacity: median 11.5%, 1.–3. quartile 5.0–27.3 versus median 74.8%, 1.–3. quartile 44.9–98.1, p = 0.002. CONCLUSIONS: Two weeks after their first mRNA- or vector-based SARS-CoV-2 vaccination, hemodialysis patients demonstrated lower antibody-related response than peritoneal dialysis patients and healthy staff or unvaccinated hemodialysis patients following prior COVID-19 infection. GRAPHIC ABSTRACT: [Image: see text] | J Nephrol | 2021 | | LitCov and CORD-19 |
3964 | An electron microscopic study of experimentally induced HEV encephalitis N/A | Vet Pathol | 1978 | | CORD-19 |
3965 | Platelet gene expression and function in patients with COVID-19 Abstract There is an urgent need to understand the pathogenesis of coronavirus disease 2019 (COVID-19). In particular, thrombotic complications in patients with COVID-19 are common and contribute to organ failure and mortality. Patients with severe COVID-19 present with hemostatic abnormalities that mimic disseminated intravascular coagulopathy associated with sepsis, with the major difference being increased risk of thrombosis rather than bleeding. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters platelet function to contribute to the pathophysiology of COVID-19 remains unknown. In this study, we report altered platelet gene expression and functional responses in patients infected with SARS-CoV-2. RNA sequencing demonstrated distinct changes in the gene-expression profile of circulating platelets of COVID-19 patients. Pathway analysis revealed differential gene-expression changes in pathways associated with protein ubiquitination, antigen presentation, and mitochondrial dysfunction. The receptor for SARS-CoV-2 binding, angiotensin-converting enzyme 2 (ACE2), was not detected by messenger RNA (mRNA) or protein in platelets. Surprisingly, mRNA from the SARS-CoV-2 N1 gene was detected in platelets from 2 of 25 COVID-19 patients, suggesting that platelets may take-up SARS-COV-2 mRNA independent of ACE2. Resting platelets from COVID-19 patients had increased P-selectin expression basally and upon activation. Circulating platelet-neutrophil, -monocyte, and -T-cell aggregates were all significantly elevated in COVID-19 patients compared with healthy donors. Furthermore, platelets from COVID-19 patients aggregated faster and showed increased spreading on both fibrinogen and collagen. The increase in platelet activation and aggregation could partially be attributed to increased MAPK pathway activation and thromboxane generation. These findings demonstrate that SARS-CoV-2 infection is associated with platelet hyperreactivity, which may contribute to COVID-19 pathophysiology. | Blood | 2020 | | LitCov and CORD-19 |
3966 | Mental health among head and neck surgeons in Brazil during the COVID-19 pandemic: A national study PURPOSE: Head and neck surgeons are among the highest risk for COVID-19 exposure, which also brings great risk to their mental wellbeing. In this study, we aim to evaluate mental health symptoms among head and neck surgeons in Brazil surrounding the time it was declared the epicenter of the virus. MATERIALS AND METHODS: A cross-sectional, survey-based study evaluating burnout, anxiety, distress, and depression among head and neck surgeons in Brazil, assessed through the single-item Mini-Z burnout assessment, 7-item Generalized Anxiety Disorder scale, 22-item Impact of Event Scale-Revised, and 2-item Patient Health Questionnaire, respectively. RESULTS: 163 physicians completed the survey (74.2% males). Anxiety, distress, burnout, and depression symptoms were reported in 74 (45.5%), 43 (26.3%), 24 (14.7%), and 26 (16.0%) physicians, respectively. On multivariable analysis, female physicians were more likely to report a positive screening for burnout compared to males (OR 2.88, CI [1.07–7.74]). Physicians 45 years or older were less likely to experience anxiety symptoms than those younger than 45 years (OR 0.40, CI [0.20–0.81]). Physicians with no self-reported prior psychiatric conditions were less likely to have symptoms of distress compared to those with such history (OR 0.11, CI [0.33–0.38]). CONCLUSION: Head and neck surgeons in Brazil reported symptoms of burnout, anxiety, distress and depression during our study period within the COVID-19 pandemic. Institutions should monitor these symptoms throughout the pandemic. Further study is required to assess the long-term implications for physician wellness. | Am J Otolaryngol | 2020 | | LitCov and CORD-19 |
3967 | Serum Neutralizing Activity of mRNA-1273 against SARS-CoV-2 Variants The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has led to growing concerns over increased transmissibility and the ability of some variants to partially escape immunity. Sera from participants immunized on a prime-boost schedule with the mRNA-1273 COVID-19 vaccine were tested for neutralizing activity against several SARS-CoV-2 variants, including variants of concern (VOCs) and variants of interest (VOIs), compared to neutralization of the wild-type SARS-CoV-2 virus (designated D614G). Results showed minimal, statistically nonsignificant effects on neutralization titers against the B.1.1.7 (Alpha) variant (1.2-fold reduction compared with D614G); other VOCs, such as B.1.351 (Beta, including B.1.351-v1, B.1.351-v2, and B.1.351-v3), P.1 (Gamma), and B.1.617.2 (Delta), showed significantly decreased neutralization titers ranging from 2.1-fold to 8.4-fold