This version of BIP! Finder aims to ease the exploration of COVID-19-related literature by enabling ranking articles based on various impact metrics.
Last Update: 18 - 01 - 2023 (628506 entries)
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| Title | Venue | Year | Impact | Source | |
|---|---|---|---|---|---|
| 6401 | Identification of a potential SARS-CoV-2 inhibitor via molecular dynamics simulations and amino acid decomposition analysis Considering lack of validated therapeutic drugs or vaccines against contagious SARS-CoV2, various efforts have been focused on repurposing of existing drugs or identifying new agents. In an attempt to identify new and potential SARS-CoV2 inhibitors targeting specific enzyme of the pathogen, a few induced fit models of SARS-CoV2 main protease (Mpro) including N-aryl amide and aryl sulfonamide based fragments were subjected to a multi-step in silico strategy. Sub-structure query of co-crystallographic fragments provided numerous ZINC15 driven commercially available compounds that entered molecular docking stage to find binding interactions/modes inside Mpro active site. Docking results were reevaluated through time dependent stability of top-ranked ligand-protease complexes by molecular dynamics (MD) simulations within 50 ns. Relative contribution of interacted residues in binding to the most probable binding pose was estimated through amino acid decomposition analysis in B3LYP level of theory with Def2-TZVPP split basis set. In confirmation of docking results, MD simulations revealed less perceptible torsional distortions (more stable binding mode) in binding of ZINC_252512772 (ΔG(b) −9.18 kcal/mol) into Mpro active site. H-bond interactions and hydrophobic contacts were determinant forces in binding interactions of in silico hit. Quantum chemical calculations confirmed MD results and proved the pivotal role of a conserved residue (Glu166) in making permanent hydrogen bond (98% of MD simulations time) with ZINC_252512772. Drug-like physicochemical properties as well as desirable target binding interactions nominated ZINC_252512772 as a desirable in silico HIGHLIGHTS: A few N-aryl amide/aryl sulfonamide based fragments were subjected to a multi-step in silico strategy to afford potential SARS-CoV2 Mpro inhibitors. MD simulations revealed less perceptible torsional distortions (more stable binding mode) in binding of ZINC_252512772 (ΔG(b) -9.18 kcal/mol) into Mpro active site. H-bond interactions and hydrophobic contacts were determinant forces in binding interactions of in silico hit. Quantum chemical calculations confirmed MD results and proved pivotal role of a conserved residue (Glu166) in making permanent hydrogen bond (98% of MD simulations time) with ZINC_252512772. Communicated by Ramaswamy H. Sarma | J Biomol Struct Dyn | 2020 | LitCov and CORD-19 | |
| 6402 | SARS-CoV-2 seroprevalence among the general population and healthcare workers in India, December 2020-January 2021 Background Earlier serosurveys in India revealed SARS-CoV-2 seroprevalence of 0.73% during May-June and 7.1% during August-September 2020. We conducted the third serosurvey during Dec 2020 and Jan 2021, to estimate the seroprevalence of SARS-CoV-2 infection among general population and healthcare workers (HCWs) in India. Methods We conducted the serosurvey in the same 70 districts selected for the first and second serosurveys. From each district, we enrolled at least 400 individuals aged ≥ 10 years from general population and 100 HCWs from sub-district level health facilities. Sera from general population were tested for presence of IgG antibodies against nucleocapsid (N) and spike protein (S1-RBD) of SARS-CoV-2, whereas sera from HCWs were tested for anti-S1-RBD. We estimated weighted seroprevalence adjusted for assay characteristics. Results Of the 28,598 sera from general population, 4585 (16%) had IgG antibodies against N, 6647 (23.2%) against S1-RBD and 7436 (26%) against either. The weighted and assay characteristic adjusted seroprevalence against either of the antibodies was 24.1 (95%CI: 23.0%-25.3%). Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI: 23.5%-27.8%). Conclusions Nearly one in four individuals aged > = 10 years from general population as well as HCWs in India were exposed to SARS-CoV-2 by December 2020. | Int J Infect Dis | 2021 | LitCov and CORD-19 | |
| 6403 | Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates [Image: see text] The coronavirus disease pandemic of 2019 (COVID-19) caused by the novel SARS-CoV-2 coronavirus resulted in economic losses and threatened human health worldwide. The pandemic highlights an urgent need for a stable, easily produced, and effective vaccine. SARS-CoV-2 uses the spike protein receptor-binding domain (RBD) to bind its cognate receptor, angiotensin-converting enzyme 2 (ACE2), and initiate membrane fusion. Thus, the RBD is an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticle vaccine candidates, namely, RBD-Ferritin (24-mer), RBD-mi3 (60-mer), and RBD-I53–50 (120-mer), via covalent conjugation using the SpyTag-SpyCatcher system. When mice were immunized with the RBD-conjugated nanoparticles (NPs) in conjunction with the AddaVax or Sigma Adjuvant System, the resulting antisera exhibited 8- to 120-fold greater neutralizing activity against both a pseudovirus and the authentic virus than those of mice immunized with monomeric RBD. Most importantly, sera from mice immunized with RBD-conjugated NPs more efficiently blocked the binding of RBD to ACE2 in vitro, further corroborating the promising immunization effect. Additionally, the vaccine has distinct advantages in terms of a relatively simple scale-up and flexible assembly. These results illustrate that the SARS-CoV-2 RBD-conjugated nanoparticles developed in this study are a competitive vaccine candidate and that the carrier nanoparticles could be adopted as a universal platform for a future vaccine development. | ACS Nano | 2021 | LitCov and CORD-19 | |
| 6404 | Antibiotics for the treatment of COVID-19 N/A | Cochrane Database Syst Rev | 2021 | LitCov and CORD-19 | |
| 6405 | Potential inhibitors of coronavirus 3-chymotrypsin-like protease (3CLpro): an in silico screening of alkaloids and terpenoids from African medicinal plants The novel coronavirus disease 2019 (COVID-19) caused by SARS-COV-2 has raised myriad of global concerns. There is currently no FDA approved antiviral strategy to alleviate the disease burden. The conserved 3-chymotrypsin-like protease (3CL(pro)), which controls coronavirus replication is a promising drug target for combating the coronavirus infection. This study screens some African plants derived alkaloids and terpenoids as potential inhibitors of coronavirus 3CL(pro) using in silico approach. Bioactive alkaloids (62) and terpenoids (100) of plants native to Africa were docked to the 3CL(pro) of the novel SARS-CoV-2. The top twenty alkaloids and terpenoids with high binding affinities to the SARS-CoV-2 3CL(pro) were further docked to the 3CL(pro) of SARS-CoV and MERS-CoV. The docking scores were compared with 3CL(pro)-referenced inhibitors (Lopinavir and Ritonavir). The top docked compounds were further subjected to ADEM/Tox and Lipinski filtering analyses for drug-likeness prediction analysis. This ligand-protein interaction study revealed that more than half of the top twenty alkaloids and terpenoids interacted favourably with the coronaviruses 3CL(pro), and had binding affinities that surpassed that of lopinavir and ritonavir. Also, a highly defined hit-list of seven compounds (10-Hydroxyusambarensine, Cryptoquindoline, 6-Oxoisoiguesterin, 22-Hydroxyhopan-3-one, Cryptospirolepine, Isoiguesterin and 20-Epibryonolic acid) were identified. Furthermore, four non-toxic, druggable plant derived alkaloids (10-Hydroxyusambarensine, and Cryptoquindoline) and terpenoids (6-Oxoisoiguesterin and 22-Hydroxyhopan-3-one), that bind to the receptor-binding site and catalytic dyad of SARS-CoV-2 3CL(pro) were identified from the predictive ADME/tox and Lipinski filter analysis. However, further experimental analyses are required for developing these possible leads into natural anti-COVID-19 therapeutic agents for combating the pandemic. Communicated by Ramaswamy H. Sarma | J Biomol Struct Dyn | 2020 | LitCov and CORD-19 | |
| 6406 | Transmission, infectivity and neutralization of a spike L452R SARS-CoV-2 variant We identified an emerging SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the Western United States. Named B.1.427/B.1.429 to denote its 2 lineages, the variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6-24% increased transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation common to variants B.1.1.7, B.1.351, and P.1. Antibody neutralization assays revealed 4.0 to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California exhibiting decreased antibody neutralization warrants further investigation. | Cell | 2021 | LitCov and CORD-19 | |
