Importance: Alpha-1-adrenergic receptor antagonists (α1-blockers) can abrogate pro-inflammatory cytokines and may improve outcomes among patients with respiratory infections. Repurposing readily available drugs such as α1-blockers could augment the medical response to the COVID-19 pandemic. Objective: To evaluate the association between α1-blocker exposure and COVID-19 mortality Design: Real-world evidence study Setting: Patient level data with 32,355 records tested for SARS-CoV-2 at the Mount Sinai Health System including 8,442 laboratory-confirmed cases extracted from five member hospitals in the New York City metropolitan area. Participants: 2,627 men aged 45 or older admitted with COVID-19 between February 24 and May 31, 2020 Exposures: α1-blocker use as an outpatient or while admitted for COVID-19 Main Outcomes and Measures: In-hospital mortality Results: Men exposed to α1-blockers (N=436) were older (median age 73 vs. 64 years, P<0.001) and more likely to have comorbidities than unexposed men (N=2,191). Overall, 758 (28.9%) patients died in hospital, 1,589 (60.5%) were discharged, and 280 (10.7%) were still hospitalized as of May 31, 2020. Outpatient exposure to α1-blockers was not associated with COVID-19 hospital outcomes, though there was a trend towards significance (OR 0.749, 95% CI 0.527-1.064; P=0.106). Conversely, inpatient use of α1-blockers was independently associated with improved in-hospital mortality in both multivariable logistic (OR 0.633, 95% CI 0.434-0.921; P=0.017) and Cox regression analyses (HR 0.721, 95% CI 0.572-0.908; P=0.006) adjusting for patient demographics, comorbidities, and baseline vitals and labs. Age-stratified analyses suggested greater benefit from inpatient α1-blocker use among younger age groups: Age 45-65 OR 0.384, 95% CI 0.164-0.896 (P=0.027); Age 55-75 OR 0.511, 95% CI 0.297-0.880 (P=0.015); Age 65-89 OR 0.810, 95% CI 0.509-1.289 (P=0.374). Conclusions and Relevance: Inpatient α1-blocker use was independently associated with improved COVID-19 mortality among hospitalized men. Clinical trials to assess the therapeutic value of α1-blockers in COVID-19 are warranted.
Background The United States (US) Expanded Access Program (EAP) to COVID-19 convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19). While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents particularly for vulnerable racial and ethnic minority populations who were disproportionately affected by the pandemic. The objective of this study is to report on the demographic, geographic, and chronological access to COVID 19 convalescent plasma in the US via the EAP. Methods and findings Mayo Clinic served as the central IRB for all participating facilities and any US physician could participate as local physician-principal investigator. Registration occurred through the EAP central website. Blood banks rapidly developed logistics to provide convalescent plasma to hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal trends in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate on a state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions as well as assessing enrollment in metropolitan and less populated areas which did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. A majority of patients were older than 60 years of age (57.8%), male (58.4%), and overweight or obese (83.8%). There was substantial inclusion of minorities and underserved populations, including 46.4% of patients with a race other than White, and 37.2% of patients were of Hispanic ethnicity. Severe or life-threatening COVID-19 was present in 61.8% of patients and 18.9% of patients were mechanically ventilated at time of convalescent plasma infusion. Chronologically and geographically, increases in enrollment in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled patients in the EAP, including both in metropolitan and less populated areas. Conclusions The EAP successfully provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The efficient study design of the EAP may serve as an example framework for future efforts when broad access to a treatment is needed in response to a dynamic disease affecting demographic groups and areas historically underrepresented in clinical studies.