reductions compared with D614G, although all remained susceptible to mRNA-1273-elicited serum neutralization. IMPORTANCE In light of multiple variants of SARS-CoV-2 that have been documented globally during the COVID-19 pandemic, it remains important to continually assess the ability of currently available vaccines to confer protection against newly emerging variants. Data presented herein indicate that immunization with the mRNA-1273 COVID-19 vaccine produces neutralizing antibodies against key emerging variants tested, including variants of concern and variants of interest. While the serum neutralization elicited by mRNA-1273 against most variants tested was reduced compared with that against the wild-type virus, the level of neutralization is still expected to be protective. Such data are crucial to inform ongoing and future vaccination strategies to combat COVID-19. | J Virol | 2021 | | LitCov and CORD-19 |
3968 | A Bold Response to the COVID-19 Pandemic: Medical Students, National Service and Public Health N/A | JAMA | 2020 | | LitCov and CORD-19 |
3969 | Characteristics of Healthcare Personnel with COVID-19-United States, February 12-April 9, 2020 As of April 9, 2020, the coronavirus disease 2019 (COVID-19) pandemic had resulted in 1,521,252 cases and 92,798 deaths worldwide, including 459,165 cases and 16,570 deaths in the United States (1,2). Health care personnel (HCP) are essential workers defined as paid and unpaid persons serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials (3). During February 12-April 9, among 315,531 COVID-19 cases reported to CDC using a standardized form, 49,370 (16%) included data on whether the patient was a health care worker in the United States; including 9,282 (19%) who were identified as HCP. Among HCP patients with data available, the median age was 42 years (interquartile range [IQR] = 32-54 years), 6,603 (73%) were female, and 1,779 (38%) reported at least one underlying health condition. Among HCP patients with data on health care, household, and community exposures, 780 (55%) reported contact with a COVID-19 patient only in health care settings. Although 4,336 (92%) HCP patients reported having at least one symptom among fever, cough, or shortness of breath, the remaining 8% did not report any of these symptoms. Most HCP with COVID-19 (6,760, 90%) were not hospitalized; however, severe outcomes, including 27 deaths, occurred across all age groups; deaths most frequently occurred in HCP aged ≥65 years. These preliminary findings highlight that whether HCP acquire infection at work or in the community, it is necessary to protect the health and safety of this essential national workforce. | MMWR Morb Mortal Wkly Rep | 2020 | | LitCov and CORD-19 |
3970 | Coagulopathy of COVID-19 Recent studies have reported a high prevalence of thrombotic events in coronavirus disease 2019. However, the significance of thromboembolic complications has not been widely appreciated. The purpose of this review is to provide current knowledge of this serious problem. DESIGN: Narrative review. DATA SOURCES: Online search of published medical literature through PubMed using the term “COVID-19,” “SARS,” “acute respiratory distress syndrome,” “coronavirus,” “coagulopathy,” “thrombus,” and “anticoagulants.” STUDY SELECTION AND DATA EXTRACTION: Articles were chosen for inclusion based on their relevance to coagulopathy and thrombosis in coronavirus disease 2019, and anticoagulant therapy. Reference lists were reviewed to identify additional relevant articles. DATA SYNTHESIS: Coronavirus disease 2019 is associated with a strikingly high prevalence of coagulopathy and venous thromboembolism that may contribute to respiratory deterioration. Monitoring coagulation variables is important, as abnormal coagulation tests are related to adverse outcomes and may necessitate adjuvant antithrombotic interventions. In the initial phase of the infection, d-dimer and fibrinogen levels are increased, while activated partial prothrombin time, prothrombin time, and platelet counts are often relatively normal. Increased d-dimer levels three times the upper limit of normal may trigger screening for venous thromboembolism. In all hospitalized patients, thromboprophylaxis using low-molecular-weight heparin is currently recommended. The etiology of the procoagulant responses is complex and thought to be a result of specific interactions between host defense mechanisms and the coagulation system. Although the coagulopathy is reminiscent of disseminated intravascular coagulation and thrombotic microangiopathy, it has features that are markedly distinct from these entities. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 frequently induces hypercoagulability with both microangiopathy and local thrombus formation, and a systemic coagulation defect that leads to large vessel thrombosis and major thromboembolic complications, including pulmonary embolism in critically ill hospitalized patients. d-dimers and fibrinogen levels should be monitored, and all hospitalized patients should undergo thromboembolism prophylaxis with an increase in therapeutic anticoagulation in certain clinical situations. | Crit Care Med | 2020 | | LitCov and CORD-19 |
3971 | Asymptomatic Transmission, the Achilles' Heel of Current Strategies to Control Covid-19 | N Engl J Med | 2020 | | LitCov and CORD-19 |