| 6407 | Public Adoption of and Trust in the NHS COVID-19 Contact Tracing App in the United Kingdom: Quantitative Online Survey Study BACKGROUND: Digital contact tracing is employed to monitor and manage the spread of COVID-19. However, to be effective the system must be adopted by a substantial proportion of the population. Studies of mostly hypothetical contact tracing apps show generally high acceptance, but little is known about the drivers and barriers to adoption of deployed systems. OBJECTIVE: The aim of this study was to investigate adoption of and attitudes toward the NHS (National Health Service) COVID-19 smartphone app, the digital contact tracing solution in the United Kingdom. METHODS: An online survey based on the extended Technology Acceptance Model with the added factor of trust was carried out with a representative sample of the UK population. Statistical analysis showed adoption rates, attitudes toward and trust in the app, and compliance with self-isolation advice and highlighted differences for vulnerable populations (ie, older adults aged 65 years and over and members of Black, Asian, and minority ethnic [BAME] communities). RESULTS: A total of 1001 participants took part in the study. Around half of the participants who had heard of the NHS COVID-19 mobile phone app (490/963, 50.9%; 95% CI 47.8%-54.0%) had downloaded and kept the app, but more than one-third (345/963, 35.8%; 95% CI 32.8%-38.8%) either did not intend to download it or had deleted it. Significantly more BAME respondents than White respondents had deleted the app (16/115, 13.9%; 95% CI 11.8%-16.0%, vs 65/876, 7.4%; 95% CI 5.8%-9.0%), and significantly more older adults 65 years and over than those under 65 years did not intend to download it (44/127, 34.6%; 95% CI 31.7%-37.5%, vs 220/874, 25.2%; 95% CI 22.5%-27.9%). Broadly, one of the reasons for uptake was to help the NHS and other people, especially among older adults, although significantly fewer BAME participants agreed that they did so to help the NHS. Reported compliance with received notifications to self-isolate was high but was significantly lower than reported intended compliance without received notifications. Only one-fifth (136/699, 19.5%; 95% CI 17.0%-22.0%) of participants understood that the decision to send self-isolation notifications was automated by the app. There were a range of significantly more negative views among BAME participants, including lower trust in the NHS, while older adults were often significantly more positive. Respondents without the app reported significantly lower trust and more negative views toward the app and were less likely to report that they understood how the app works. CONCLUSIONS: While compliance on the part of the approximately 50% of participants who had the app was fairly high, there were issues surrounding trust and understanding that hindered adoption and, therefore, the effectiveness of digital contact tracing, particularly among BAME communities. This study highlights that more needs to be done to improve adoption among groups who are more vulnerable to the effects of the virus in order to enhance uptake and acceptance of contact tracing apps. | J Med Internet Res | 2021 | LitCov and CORD-19 | |
| 6408 | ECMM/ISHAM recommendations for clinical management of COVID-19 associated mucormycosis in low- and middle-income countries Reports are increasing on the emergence of COVID‐19–associated mucormycosis (CAM) globally, driven particularly by low‐ and middle‐income countries. The recent unprecedented surge of CAM in India has drawn worldwide attention. More than 28,252 mucormycosis cases are counted and India is the first country where mucormycosis has been declared a notifiable disease. However, misconception of management, diagnosing and treating this infection continue to occur. Thus, European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) felt the need to address clinical management of CAM in low‐ and middle‐income countries. This article provides a comprehensive document to help clinicians in managing this infection. Uncontrolled diabetes mellitus and inappropriate (high dose or not indicated) corticosteroid use are the major predisposing factors for this surge. High counts of Mucorales spores in both the indoor and outdoor environments, and the immunosuppressive impact of COVID‐19 patients as well as immunotherapy are possible additional factors. Furthermore, a hyperglycaemic state leads to an increased expression of glucose regulated protein (GRP‐ 78) in endothelial cells that may help the entry of Mucorales into tissues. Rhino‐orbital mucormycosis is the most common presentation followed by pulmonary mucormycosis. Recommendations are focused on the early suspicion of the disease and confirmation of diagnosis. Regarding management, glycaemic control, elimination of corticosteroid therapy, extensive surgical debridement and antifungal therapy are the standards for proper care. Due to limited availability of amphotericin B formulations during the present epidemic, alternative antifungal therapies are also discussed. | Mycoses | 2021 | LitCov and CORD-19 | |
| 6409 | COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features | Radiology | 2020 | LitCov and CORD-19 | |
| 6410 | Patients With Autoimmune Thyroiditis Present Similar Immunological Response to COVID-19 BNT162b2 mRNA Vaccine With Healthy Subjects, While Vaccination May Affect Thyroid Function: A Clinical Study BACKGROUND: This is the first study, that aimed: a) to compare immune response, namely the kinetics of neutralizing antibodies (Nabs), after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with autoimmune thyroiditis and controls, and b) to investigate changes in thyroid function in healthy subjects with no history of thyroid dysfunction before and after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech). METHODS: The entire study consisted of two sub-studies. In the first sub-study, NAbs levels after BNT162b2 mRNA vaccination were compared between 56 patients with autoimmune thyroiditis and 56 age and gender-matched healthy controls from the day of the first dose until a period of up to three months after the second dose. In the second sub-study, thyroid hormones (T3, T4, TSH) and thyroid auto-antibodies levels (anti-TG, anti-TPO) of 72 healthy subjects with no history of thyroid disease were examined before (D1) and one month after completion of the second dose (D50). RESULTS: Among patients with autoimmune thyroiditis, the median neutralizing inhibition on D22, immediately before second dose, was 62.5%. One month later (D50), values increased to 96.7%, while three months after the second dose NAbs titers remained almost the same (94.5%). In the healthy group, median NAbs levels at D22 were 53.6%. On D50 the median inhibition values increased to 95.1%, while after three months they were 89.2%. The statistical analysis did not show significant differences between two groups (p-values 0.164, 0.390, 0.105 for D22, D50 and three months). Regarding changes in thyroid function, the mean value for T4 before vaccination was 89.797 nmol/L and one month after the second dose was 89.11 nmol/L (p-value=0.649). On D1 the mean T3 value was 1.464 nmol/L, which dropped to 1.389 nmol/L on D50 (p-value = 0.004). For TSH, mean levels were 2.064 mIU/ml on D1 and fell to 1.840 mIU/ml one month after the second dose (p-value=0.037). Despite decrease, all thyroid hormone levels remained within the normal range. No changes were found for anti-TPO or anti-TG. CONCLUSIONS: This study provided evidence that patients with autoimmune thyroiditis present similar immunological response to COVID-19 BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) with healthy subjects, while vaccination may affect thyroid function. | Front Endocrinol (Lausanne) | 2022 | LitCov and CORD-19 | |
| 6411 | Performance of Saliva, Oropharyngeal Swabs and Nasal Swabs for SARS-CoV-2 Molecular Detection: a Systematic Review and Meta-analysis Nasopharyngeal (NP) swabs are considered the highest-yield sample for diagnostic testing for respiratory viruses, including SARS-CoV-2. The need to increase capacity for SARS-CoV-2 testing in a variety of settings, combined with shortages of sample collection supplies, have motivated a search for alternative sample types with high sensitivity. We systematically reviewed the literature to understand the performance of alternative sample types compared to NP swabs. We systematically searched PubMed, Google Scholar, medRxiv, and bioRxiv (last retrieval 1 October 2020) for comparative studies of alternative specimen types (saliva, oropharyngeal [OP], and nasal [NS] swabs) versus NP swabs for SARS-CoV-2 diagnosis using nucleic acid amplification testing (NAAT). A logistic-normal random-effects meta-analysis was performed to calculate % positive alternative-specimen, % positive NP, and % dual positives overall and in subgroups. The QUADAS 2 tool was used to assess bias. From 1,253 unique citations, we identified 25 saliva, 11 NS, 6 OP, and 4 OP/NS studies meeting inclusion criteria. Three specimen types captured lower % positives (NS [82%, 95% CI: 73 to 90%], OP [84%, 95% CI: 57 to 100%], and saliva [88%, 95% CI: 81 to 93%]) than NP swabs, while combined OP/NS matched NP performance (97%, 95% CI: 90 to 100%). Absence of RNA extraction (saliva) and utilization of a more sensitive NAAT (NS) substantially decreased alternative-specimen yield of positive samples. NP swabs remain the gold standard for diagnosis of SARS-CoV-2, although alternative specimens are promising. Much remains unknown about the impact of variations in specimen collection, processing protocols, and population (pediatric versus adult, late versus early in disease course), such that head-to head studies of sampling strategies are urgently needed. | J Clin Microbiol | 2021 | LitCov and CORD-19 | |
| 6412 | Factors Associated with COVID-19 Vaccine Hesitancy It is critical to develop tailored strategies to increase acceptability of the COVID-19 vaccine and decrease hesitancy. Hence, this study aims to assess and identify factors associated with COVID-19 vaccine hesitancy in Portugal. We used data from a community-based survey, “COVID-19 Barometer: Social Opinion”, which includes data regarding intention to take COVID-19 vaccines, health status, and risk perception in Portugal from September 2020 to January 2021. We used multinomial regression to identify factors associated with intention to delay or refuse to take COVID-19 vaccines. COVID-19 vaccine hesitancy in Portugal was high: 56% would wait and 9% refuse. Several factors were associated with both refusal and delay: being younger, loss of income during the pandemic, no intention of taking the flu vaccine, low confidence in the COVID-19 vaccine and the health service response during the pandemic, worse perception of government measures, perception of the information provided as inconsistent and contradictory, and answering the questionnaire before the release of information regarding the safety and efficacy of COVID-19 vaccines. It is crucial to build confidence in the COVID-19 vaccine as its perceived safety and efficacy were strongly associated with intention to take the vaccine. Governments and health authorities should improve communication and increase trust. | Vaccines (Basel) | 2021 | LitCov and CORD-19 | |