Objectives SARS-CoV-2 infection induces the formation of different antibodies. However, not all of which might prevent the virus from entering the cell, although their concentrations correlate with the titers of viral neutralization tests (NTs). Antibodies against the viral nucleocapsid (NC), e.g., can be classified as such. We aimed to prove the hypothesis that the apparent correlation between NC-antibody levels and NT-titers is mediated by simultaneously occurring antibodies against viral spike-protein components. Methods We included 64 individuals with previous SARS-CoV-2 infection (>14d after symptom onset). SARS-CoV-2 antibodies against the NC (Roche total antibody ECLIA, Abbott IgG CMIA) and spike-protein (Technozym RBD ELISA, DiaSorin S1/S2 CLIA) were measured, and neutralization tests were performed. The effect of spike-protein antibodies on the correlation between NC-antibodies and NT-titers was evaluated by partial correlation and mediation analyses. Results Both tested assays assessing antibodies against the NC correlated significantly with NT titers: Abbott ρ=0.742, P<0.0001; Roche ρ=0.365, P<0.01. However, when controlling the rank correlations for the presence of RBD or S1/S2 antibodies, correlation coefficients dropped to ρ=0.318/ρ=0.329 (P<0.05/P<0.01) , respectively for Abbott and vanished for Roche. As a result, only a maximum of 11% of NT titer variability could be explained by NC-antibody levels. Conclusions Our data suggest that the apparent correlation between NC antibodies and NT titers is strongly mediated by co-occurring RBD antibody concentrations. To avoid falsely implied causal relationships, all correlation analyses of non-spike-associated antibody assays and neutralization assays should include a partial correlation analysis to exclude a possible mediator effect of spike-associated antibodies.
Background: Severe COVID-19 disease could induce acute respiratory distress which is characterized by tachypnea, hypoxia, and dyspnea. Intubation and mechanical ventilation are a strategic treatment of COVID-19 distress or hypoxia. Methods: We searched PubMed, Embase, and Scopus databases through April 1, 2021, to identify relevant randomized control trials, observational studies, and case series. Results: 24 studies were included in this review. Studies were conducted in the USA, China, Spain, South Korea, Italy, Iran, and Brazil. Most patients were intubated in the intensive care unit. Rapid sequence induction was mostly used for intubation. ROX index might be utilized for the predictor of the necessity of intubation in COVID-19 patients. According to the previous studies the rate of intubation reported 5 to 88%. It was revealed that 1.4 - 44.5% of patients might be extubated. Yet obesity and age (elderly) are the only risk factors of delayed or difficult extubation. Discussion and conclusion: Acute respiratory distress in COVID-19 patients could require endotracheal intubation and mechanical ventilation. Severe respiratory distress, loss of consciousness, and hypoxia were the most important reasons for intubation. Also, increased levels of ferritin, d-dimer, and lipase in common with hypoxia are correlated with intubation and ICU admission Mortality following intubation is reported to be 15 to 36%. Awake-prone positioning in comparison to high-flow nasal oxygen therapy did not reduce the risk of intubation and mechanical ventilation. There was no association between intubation timing and mortality of infected patients. noninvasive ventilation may have survival benefits. Keywords: Intubation, COVID-19, critical care, respiratory disease, infectious disease, hypoxia, airway management.
Importance: Persistent symptoms are reported in patients who survive the initial stage of COVID-19, often referred to as ″long COVID″ or ″post-acute sequelae of SARS-CoV-2 infection″ (PASC); however, evidence on incidence is still lacking, and symptoms relevant to pain are yet to be assessed. Objective: To determine long-term symptoms in COVID-19 survivors after infection. Data Sources: A literature search was performed using the electronic databases PubMed, EMBASE, Scopus, and CHINAL and preprint servers MedRχiv and BioRχiv through January 15, 2021. Study Selection: Eligible studies were those reporting patients with a confirmed diagnosis of SARS-CoV-2 and who showed any symptoms persisting beyond the acute phase. Data Extraction and Synthesis: Incidence rate of symptoms were pooled using inverse variance methods with a DerSimonian-Laird random-effects model. Main Outcomes and Measures: The primary outcome was pain-related symptoms such as headache or myalgia. Secondary outcomes were symptoms relevant to pain (depression or muscle weakness) and symptoms frequently reported (anosmia and dyspnea). Heterogeneity among studies and publication bias for each symptom were estimated. The source of heterogeneity was explored using meta-regression, with follow-up period, age and sex as covariates. Results: In total, 35 studies including 18,711 patients were eligible. Eight pain-related symptoms and 26 other symptoms were identified. The highest pooled incidence among pain-related symptoms was chest pain (17%, 95% CI, 12%-25%), followed by headache (16%, 95% CI, 9%-27%), arthralgia (13%, 95% CI, 7%-24%), neuralgia (12%, 95% CI, 3%-38%) and abdominal pain (11%, 95% CI, 7%-16%). The highest pooled incidence among other symptoms was fatigue (45%, 95% CI, 32%-59%), followed by insomnia (26%, 95% CI, 9%-57%), dyspnea (25%, 95% CI, 15%-38%), weakness (25%, 95% CI, 8%-56%) and anosmia (19%, 95% CI, 13%-27%). Substantial heterogeneity was identified (I2, 50-100%). Meta-regression analyses partially accounted for the source of heterogeneity, and yet, 53% of the symptoms remained unexplained. Conclusions and Relevance: The current meta-analysis may provide a complete picture of incidence in PASC. It remains unclear, however, whether post-COVID symptoms progress or regress over time or to what extent PASC are associated with age or sex.
