Background It is unclear if people with immune-mediated inflammatory diseases (IMIDs) (joint, bowel and skin) and on immune modifying therapy have increased risk of serious COVID-19 outcomes. Methods With the approval of NHS England we conducted a cohort study, using OpenSAFELY, analysing routinely-collected primary care data linked to hospital admission, death and previously unavailable hospital prescription data. We used Cox regression (adjusting for confounders) to estimate hazard ratios (HR) comparing risk of COVID-19-death, death/critical care admission, and hospitalisation (March to September 2020) in: 1) people with IMIDs compared to the general population; and 2) people with IMIDs on targeted immune modifying drugs (e.g., biologics) compared to standard systemic treatment (e.g., methotrexate). Findings We identified 17,672,065 adults; of 1,163,438 (7%) with IMIDs, 19,119 people received targeted immune modifying drugs, and 200,813 received standard systemics. We saw evidence of increased COVID-19-death (HR 1.23, 95%CI 1.20, 1.27), and COVID-19 hospitalisation (HR 1.32, 95%CI 1.29, 1.35) in individuals with IMIDs overall compared to individuals without IMIDs of the same age, sex, deprivation and smoking status. We saw no evidence of increased COVID-19 deaths with targeted compared to standard systemic treatments (HR 1.03, 95%CI 0.80, 1.33). There was no evidence of increased COVID-19-related death in those prescribed TNF inhibitors, IL-12/23, IL7, IL-6 or JAK inhibitors compared to standard systemics. Rituximab was associated with increased COVID-19 death (HR 1.68, 95%CI 1.11, 2.56); however, this finding may relate to confounding. Interpretation COVID-19 death and hospitalisation was higher in people with IMIDs. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune modifying drugs for IMIDs compared to standard systemics.
Background The prevalence of SARS-CoV-2 infection continues to drive rates of illness and hospitalisations despite high levels of vaccination, with the proportion of cases caused by the Delta lineage increasing in many populations. As vaccination programs roll out globally and social distancing is relaxed, future SARS-CoV-2 trends are uncertain. Methods We analysed prevalence trends and their drivers using reverse transcription-polymerase chain reaction (RT-PCR) swab-positivity data from round 12 (between 20 May and 7 June 2021) and round 13 (between 24 June and 12 July
Despite the effectiveness of the COVID-19 vaccine, global vaccination distribution efforts have thus far had varying levels of success. Vaccine hesitancy remains a threat to vaccine uptake. This study has four objectives: 1) describe and compare vaccine hesitancy proportions by country; 2) categorize vaccine-related concerns; 3) rank vaccine- related concerns; and 4) compare vaccine-related concerns by country and hesitancy status in four countries- the United States, Canada, Sweden, and Italy. Using the Pollfish survey platform, we sampled 1000 respondents in Canada, Sweden, and Italy and 750 respondents in the United States between May 21-28, 2021. Results showed vaccine related concerns varied across three topical areas- vaccine safety and government control, vaccine effectiveness and population control, and freedom. For each thematic area, the top concern was statistically significantly different in each country and among the hesitant and non-hesitant subsamples within each county. Understanding the specific concerns among individuals when it comes to the COVID-19 vaccine can help to inform public communications and identify which, if any, salient narratives, are global.
“Living” evidence synthesis is of primary interest for decision-makers to overcome the COVID-19 pandemic. The COVID-NMA provides open-access living meta-analyses assessing different therapeutic and preventive interventions. Data are posted on a platform (https://covid-nma.com/) and analyses are updated every week. However, guideline developers and other stakeholders also need to investigate the data and perform their own analyses. This requires resources, time, statistical expertise, and software knowledge. To assist them, we created the “metaCOVID” application which, based on automation processes, facilitates the fast exploration of the data and the conduct of analyses tailored to end-users needs. metaCOVID has been created in R and is freely available as an R-Shiny application. The application conducts living meta-analyses for every outcome. Several options are available for subgroup and sensitivity analyses. The results are presented in downloadable forest plots. metaCOVID is freely available from https://covid-nma.com/metacovid/ and the source code from https://github.com/TEvrenoglou/metaCovid.