| 6413 | Managing the COVID-19 pandemic in people with mental disorders: An exploratory telephone interview study in a psychiatric outpatient department BACKGROUND: The COVID-19 pandemic and associated lockdown measures reduced well-being in the general population significantly and led to an increase in anxiety and depression symptoms, however, results on the impact on people with mental disorders are heterogeneous to date. The aim of this study was to investigate the mental health status, social support, perceived stress, and the medical care provision of people with mental disorders during the time period immediately after the first COVID-19 lockdown in spring 2020 in Germany. METHODS: Participants were people with mental disorders currently receiving treatment in the psychiatric outpatient department of the University Hospital Leipzig, Germany. Structured telephone interviews were administered to assess depressive symptoms, self-rated medical care provision, attitudes and social and emotional aspects of the pandemic (social support, perceived stress, loneliness, resilience, and agreeableness). RESULTS: A total of N = 106 people completed the telephone interview. The most frequent clinician-rated diagnoses were attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD; n = 29, 27.4%) and obsessive-compulsive disorder (OCD; n = 24, 22.6%). The mean Patient Health Questionnaire-9 sum score was 10.91 (SD = 5.71) and the majority of participants (n = 56, 52.8%) reported clinically relevant depressive symptoms. A low self-rated medical care provision was significantly associated with higher depressive symptom load. In a regression analysis, higher perceived stress levels and low medical care provision significantly predicted depressive symptoms. Furthermore, 38.1% (n = 40) reported to feel relieved as a result of the restrictions and, due to previous experience in dealing with crisis, half of the participants (n = 53, 50.5%) stated they were better able to deal with the current situation than the general population. CONCLUSIONS: This study emphasizes the importance of maintenance of medical care provision for people with mental disorders, as cancelled or postponed treatment appointments and perceived stress were associated with higher depressive symptoms. Regular treatment services showed to have a protective effect. In addition, a majority of people with mental disorders felt prepared for managing the COVID pandemic due to existing crisis management abilities. These resources should also be taken into account for further future treatment considerations. Trial Registration: German Clinical Trials Register (DRKS00022071). | Compr Psychiatry | 2022 | LitCov and CORD-19 | |
| 6414 | Malignant Cerebral Ischemia in A COVID-19 Infected Patient: Case Review and Histopathological Findings Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is responsible for an unprecedented worldwide pandemic that has severely impacted the United States. As the pandemic continues, a growing body of evidence suggests that infected patients may develop significant coagulopathy with resultant thromboembolic complications including deep vein thrombosis, pulmonary embolism, myocardial infarction, and ischemic stroke. However, this data is limited and comes from recent small case series and observational studies on stroke types, mechanisms, and outcomes.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 Furthermore, evidence on the role of therapeutic anticoagulation in SARS-CoV-2 infected patients with elevated inflammatory markers, such as D-dimer, is also limited. We report the case of a middle-aged patient who presented with a large vessel ischemic stroke likely resulting from an underlying inflammatory response in the setting of known novel coronavirus infection (COVID-19). Histopathologic analysis of the patient's ischemic brain tissue revealed hypoxic neurons and significant edema from the underlying ischemic insult, fibrin thrombi in small vessels, and fibroid necrosis of the vascular wall without any signs of vasculature inflammation. Brain biopsy was negative for the presence of SARS-CoV-2 RNA (RT-PCR assay). Along with a growing body of literature, our case suggests that cerebrovascular thromboembolic events in COVID-19 infection may be related to acquired hypercoagulability and coagulation cascade activation due to the release of inflammatory markers and cytokines, rather than virus-induced vasculitis. Further studies to investigate the mechanism of cerebrovascular thromboembolic events and their prevention is warranted. | J Stroke Cerebrovasc Dis | 2020 | LitCov and CORD-19 | |
| 6415 | SARS-CoV-2 Vaccines: Where Are We Now? The best and safest way to control the coronavirus disease 2019 (COVID-19) pandemic is by using vaccination to generate widespread immunity. The urgent need to develop safe and effective COVID-19 vaccines was met with unprecedented speed and action from the global community. There are now 289 vaccines in the development pipeline. More remarkably, there are 20 publicly available vaccines, and more than 3.3 billion doses of COVID-19 vaccines have been administered across 180 countries. This is just the beginning of our fight against the pandemic. Even at the current vaccination rate, it could take years to vaccinate the world's population; many high-income countries are focusing on their needs, whereas the poorer nations are waiting for vaccines. There is still much that we do not understand about immunity to this new disease, and we will have to contend with the emerging variants. In this commentary, we describe the current status of COVID-19 vaccine development and provide insights into how the development and approvals happened so quickly. We discuss the clinical trial data that led to rapid emergency use authorization and the many challenges of global rollout. We also comment on some of the key unanswered questions and future directions for COVID-19 vaccine development and deployment. | J Allergy Clin Immunol Pract | 2021 | LitCov and CORD-19 | |
| 6416 | Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis N/A | Nature | 2021 | LitCov and CORD-19 | |
| 6417 | Recognizing COVID-19-related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management Abstract Human coronavirus-associated myocarditis is known, and a number of COVID-19-related myocarditis cases have been reported. The pathophysiology of COVID-19-related myocarditis is thought to be a combination of direct viral injury and cardiac damage due to the host’s immune response. COVID-19 myocarditis diagnosis should be guided by insights from previous coronavirus and other myocarditis experience. The clinical findings include changes in ECG, cardiac biomarkers, and impaired cardiac function. When cardiac MRI is infeasible, cardiac CT angiography with delayed myocardial imaging may serve to exclude significant coronary artery disease and identify myocardial inflammatory patterns. Because many COVID-19 patients have cardiovascular comorbidities, myocardial infarction should be considered. Where the diagnosis remains uncertain, an endomyocardial biopsy may help identify active cardiac infection through viral genome amplification and possibly refine the treatment risks of systemic immunosuppression. Arrhythmias are not uncommon in the COVID-19 patients; however, its pathophysiology is still speculative. Nevertheless, clinicians should be vigilant to provide prompt monitoring and treatments. The long-term impact of COVID-19 myocarditis, including in the majority of mild cases remains unknown. | Heart Rhythm | 2020 | LitCov and CORD-19 | |
| 6418 | Evaluation of Rooming-in Practice for Neonates Born to Mothers With SARS-CoV-2 Infection in Italy N/A | JAMA Pediatr | 2021 | LitCov and CORD-19 | |
| 6419 | Parkinson's Disease and Post-COVID-19 Syndrome: The Parkinson's Long-COVID Spectrum | Mov Disord | 2021 | LitCov and CORD-19 | |
| 6420 | Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus Based on SARS-CoV Immunological Studies The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2. | Viruses | 2020 | LitCov and CORD-19 | |
| 6421 | Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19 Abstract Background Several studies have described the clinical characteristics of patients with novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19), indicating severe patients tended to have higher neutrophil to lymphocyte ratio (NLR). Whether baseline NLR could be an independent predictor of in-hospital death in Chinese COVID-19 patients remains to be investigated. Methods A cohort of patients with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from January 1 to February 29 was retrospectively analyzed. The baseline data of laboratory examinations, including NLR, were collected. Univariate and multivariate logistic regression models were developed to assess the independent relationship between the baseline NLR and in-hospital all-cause death. A sensitivity analysis was performed by converting NLR from a continuous variable to a categorical variable according to tertile. Interaction and stratified analyses were conducted as well. Results 245 COVID-19 patients were included in the final analyses, and the in-hospital mortality was 13.47%. Multivariate analysis demonstrated that there was 8% higher risk of in-hospital mortality for each unit increase in NLR (Odds ratio [OR] = 1.08; 95% confidence interval [95% CI], 1.01 to 1.14; P = 0.0147). Compared with patients in the lowest tertile, the NLR of patients in the highest tertile had a 15.04-fold higher risk of death (OR = 16.04; 95% CI, 1.14 to 224.95; P = 0.0395) after adjustment for potential confounders. Notably, the fully adjusted OR for mortality was 1.10 in males for each unit increase of NLR (OR = 1.10; 95% CI, 1.02 to 1.19; P = 0.016). Conclusions NLR is an independent risk factor of the in-hospital mortality for COVID-19 patients especially for male. Assessment of NLR may help identify high risk individuals with COVID-19. | J Infect | 2020 | LitCov and CORD-19 | |
| 6422 | Early humoral immune response to two doses of SARS-CoV-2 vaccine in a diverse group of solid organ transplant candidates and recipients N/A | Clin Transplant | 2022 | LitCov and CORD-19 | |