3972 | Reconvalescent plasma/camostat mesylate in early SARS-CoV-2 Q-PCR positive high-risk individuals (RES-Q-HR): a structured summary of a study protocol for a randomized controlled trial OBJECTIVES: Currently, there are no approved treatments for early disease stages of COVID-19 and few strategies to prevent disease progression after infection with SARS-CoV-2. The objective of this study is to evaluate the safety and efficacy of convalescent plasma (CP) or camostat mesylate administered within 72 h of diagnosis of SARS-CoV-2 infection in adult individuals with pre-existing risk factors at higher risk of getting seriously ill with COVID-19. Camostat mesylate acts as an inhibitor of the host cell serine protease TMPRSS2 and prevents the virus from entering the cell. CP represents another antiviral strategy in terms of passive immunization. The working hypothesis to be tested in the RES-Q-HR study is that the early use of CP or camostat mesylate reduces the likelihood of disease progression to (modified) WHO stages 4b-8 in SARS-CoV-2-positive adult patients at high risk of moderate or severe COVID-19 progression. TRIAL DESIGN: This study is a 4-arm (parallel group), multicenter, randomized (2:2:1:1 ratio), partly double-blind, controlled trial to evaluate the safety and efficacy of convalescent plasma (CP) or camostat mesylate with control or placebo in adult patients diagnosed with SARS-CoV-2 infection and high risk for progression to moderate/severe COVID-19. Superiority of the intervention arms will be tested. PARTICIPANTS: The trial is conducted at 10–15 tertiary care centers in Germany. Individuals aged 18 years or above with ability to provide written informed consent with SARS-CoV-2 infection, confirmed by PCR within 3 days or less before enrolment and the presence of at least one SARS-CoV-2 symptom (such as fever, cough, shortness of breath, sore throat, headache, fatigue, smell/and or taste disorder, diarrhea, abdominal symptoms, exanthema) and symptom duration of not more than 3 days. Further inclusion criteria comprise: Age > 75 years. Chronic obstructive pulmonary disease (COPD) and/or pulmonary fibrosis. BMI > 40 kg/m(2.) Age > 65 years with at least one other risk factor (BMI > 35 kg/m(2), coronary artery disease (CAD), chronic kidney disease (CKD) with GFR < 60 ml/min but ≥ 30 ml/min, diabetes mellitus, active tumor disease). BMI > 35 kg/m(2) with at least one other risk factor (CAD, CKD with GFR < 60 ml/min but ≥ 30 ml/min, diabetes mellitus, active tumor disease). 1. Age < 18 years. 2. Unable to give informed consent. 3. Pregnant women or breastfeeding mothers. 4. Previous transfusion reaction or other contraindication to a plasma transfusion. 5. Known hypersensitivity to camostat mesylate and/or severe pancreatitis. 6. Volume stress due to CP administration would be intolerable. 7. Known IgA deficiency. 8. Life expectancy < 6 months. 9. Duration SARS-CoV-2 typical symptoms > 3 days. 10. SARS-CoV-2 PCR detection older than 3 days. 11. SARS-CoV-2 associated clinical condition ≥ WHO stage 3 (patients hospitalized for other reasons than COVID-19 may be included if they fulfill all inclusion and none of the exclusion criteria). 12. Previously or currently hospitalized due to SARS-CoV-2. 13. Previous antiviral therapy for SARS-CoV-2. 14. ALT or AST > 5 x ULN at screening. 15. Liver cirrhosis > Child A (patients with Child B/C cirrhosis are excluded from the trial). 16. Chronic kidney disease with GFR < 30 ml/min. 17. Concurrent or planned anticancer treatment during trial period. 18. Accommodation in an institution due to legal orders (§40(4) AMG). 19. Any psycho-social condition hampering compliance with the study protocol. 20. Evidence of current drug or alcohol abuse. 21. Use of other investigational treatment within 5 half-lives of enrolment is prohibited. 22. Previous use of convalescent plasma for COVID-19. 23. Concomitant proven influenza A infection. 24. Patients with organ or bone marrow transplant in the three months prior to screening visit. INTERVENTION AND COMPARATOR: 1. Convalescent plasma (CP), 2 units at screening/baseline visit (day 0) or day 1; CP is defined by the presence of neutralizing anti-SARS-CoV-2 antibodies with titers ≥ 1:160; individuals with body weight ≥ 150 kg will receive a third unit of plasma on day 3. 2. Camostat mesylate (200 mg per capsule, one capsule taken each in the morning, afternoon and evening on days 1–7). 3. Standard of care (SOC, control for CP). 4. Placebo (identical in appearance to camostat mesylate capsules, one capsule taken each morning, afternoon and evening on days 1–7; for camostat mesylate control group). Participants will be monitored after screening/baseline on day 3, day 5, day 8, and day 14. On day 28 and day 56, telephone visits and on day 90, another outpatient visit are scheduled. Adverse events and serious adverse events will be monitored and reported until the end of the study. An independent data safety monitoring committee will review trial progression and safety. MAIN OUTCOMES: The primary endpoint of the study is the cumulative number of individuals who progress to or beyond category 4b on the modified WHO COVID-19 ordinal scale (defined as hospitalization with COVID-19 pneumonia and additional oxygen demand via nasal cannula or mask) within 28 days after randomization. RANDOMIZATION: Participants will be randomized using the Alea-Tool (aleaclinical.com) in a 2:2:1:1 ratio to the treatment arms (1) CP, (2) camostat mesylate, (3) standard of care (SoC), and (4) placebo matching camostat mesylate. Randomization will be stratified by study center. BLINDING (MASKING): The camostat mesylate treatment arm and the respective placebo will be blinded for participants, caregivers, and those assessing outcomes. The treatment arms convalescent plasma and standard of care will not be blinded and thus are open-labeled, unblinded. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Overall, n = 994 participants will be randomized to the following groups: n = 331 to convalescent plasma (CP), n = 331 to camostat mesylate, n = 166 to standard of care (SoC), and n = 166 to placebo matching camostat mesylate. TRIAL STATUS: The RES-Q-HR protocol (V04F) was approved on the 18 December 2020 by the local ethics committee and by the regulatory institutions PEI/BfARM on the 2 December 2020. The trial was opened for recruitment on 26 December 2020; the first patient was enrolled on 7 January 2021 and randomized on 8 January 2021. Recruitment shall be completed by June 2021. The current protocol version RES-Q HR V05F is from 4 January 2021, which was approved on the 18 January 2021. TRIAL REGISTRATION: EudraCT Number 2020-004695-18. Registered on September 29, 2020. ClinicalTrial.gov NCT04681430. Registered on December 23, 2020, prior to the start of the enrollment (which was opened on December 26, 2020). FULL PROTOCOL: The full protocol (V05F) 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). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05181-0. | Trials | 2021 | | LitCov and CORD-19 |
3973 | Have we found the panacea to COVID-19 with remdesivir, an old but newly packaged drug? N/A | J R Coll Physicians Edinb | 2020 | | LitCov and CORD-19 |
3974 | Molecular evolution and phylogenetic analysis of SARS-CoV-2 and hosts ACE2 protein suggest Malayan pangolin as intermediary host An emergence of a novel coronavirus, causative agent of COVID19, named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred due to cross-species transmission. Coronaviruses are a large family of viruses able to infect a great number of hosts. Entrance of SARS-CoV-2 depends on the surface (S) protein interaction with host ACE2 protein and cleavage by TMPRSS2. ACE2 could be a species-specific barrier that interferes with bat-to-human coronavirus cross-species transmission. Molecular analysis supported bats as natural hosts for SARS-CoV and involved them in MERS-CoV origin. The genomic similarity between bat RaTG13 CoV strain and SARS-CoV-2 implicates bats in the origin of the new outbreak. Additionally, there is a hypothesis for the zoonotic transmission based on contact with Malayan pangolins by humans in Huanan seafood market in Wuhan, China. To investigate bats and pangolin as hosts in SARS-CoV-2 cross-species transmission, we perform an evolutionary analysis combining viral and host phylogenies and divergence of ACE2 and TMPRSS2 amino acid sequences between CoV hosts. Phylogeny showed SARS-like-CoV-2 strains that infected pangolin and bats are close to SARS-CoV-2. In contrast to TMPRSS2, pangolin ACE2 amino acid sequence has low evolutionary divergence compared with humans and is more divergent from bats. Comparing SARS-CoV with SARS-CoV-2 origins, pangolin has yet lower ACE2 evolutionary divergence with humans than civet—the main intermediary host of SARS-CoV. Thus, pangolin has become an opportune host to intermediates bat-to-human SARS-CoV-2 jump and entry. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42770-020-00321-1) contains supplementary material, which is available to authorized users. | Braz J Microbiol | 2020 | | LitCov and CORD-19 |
3975 | Social distancing measures in the fight against COVID-19 in Brazil: description and epidemiological analysis by state N/A | Cad Saude Publica | 2020 | | LitCov and CORD-19 |
3976 | Working in the Times of COVID-19. Psychological Impact of the Pandemic in Frontline Workers in Spain This study evaluates the psychological impact (PI) of the COVID-19 pandemic in frontline workers in Spain. Participants were 546 workers (296 healthcare workers, 105 media professionals, 89 grocery workers, and 83 protective service workers). They all completed online questionnaires assessing PI, sadness, concerns related to the COVID-19 pandemic, and demographic and work-related variables. All groups but protective services workers showed higher PI levels than the general population. Healthcare and grocery workers were the most affected, with 73.6% and 65.2% of the participants, respectively, showing a severe PI. Women showed a higher PI level. Healthcare workers in the regions with higher COVID-19 incidences reported greater PI levels. The main concerns were being infected by COVID-19 or infecting others. Levels of concern correlated with higher PI levels. The protection equipment was generally reported as insufficient, which correlated with higher PI levels. Professionals reporting to overwork during the crisis (60% mass-media, 38% of healthcare and grocery and 21.7% of protective service) showed higher PI levels. In the healthcare group, taking care of patients with COVID-19 (77%) or of dying patients with COVID-19 (43.9%) was associated with higher PI levels. The perceived social recognition of their work was inversely related to PI. Most of the sample had not received psychological support. We suggest some organizational measures for frontline institutions, such as the periodical monitoring or inclusion of psychologists specialized in crisis-management to prevent negative symptoms and provide timely support. | Int J Environ Res Public Healt | 2020 | | LitCov and CORD-19 |