Objective Evaluate antithrombotic (AT) use in individuals with atrial fibrillation (AF) and high stroke risk (CHA2DS2-VASc score>=2) and investigate whether pre-existing AT use may improve COVID-19 outcomes. Methods Individuals with AF and a CHA2DS2-VASc score>=2 on January 1st 2020 were identified using pseudonymised, linked electronic health records for 56 million people in England and followed-up until May 1st 2021. Factors associated with pre-existing AT use were analysed using logistic regression. Differences in COVID-19 related hospitalisation and death were analysed using logistic and Cox regression for individuals exposed to pre-existing AT use vs no AT use, anticoagulants (AC) vs antiplatelets (AP) and direct oral anticoagulants (DOACs) vs warfarin. Results From 972,971 individuals with AF and a CHA2DS2-VASc score>=2, 88.0% (n=856,336) had pre-existing AT use, 3.8% (n=37,418) had a COVID-19 related hospitalisation and 2.2% (n=21,116) died. Factors associated with no AT use included comorbidities that may contraindicate AT use (liver disease and history of falls) and demographics (socioeconomic status and ethnicity). Pre-existing AT use was associated with lower odds of death (OR=0.92 [0.87-0.96 at 95% CI]), but higher odds of hospitalisation OR=1.20 [1.15-1.26 at 95% CI]). The same pattern was observed for AC vs AP (death (OR=0.93 [0.87-0.98]), hospitalisation (OR=1.17 [1.11-1.24])) but not for DOACs vs warfarin (death (OR=1.00 [0.95-1.05]), hospitalisation (OR=0.86 [0.82-0.89]). Conclusions Pre-existing AT use may offer marginal protection against COVID-19 death, with AC offering more protection than AP. Although this association may not be causal, it provides further incentive to improve AT coverage for eligible individuals with AF.
Non-specific protective effects of certain vaccines have been reported, and long-term boosting of innate immunity, termed trained immunity, has been proposed as one of the mechanisms mediating these effects. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19. In a large academic Dutch hospital, we found that SARS-CoV-2 infection was less common among employees who had received a previous influenza vaccination: relative risk reductions of 37% and 49% were observed following influenza vaccination during the first and second COVID-19 waves, respectively. The quadrivalent inactivated influenza vaccine induced a trained immunity program that boosted innate immune responses against various viral stimuli and fine-tuned the anti-SARS-CoV-2 response, which may result in better protection against COVID-19. Influenza vaccination led to transcriptional reprogramming of monocytes and reduced systemic inflammation. These epidemiological and immunological data argue for potential benefits of influenza vaccination against COVID-19, and future randomized trials are warranted to test this possibility.
Background: COVID-19 exposure in Central Asia appears underestimated and SARS-CoV-2 seroprevalence data are urgently needed to inform ongoing vaccination efforts and other strategies to mitigate the regional pandemic. Here, we assessed the prevalence of anti-SARS-CoV-2 antibody-mediated immunity in a heterogeneous cohort of public university employees in Karaganda, Kazakhstan. Methods: Asymptomatic subjects (n=100) were randomly recruited prior to their first COVID-19 vaccination. Questionnaires were administered to capture a range of demographic and clinical characteristics. Nasopharyngeal swabs were collected for SARS-CoV-2 RT-qPCR testing. Serological assays were performed to detect spike (S)-reactive IgG and IgA. Results: Anti-S IgG and IgA seropositivity rates among SARS-CoV-2 PCR-negative participants (n=100) were 42% and 53%, respectively, and 61% of subjects tested positive for at least one of the antibodies. Serologically confirmed history of COVID-19 was associated with self-reported history of respiratory illness since March 2020 (p<0.001). Conclusions: SARS-CoV-2 exposure in this cohort is ~15-fold higher compared to the reported all-time national and regional COVID-19 prevalence. Continuous serological surveillance is critical for understanding the COVID-19 transmission dynamics and should be nationally implemented to better inform the public health response in Central Asia.