Background: In the context of the COVID-19 pandemic, public health teams have struggled to conduct monitoring for confirmed or suspicious COVID-19 patients. However, monitoring these patients is critical to improving the chances of survival, and therefore, a prioritization strategy for these patients is warranted. This study developed a monitoring algorithm for COVID-19 patients for the Colombian Ministry of Health and Social Protection (MOH). Methods: This work included 1) a literature review, 2) consultations with MOH and National Institute of Health officials, and 3) data analysis of all positive COVID-19 cases and their outcomes. We used clinical and socioeconomic variables to develop a set of risk categories to identify severe cases of COVID-19. Results: This tool provided four different risk categories for COVID-19 patients. As soon as the time of diagnosis, this tool can identify 91% of all severe and fatal COVID-19 cases within the first two risk categories. Conclusion: This tool is a low-cost strategy to prioritize patients at higher risk of experiencing severe COVID-19. This tool was developed so public health teams can focus their scarce monitoring resources on individuals at higher mortality risk. This tool can be easily adapted to the context of other lower and middle-income countries. Policymakers would benefit from this low-cost strategy to reduce COVID-19 mortality, particularly during outbreaks.
Background: Nasopharyngeal sampling for nucleic acid amplification testing (NAAT) is the current standard diagnostic test for of coronavirus disease 2019 (COVID-19). However, the NAAT technique is lengthy and nasopharyngeal sampling requires trained personnel. Saliva NAAT represents an interesting alternative but diagnostic performances vary widely between studies. Objective: To assess the diagnostic accuracy of a nasopharyngeal point-of-care antigen (Ag) test and of saliva NAAT for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), as compared to nasopharyngeal NAAT. Design: Prospective participant enrollment from 19 October through 18 December 2020. Setting: Two community COVID-19 screening centers in Paris, France. Participants: 1452 ambulatory children and adults referred for SARS-CoV-2 testing. Interventions: NAAT on a saliva sample (performed with three different protocols for pre-processing, amplification and detection of SARS-CoV-2) and Ag testing on a nasopharyngeal sample. Measurements: Performance of saliva NAAT and nasopharyngeal Ag testing. Results: Overall, 129/1443 (9%) participants tested positive on nasopharyngeal NAAT (102/564 [18%] in symptomatic and 27/879 [3%] in asymptomatic participants). Sensitivity was of 94% (95% CI, 86% to 98%), 23% (CI, 14% to 35%), 94% (CI, 88% to 97%) and 96% (CI, 91% to 99%) for the nasopharyngeal Ag test and the three different protocols of saliva NAAT, respectively. Estimates of specificity were above 95% for all methods. Diagnostic accuracy was similar in symptomatic and asymptomatic individuals. Limitations: Few children (n=122, 8%) were included. Conclusion: In the ambulatory setting, diagnostic accuracy of nasopharyngeal Ag testing and of saliva NAAT seems similar to that of nasopharyngeal NAAT, subject to strict compliance with specific pre-processing and amplification protocols. Registration number: NCT04578509 Funding Sources: French Ministry of Health and the Assistance Publique-Hopitaux de Paris Foundation.
