Background The Coronavirus disease 2019 (Covid-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted accelerated vaccines development. Their use was prioritized to protect the most vulnerable, notably, the elderly. Because of fluctuations in vaccine availability, strategies such as delayed second dose and heterologous prime-boost have been employed. The effectiveness of these strategies in the frail elderly are unknown. Methods In this real-world vaccination study, under a government-decreed rationing strategy, elderly adults residing in long-term care facilities, with or without previously-documented SARS-CoV-2 infection, were administered homologous or heterologous mRNA vaccines, with an extended 16-week interval between doses. Clinical data and blood were serially collected during and after this interval period. Sera were tested for SARS-CoV-2-specific IgG antibodies (to trimeric S; RBD; nucleocapsid) by automated chemiluminescent ELISA. Findings After a significant increase 4 weeks post- prime dose, there was a significant decline in anti-RBD and anti-S IgG levels until the boost dose, followed by an increase 4 weeks later. Previously uninfected individuals exhibited lower antibody responses up to 16 weeks post-prime dose, but achieved comparable levels to previously infected counterparts by 4 weeks post-second dose. Individuals primed with BNT162b2 exhibited larger decrease in anti-RBD and anti-S IgG levels with 16-week interval between doses, compared to those who received mRNA-1273. No differences in antibody levels 4 weeks after the second dose were noted between the two vaccines, in either homologous or heterologous combinations. Interpretations These interim results of this ongoing longitudinal study show that, among frail elderly, neither age, sex, nor comorbidity affect antigenicity of mRNA-based COVID vaccines, but previous SARS-CoV-2 infection and type of mRNA vaccine influenced antibody responses when used with a 16-week interval between doses. Homologous/heterologous use of mRNA vaccines was not associated with significant differences in antibody responses 4 weeks following second dose, supporting their interchangeability.
BACKGROUND: We present a systematic review and pooled analysis of clinical studies to date, that (1) specifically compare the protection of natural immunity in the COVID-recovered versus the efficacy of full vaccination in the COVID-naive, and (2) the added benefit of vaccination in the COVID-recovered, for prevention of subsequent SARS- CoV-2 infection. METHODS: Using the PRISMA 2020 guidance, we first conducted a systematic review of available literature on PubMed, MedRxIV and FDA briefings to identify clinical studies either comparing COVID vaccination to natural immunity or delineating the benefit of vaccination in recovered individuals. After assessing for eligibility, studies were qualitatively appraised and formally graded using the NOS system for observational, case-control and RCTs. Incidence rates were tabulated for the following groups: never infected (NI) and unvaccinated (UV), NI and vaccinated (V), previously infected (PI) and UV, PI and UV. Pooling was performed by grouping the RCTs and observational studies separately, and then all studies in total. Risk ratios and risk differences are reported for individual studies and pooled groups, in 1) NPI/V vs. PI/UV and 2) PI/UV vs. PI/V analysis. In addition, number needed to treat (NNT) analysis was performed for vaccination in naive and previously infected cohorts. RESULTS: Nine clinical studies were identified including three randomized controlled studies, four retrospective observational cohorts, one prospective observational cohort, and a case-control study. The NOS quality appraisals of these articles ranged from four to nine (out of nine stars). All of the included studies found at least statistical equivalence between the protection of full vaccination and natural immunity; and, three studies found superiority of natural immunity. Four observational studies found a statistically significant incremental benefit to vaccination in the COVID-recovered individuals. In total pooled analysis, incidence in NPI/V trended higher than PI/UV groups (RR=1.86 [95%CI 0.77-4.51], P=0.17). Vaccination in COVID-recovered individuals provided modest protection from reinfection (RR=1.82 [95%CI 1.21-2.73], P=0.004), but the absolute risk difference was extremely small (AR= 0.004 person-years [95% CI 0.001-0.007], P=0.02). The NNT to prevent one annual case of infection in COVID-recovered patients was 218, compared to 6.5 in COVID-naive patients, representing a 33.5-fold difference in benefit between the two populations. CONCLUSIONS: While vaccinations are highly effective at protecting against infection and severe COVID-19 disease, our review demonstrates that natural immunity in COVID-recovered individuals is, at least, equivalent to the protection afforded by full vaccination of COVID-naive populations. There is a modest and incremental relative benefit to vaccination in COVID-recovered individuals; however, the net benefit is marginal on an absolute basis. COVID-recovered individuals represent a distinctly different benefit-risk calculus. Therefore, vaccination of COVID-recovered individuals should be subject to clinical equipoise and individual preference.