High-dose Intravenous Vitamin C (HDIVC) as Adjuvant Therapy in Critical Patients With Positive COVID-19. A Pilot Randomized Controlled Dose-comparison Trial. - Condition: Covid19
Interventions: Drug: High doses of intravenous vitamin C; Drug: Dextrose 500 mL
Sponsor: Hugo Galindo
Not yet recruiting
Developing and Testing a COVID-19 Vaccination Acceptance Intervention - Condition: COVID-19 Vaccination
Intervention: Behavioral: Moving to COVID-19 Vaccine Acceptance Intervention
Sponsors: VA Office of Research and Development; VA Bedford Healthcare System
Not yet recruiting
Study on Safety and Clinical Efficacy of AZVUDINE in Initial Stage COVID-19 Patients (SARS-CoV-2 Infected) - Condition: COVID-19
Interventions: Drug: AZVUDINE; Drug: AZVUDINE placebo
Sponsors: HRH Holdngs Limited; GALZU INSTITUTE OF RESEARCH, TEACHING, APPLIED SCIENCE AND TECHNOLOGY, Brazil; SANTA CASA DE MISERICORDIA DE CAMPOS HOSPITAL (SCMCH), Brazil; UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil
Not yet recruiting
COVID-19 Morbidity in Healthcare Workers and Vitamin D Supplementation - Condition: COVID-19 Respiratory Infection
Intervention: Drug: Vitamin D
Sponsor: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
Completed
Text Message Nudges for COVID-19 Vaccination - Condition: Covid19
Intervention: Behavioral: Text message
Sponsor:
Ascension South East Michigan
Not yet recruiting
A Pilot Study of a PhysiOthErapy-based Tailored Intervention for Long Covid - Condition: COVID-19
Intervention: Behavioral: Physiotherapy
Sponsors:
University of Calgary; Alberta Health Services
Not yet recruiting
Quercetin in the Prevention of Covid-19 Infection - Condition: Covid19
Interventions: Dietary Supplement: Quercetin; Combination Product: Placebo
Sponsor: Azienda di Servizi alla Persona di Pavia
Completed
A Study to Evaluate Change in Viral Load After OPN-019 in Adults With COVID-19 - Condition: Covid19
Intervention: Drug: OPN-019
Sponsor: Optinose US Inc.
Recruiting
Physical Activity and Smell Trainings to Help Individuals With Coronavirus Disease (COVID-19) Recover From Persistent Smell and Taste Impairments - A Pilot Study - Condition: Covid19
Interventions: Behavioral: Physical activity; Other: Smell training
Sponsor: Université de Montréal
Not yet recruiting
Phase 3 Study to Evaluate the Lot Consistency of a Recombinant Coronavirus-Like Particle COVID-19 Vaccine - Condition: COVID-19
Intervention: Biological: CoVLP formulation
Sponsor:
Medicago
Not yet recruiting
Evaluation of the Efficacy, Safety and Immunogenicity of Inactivated COVID 19 Vaccine(TURKOVAC) in Healthy Population of 18 and 64 Years of Age (Both Inclusive):a Randomized, Double-blind, Phase IIb Clinical Trial - Condition: Covid19
Intervention: Biological: Triple dose vaccination by inactivated Covid19 vaccine
Sponsors: Health Institutes of Turkey; TC Erciyes University; Kocak Farma; Mene Research
Not yet recruiting
Cardiopulmonary Rehabilitation in Long COVID-19 Patients With Persistent Breathlessness and Fatigue - Condition: COVID-19 Respiratory Infection
Intervention:
Other: Cardiopulmonary exercise training
Sponsor: Louis Bherer
Recruiting
Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above - Conditions: COVID-19 Pneumonia; Coronavirus Infections
Interventions: Biological: Recombinant COVID-19 Vaccine (CHO cell); Biological: COVID-19 vaccine (Vero cells)
Sponsors:
National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd
Not yet recruiting
Abbott ID NOW COVID-19 - Conditions: Covid19; SARS-CoV-2 Infection
Interventions:
Diagnostic Test: Buccal Swab- Copan flocked swab; Diagnostic Test: Standard of Care COVID-19 swab
Sponsors: University of Calgary; Health Canada
Not yet recruiting
Study to Evaluate the Efficacy and Safety of Colchicine Tablets in Patients With COVID-19 - Conditions: Covid19; Colchicine
Interventions: Drug: Colchicine Tablets; Drug: Standard therapy
Sponsors: Shanghai Public Health Clinical Center; Kunming Pharmaceuticals, Inc.