SARS-CoV-2 Variants of Concerns (VOC), e.g., B.1.351 (20H/501Y.V2) and P1 (20J/501Y.V3), harboring N-terminal domain (NTD) or the receptor-binding domain (RBD) (e.g., E484K) mutations, exhibit reduced in vitro susceptibility to convalescent serum, commercial antibody cocktails, and vaccine neutralization, and have been associated with reinfection. The accumulation of these mutations could be the consequence of intra-host viral evolution due to prolonged infection in immunocompromised hosts. In this study, we document the microevolution of SARS-CoV-2 recovered from sequential tracheal aspirates from an immunosuppressed patient on tacrolimus, steroids and convalescent plasma therapy, and identify the emergence of multiple NTD and RBD mutations associated with reduced antibody neutralization as early as three weeks after infection. SARS-CoV-2 genomes from the first swab (Day 0) and three tracheal aspirates (Day 7, 21 and 27) were compared at the sequence level. We identified five different S protein mutations at the NTD or RBD regions from the second tracheal aspirate sample (21 Day). The S:Q493R substitution and S:243-244LA deletion had ~70% frequency, while ORF1a:A138T, S:141-144LGVY deletion, S:E484K and S:Q493K substitutions demonstrated ~30%, ~30%, ~20% and ~10% mutation frequency, respectively. However, the third tracheal aspirate sample collected one week later (Day 27) was predominated by the haplotype of ORF1a:A138T, S:141-144LGVY deletion and S:E484K (> 95% mutation frequency). Notably, S protein deletions (141-144LGVY and 243-244LA deletions in NTD region) and substitutions (Q493K/R and E484K in the RBD region) previously showed reduced susceptibly to monoclonal antibody or convalescent plasma. The observation supports the hypothesis that VOCs can independently arise and that immunocompromised patients on convalescent plasma therapy are potential breeding grounds for immune-escape mutants.
Infection born by Coronavirus SARS-CoV-2 has swept the world within a time of a few months. It has created a devastating effect on humanity with social and economic depression. Europe and America were the hardest hit continents. India has also lost lives, making the country fourth most deadly worldwide. However, the infection and death rate per million and the case fatality ratio in India were substantially lower than in many developed nations. Several factors have been proposed including genetics. One of the important facts is that a large chunk of Indian population is asymptomatic to the SARS-CoV-2 infection. Thus, the real infection in India is much higher than the reported number of cases. Therefore, the majority of people are already immune in the country. To understand the dynamics of real infection as well as the level of immunity against SARS-CoV-2, we have performed antibody testing (serosurveillance) in the urban region of fourteen Indian districts encompassing six states. In our survey, the seroprevalence frequency varied between 0.01-0.48, suggesting high variability of viral transmission between states. We also found out that the cases reported by the government were several fold lower than the real incidence of infection. This discrepancy is mainly driven by the higher number of asymptomatic cases. Overall, we suggest that with the high level of immunity developed against SARS-CoV-2 in the majority of the districts, the case fatality rate of second wave in India will be minor than first wave.
There is a worldwide need for reagents to perform SARS-CoV-2 detection. Some laboratories have implemented kit-free protocols, but many others do not have the capacity to develop these and/or perform manual processing. We provide multiple workflows for SARS-CoV-2 nucleic acid detection in clinical samples by comparing several commercially available RNA extraction methods: QIAamp Viral RNA Mini Kit (QIAgen), RNAdvance Blood/Viral (Beckman) and Mag-Bind Viral DNA/RNA 96 Kit (Omega Bio-tek). We also compared One-step RT-qPCR reagents: TaqMan Fast Virus 1-Step Master Mix (FastVirus, ThermoFisher Scientific), qPCRBIO Probe 1-Step Go Lo-ROX (PCR Biosystems) and Luna® Universal Probe One-Step RT-qPCR Kit (Luna, NEB). We used primer-probes that detect viral N (EUA CDC) and RdRP (PHE guidelines). All RNA extraction methods provided similar results. FastVirus and Luna proved most sensitive. N detection was more reliable than that of RdRP, particularly in samples with low viral titres. Importantly, we demonstrate that treatment of nasopharyngeal swabs with 70 degrees for 10 or 30 min, or 90 degrees for 10 or 30 min (both original variant and B 1.1.7) inactivates SARS-CoV-2 employing plaque assays, and that it has minimal impact on the sensitivity of the qPCR in clinical samples. These findings make SARS-CoV-2 testing portable to settings that do not have CL-3 facilities. In summary, we provide several testing pipelines that can be easily implemented in other laboratories and have made all our protocols and SOPs freely available at https://osf.io/uebvj/.