3977 | Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2 The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19. | Viruses | 2020 | | LitCov and CORD-19 |
3978 | Results of carotid artery stenting with distal embolic protection with improved systems: Protected Carotid Artery Stenting in Patients at High Risk for Carotid Endarterectomy (PROTECT) trial N/A | J Vasc Surg | 2012 | | CORD-19 |
3979 | Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice N/A | Proc Natl Acad Sci U S A | 2008 | | CORD-19 |
3980 | Radiofrequency ablation for the treatment of lung neoplasm N/A | Expert Rev Med Devices | 2008 | | CORD-19 |
3981 | Targeting COVID-19 main protease through active phytochemicals of ayurvedic medicinal plants-Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi)-a molecular docking study COVID-19 (Coronavirus disease 2019) is a transmissible disease initiated and propagated through a new virus strain SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) since 31(st) December 2019 in Wuhan city of China and the infection has outspread globally influencing millions of people. Here, an attempt was made to recognize natural phytochemicals from medicinal plants, in order to reutilize them against COVID-19 by the virtue of molecular docking and molecular dynamics (MD) simulation study. Molecular docking study showed six probable inhibitors against SARS-CoV-2 M(pro) (Main protease), two from Withania somnifera (Ashwagandha) (Withanoside V [10.32 kcal/mol] and Somniferine [9.62 kcal/mol]), one from Tinospora cordifolia (Giloy) (Tinocordiside [8.10 kcal/mol]) and three from Ocimum sanctum (Tulsi) (Vicenin [8.97 kcal/mol], Isorientin 4′-O-glucoside 2″-O-p-hydroxybenzoagte [8.55 kcal/mol] and Ursolic acid [8.52 kcal/mol]). ADMET profile prediction showed that the best docked phytochemicals from present work were safe and possesses drug-like properties. Further MD simulation study was performed to assess the constancy of docked complexes and found stable. Hence from present study it could be suggested that active phytochemicals from medicinal plants could potentially inhibit M(pro) HIGHLIGHTS: Holistic approach of Ayurvedic medicinal plants to avenge against COVID-19 pandemic. Active phytoconstituents of Ayurvedic medicinal plants Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) predicted to significantly hinder main protease (M(pro) or 3Cl(pro)) of SARS-CoV-2. Through molecular docking and molecular dynamic simulation study, Withanoside V, Somniferine, Tinocordiside, Vicenin, Ursolic acid and Isorientin 4′-O-glucoside 2″-O-p-hydroxybenzoagte were anticipated to impede the activity of SARS-CoV-2 M(pro). Drug-likeness and ADMET profile prediction of best docked compounds from present study were predicted to be safe, drug-like compounds with no toxicity. Communicated by Ramaswamy H. Sarma | J Biomol Struct Dyn | 2020 | | LitCov and CORD-19 |
3982 | Evidence of a Novel Human Coronavirus That Is Associated with Respiratory Tract Disease in Infants and Young Children Background. The etiological agents responsible for a substantial proportion of respiratory tract diseases have not been identified. We sought to determine whether novel human coronaviruses (HCoVs) are circulating in New Haven, Connecticut, and, if so, whether they are associated with respiratory tract disease in infants and young children. Methods. We developed a polymerase chain reaction (PCR)-based approach for screening specimens from the respiratory tracts of symptomatic children. PCR probes that target regions of the replicase 1a gene that are conserved among genetically diverse animal CoVs and HCoVs were designed. Using these probes, we identified genomic sequences of a novel HCoV, designated “New Haven coronavirus” (HCoV-NH). Thereafter, we designed specific probes to screen respiratory specimens from children <5 years old for this novel HCoV. Clinical features associated with HCoV-NH infection were identified. Results. Seventy-nine (8.8%) of 895 children tested positive for HCoV-NH. Cough, rhinorrhea, tachypnea, fever, abnormal breath sounds, and hypoxia were the most common findings associated with HCoV-NH infection. Sequence analysis revealed that HCoV-NH is closely related to a novel HCoV recently reported in The Netherlands. Conclusions. The novel HCoVs identified in New Haven and The Netherlands are similar and likely represent the same species. This newly discovered virus may have worldwide distribution and may account for a significant proportion of respiratory tract disease in infants and young children. | J Infect Dis | 2005 | | CORD-19 |
3983 | Effect of national and local lockdowns on the control of COVID-19 pandemic: a rapid review N/A | Epidemiol Prev | 2020 | | LitCov and CORD-19 |
3984 | SARS-CoV-2 and HIV: Epidemiology, Treatment and Lessons Learned from HIV N/A | AIDS Rev | 2020 | | LitCov and CORD-19 |