Not yet recruiting
Supporting newly graduated medical doctors in managing COVID-19: An evaluation of a Massive Open Online Course in a limited-resource setting - INTRODUCTION: Newly graduated medical doctors in their internships are positioned to strengthen the front line in combating COVID-19. We developed a Massive Open Online Course (MOOC) to equip them with adequate knowledge for COVID-19 management. This paper aims to analyze the MOOC and evaluate participant satisfaction and increase in knowledge after completing the course.
Tie2 activation protects against prothrombotic endothelial dysfunction in COVID-19 - Endothelial dysfunction accompanies the microvascular thrombosis commonly observed in severe COVID-19. Constitutively, the endothelial surface is anticoagulant, a property maintained at least in part via signaling through the Tie2 receptor. During inflammation, the Tie2 antagonist angiopoietin-2 (Angpt-2) is released from endothelial cells and inhibits Tie2, promoting a prothrombotic phenotypic shift. We sought to assess whether severe COVID-19 is associated with procoagulant endothelial…
Pan-3C Protease Inhibitor Rupintrivir Binds SARS-CoV-2 Main Protease in a Unique Binding Mode - Rupintrivir targets the 3C cysteine proteases of the picornaviridae family, which includes rhinoviruses and enteroviruses that cause a range of human diseases. Despite being a pan-3C protease inhibitor, rupintrivir activity is extremely weak against the homologous 3C-like protease of SARS-CoV-2. In this study, the crystal structures of rupintrivir were determined bound to enterovirus 68 (EV68) 3C protease and the 3C-like main protease (M^(pro)) from SARS-CoV-2. While the EV68 3C…
Remdesivir and EIDD-1931 Interact with Human Equilibrative Nucleoside Transporters 1 and 2: Implications for Reaching SARS-CoV-2 Viral Sanctuary Sites - Equilibrative nucleoside transporters (ENTs) are present at the blood-testis barrier (BTB), where they can facilitate antiviral drug disposition to eliminate a sanctuary site for viruses detectable in semen. The purpose of this study was to investigate ENT-drug interactions with three nucleoside analogs remdesivir, molnupiravir and its active metabolite, EIDD-1931 and four non-nucleoside molecules repurposed as antivirals for COVID-19. The study used 3D pharmacophores for ENT1 and ENT2…
Identifying FDA-approved drugs with multimodal properties against COVID-19 using a data-driven approach and a lung organoid model of SARS-CoV-2 entry - CONCLUSIONS: Small clinical studies reported that general statin use, and specifically, atorvastatin use, are associated with protective effects against COVID-19. Our study corroborrates these findings and supports the investigation of atorvastatin in larger clinical studies. Ultimately, our framework demonstrates one promising way to fast-track the identification of compounds for COVID-19, which could similarly be applied when tackling future pandemics.