Background: The COVID-19 pandemic followed a unique trajectory in Eastern Europe compared to other heavily affected regions, with most countries there only experiencing a major surge of cases and deaths towards the end of 2020 after a relatively uneventful first half of the year. However, the consequences of that surge have not received as much attention as the situation in Western countries. Bulgaria, even though it has been one of the most heavily affected countries, has been one of those neglected cases. Methods: We use mortality and mobility data from Eurostat, official governmental and other sources to examine the development and impact of the COVID-19 pandemic in Bulgaria and other European countries. Results: We find a very high level of excess mortality in Eastern European countries measured by several metrics including excess mortality rate (EMR), P-scores and potential years of life lost. By the last metric Eastern Europe emerges as the hardest hit region by the pandemic in Europe in 2020. With a record EMR at ~0.25% and a strikingly large and mostly unique to it mortality rate in the working age demographics, Bulgaria emerges as one of the most affected countries in Eastern Europe. The high excess mortality in Bulgaria correlates with insufficient intensity of testing and with delayed imposition of lockdown measures. We also find major geographic and demographic disparities within the country, with considerably lower mortality observed in major cities relative to more remote areas (likely due to disparities in the availability of medical resources). Analysis of the course of the epidemic revealed that individual mobility measures were predictive of the eventual decline in cases and deaths. However, while mobility declined as a result of the imposition of a lockdown, it already trended downwards before such measures were introduced, which resulted in a reduction of deaths independent of the effect of restrictions. Conclusions: Large excess mortality and high numbers of potential years of life lost are observed as a result of the COVID pandemic in Bulgaria, as well as in several other countries in Eastern Europe. Significant delays in the imposition of stringent mobility-reducing measures combined with a lack of medical resources likely caused a substantial loss of life, including in the working age population.
Rehabilitation for Patients With Persistent Symptoms Post COVID-19 - Condition: Covid19
Intervention: Other: Concentrated rehabilitation for patients with persistent symptoms post COVID-19
Sponsors: Western Norway University of Applied Sciences; Helse-Bergen HF
Recruiting
Study of DS-5670a (COVID-19 Vaccine) in Japanese Healthy Adults and Elderly Subjects - Condition: Covid19
Interventions: Biological: DS-5670a; Biological: Placebo
Sponsor: Daiichi Sankyo Co., Ltd.
Recruiting
Efficacy, Immunogenicity and Safety of Inactivated ERUCOV-VAC Compared With Placebo in COVID-19 - Condition: COVID-19
Interventions: Biological: ERUCOV-VAC 3 µg/0.5 ml Vaccine; Biological: ERUCOV-VAC 6 µg/0.5 ml Vaccine; Other: Placebo
Sponsors: Health Institutes of Turkey; Erciyes University Scientific Research Projects Coordination
Recruiting
Efficacy and Safety of Three Different Doses of an Anti SARS-CoV-2 Hyperimmune Equine Serum in COVID-19 Patients - Condition: Covid19
Interventions: Biological: Anti SARS-CoV-2 equine hyperimmune serum; Biological: placebo
Sponsors: Caja Costarricense de Seguro Social; Universidad de Costa Rica; Ministry of Health Costa Rica
Not yet recruiting
Viral Clearance, PK and Tolerability of Ensovibep in COVID-19 Patients - Condition: Covid19
Intervention: Drug: ensovibep
Sponsor: Molecular Partners AG
Recruiting
A Nurse-Community Health Worker-Family Partnership Model: Addressing Uptake of COVID-19 Testing and Control Measures - Condition: COVID-19
Intervention: Behavioral: Nurse-Community-Family Partnership Intervention
Sponsor: New York University
Not yet recruiting
Safety and Immunogenicity of the Inactivated Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine Compared to Placebo - Condition: COVID-19 Vaccine
Interventions: Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 4 µg/0.5 ml Vaccine; Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 6 µg/0.5 ml Vaccine; Biological: Placebo
Sponsor: Kocak Farma
Recruiting
A Dose Finding, Efficacy and Safety Study of Ensovibep (MP0420) in Ambulatory Adult Patients With Symptomatic COVID-19 - Condition: COVID-19
Interventions: Drug: ensovibep; Drug: Placebo
Sponsors: Molecular Partners AG; Novartis Pharmaceuticals; Iqvia Pty Ltd; Datamap; SYNLAB Analytics & Services Switzerland AG; Q2 Solutions