3985 | Assessing concerns for the economic consequence of the COVID-19 response and mental health problems associated with economic vulnerability and negative economic shock in Italy, Spain and the UK Many different countries have been under lockdown or extreme social distancing measures to control the spread of COVID-19. The potentially far-reaching side effects of these measures have not yet been fully understood. In this study we analyse the results of a multi-country survey conducted in Italy (N = 3,504), Spain (N = 3,524) and the United Kingdom (N = 3,523), with two separate analyses. In the first analysis, we examine the elicitation of citizens’ concerns over the downplaying of the economic consequences of the lockdown during the COVID-19 pandemic. We control for Social Desirability Bias through a list experiment included in the survey. In the second analysis, we examine the data from the same survey to predict the level of stress, anxiety and depression associated with being economically vulnerable and having been affected by a negative economic shock. To accomplish this, we have used a prediction algorithm based on machine learning techniques. To quantify the size of this affected population, we compare its magnitude with the number of people affected by COVID-19 using measures of susceptibility, vulnerability and behavioural change collected in the same questionnaire. We find that the concern for the economy and for “the way out” of the lockdown is diffuse and there is evidence of minor underreporting. Additionally, we estimate that around 42.8% of the populations in the three countries are at high risk of stress, anxiety, and depression, based on their level of economic vulnerability and their exposure to a negative economic shock. | PLoS One | 2020 | | LitCov and CORD-19 |
3986 | Predicting infectious SARS-CoV-2 from diagnostic samples BACKGROUND: RT-PCR has become the primary method to diagnose viral diseases, including SARS-CoV-2. RT-PCR detects RNA, not infectious virus, thus its ability to determine duration of infectivity of patients is limited. Infectivity is a critical determinant in informing public health guidelines/interventions. Our goal was to determine the relationship between E gene SARS-CoV-2 RT-PCR cycle threshold (Ct) values from respiratory samples, symptom onset to test (STT) and infectivity in cell culture. METHODS: In this retrospective cross-sectional study, we took SARS-CoV-2 RT-PCR confirmed positive samples and determined their ability to infect Vero cell lines. RESULTS: Ninety RT-PCR SARS-CoV-2 positive samples were incubated on Vero cells. Twenty-six samples (28.9%) demonstrated viral growth. Median TCID50/ml was 1780 (282-8511). There was no growth in samples with a Ct > 24 or STT > 8 days. Multivariate logistic regression using positive viral culture as a binary predictor variable, STT and Ct demonstrated an odds ratio for positive viral culture of 0.64 (95% CI 0.49-0.84, p<0.001) for every one unit increase in Ct. Area under the receiver operating characteristic curve for Ct vs. positive culture was OR 0.91 (95% CI 0.85-0.97, p<0.001), with 97% specificity obtained at a Ct of >24. CONCLUSIONS: SARS-CoV-2 Vero cell infectivity was only observed for RT-PCR Ct < 24 and STT < 8 days. Infectivity of patients with Ct >24 and duration of symptoms >8 days may be low. This information can inform public health policy and guide clinical, infection control and occupational health decisions. Further studies of larger size are needed. | Clin Infect Dis | 2020 | | LitCov and CORD-19 |
3987 | Novel Wuhan (2019-nCoV) Coronavirus N/A | Am J Respir Crit Care Med | 2020 | | LitCov and CORD-19 |
3988 | Respiratory viruses predisposing to bacterial infections: role of neuraminidase N/A | Pediatr Infect Dis J | 2004 | | CORD-19 |
3989 | Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia BACKGROUND: Pneumonia with respiratory failure represents the main cause of death in COVID-19, where hyper inflammation plays an important role in lung damage. This study aims to evaluate if tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, reduces patients’ mortality. METHODS: 85 consecutive patients admitted to the Montichiari Hospital (Italy) with COVID-19 related pneumonia and respiratory failure, not needing mechanical ventilation, were included if satisfying at least one among: respiratory rate ≥ 30 breaths/min, peripheral capillary oxygen saturation ≤ 93% or PaO2/FiO2<=300 mmHg. Patients admitted before March 13th (n=23) were prescribed the standard therapy (hydroxychloroquine, lopinavir and ritonavir) and were considered controls. On March 13th tocilizumab was available and patients admitted thereafter (n=62) received tocilizumab once within 4 days from admission, plus the standard care. RESULTS: Patients receiving tocilizumab showed significantly greater survival rate as compared to control patients (hazard ratio for death, 0.035; 95% confidence interval [CI], 0.004 to 0.347; p = 0.004), adjusting for baseline clinical characteristics. Two out of 62 patients of the tocilizumab group and 11 out of 23 in the control group died. 92% and 42.1% of the discharged patients in the tocilizumab and control group respectively, recovered. The respiratory function resulted improved in 64.8% of the observations in tocilizumab patients who were still hospitalized, whereas 100% of controls worsened and needed mechanical ventilation. No infections were reported. CONCLUSIONS: Tocilizumab results to have a positive impact if used early during Covid-19 pneumonia with severe respiratory syndrome in terms of increased survival and favorable clinical course. | Eur J Intern Med | 2020 | | LitCov and CORD-19 |