Background COVID-19 vaccines have been used for 9 months in the UK. Real world data have demonstrated the vaccines to be highly effective against COVID-19, severe disease and death. Here, we estimate vaccine effectiveness over time since the second dose of Comirnaty, Vaxzevria and Spikevax in England. Methods We used a test-negative case- control design to estimate vaccine effectiveness against symptomatic disease, hospitalisation and mortality by age, comorbidity status and over time after the second dose to investigate waning separately for Alpha and Delta variants. Results Vaccine effectiveness against symptomatic disease peaked in the early weeks after the second dose and then fell to 47.3 (95% CI 45 to 49.6) and 69.7 (95% CI 68.7 to 70.5) by 20+ weeks against the Delta variant for Vaxzevria and Comirnaty, respectively. Waning of vaccine effectiveness was greater for 65+ year-olds compared to 40-64 year-olds. Vaccine effectiveness fell less against hospitalisations to 77.0 (70.3 to 82.3) and 92.7 (90.3 to 94.6) beyond 20 weeks post-vaccination and 78.7 (95% CI 52.7 to 90.4) and 90.4 (95% CI 85.1 to 93.8) against death for Vaxzevria and Comirnaty, respectively. Greater waning was observed among 65+ year-olds in a clinically extremely vulnerable group and 40-64-year olds with underlying medical conditions compared to healthy adults. Conclusions We observed limited waning in vaccine effectiveness against hospitalisation and death more than 20 weeks post-vaccination with Vaxzevria or Comirnaty. Waning was greater in older adults and those in a clinical risk group, suggesting that these individuals should be prioritised for booster doses.
Objectives Assays using ELISA measurements on serially diluted serum samples have been heavily used to measure serum reactivity to SARS-CoV-2 antigens and are widely used in virology and elsewhere in biology. We test a method to reduce the workload of these assays, and measure reactivity of SARS-CoV-2 and HCoV antigens to human serum samples collected before and during the COVID-19 pandemic. Methods We apply Bayesian hierarchical modelling to ELISA measurements of human serum samples against SARS-CoV-2 and HCoV antigens. Results Inflection titers for SARS-CoV-2 full- length spike protein (S1S2), spike protein receptor-binding domain (RBD), and nucleoprotein (N) inferred from three spread-out dilutions correlated with those inferred from eight consecutive dilutions with an R2 value of 0.97 or higher. We confirm existing findings showing a small proportion of pre-pandemic human serum samples contain cross-reactive antibodies to SARS-CoV-2 S1S2 and N, and that SARS-CoV-2 infection increases serum reactivity to the beta-HCoVs OC43 and HKU1 S1S2. Conclusions In serial dilution assays, large savings in resources and/or increases in throughput can be achieved by reducing the number of dilutions measured and using Bayesian hierarchical modelling to infer inflection or endpoint titers. We have released software for conducting these types of analysis.
Background: The SIR model is often used to analyse and forecast the expansion of an epidemic. In this model, the number of patients exponentially increases and decreases, resulting in two phases. Therefore, in these phases, the logarithm of infectious patients changes at a constant rate, the logarithmic growth rate K. However, in the case of the coronavirus disease 2019 (COVID19) epidemic, K never remains constant but increases and decreases linearly; therefore, the SIR model does not fit that seen in reality. We would like to clarify the cause of this phenomenon and predict the occurrence of COVID19 epidemics. Methods: We simulated a situation in which smaller epidemics were repeated with short time intervals. The results were compared with the epidemic data from 279 countries and regions. Results: In the simulations, the K values increased and decreased linearly, similar to the real data. Because the previous peak covered the initial increase in the epidemic, K did not increase as much as expected; rather, the difference in the basic reproduction number R0 appeared in the slope of increasing K. Additionally, the mean infectious time τ appeared in the negative peaks of K. By using the R0 and τ estimated from the changes in K, changes in the number of patients could be approximated using the SIR model. This supports the appropriateness of the model for evaluating COVID-19 epidemics. By using the model, the distributions of the parameters were identified. On average, an epidemic started every eleven days in a country. The worldwide mean R0 was 2.9; however, this value showed an exponential character and could thus increase explosively. In addition, the average τ was 12 days; this is not the native value but represents a shortened period because of the isolation of patients. As τ represents the half-life, the infectious time varies among patients; hence, prior testing should be performed before isolation is lifted. The changes in K represented the state of epidemics and were several weeks to a month ahead of the changes in the number of confirmed cases. In the actual data, when K was positive on consecutive days, the number of patients increased a few weeks later. In addition, if the negative peaks of K could not be reduced to as small as 0.1, the number of patients remained high. Thus, the number of K-positive days and mean infectious time had a clear correlation with the total number of patients. In such cases, mortality, which was lognormally distributed, with a mean of 1.7%, increased. To control the epidemic, it is important to observe K daily, not to allow K to remain positive continuously, and to terminate a peak with a series of K-negative days. To do this, it was necessary to shorten τ by finding and isolating a patient earlier. The effectiveness of the countermeasures is apparent in τ. The effect of vaccination, in terms of controlling the epidemic, was limited.