Not yet recruiting
Vitamin D, Omega-3, and Combination Vitamins B, C and Zinc Supplementation for the Treatment and Prevention of COVID-19 - Condition: Covid19
Interventions: Dietary Supplement: Vitamin D; Dietary Supplement: Omega DHA / EPA; Dietary Supplement: Vitamin C, Vitamin B complex and Zinc Acetate
Sponsors: Hospital de la Soledad; Microclinic International
Recruiting
Study on Sequential Immunization of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine - Condition: COVID-19
Interventions: Biological: recombinant Ad5 vectored COVID-19 vaccine; Biological: RBD-based protein subunit vaccine (ZF2001) against COVID-19; Biological: trivalent split influenza vaccine
Sponsor: Jiangsu Province Centers for Disease Control and Prevention
Not yet recruiting
Respiratory Tele Monitoring COVID 19 (TMR COVID-19) - Condition: Covid19
Interventions: Device: Radius PPG Tetherless Pulse Oximetry (Masimo); Device: usual monitoring
Sponsor: Assistance Publique Hopitaux De Marseille
Recruiting
Omega-3 Oil Use in COVID-19 Patients in Qatar - Condition: COVID-19
Intervention: Drug: Omega 3 fatty acid
Sponsor: Hamad Medical Corporation
Recruiting
Cetirizine and Famotidine for COVID-19 - Condition: Covid19
Interventions: Drug: Cetirizine and Famotidine; Drug: Placebo
Sponsor: Emory University
Not yet recruiting
TCB008 in Patients With COVID-19 - Condition: Covid19
Intervention: Drug: TCB008
Sponsor: TC Biopharm
Not yet recruiting
Dual MRI for Cardiopulmonary COVID-19 Long Haulers - Condition: Covid19
Intervention: Drug: Hyperpolarized 129Xenon gas
Sponsor: Bastiaan Driehuys
Not yet recruiting
Antiviralis es gyulladasellenes kezelesi lehetosegek COVID-19-ben - Összefoglaló. Az új típusú koronavírus-fertőzés (COVID-19) nagy terhet ró az egészségügyi ellátórendszerre és a társadalomra. A betegségnek három nagy szakasza van, melyek alapvetően meghatározzák a kezelést. Az I-IIA fázisban az antivirális, míg a IIB-III. fázisban a gyulladásgátló kezelés áll előtérben, melyhez intenzív terápiás, szupportív kezelés csatlakozik. A jelen ajánlás kizárólag a gyógyszeres kezelésre vonatkozik, és a rendelkezésre álló bizonyítékok alapján foglalja össze a terápiás…
Coronavirus genomic nsp14-ExoN, structure, role, mechanism, and potential application as a drug target - The recent coronavirus disease 2019 (COVID-19), causing a global pandemic with devastating effects on healthcare and social-economic systems, has no special antiviral therapies available for human coronaviruses (CoVs). The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) possesses a non-structural protein (nsp14), with amino terminal domain coding for a proofreading exoribonuclease (ExoN) that is required for high-fidelity replication. The ability of CoVs during genome replication…
Silencing of SARS-CoV-2 with modified siRNA-peptide dendrimer formulation - CONCLUSIONS: Thus, we developed a therapeutic strategy for COVID-19 based on inhalation of a modified siRNA-peptide dendrimer formulation. The developed medication is intended for inhalation treatmentof COVID-19 patients.
GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein - Lack of detailed knowledge of SARS-CoV-2 infection has been hampering the development of treatments for coronavirus disease 2019 (COVID-19). Here, we report that RNA triggers the liquid-liquid phase separation (LLPS) of the SARS-CoV-2 nucleocapsid protein, N. By analyzing all 29 proteins of SARS-CoV-2, we find that only N is predicted as an LLPS protein. We further confirm the LLPS of N during SARS-CoV-2 infection. Among the 100,849 genome variants of SARS-CoV-2 in the GISAID database, we…
Identification of COVID-19 subtypes based on immunogenomic profiling - Although previous studies have shown that the host immune response is crucial in determining clinical outcomes in COVID-19 patients, the association between host immune signatures and COVID-19 patient outcomes remains unclear. Based on the enrichment levels of 11 immune signatures (eight immune-inciting and three immune-inhibiting signatures) in leukocytes of 100 COVID-19 patients, we identified three COVID-19 subtypes: Im-C1, Im-C2, and Im-C3, by clustering analysis. Im-C1 had the lowest…
TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation - The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro, and in vivo analyses, we report that topoisomerase 1 (TOP1) inhibition suppresses lethal inflammation…
Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination - CONCLUSIONS: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).