| 6423 | Rhino-Orbital Mucormycosis Associated With COVID-19 Coronavirus disease 2019 (COVID-19) infections may be associated with a wide range of bacterial and fungal co-infections. We report the case of a patient with COVID-19 infection, which, during the course of the treatment, developed rhino-orbital mucormycosis. A 60- year-old male patient, a longstanding diabetic, with a positive reverse-transcriptase polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was admitted for treatment. He received parenteral meropenem and oral oseltamivir with parenteral methylprednisolone. Over the course of the admission, he developed signs of orbital cellulitis. Magnetic resonance imaging (MRI) of the brain, orbits, and paranasal sinuses, revealed soft tissue swelling in the right preseptal, malar, premaxillary and retrobulbar regions with paranasal sinusitis. A nasal biopsy revealed broad aseptate filamentous fungal hyphae suggestive of mucormycosis, which was confirmed on culture. Extensive use of steroids/monoclonal antibodies/broad-spectrum antibiotics may lead to the development/exacerbation of a preexisting fungal disease. Physicians should be aware of the possibility of secondary invasive fungal infections in patients with COVID-19 infection. | Cureus | 2020 | LitCov and CORD-19 | |
| 6424 | Recommendations for use of antigenic tests in the diagnosis of acute SARS-CoV-2 infection in the second pandemic wave: attitude in different clinical settings The high transmissibility of SARS-CoV-2 before and shortly after the onset of symptoms suggests that only diagnosing and isolating symptomatic patients may not be sufficient to interrupt the spread of infection; therefore, public health measures such as personal distancing are also necessary. Additionally, it will be important to detect the newly infected individuals who remain asymptomatic, which may account for 50% or more of the cases. Molecular techniques are the “gold standard” for the diagnosis of SARS-CoV-2 infection. However, the massive use of these techniques has generated some problems. On the one hand, the scarcity of resources (analyzers, fungibles and reagents), and on the other the delay in the notification of results. These two facts translate into a lag in the application of isolation measures among cases and contacts, which favors the spread of the infection. Antigen detection tests are also direct diagnostic methods, with the advantage of obtaining the result in a few minutes and at the very “point-of-care”. Furthermore, the simplicity and low cost of these tests allow them to be repeated on successive days in certain clinical settings. The sensitivity of antigen tests is generally lower than that of nucleic acid tests, although their specificity is comparable. Antigenic tests have been shown to be more valid in the days around the onset of symptoms, when the viral load in the nasopharynx is higher. Having a rapid and real-time viral detection assay such as the antigen test has been shown to be more useful to control the spread of the infection than more sensitive tests, but with greater cost and response time, such as in case of molecular tests. The main health institutions such as the WHO, the CDC and the Ministry of Health of the Government of Spain propose the use of antigenic tests in a wide variety of strategies to respond to the pandemic. This document aims to support physicians involved in the care of patients with suspected SC2 infection, in the context of a growing incidence in Spain since September 2020, which already represents the second pandemic wave of COVID-19. | Rev Esp Quimioter | 2020 | LitCov and CORD-19 | |
| 6425 | Burnout syndrome and its determinants among healthcare workers during the first wave of the Covid-19 outbreak in Italy: a cross-sectional study to identify sex-related differences INTRODUCTION: Several studies described burnout levels of healthcare workers (HCWs) during the COVID-19 pandemic; however, sex-related differences remain poorly investigated. Objective: To describe sex-related differences in burnout and its determinants among HCWs during the first pandemic wave of the COVID-19 in Italy. METHODS: A cross-sectional study was performed between April and May 2020. The framework given by the Job Demands Resources (JD-R) model was used to assess burnout determinants (risk and protective factors). RESULTS: Male HCWs (n=133) had higher levels of depersonalization than female HCWs (P=0,017) and female HCWs (n=399) reported greater emotional exhaustion rates (P=0,005). Female nurses were the most exposed to burnout (OR=2,47; 95%CI=1,33-4,60; P=0,004), emotional exhaustion (OR=1,89; 95% CI=1,03-3,48; P=0,041), and depersonalization (OR=1,91; 95% CI=1,03-3,53; P=0,039). Determinants of burnout differed between sexes, and some paradoxical associations were detected: the score of job demands was a protective factor in females for burnout, emotional exhaustion, and depersonalization, resilience was a risk factor for males. CONCLUSIONS: This study reveals that the stressors in male and female HCWs tended to be associated with burnout differently. Both sexes showed alarming burnout levels, even if the weights of emotional exhaustion and depersonalization acted in different ways between the sexes. The revealed paradoxical effects in this study could reflect the study’s cross-sectional nature, highlighting that more resilient and empathic individuals were more consciously overwhelmed by the challenges related to the COVID-19 pandemic, thus reporting higher scores of emotional exhaustion and burnout. Future in-depth and longitudinal analyses are recommended to further explore sex-related differences in burnout among HCWs. | Med Lav | 2021 | LitCov and CORD-19 | |
| 6426 | Difference in safety and humoral response to mRNA SARS-CoV-2 vaccines in patients with autoimmune neurological disorders: the ANCOVAX study BACKGROUND: Assessing the safety of SARS-CoV-2 mRNA vaccines and the effect of immunotherapies on the seroconversion rate in patients with autoimmune neurological conditions (ANC) is relevant to clinical practice. Our aim was to assess the antibody response to and safety of SARS-CoV-2 mRNA vaccines in ANC. METHODS: This longitudinal study included ANC patients vaccinated with two doses of BNT162b2 or mRNA-1273 between March and August 2021. Side effects were assessed 2–10 days after each dose. Neurological status and anti-spike receptor binding domain antibody levels were evaluated before vaccination and 4 weeks after the second dose. Healthcare-workers served as controls for antibody levels. RESULTS: We included 300 ANC patients (median age 52, IQR 40–65), and 347 healthcare-workers (median age 45, IQR 34–54). mRNA-1273 vaccine was associated with an increased risk of both local (OR 2.52 95% CI 1.45–4.39, p = 0.001) and systemic reactions (OR 2.51% CI 1.49–4.23, p = 0.001). The incidence of relapse was not different before and after vaccine (Incidence rate ratio 0.72, 95% CI 0.29–1.83). Anti-SARS-CoV-2 IgG were detected in 268 (89.9%) patients and in all controls (p < 0.0001). BNT162b2 vaccine (OR 8.84 95% CI 2.32–33.65, p = 0.001), anti-CD20 mAb (OR 0.004 95% CI 0.0007–0.026, p < 0.0001) and fingolimod (OR 0.036 95% CI 0.002–0.628, p = 0·023) were associated with an increased risk of not developing anti-SARS-CoV-2 IgG. CONCLUSION: SARS-CoV-2 mRNA vaccines were safe in a large group of ANC patients. Anti-CD20 and fingolimod treatment, as well as vaccination with the BNT162b2 vaccine, led to a reduced humoral response. These findings could inform vaccine policies in ANC patients undergoing immunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-022-11142-7. | J Neurol | 2022 | LitCov and CORD-19 | |
| 6427 | Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era AIMS: To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). METHODS AND RESULTS: We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7–32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3–70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7–6.6; P < 0.001]. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1–2.8; P = 0.009). CONCLUSION: Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies. | Eur Heart J | 2020 | LitCov and CORD-19 | |
| 6428 | Comparison of Seroconversion in Children and Adults With Mild COVID-19 IMPORTANCE: The immune response in children with SARS-CoV-2 infection is not well understood. OBJECTIVE: To compare seroconversion in nonhospitalized children and adults with mild SARS-CoV-2 infection and identify factors that are associated with seroconversion. DESIGN, SETTING, AND PARTICIPANTS: This household cohort study of SARS-CoV-2 infection collected weekly nasopharyngeal and throat swabs and blood samples during the acute (median, 7 days for children and 12 days for adults [IQR, 4-13] days) and convalescent (median, 41 [IQR, 31-49] days) periods after polymerase chain reaction (PCR) diagnosis for analysis. Participants were recruited at The Royal Children’s Hospital, Melbourne, Australia, from May 10 to October 28, 2020. Participants included patients who had a SARS-CoV-2–positive nasopharyngeal or oropharyngeal swab specimen using PCR analysis. MAIN OUTCOMES AND MEASURES: SARS-CoV-2 immunoglobulin G (IgG) and cellular (T cell and B cell) responses in children and adults. Seroconversion was defined by seropositivity in all 3 (an in-house enzyme-linked immunosorbent assay [ELISA] and 2 commercial assays: a SARS-CoV-2 S1/S2 IgG assay and a SARS-CoV-2 antibody ELISA) serological assays. RESULTS: Among 108 participants with SARS-CoV-2–positive PCR findings, 57 were children (35 boys [61.4%]; median age, 4 [IQR, 2-10] years) and 51 were adults (28 women [54.9%]; median age, 37 [IQR, 34-45] years). Using the 3 established serological assays, a lower proportion of children had seroconversion to IgG compared with adults (20 of 54 [37.0%] vs 32 of 42 [76.2%]; P < .001). This result was not associated with viral load, which was similar in children and adults (mean [SD] cycle threshold [Ct] value, 28.58 [6.83] vs 24.14 [8.47]; P = .09). In addition, age and sex were not associated with seroconversion within children (median age, 4 [IQR, 2-14] years for both seropositive and seronegative groups; seroconversion by sex, 10 of 21 girls [47.6%] vs 10 of 33 boys [30.3%]) or adults (median ages, 37 years for seropositive and 40 years for seronegative adults [IQR, 34-39 years]; seroconversion by sex, 18 of 24 women [75.0%] vs 14 of 18 men [77.8%]) (P > .05 for all comparisons between seronegative and seropositive groups). Symptomatic adults had 3-fold higher SARS-CoV-2 IgG levels than asymptomatic adults (median, 227.5 [IQR, 133.7-521.6] vs 75.3 [IQR, 36.9-113.6] IU/mL), whereas no differences were observed in children regardless of symptoms. Moreover, differences in cellular immune responses were observed in adults compared with children with seroconversion. CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that among patients with mild COVID-19, children may be less likely to have seroconversion than adults despite similar viral loads. This finding has implications for future protection after SARS-CoV-2 infection in children and for interpretation of serosurveys that involve children. Further research to understand why seroconversion and development of symptoms are potentially less likely in children after SARS-CoV-2 infection and to compare vaccine responses may be of clinical and scientific importance. | JAMA Netw Open | 2022 | LitCov and CORD-19 | |