Development of Effective Therapeutic Molecule from Natural Sources against Coronavirus Protease - The SARS-CoV-2 main protease (M^(pro)) is one of the molecular targets for drug design. Effective vaccines have been identified as a long-term solution but the rate at which they are being administered is slow in several countries, and mutations of SARS-CoV-2 could render them less effective. Moreover, remdesivir seems to work only with some types of COVID-19 patients. Hence, the continuous investigation of new treatments for this disease is pivotal. This study investigated the inhibitory role…
Phosphorylation of SARS-CoV-2 Orf9b Regulates Its Targeting to Two Binding Sites in TOM70 and Recruitment of Hsp90 - SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the causative agent of the COVID19 pandemic. The SARS- CoV-2 genome encodes for a small accessory protein termed Orf9b, which targets the mitochondrial outer membrane protein TOM70 in infected cells. TOM70 is involved in a signaling cascade that ultimately leads to the induction of type I interferons (IFN-I). This cascade depends on the recruitment of Hsp90-bound proteins to the N-terminal domain of TOM70. Binding of Orf9b to TOM70…
Structural Insight into the Binding of Cyanovirin-N with the Spike Glycoprotein, M(pro) and PL(pro) of SARS-CoV-2: Protein-Protein Interactions, Dynamics Simulations and Free Energy Calculations - The emergence of COVID-19 continues to pose severe threats to global public health. The pandemic has infected over 171 million people and claimed more than 3.5 million lives to date. We investigated the binding potential of antiviral cyanobacterial proteins including cyanovirin-N, scytovirin and phycocyanin with fundamental proteins involved in attachment and replication of SARS-CoV-2. Cyanovirin-N displayed the highest binding energy scores (-16.8 ± 0.02 kcal/mol, -12.3 ± 0.03 kcal/mol and…
In silico evaluation of COVID-19 main protease interactions with honeybee natural products for discovery of high potential antiviral compounds - This research investigates antiviral potential of extracted honeybee products against COVID-19 main protease (Mpro) by computational methods. The crystal structure of COVID-19 Mpro was obtained from the protein data bank. Six synthetic drugs with antiviral properties were used as control samples in order to compare the results with those of natural ligands. The six honeybee components, namely 3,4,5-Tricaffeoylquinic acid, Kaempferol-3-O-glucoside, (E)-2’-Geranyl-3’,4’,7-Trihydroxyflavanone,…
Inhibitors of L-Type Calcium Channels Show Therapeutic Potential for Treating SARS-CoV-2 Infections by Preventing Virus Entry and Spread - COVID-19 is caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2). The virus is responsible for an ongoing pandemic and concomitant public health crisis around the world. While vaccine development is proving to be highly successful, parallel drug development approaches are also critical in the response to SARS-CoV-2 and other emerging viruses. Coronaviruses require Ca^(2+) ions for host cell entry, and we have previously shown that Ca^(2+)…
A novel competition ELISA for the rapid quantification of SARS-CoV-2 neutralizing antibodies in convalescent plasma - CONCLUSION: The competition ELISA screens for neutralizing antibodies in CCP by competition for just a single epitope. It exerts a sensitivity of 61% with no false identifications. These ELISA designs can be used for epitope mapping or for selection of CCP.
Computational simulations on the binding and reactivity of a nitrile inhibitor of the SARS-CoV-2 main protease - We present a detailed computational analysis of the binding mode and reactivity of the novel oral inhibitor PF-07321332 developed against the SARS-CoV-2 3CL protease. Alchemical free energy calculations suggest that positions P3 and P4 could be susceptible to improvement in order to get a larger binding strength. QM/MM simulations unveil the reaction mechanism for covalent inhibition, showing that the nitrile warhead facilitates the recruitment of a water molecule for the proton transfer step.