Involvement of the complement cascade in severe forms of COVID-19 - The complement system is an essential component of the innate immune system. Its excessive activation during COVID-19 contributes to cytokine storm, disease-specific endothelial inflammation (endotheliitis) and thrombosis that comes with the disease. Targeted therapies of complement inhibition in COVID-19, in particular blocking the C5a-C5aR1 axis have to be taken into account in the establishment of potential biomarkers and development of therapeutic strategies in the most severe forms of the…
Ultraviolet A Radiation and COVID-19 Deaths in the USA with replication studies in England and Italy - CONCLUSIONS: Our analysis suggests that higher ambient UVA exposure is associated with lower COVID-19 specific mortality. Further research on the mechanism may indicate novel treatments. Optimised UVA exposure may have population health benefits.
Interferon-lambda3 Exacerbates the Inflammatory Response to Microbial Ligands: Implications for SARS-CoV-2 Pathogenesis - INTRODUCTION: Interferon lambdas (IFN-λs) are antiviral cytokines that restrict pathogen infection and dissemination at barrier surfaces. Controlled expression of IFN-λs efficiently eliminates acute infections by activating a suite of interferon stimulated genes that inhibit viral propagation and activate local immune cells. Excessive or prolonged production of IFN-λs can however mediate tissue inflammation and disrupt epithelial barriers in both viral and non-viral disease. The mechanism by…
MUC1-C influences cell survival in lung adenocarcinoma Calu-3 cells after SARS-CoV-2 infection - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus disease 2019 (COVID-19) and may increase the risk of adverse outcomes in lung cancer patients. In this study, we investigated the expression and function of mucin 1 (MUC1) after SARS-CoV-2 infection in the lung epithelial cancer cell line Calu-3. MUC1 is a major constituent of the mucus layer in the respiratory tract and contributes to pathogen defense. SARS-CoV-2 infection induced MUC1 C-terminal subunit (MUC1-C)…
The green tea catechin epigallocatechin gallate inhibits SARS-CoV-2 infection - The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and more than a million deaths. The infection causes COVID-19, a disease of the respiratory system of divergent severity. No treatment exists. Epigallocatechin-3-gallate (EGCG), the major component of green tea, has several beneficial properties, including antiviral activities. Therefore, we examined whether EGCG has antiviral activity against SARS-CoV-2. EGCG blocked…
C-Phycocyanin-derived Phycocyanobilin as a Potential Nutraceutical Approach for Major Neurodegenerative Disorders and COVID-19-induced Damage to the Nervous System - The edible cyanobacterium Spirulina platensis and its chief biliprotein C-Phycocyanin have shown protective activity in animal models of diverse human health diseases, often reflecting antioxidant and anti-inflammatory effects. The beneficial effects of C-Phycocyanin seem likely to be primarily attributable to its covalently attached chromophore Phycocyanobilin (PCB). Within cells, biliverdin is generated from free heme and it is subsequently reduced to bilirubin. Although bilirubin can function…
ATP energy-independently controls protein homeostasis with unique structure and diverse mechanisms - Proteins function in the crowded cellular environments with high salt concentrations, thus facing tremendous challenges of misfolding/aggregation which represents a pathological hallmark of aging and an increasing spectrum of human diseases. Recently, intrinsically disordered regions (IDRs) were recognized to drive liquid-liquid phase separation (LLPS), a common principle for organizing cellular membraneless organelles (MLOs). ATP, the universal energy currency for all living cells, mysteriously…