| 6429 | Is wearing a face mask safe for people with epilepsy? Since December 2019, the world has been experiencing a catastrophic pandemic of coronavirus disease (COVID‐19) caused by SARS‐CoV‐2. This virus primarily targets the human respiratory system. Available information suggests that people with epilepsy (PWE) are not at higher risk of being infected by the virus, nor of more severe COVID‐19 manifestations, as a result of the epilepsy alone. However, COVID‐19 is a serious disease that currently has no effective treatment or vaccine. A face mask is probably effective in preventing the spread of a respiratory pathogen, at least to some extent. So, should we recommend wearing a face mask to all during a pandemic of respiratory infectious disease (eg, COVID‐19) without any precautions or exemptions? While concrete evidence is lacking, if we consider that wearing a face mask may simulate hyperventilation, at least to some extent, we would probably avoid recommending this practice indiscriminately to all PWE. On the other hand, in the absence of any proven treatment or vaccine to combat COVID‐19, prevention is the best available strategy and it is probably not reasonable to suggest avoid wearing face masks in PWE under any circumstances. Logically, PWE do not need to wear a face mask most of the time, as long as there is no close contact with others, especially during intense physical activities such as exercise. To the contrary, it is probably more advantageous to wear a face mask in crowded locations, with intermittent breaks in safe locations, away from others. | Acta Neurol Scand | 2020 | LitCov and CORD-19 | |
| 6430 | Antibody and T Cell Responses against SARS-CoV-2 Elicited by the Third Dose of BBIBP-CorV (Sinopharm) and BNT162b2 (Pfizer-BioNTech) Vaccines Using a Homologous or Heterologous Booster Vaccination Strategy In the present study, antibody and T cell-mediated immune responses elicited by BBIBP-CorV and BNT162b2 vaccines were compared 6 months after the two-dose immunization of healthy individuals. Additionally, antibody and T cell responses after the third dose of BBIBP-CorV or BNT162b2 were compared using a homologous or heterologous vaccination strategy. The third dose was consistently administered 6 months after the second dose. Six months following the two-dose vaccination, the cumulative IFNγ-positive T cell response was almost identical in participants immunized with either two doses of BNT162b2 or BBIBP-CorV vaccines; however, significant differences were revealed regarding humoral immunity: the two-dose BNT162b2 vaccine maintained a significantly higher antireceptor-binding domain (RBD) IgG, anti-spike (S1/S2) IgG, and IgA antibody levels. The BNT162b2 + BNT162b2 + BBIBP-CorV vaccine series elicited significantly lower anti-RBD IgG and anti-S1/S2 IgG levels than three doses of BNT162b2, while the anti-S IgA level was equally negligible in both groups. Importantly, the cumulative IFNγ-positive T cell response was highly similar in both groups. Surprisingly, the BBIBP-CorV + BBIBP-CorV + BNT162b2 vaccination series provided a much higher cumulative IFNγ-positive T cell response than that elicited by three doses of BNT162b2; moreover, the levels of anti-RBD IgG and anti-S IgA were almost identical. Only the mean anti-S1/S2 IgG levels were higher after receiving three mRNA vaccines. Based on these data, we can conclude that administering a third dose of BNT162b2 after two doses of BBIBP-CorV is an effective strategy to significantly enhance both humoral and T cell-mediated immune response, and its effectiveness is comparable to that of three BNT162b2 vaccines. | Vaccines (Basel) | 2022 | LitCov and CORD-19 | |
| 6431 | Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy. Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response. The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy. METHODS: This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands. With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020. In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course. FINDINGS: Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41–78). Median disease course (time from onset of symptoms to death) was 22 days (range 5–44 days). In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course. Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract. In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain. In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata. Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5–44]; ten patients with neutrophilic plugs, 21 days [5–44]). Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets.. INTERPRETATION: In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs. However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19. This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19. FUNDING: Amsterdam UMC Corona Research Fund. | Lancet Microbe | 2020 | LitCov and CORD-19 | |
| 6432 | Health-protective behaviour, social media usage and conspiracy belief during the COVID-19 public health emergency BACKGROUND: Social media platforms have long been recognised as major disseminators of health misinformation. Many previous studies have found a negative association between health-protective behaviours and belief in the specific form of misinformation popularly known as ‘conspiracy theory’. Concerns have arisen regarding the spread of COVID-19 conspiracy theories on social media. METHODS: Three questionnaire surveys of social media use, conspiracy beliefs and health-protective behaviours with regard to COVID-19 among UK residents were carried out online, one using a self-selecting sample (N = 949) and two using stratified random samples from a recruited panel (N = 2250, N = 2254). RESULTS: All three studies found a negative relationship between COVID-19 conspiracy beliefs and COVID-19 health-protective behaviours, and a positive relationship between COVID-19 conspiracy beliefs and use of social media as a source of information about COVID-19. Studies 2 and 3 also found a negative relationship between COVID-19 health-protective behaviours and use of social media as a source of information, and Study 3 found a positive relationship between health-protective behaviours and use of broadcast media as a source of information. CONCLUSIONS: When used as an information source, unregulated social media may present a health risk that is partly but not wholly reducible to their role as disseminators of health-related conspiracy beliefs. | Psychol Med | 2020 | LitCov and CORD-19 | |
| 6433 | Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19 OBJECTIVE: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in the GI tract during disease course is largely unknown. We investigated temporal transcriptional activity of SARS-CoV-2 and its association with longitudinal faecal microbiome alterations in patients with COVID-19. DESIGN: We performed RNA shotgun metagenomics sequencing on serial faecal viral extractions from 15 hospitalised patients with COVID-19. Sequencing coverage of the SARS-CoV-2 genome was quantified. We assessed faecal microbiome composition and microbiome functionality in association with signatures of faecal SARS-CoV-2 infectivity. RESULTS: Seven (46.7%) of 15 patients with COVID-19 had stool positivity for SARS-CoV-2 by viral RNA metagenomic sequencing. Even in the absence of GI manifestations, all seven patients showed strikingly higher coverage (p=0.0261) and density (p=0.0094) of the 3’ vs 5’ end of SARS-CoV-2 genome in their faecal viral metagenome profile. Faecal viral metagenome of three patients continued to display active viral infection signature (higher 3’ vs 5’ end coverage) up to 6 days after clearance of SARS-CoV-2 from respiratory samples. Faecal samples with signature of high SARS-CoV-2 infectivity had higher abundances of bacterial species Collinsella aerofaciens, Collinsella tanakaei, Streptococcus infantis, Morganella morganii, and higher functional capacity for nucleotide de novo biosynthesis, amino acid biosynthesis and glycolysis, whereas faecal samples with signature of low-to-none SARS-CoV-2 infectivity had higher abundances of short-chain fatty acid producing bacteria, Parabacteroides merdae, Bacteroides stercoris, Alistipes onderdonkii and Lachnospiraceae bacterium 1_1_57FAA. CONCLUSION: This pilot study provides evidence for active and prolonged ‘quiescent’ GI infection even in the absence of GI manifestations and after recovery from respiratory infection of SARS-CoV-2. Gut microbiota of patients with active SARS-CoV-2 GI infection was characterised by enrichment of opportunistic pathogens, loss of salutary bacteria and increased functional capacity for nucleotide and amino acid biosynthesis and carbohydrate metabolism. | Gut | 2020 | LitCov and CORD-19 | |