Transcriptomic Signatures of Airway Epithelium Infected With SARS-CoV-2: A Balance Between Anti-infection and Virus Load - COVID-19 pneumonia requires effective medical therapies. However, it is a challenge to find therapeutic drugs that not only inhibit viral replication, but also inhibit the accompanying cytokine storm and maintain an appropriate immune response. In this study, the effects of SARS-CoV-2 on gene expression in lung epithelial cells from patients with COVID-19 were systematically evaluated with bioinformatics analysis methods. Transcriptome expression specific to bystander (exposed but uninfected)…
The Antiviral Roles of Hydrogen Sulfide by Blocking the Interaction between SARS-CoV-2 and Its Potential Cell Surface Receptors - The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is posing a great threat to the global economy and public health security. Together with the acknowledged angiotensin-converting enzyme 2, glucose-regulated protein 78, transferrin receptor, AXL, kidney injury molecule-1, and neuropilin 1 are also identified as potential receptors to mediate SARS-CoV-2 infection. Therefore, how to inhibit or delay the binding of…
Long-Term Persistence and Relevant Therapeutic Impact of High-Titer Viral-Neutralizing Antibody in a Convalescent COVID-19 Plasma Super-Donor: A Case Report - A convalescent, non-severe, patient with COVID-19 was enrolled as a hyper-immune plasma voluntary donor by the Immuno- Hematology and Transfusion Unit of the Regina Elena National Cancer Institute in Rome, under the TSUNAMI national study criteria. During a nearly 6-month period (May-October 2020), the patient was closely monitored and underwent four hyperimmune plasma collections. Serum SARS-CoV-2 (anti-S + anti-N) IgG and IgM, anti-S1 IgA, and neutralizing titers (NTs) were measured….
MACHINE LEARNING TECHNIQUE TO ANALYSE THE CONDITION OF COVID-19 PATIENTS BASED ON THEIR SATURATION LEVELS - - link
A HERB BASED COMPOSITION ANTI VIRAL MEDICINE FOR TREATMENT OF SARS COV 2 AND A METHOD FOR TREATING A PERSON INFECTED BY THE SARS COV 2 VIRUS - A Herbal composition, viz., PONNU MARUNTHU essentially comprising of ALLUIUM CEPA extract. [concentrated to 30%] 75%, SAPINDUS MUKOROSSI - extract [Optimised] 10%, CITRUS X LIMON - extract in its natural form 05 TRACYSPERMUM AMMI (L) – extract 07%,ROSA HYBRIDA - extract 03%, PONNU MARUNTHU solution 50 ml, or as a capsulated PONNU MARUNTHU can be given to SARS cov2 positive Patients, three times a day that is ½ an hour before food; continued for 3 days to 5 days and further taking it for 2 days if need be there; It will completely cure a person. When the SARS cov2 test shows negative this medicine can be discontinued. This indigenous medicine and method for treating a person inflicted with SARS COV 2 viral infection is quite effective in achieving of much needed remedy for the patients and saving precious lives from the pangs of death and ensuring better health of people. - link
Anti-Sars-Cov-2 Neutralizing Antibodies - - link
Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies - - link
DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH - - link
SARS-COV-2 BINDING PROTEINS - - link
COVID-19胸部CT图像识别方法、装置及电子设备 - 本申请涉及一种COVID‑19胸部CT图像识别方法、装置及电子设备。所述方法获取COVID‑19的胸部CT图像，并针对胸部CT图像的特点，构建新冠肺炎CT识别网络，对该网络进行训练得到COVID‑19胸部CT图像识别模型，并利用该模型对待测CT图像进行分类。采用空洞卷积、深度卷积以及点卷积算子，减少冗余参数；采用并行结构连接方式，实现多尺度特征融合、降低模型复杂度；采用下采样方式，使用最大模糊池化以减少锯齿效应，保持信号的平移不变性；采用通道混洗操作，减少参数量与计算量，提高分类准确率，引入坐标注意力机制，使空间坐标信息与通道信息被关注，抑制不重要的信息，以解决资源匹配问题。 - link
A PROCESS FOR PREPARING MONTELUKAST SODIUM FOR TREATING COVID 19 PATIENTS - - link
IDENTIFICATION OF ANTI-COVID 19 AGENT SOMNIFERINE AS INHIBITOR OF MPRO & ACE2-RBD INTERACTION - - link
一种脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂 - 本发明属于基因治疗技术领域，具体涉及一系列脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂。本发明提供的具有式（I）结构的化合物，可与其它脂质化合物共同制备脂质载体，展现出pH响应性，对核酸药物的包封效率高，大大提升了核酸药物在体内的递送效率；而且，可根据核酸药物需要富集的器官而选用特定结构的脂质化合物作为脂质载体，具有良好的市场应用前景。 - link