3990 | Disparities In Outcomes Among COVID-19 Patients In A Large Healthcare System In California N/A | Health Aff (Millwood) | 2020 | | LitCov and CORD-19 |
3991 | An exposed domain in the severe acute respiratory syndrome coronavirus spike protein induces neutralizing antibodies N/A | J Virol | 2004 | | CORD-19 |
3992 | Coronavirus transcription: subgenomic mouse hepatitis virus replicative intermediates function in RNA synthesis N/A | J Virol | 1990 | | CORD-19 |
3993 | Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme N/A | Proc Natl Acad Sci U S A | 2006 | | CORD-19 |
3994 | Psychological impact of coronavirus disease (2019) epidemic on medical staff in different posts in China: A multicenter study OBJECTIVE: An outbreak of coronavirus disease 2019 (COVID-19) is a public health emergency of international concern and poses a big challenge to medical staff and general public. The aim is to investigate psychological impact of COVID-19 epidemic on medical staff in different working posts in China, and to explore the correlation between psychological disorder and the exposure to COVID-19. METHODS: A multicenter WeChat-based online survey was conducted among medical staff in China between 26 February and 3 March 2020. Medical staff deployed to Hubei province from other provinces and medical staffs in different posts outside Hubei were selected to represent diverse exposure intensities to the threat of COVID-19. Anxiety, depression, sleep quality, stress and resilience were evaluated using scales including GAD-7, PHQ-9, PSQI, PSS-14, and CD-RISC-10. Latent class analysis was performed to identify potential staff requiring psychological support. RESULTS: A total of 274 respondents were included, who serving at 4 posts as follows, staff backing Hubei province, isolation wards outside Hubei, fever clinic and infectious disease department, and other departments outside Hubei. The total scores of anxiety, depression, sleep quality and stress were statistically different among groups, meanwhile an increasing tendency of anxiety, depression and sleep quality scores with increasing risk of exposure to COVID-19 was found (p < 0.05). Subsequent post-hoc analysis indicated that the staff backing Hubei had higher scores of anxiety, depression, sleep quality and perceived stress (adjusted p < 0.05). The combined prevalence of anxiety, depression and insomnia of staff backing Hubei reached as high as 38%. Four-class latent class analysis showed 3 categories of population (69.4%) may need psychological support. CONCLUSIONS: High prevalence of anxiety, depression and insomnia exist in medical staff related to COVID-19. The higher the probability and intensity of exposure to COVID-19 patients, the greater the risk that medical staff will suffer from mental disorders, suggesting continuous and proper psychiatric intervention are needed. | J Psychiatr Res | 2020 | | LitCov and CORD-19 |
3995 | Potential Antiviral Drugs for SARS-Cov-2 Treatment: Preclinical Findings and Ongoing Clinical Research N/A | In Vivo | 2020 | | LitCov and CORD-19 |
3996 | Structure of the RNA-dependent RNA polymerase from COVID-19 virus A novel coronavirus (COVID-19 virus) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12) is the central component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. We report the cryo-EM structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-Å resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified β-hairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics targeting viral RdRp. | Science | 2020 | | LitCov and CORD-19 |
3997 | Medical education in times of COVID-19: German students' expectations-A cross-sectional study BACKGROUND: Since the COVID-19 pandemic has affected the education of medical students, medical faculties have faced the challenge of adapting instruction to digital platforms. Although medical students are willing to support pandemic response efforts, how the crisis will affect their medical training remains uncertain. Thus, in this study, we investigated the teaching- and learning-related stressors and expectations of medical students in Germany during the COVID-19 pandemic. METHODS: A cross-sectional survey was distributed online to undergraduate medical students at medical faculties in Germany. Students answered questions about COVID-19 and teaching (on a 7-point Likert scale from 0 (“not at all”) to 6 (“completely”)) and completed mental well-being measurements, including the State–Trait Anxiety Inventory (STAI), the Generalised Anxiety Disorder scale (GAD-7) and the Perceived Health Questionnaire (PHQ-9). Descriptive data analysis, a t-test and Pearson correlations were performed to process the data. RESULTS: Medical students felt well-informed about COVID-19 in general (M = 5.64, SD = 1.28) and in the medical context (M = 5.14, SD = 1.34) but significantly less informed about the pandemic in the academic context, M = 2.47, SD = 1.49, t(371) = 31.98, p < .001. Their distress levels were high (STAI: M = 45.12, SD = 4.73) and significantly correlated with the academic context (r(p) = .164, p < .01) but not their private lives. Concerning how they were taught, they most often expected online lectures (91.7%) and live broadcasts (67.2%) and less often expected innovative digital teaching strategies, including serious games (17.3%) and virtual-reality exercises (16.7%). DISCUSSION: Medical students seem to be aware of the COVID-19 pandemic and its consequences for academic and healthcare contexts. They also seem to think that their teachers will enhance their digital competencies during the pandemic. Therefore, faculties of medicine need to rapidly and adequately digitalise their approaches to teaching. | PLoS One | 2020 | | LitCov and CORD-19 |