| 6434 | Venous thromboembolism in critically ill COVID-19 patients receiving prophylactic or therapeutic anticoagulation: a systematic review and meta-analysis Many aspects of care such as management of hypercoagulable state in COVID-19 patients, especially those admitted to intensive care units is challenging in the rapidly evolving pandemic of novel coronavirus disease 2019 (COVID-19). We seek to systematically review the available evidence regarding the anticoagulation approach to prevent venous thromboembolism (VTE) among COVID-19 patients admitted to intensive care units. Electronic databases were searched for studies reporting venous thromboembolic events in patients admitted to the intensive care unit receiving any type of anticoagulation (prophylactic or therapeutic). The pooled prevalence (and 95% confidence interval [CI]) of VTE among patients receiving anticoagulant were calculated using the random-effects model. Subgroup pooled analyses were performed with studies reported prophylactic anticoagulation alone and with studies reported mixed prophylactic and therapeutic anticoagulation. We included twelve studies (8 Europe; 2 UK; 1 each from the US and China) in our systematic review and meta-analysis. All studies utilized LMWH or unfractionated heparin as their pharmacologic thromboprophylaxis, either prophylactic doses or therapeutic doses. Seven studies reported on the proportion of patients with the previous history of VTE (range 0–10%). The pooled prevalence of VTE among ICU patients receiving prophylactic or therapeutic anticoagulation across all studies was 31% (95% CI 20–43%). Subgroup pooled analysis limited to studies reported prophylactic anticoagulation alone and mixed (therapeutic and prophylactic anticoagulation) reported pooled prevalences of VTE of 38% (95% CI 10–70%) and 27% (95% CI 17–40%) respectively. With a high prevalence of thromboprophylaxis failure among COVID-19 patients admitted to intensive care units, individualised rather than protocolised VTE thromboprophylaxis would appear prudent at interim. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11239-020-02235-z) contains supplementary material, which is available to authorized users. | J Thromb Thrombolysis | 2020 | LitCov and CORD-19 | |
| 6435 | First reported nosocomial outbreak of SARS-CoV-2 in a pediatric dialysis unit BACKGROUND: Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany over 140,000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital of Münster (UHM). METHODS: Single-step real-time RT-PCR from nasopharyngeal swaps was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and chart reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Threshold cycle (C(t)) values of all positive test results were compared between symptomatic and asymptomatic cases. RESULTS: Forty-eight cases were involved in this nosocomial outbreak. Nine contact cases developed laboratory confirmed COVID-19 infections. Two SARS-CoV-2 positive cases remained clinically asymptomatic. Eleven cases reported flu-like symptoms without positive results. C(t) values were significantly lower in cases presenting typical COVID-19 symptoms, suggesting high viral shedding (p =0.007). CONCLUSION: Person-to-person transmission was at the heart of a hospital outbreak of SARS-CoV-2 between healthcare workers (HCWs) and patients in the pediatric dialysis unit at the UHM. Semi quantitative real-time RT-PCR results suggest that individuals with high viral load pose a risk to spread SARS-CoV-2 in the hospital setting. Our epidemiological observation highlights the need to develop strategies to trace and monitor SARS-CoV-2 infected HCWs in order to prevent COVID-19 outbreaks in the hospital setting. | Clin Infect Dis | 2020 | LitCov and CORD-19 | |
| 6436 | Epitope-based peptide vaccines predicted against novel coronavirus disease caused by SARS-CoV-2 The outbreak of the 2019 novel coronavirus (SARS-CoV-2) has infected millions of people with a large number of deaths across the globe. The existing therapies are limited in dealing with SARS-CoV-2 due to the sudden appearance of the virus. Therefore, vaccines and antiviral medicines are in desperate need. We took immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein (S), membrane glycoprotein (M) and nucleocapsid protein (N) of SARS-CoV-2, followed by estimating their antigenicity and interactions with the human leukocyte antigen (HLA) alleles. Allergenicity, toxicity, physiochemical properties analysis and stability were examined to confirm the specificity and selectivity of the epitope candidates. We identified a total of five B cell epitopes in RBD of S protein, seven MHC class-I, and 18 MHC class-II binding T-cell epitopes from S, M and N protein which showed non-allergenic, non-toxic and highly antigenic features and non-mutated in 55,179 SARS-CoV-2 virus strains until June 25, 2020. The epitopes identified here can be a potentially good candidate repertoire for vaccine development. | Virus Res | 2020 | LitCov and CORD-19 | |
| 6437 | Rhino-orbital-cerebral mucormycosis: fungal epidemic in a viral pandemic BACKGROUND: Treatment of coronavirus disease 2019 infection can result in immunosuppression. Rhino-orbital-cerebral mucormycosis is a frequent co-infection, even after recovery. METHODS: An ambispective interventional study was conducted of 41 coronavirus patients with rhino-orbital-cerebral mucormycosis at a tertiary care centre from March to May 2021. RESULTS: There were 28 males and 13 females with a mean age of 48.2 years (range, 21–68 years). Twelve had long-standing diabetes mellitus and 28 had been recently diagnosed. Thirty-six had received systemic corticosteroids for coronavirus disease 2019. Nasal signs were present in 95 per cent of patients, ophthalmic symptoms and signs in 87 per cent, palatal necrosis in 46.3 per cent, facial signs in 24.3 per cent, nerve palsies in 60.9 per cent, and intracranial involvement in 21.9 per cent. Treatment with amphotericin B was based on clinical features and co-morbidities. Endonasal debridement was performed in 51.2 per cent of patients, total maxillectomy in 14.6 per cent and orbital exenteration in 9.7 per cent. At the last follow up, 37 patients (90.24 per cent) were on antifungal therapy; 4 (9.75 per cent) did not survive. CONCLUSION: Early detection may improve survival. Follow up of high-risk patients after coronavirus disease 2019 infection is paramount. | J Laryngol Otol | 2021 | LitCov and CORD-19 | |
| 6438 | Transmission of SARS-CoV-2 delta variant (AY.127) from pet hamsters to humans, leading to onward human-to-human transmission: a case study BACKGROUND: Transmission of SARS-CoV-2 from humans to other mammals, including pet animals, has been reported. However, with the exception of farmed mink, there is no previous evidence that these infected animals can infect humans, resulting in sustained human-to-human transmission. Following a confirmed SARS-CoV-2 infection of a pet shop worker, animals in the shop and the warehouse supplying it were tested for evidence of SARS-CoV-2 infection. METHODS: In this case study, viral swabs and blood samples were collected from animals in a pet shop and its corresponding warehouse in Hong Kong. Nasal swab or saliva samples from human COVID-19 patients epidemiologically linked to the pet shop and from subsequent local cases confirmed to be infected by SARS-CoV-2 delta variant were collected. Oral swabs were tested by quantitative RT-PCR (RT-qPCR) for SARS-CoV-2 and blood samples were serologically tested by a surrogate virus neutralisation test and plaque reduction neutralisation test. The SARS-CoV-2 RT-qPCR positive samples were sequenced by next generation viral full genome sequencing using the ISeq sequencing platform (Illumina), and the viral genomes were phylogenetically analysed. FINDINGS: Eight (50%) of 16 individually tested Syrian hamsters in the pet shop and seven (58%) of 12 Syrian hamsters in the corresponding warehouse were positive for SARS-CoV-2 infection in RT-qPCR or serological tests. None of the dwarf hamsters (n=75), rabbits (n=246), guinea pigs (n=66), chinchillas (n=116), and mice (n=2) were confirmed positive for SARS-CoV-2 in RT-qPCR tests. SARS-CoV-2 viral genomes deduced from human and hamster cases in this incident all belong to the delta variant of concern (AY.127) that had not been circulating locally before this outbreak. The viral genomes obtained from hamsters were phylogenetically related with some sequence heterogeneity. Phylogenetic dating suggests infection in these hamsters occurred around Oct 14, 2021 (95% CI Sept 15 to Nov 9, 2021). Multiple zoonotic transmission events to humans were detected, leading to onward human-to-human transmission. INTERPRETATION: Pet hamsters can be naturally infected with SARS-CoV-2. The virus can circulate among hamsters and lead to human infections. Both genetic and epidemiological results strongly suggest that there was more than one hamster-to-human transmission event in this study. This incident also led to onward human transmission. Importation of SARS-CoV-2-infected hamsters was a likely source of this outbreak. FUNDING: US National Institutes of Health, Research Grants Council of Hong Kong, Food and Health Bureau, and InnoHK. | Lancet | 2022 | LitCov and CORD-19 | |
| 6439 | Equitable Pandemic Preparedness and Rapid Response: Lessons from COVID-19 for Pandemic Health Equity N/A | J Health Polit Policy Law | 2020 | LitCov and CORD-19 | |
| 6440 | Mental health outcomes of the CoViD-19 pandemic N/A | Riv Psichiatr | 2020 | LitCov and CORD-19 | |
| 6441 | COVID-19 vaccine hesitancy among medical students BACKGROUND: Medical students are among the group of frontline healthcare providers likely to be exposed to COVID-19 patients. It is important to achieve high COVID-19 vaccination coverage rates in this group as soon as a vaccine is available. As future healthcare providers, they will be entrusted with providing vaccine recommendations and counseling vaccine-hesitant patients. METHODS: This project used self-report to assess vaccine hesitancy and acceptance among medical students towards the novel COVID-19 vaccine. RESULTS: Nearly all participants had positive attitudes towards vaccines and agreed they would likely be exposed to COVID-19; however, only 53% indicated they would participate in a COVID-19 vaccine trial and 23% were unwilling to take a COVID-19 vaccine immediately upon FDA approval. Students willing to immediately take the vaccine were more likely to trust public health experts, have fewer concerns about side effects and agree with vaccine mandates (P < 0.05). Concern for serious side effects was independently predictive of lower odds of intent to participate in a COVID-19 vaccine trial (AOR = 0.41, P = 0.01). CONCLUSION: This is the first study to evaluate COVID-19 vaccine hesitancy among US medical students and highlights the need for an educational curriculum about the safety and effectiveness to promote uptake of the COVID-19 vaccine. | J Public Health (Oxf) | 2020 | LitCov and CORD-19 | |