ORF10-Cullin-2-ZYG11B complex is not required for SARS-CoV-2 infection - In order to understand the transmission and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is necessary to understand the functions of each of the gene products encoded in the viral genome. One feature of the SARS-CoV-2 genome that is not present in related, common coronaviruses is ORF10, a putative 38-amino acid protein-coding gene. Proteomic studies found that ORF10 binds to an E3 ubiquitin ligase containing Cullin-2, Rbx1, Elongin B, Elongin C, and ZYG11B…
5-(4-TERT-BUTOXY PHENYL)-3-(4N-OCTYLOXYPHENYL)-4,5-DIHYDROISOXAZOLE MOLECULE (C-I): A PROMISING DRUG FOR SARS-COV-2 (TARGET I) AND BLOOD CANCER (TARGET II) - The present invention relates to a method ofmolecular docking of crystalline compound (C-I) with SARS-COV 2 proteins and its repurposing with proteins of blood cancer, comprising the steps of ; employing an algorithmto carry molecular docking calculations of the crystalized compound (C-I); studying the compound computationally to understand the effect of binding groups with the atoms of the amino acids on at least four target proteins of SARS-COV 2; downloading the structure of the proteins; removing water molecules, co enzymes and inhibitors attached to the enzymes; drawing the structure using Chem Sketch software; converting the mol file into a PDB file; using crystalized compound (C-I) for comparative and drug repurposing with two other mutated proteins; docking compound into the groove of the proteins; saving format of docked molecules retrieved; and filtering and docking the best docked results. - link
USING CLINICAL ONTOLOGIES TO BUILD KNOWLEDGE BASED CLINICAL DECISION SUPPORT SYSTEM FOR NOVEL CORONAVIRUS (COVID-19) WITH THE ADOPTION OF TELECONFERENCING FOR THE PRIMARY HEALTH CENTRES/SATELLITE CLINICS OF ROYAL OMAN POLICE IN SULTANATE OF OMAN - - link
Peptides and their use in diagnosis of SARS-CoV-2 infection - - link
A PROCESS FOR SUCCESSFUL MANAGEMENT OF COVID 19 POSITIVE PATIENTS - - link
IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2 - IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2Insilico screening of antimycobacterial natural compounds with the potential to directly inhibit SARS COV2 relates to the composition for treating SARS-COV-2 comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. The composition also treats treating SARS, Ebola, Hepatitis-B and Hepatitis–C comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. - link
Anordnung zum Versprühen einer Substanz in die menschliche Mundhöhle und/oder in den Rachen oder zum Trinken, dadurch gekennzeichnet, dass die Anordnung eine Flasche mit einer Substanz aufweist, die wenigstens Aroniasaft und eine Alkoholkomponente aufweist und einen Sprühkopf besitzt.
INTERFASE ANTIBACTERIANA Y VIRICIDA PARA VENTILACION MECANICA NO INVASIVA - - link
一种用于检测新型冠状病毒COVID-19的引物组及试剂盒 - 本发明涉及生物技术领域，特别是涉及一种用于检测冠状病毒的引物组及试剂盒，所述引物组包括以下中的一对或多对：外侧引物对：所述外侧引物对包括如SEQ ID NO:1所示的上游引物F3和如SEQ ID NO:2所示的下游引物B3；内侧引物对：所述内侧引物对包括如SEQ ID NO:3所示的上游引物FIP和如SEQ ID NO:4所示的下游引物BIP；环引物对：所述环引物对包括如SEQ ID NO:5所示的上游引物LF和如SEQ ID NO:6所示的下游引物LB。试剂盒包括所述引物组。本发明在一个管中整合了RT‑LAMP和CRISPR，能依据两次颜色变化检测病毒和各种靶标核酸。 - link
新冠病毒中和性抗体检测试剂盒 - 本发明提供一种新冠病毒中和性抗体检测试剂盒。所述试剂盒基于BAS‑HTRF技术，主要包含：生物素标记的hACE2、新冠病毒棘突蛋白RBD‑Tag1、能量供体Streptavidin‑Eu cryptate、能量受体MAb Anti‑Tag1‑d2和新冠病毒中和性抗体。本发明将BAS和HTRF两种技术相结合，用于筛选新型冠状病毒中和性抗体，3小时内即可实现筛选，且操作简单，无需经过多次洗板过程。BAS和HTRF联用大大提升了反应灵敏度，且两种体系都能最大限度地减少非特异的干扰，适用于血清样品的检测。该方法可实现高通量检测，对解决大批量样品的新冠病毒中和性抗体的检测具有重要意义。 - link
Infektionsschutzmaske (1) zum Schutz vor Übertragung von Infektionskrankheiten mit einer Außen - und einer Innenseite (2,3) sowie Haltemitteln (5) zum Befestigen der Infektionsschutzmaske (1) am Kopf eines Maskenträgers, dadurch gekennzeichnet, dass an der Infektionsschutzmaske (1) mindestens eine Testoberfläche (6) zum Nachweis von Auslösern einer Infektionskrankheit derart angeordnet ist, dass diese bei korrekt angelegter Infektionsschutzmaske (1) mit der Ausatemluft des Maskenträgers unmittelbar in Kontakt gelangt.