3998 | Clinical Characteristics of Refractory COVID-19 in Wuhan, China BACKGROUND: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. METHODS: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from January 1(st) to February 5(th). The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy after hospitalization, and the difference between groups were compared. RESULTS: Compared with general COVID-19 patients (45.2%), refractory patients had an older age, male sex, more underlying comorbidities, lower incidence of fever, higher levels of maximum temperature among fever cases, higher incidence of breath shortness and anorexia, severer disease assessment on admission, high levels of neutrophil, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and C-reactive protein, lower levels of platelets and albumin, and higher incidence of bilateral pneumonia and pleural effusion (P<0.05). Refractory COVID-19 patients were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment including corticosteroid, antiviral drugs and immune enhancer (P<0.05). After adjustment, those with refractory COVID-19 were also more likely to have a male sex and manifestations of anorexia and fever on admission, and receive oxygen, expectorant and adjunctive agents (P<0.05) when considering the factors of disease severity on admission, mechanical ventilation, and ICU transfer. CONCLUSION: Nearly 50% COVID-19 patients could not reach obvious clinical and radiological remission within 10 days after hospitalization. The patients with male sex, anorexia and no fever on admission predicted poor efficacy. | Clin Infect Dis | 2020 | | LitCov and CORD-19 |
3999 | Wearing of Cloth or Disposable Surgical Face Masks has no Effect on Vigorous Exercise Performance in Healthy Individuals Wearing face masks is recommended for the prevention of contracting or exposing others to cardiorespiratory infections, such as COVID-19. Controversy exists on whether wearing face masks during vigorous exercise affects performance. We used a randomized, counterbalanced cross-over design to evaluate the effects of wearing a surgical mask, a cloth mask, or no mask in 14 participants (7 men and 7 women; 28.2 ± 8.7 y) during a cycle ergometry test to exhaustion. Arterial oxygen saturation (pulse oximetry) and tissue oxygenation index (indicator of hemoglobin saturation/desaturation) at vastus lateralis (near-infrared spectroscopy) were assessed throughout the exercise tests. Wearing face masks had no effect on performance (time to exhaustion (mean ± SD): no mask 622 ± 141 s, surgical mask 657 ± 158 s, cloth mask 637 ± 153 s (p = 0.20); peak power: no mask 234 ± 56 W, surgical mask 241 ± 57 W, cloth mask 241 ± 51 W (p = 0.49)). When expressed relative to peak exercise performance, no differences were evident between wearing or not wearing a mask for arterial oxygen saturation, tissue oxygenation index, rating of perceived exertion, or heart rate at any time during the exercise tests. Wearing a face mask during vigorous exercise had no discernable detrimental effect on blood or muscle oxygenation, and exercise performance in young, healthy participants (ClinicalTrials.gov, NCT04557605). | Int J Environ Res Public Healt | 2020 | | LitCov and CORD-19 |
4000 | The Psychological Impact of COVID-19 Pandemic and Lockdown on Caregivers of People With Dementia BACKGROUND: Caregivers of people with dementia (pwD) are at risk of depression, anxiety and burden. COVID-19 pandemic and government-imposed lockdown as a preventive measure might increase psychological symptoms in caregivers. We performed a study to measure the change of psychological symptoms during quarantine/self-isolation for COVID-19 in a sample of Italian caregivers of pwD, and to investigate if the resilience is associated with psychological changes in the sample. METHODS: Eighty-four caregivers of pwD completed an online survey including questionnaires assessing depressive symptomatology and anxiety before and during the lockdown, caregiver burden and levels of resilience. RESULTS: The MANOVA revealed an effect of time (before and during the lockdown) in the whole group on depression scores; a significant interaction between time and resilience was found on anxiety scores, revealing that caregivers with high resilience showed a more significant increase of anxiety levels during lockdown than caregivers with low resilience. Moreover, the regression analysis revealed that caregiver burden was associated negatively with resilience scores, and positively with higher functional dependence. CONCLUSIONS: COVID-19 pandemic and the lockdown produced psychological consequences in caregivers of pwD, with an increase of levels of depression. Moreover, high resilience had a negative effect on anxiety levels and no effect on depressive symptomatology during the lockdown; moreover, it was associated with lower levels of caregiver burden. All caregivers, even those with high resilience levels, should be addressed to psychological interventions to reduce levels of depression, anxiety and caregiver burden. | Am J Geriatr Psychiatry | 2020 | | LitCov and CORD-19 |