| 6442 | Depressive and Anxiety Symptoms of Healthcare Workers in Intensive Care Unit Under the COVID-19 Epidemic: An Online Cross-Sectional Study in China Background: Since the coronavirus disease-2019 (COVID-19) outbreak, intensive care unit (ICU) healthcare workers were responsible for the critical infected patients. However, few studies focused on the mental health of ICU healthcare workers. This study aimed to investigate the psychological impact of COVID-19 on ICU healthcare workers in China. Methods: We distributed the nine-item Patient Health Questionnaire (PHQ-9) and seven-item General Anxiety Disorder questionnaire (GAD-7) online to ICU healthcare workers in China. Respondents were divided into frontline and second-line according to whether they have contact with COVID-19 patients. Depressive and anxiety symptoms of all respondents were evaluated based on their questionnaire scores. Results: There were 731 ICU healthcare workers finally enrolled in our study, including 303 (41.5%) male, 383 (52.4%) doctors, and 617 (84.4%) aged 26–45 years. All in all, 482 (65.9%) ICU healthcare workers reported symptoms of depression, while 429 (58.7%) reported anxiety. There was no significant difference between frontline (n = 325) and second-line (n = 406) respondents in depression (P = 0.15) and anxiety severity (P = 0.56). Logistic regression analysis showed that being female, ICU work time >5 years, and night duty number ≥10 were risk factors of developing depressive and anxiety symptoms. Income reduction was separately identified as risk of anxiety. Additionally, ICU work time >5 years was also identified as risk of developing moderate–severe depressive and anxiety symptoms. Conclusions: Frontline ICU work was not associated with higher risk of depressive and anxiety symptoms during COVID-19 pandemic remission period in China. Actions like controlling night duty number, ensuring vacation, and increasing income should be taken to relieve mental health problem. Furthermore, we should pay close attention to those who had worked long years in ICU. | Front Public Health | 2021 | LitCov and CORD-19 | |
| 6443 | Outcome of acute respiratory distress syndrome requiring extracorporeal membrane oxygenation in Covid-19 or influenza: A single-center registry study Veno‐venous extracorporeal membrane oxygenation (V‐V ECMO) is used to sustain blood oxygenation and decarboxylation in severe acute respiratory distress syndrome (ARDS). It is under debate if V‐V ECMO is as appropriate for coronavirus disease 2019 (Covid‐19) ARDS as it is for influenza. In this retrospective study, we analyzed all patients with confirmed SARS‐CoV‐2 or influenza A/B infection, ARDS and V‐V ECMO, treated at our medical intensive care unit (ICU) between October 2010 and June 2020. Baseline and procedural characteristics as well as survival 30 days after ECMO cannulation were analyzed. A total of 62 V‐V ECMO patients were included (15 with Covid‐19 and 47 with influenza). Both groups had similar baseline characteristics at cannulation. Thirty days after ECMO cannulation, 13.3% of all patients with Covid‐19 were discharged alive from our ICU compared to 44.7% with influenza (P = .03). Patients with Covid‐19 had fewer ECMO‐free days (0 (0‐9.7) days vs. 13.2 (0‐22.1) days; P = .05). Cumulative incidences of 30‐day‐survival showed no significant differences (48.6% in Covid‐19 patients, 63.7% in influenza patients; P = .23). ICU treatment duration was significantly longer in ARDS patients with V‐V ECMO for Covid‐19 compared to influenza. Thirty‐day mortality was higher in Covid‐19, but not significant. | Artif Organs | 2020 | LitCov and CORD-19 | |
| 6444 | The Utility of Native MS for Understanding the Mechanism of Action of Repurposed Therapeutics in COVID-19: Heparin as a Disruptor of the SARS-CoV-2 Interaction with Its Host Cell Receptor [Image: see text] The emergence and rapid proliferation of the novel coronavirus (SARS-CoV-2) resulted in a global pandemic, with over 6,000,000 cases and nearly 400,000 deaths reported worldwide by the end of May 2020. A rush to find a cure prompted re-evaluation of a range of existing therapeutics vis-à-vis their potential role in treating COVID-19, placing a premium on analytical tools capable of supporting such efforts. Native mass spectrometry (MS) has long been a tool of choice in supporting the mechanistic studies of drug/therapeutic target interactions, but its applications remain limited in the cases that involve systems with a high level of structural heterogeneity. Both SARS-CoV-2 spike protein (S-protein), a critical element of the viral entry to the host cell, and ACE2, its docking site on the host cell surface, are extensively glycosylated, making them challenging targets for native MS. However, supplementing native MS with a gas-phase ion manipulation technique (limited charge reduction) allows meaningful information to be obtained on the noncovalent complexes formed by ACE2 and the receptor-binding domain (RBD) of the S-protein. Using this technique in combination with molecular modeling also allows the role of heparin in destabilizing the ACE2/RBD association to be studied, providing critical information for understanding the molecular mechanism of its interference with the virus docking to the host cell receptor. Both short (pentasaccharide) and relatively long (eicosasaccharide) heparin oligomers form 1:1 complexes with RBD, indicating the presence of a single binding site. This association alters the protein conformation (to maximize the contiguous patch of the positive charge on the RBD surface), resulting in a notable decrease in its ability to associate with ACE2. The destabilizing effect of heparin is more pronounced in the case of the longer chains due to the electrostatic repulsion between the low-pI ACE2 and the heparin segments not accommodated on the RBD surface. In addition to providing important mechanistic information on attenuation of the ACE2/RBD association by heparin, the study demonstrates the yet untapped potential of native MS coupled to gas-phase ion chemistry as a means of facilitating rational repurposing of the existing medicines for treating COVID-19. | Anal Chem | 2020 | LitCov and CORD-19 | |
| 6445 | Évaluation d'un dispositif de continuité pédagogique à distance mis en place auprès d'étudiants MERM pendant le confinement sanitaire lié au COVID-19 INTRODUCTION: The specific context related to the COVID-19 pandemic necessitated the implementation of distance learning continuity for students. In France, teachers and radiography students in initial training, not specially prepared for this, had to adapt. An evaluation of the system was proposed to the students. MATERIALS AND METHODS: An anonymous online questionnaire with 4 main sections (pedagogy, communication, learning and concerns) was sent to 91 students at the end of the semester. RESULTS: 91 responses were received. The slideshows with sound or presented during a virtual class are appreciated by the students. Online quizzes are ideal for learning/reviewing. For assessments, individual assignments and online questionnaires are appreciated. Teacher/student interaction via e-mail or video conferencing was considered satisfactory by the large majority of students. Student-student interactions via social networks, for course explanations or document exchange, are very suitable. The majority of students felt they were working a lot and much more compared to face-to-face teaching. Less than half of the students worked more than 20 h per week. Their motivation varied widely. Organizational habits were disrupted, but the autonomy granted was appreciated. The students were mainly concerned about the health of their loved ones and not about their own health. DISCUSSION: The use of distance education tools requires teacher commitment and technical skills. The frequency of communication by e-mail and/or videoconference between members of the teaching team and students must be adapted to the situation. Exchanges by e-mail allow for traceability, while videoconferencing allows direct interaction and a way out of isolation. Autonomy, appreciated by the students, was nevertheless combined with a strong variation in motivation; the anxiety-provoking period in which pedagogical continuity was built up may explain this contradictory observation. CONCLUSION: The results obtained largely confirm the data in the literature. The experience gained through this survey should lead teachers to continue their reflection by test/integrating and evaluating distance education systems, while continuing face-to-face activities. | J Med Imaging Radiat Sci | 2020 | LitCov and CORD-19 | |
| 6446 | Smell dysfunction: a biomarker for COVID-19 BACKGROUND: SARS‐CoV‐2, the virus that causes COVID‐19 disease, is responsible for the largest pandemic since the 1918 H1N1 influenza outbreak. The symptoms presently recognized by the World Health Organization are cough, fever, tiredness, and difficulty breathing. Patient‐reported smell and taste loss has been associated with COVID‐19 infection, yet no empirical olfactory testing on a cohort of COVID‐19 patients has been performed. METHODS: The University of Pennsylvania Smell Identification Test (UPSIT), a well‐validated 40‐odorant test, was administered to 60 confirmed COVID‐19 inpatients and 60 age‐ and sex‐matched controls to assess the magnitude and frequency of their olfactory dysfunction. A mixed effects analysis of variance determined whether meaningful differences in test scores existed between the two groups and if the test scores were differentially influenced by sex. RESULTS: Fifty‐nine (98%) of the 60 patients exhibited some smell dysfunction [mean (95% CI) UPSIT score: 20.98 (19.47,22.48); controls: 34.10 (33.31,34.88); p<0.0001]. Thirty‐five of the 60 patients (58%) were either anosmic (15/60; 25%) or severely microsmic (20/60; 33%); 16 exhibited moderate microsmia (16/60; 27%), 8 mild microsmia (8/60; 13%), and one normosmia (1/60; 2%). Deficits were evident for all 40 UPSIT odorants. No meaningful relationships between the test scores and sex, disease severity, or comorbidities were found. CONCLUSIONS: Quantitative smell testing demonstrates that decreased smell function, but not always anosmia, is a major marker for SARS‐CoV‐2 infection and suggests the possibility that smell testing may help, in some cases, to identify COVID‐19 patients in need of early treatment or quarantine. This article is protected by copyright. All rights reserved | Int Forum Allergy Rhinol | 2020 | LitCov and CORD-19 | |
| 6447 | Mistrust in biomedical research and vaccine hesitancy: the forefront challenge in the battle against COVID-19 in Italy Researchers have been working quickly and collaboratively for the development of vaccines against the COVID-19 virus. The effort of the scientific community in searching a vaccine for COVID-19 may be hampered by a diffused vaccine hesitancy. Two waves of data collection on representative samples of the Italian population (during the “first” and “second” phase of the Italian Covid-19 mitigation strategy) were conducted to understand citizens’ perceptions and behaviors about preventive behaviors willingness to vaccine for COVID-19. Our study shows that willingness to COVID-19 vaccine is correlated to trust in research and in vaccines, which decreased between phase 1 and phase 2 of the Italian pandemic. According to the results of our study, the proportion of citizens that seem to be intentioned to get the Covid-19 vaccine is probably too small to effectively stop the spreading of the disease. This requires to foster a climate of respectful mutual trust between science and society, where scientific knowledge is not only preached but also cultivated and sustained thanks to the emphatic understanding of citizens worries, needs of reassurance and health expectations. | Eur J Epidemiol | 2020 | LitCov and CORD-19 | |
| 6448 | Multi-arm Trial of Inflammatory Signal Inhibitors (MATIS) for hospitalised patients with mild or moderate COVID-19 pneumonia: a structured summary of a study protocol for a randomised controlled trial OBJECTIVES: The primary objective of MATIS is to determine the efficacy of ruxolitinib (RUX) or fostamatinib (FOS) compared to standard of care (SOC) with respect to reducing the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Determine the efficacy of RUX or FOS to reduce mortality. Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation or ECMO. Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation. Determine the efficacy of RUX or FOS to reduce the proportion of participants suffering significant oxygen desaturation. Determine the efficacy of RUX or FOS to reduce the need for renal replacement therapy. Determine the efficacy of RUX and FOS to reduce the incidence of venous thromboembolism. Determine the efficacy of RUX and FOS to reduce the severity of COVID-19 pneumonia [graded by a 9-point modified WHO Ordinal Scale*. Determine the efficacy of RUX or FOS to reduce systemic inflammation. Determine the efficacy of RUX or FOS to the incidence of renal impairment. Determine the efficacy of RUX or FOS to reduce duration of hospital stay. Evaluate the safety of RUX and FOS for treatment of COVID-19 pneumonia. TRIAL DESIGN: A multi-arm, multi-stage (3-arm parallel-group, 2-stage) randomised controlled trial that allocates participants 1:1:1 and tests for superiority in experimental arms versus standard of care. PARTICIPANTS: Patients will be recruited while inpatients during hospitalisation for COVID-19 in multiple centres throughout the UK including Imperial College Healthcare NHS Trust. Patients age ≥ 18 years at screening. Patients with mild or moderate COVID-19 pneumonia, defined as Grade 3 or 4 severity by the WHO COVID-19 Ordinal Scale. Hospitalization AND. SARS-CoV2 infection (clinically suspected or laboratory confirmed) AND. Radiological change consistent with COVID-19 disease. CRP ≥ 30mg/L at any time point. Informed consent from patient or personal or professional representative. Agreement to abstain from sexual intercourse or use contraception that is >99% effective for all participants of childbearing potential for 42 days after the last dose of study drug. For male participants, agreement to abstain from sperm donation for 42 days after the last dose of study drug. Requiring either invasive or non-invasive ventilation including CPAP or high flow nasal oxygen at any point after hospital admission but before baseline, not related to a pre-existing condition (e.g., obstructive sleep apnoea). Grade ≥ 5 severity on the modified WHO COVID-19 Ordinal Scale, i.e. SpO(2) < 90% on ≥ 60% inspired oxygen by facemask at baseline; non-invasive ventilation; or invasive mechanical ventilation. In the opinion of the investigator, progression to death is inevitable within the next 24 hours, irrespective of the provision of therapy. Known severe allergic reactions to the investigational agents. Child-Pugh B or C grade hepatic dysfunction. Use of drugs within the preceding 14 days that are known to interact with any study treatment (FOS or RUX), as listed in the Summary of Product Characteristics. Pregnant or breastfeeding. Any medical condition or concomitant medication that in the opinion of the investigator would compromise subjects’ safety or compliance with study procedures. Any medical condition which in the opinion of the principal investigator would compromise the scientific integrity of the study. Non-English speakers will be able to join the study. If participants are unable to understand verbal or written information in English, then hospital translation services will be requested at the participating site for the participant where possible. INTERVENTION AND COMPARATOR: RUXOLITINIB (RUX) (14 days): An oral selective and potent inhibitor of Janus Associated Kinases (JAK1 and JAK2) and cell proliferation (Verstovek, 2010). It is approved for the treatment of disease-related splenomegaly or constitutional symptoms in myelofibrosis, polycythaemia vera and graft-versus-host-disease. RUX will be administered orally 10mg bd Day 1-7 and 5mg bd Day 8-14. FOSTAMATINIB (FOS) (14 days): An oral spleen tyrosine kinase inhibitor approved for the treatment of thrombocytopenia in adult participants with chronic immune thrombocytopenia. FOS will be administered orally 150mg bd Day 1-7 and 100mg bd Day 8-14. Please see protocol for recommended dose modifications where required. COMPARATOR (Standard of Care, SOC): experimental arms will be compared to participants receiving standard of care. It is accepted that SOC may change during a rapidly evolving pandemic. Co-enrolment to other trials and rescue therapy, either pre- or post-randomisation, is permitted and will be accounted for in the statistical analysis. MAIN OUTCOMES: Death OR. Requirement for invasive ventilation OR. Requirement for non-invasive ventilation including CPAP or high flow oxygen OR. O(2) saturation < 90% on ≥60% inspired oxygen. RANDOMISATION: Participants will be allocated to interventions using a central web-based randomisation service that generates random sequences using random permuted blocks (1:1:1), with stratification by age (<65 and ≥65 years) and site. BLINDING (MASKING): No participants or caregivers are blinded to group assignment. Clinical outcomes will be compared blind to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): For an early informal dose examination by the Data Monitoring Committee a minimum of 30 participants will be recruited. For Stage 1 of this multi-arm multi-stage study, 171 participants will be randomised, with 57 participants in each arm. If at least one experimental intervention shows promise, then Stage 2 will recruit a further 95 participants per arm. Sample size calculations are given in the protocol. TRIAL STATUS: Recruitment is ongoing and started 2(nd) October 2020. We anticipate completion of Stage 1 by July 2021 and Stage 2 by April 2022. The current protocol version 2.0 of 11(th) February 2021 is appended. TRIAL REGISTRATION: EudraCT: 2020-001750-22, 9(th) July 2020 ClinicalTrials.gov: NCT04581954, 9(th) October 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05190-z. | Trials | 2021 | LitCov and CORD-19 | |
| 6449 | Dealing with sleep problems during home confinement due to the COVID-19 outbreak: Practical recommendations from a task force of the European CBT-I Academy N/A | J Sleep Res | 2020 | LitCov and CORD-19 | |
| 6450 | Targeting the SARS-CoV-2 spike glycoprotein prefusion conformation: virtual screening and molecular dynamics simulations applied to the identification of potential fusion inhibitors The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a renewed interest in studying the role of the spike S glycoprotein in regulating coronavirus infections in the natural host. Taking advantage of the cryo-electron microscopy structure of SARS-CoV-2 S trimer in the prefusion conformation, we performed a virtual screening simulation with the aim to identify novel molecules that could be used as fusion inhibitors. The spike glycoprotein structure has been completed using modeling techniques and its inner cavity, needful for the postfusion transition of the trimer, has been scanned for the identification of strongly interacting available drugs. Finally, the stability of the protein-drug top complexes has been tested using classical molecular dynamics simulations. The free energy of interaction of the molecules to the spike protein has been evaluated through the MM/GBSA method and per-residue decomposition analysis. Results have been critically discussed considering previous scientific knowledge concerning the selected compounds and sequence alignments have been carried out to evaluate the spike glycoprotein similarity among the betacoronavirus family members. Finally, a cocktail of drugs that may be used as SARS-CoV-2 fusion inhibitors has been suggested. | Virus Res | 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
(2) Chen Q, Allot A, & Lu Z. (2020) Keep up with the latest coronavirus research, Nature 579:193 and Chen Q, Allot A, Lu Z. LitCovid: an open database of COVID-19 literature. Nucleic Acids Research. 2020. (version 2023-01-10)
(3) Currently tweets of June 23rd to June 29th 2022 have been considered.