Robust polyclonal humoral immune responses have the potential to generate a diverse set of antibodies to neutralize and eliminate viruses such as SARS-CoV-2 and protect against transmission, re-infection and the evolution of variants that evade immunity. CD73 is present on subsets of human B and T cells where it plays a role in lymphocyte activation and migration. CD73 also functions as an ectoenzyme that converts AMP into immunosuppressive adenosine. We have developed a humanized anti-CD73 antibody, mupadolimab (CPI-006), that blocks CD73 enzymatic activity and activates CD73POS B cells, thereby inducing differentiation into plasmablasts, immunoglobulin class switching, and antibody secretion independent of the adenosine modulatory activity. These effects suggest mupadolimab may enhance the magnitude, diversity, and duration of anti-viral responses in patients with COVID-19. This hypothesis was tested in a dose escalation phase 1 trial in 29 hospitalized patients with COVID-19. Single doses of 0.3 mg/kg - 5 mg/kg mupadolimab were well tolerated with no drug related adverse events. Doses greater than 0.3 mg/kg resulted in rapid generation of IgG and IgM to SARS-CoV-2 significantly above titers measured in convalescent controls, with elevated IgG titers sustained for more than 6 months beyond presentation of symptoms. Based on these findings, a randomized double-blind, placebo-controlled Phase 3 study in hospitalized patients was initiated. The primary endpoint was proportion of patients alive and free from respiratory failure within 28 days. This trial was discontinued early during the period of waning COVID-19 incidence after enrolling 40 patients. Although underpowered, results from this trial suggest improvement in the primary and key secondary endpoints in patients treated with single doses of 2 mg/kg and 1 mg/kg compared to placebo. The presumed mechanism of action, stimulation of B cells, may represent a novel approach to immunotherapy of COVID-19 and other viral infections.
Background: Information is needed to monitor progress toward a level of population immunity to SARS-CoV-2 sufficient to disrupt viral transmission. We estimated the percentage of the United States (US) population with presumed immunity to SARS-CoV-2 due to vaccination, natural infection, or both as of August 26, 2021. Methods: Publicly available data as of August 26, 2021, from the Centers for Disease Control and Prevention (CDC) were used to calculate presumed population immunity by state. Seroprevalence data were used to estimate the percentage of the population previously infected with SARS-CoV-2, with adjustments for underreporting. Vaccination coverage data for both fully and partially vaccinated persons were used to calculate presumed immunity from vaccination. Finally, we estimated the percentage of the total population in each state with presumed immunity to SARS-CoV-2, with a sensitivity analysis to account for waning immunity, and compared these estimates to a range of population immunity thresholds. Results: Presumed population immunity varied among states (43.1% to 70.6%), with 19 states with 60% or less of their population having been infected or vaccinated. Four states have presumed immunity greater than thresholds estimated to be sufficient to disrupt transmission of less infectious variants (67%), and none were greater than the threshold estimated for more infectious variants (78% or higher). Conclusions: The US remains a distance below the threshold sufficient to disrupt viral transmission, with some states remarkably low. As more infectious variants emerge, it is critical that vaccination efforts intensify across all states and ages for which the vaccines are approved.
Background: The coronavirus disease 2019 (COVID-19) resulted in a marked decrease in the number of patient visits for acute myocardial infarction (AMI) and delayed patient response and intervention in several countries. This study evaluated the effect of the COVID-19 pandemic on the number of patients, patient response time (pain-to-door), and intervention time (door-to-balloon) for patients with ST-segment elevation myocardial infarction (STEMI) and non-ST- segment elevation myocardial infarction (NSTEMI). Methods: Patients with STEMI or NSTEMI visiting a hospital in South Korea who underwent primary coronary intervention during the COVID-19 pandemic (January 29, 2020, to December 31, 2020) were compared with those in the equivalent period in 2018 to 2019. Patient response and intervention times were compared for the COVID-19 pandemic window (2020) and the equivalent period in 2018 to 2019. Results: We observed no decrease in the number of patients with STEMI (P=0.50) and NSTEMI (P=0.94) during the COVID-19 pandemic compared to that in the previous years. Patient response times (STEMI: P=0.34; NSTEMI: P=0.89) during the overall COVID-19 pandemic period did not differ significantly. However, we identified a significant decrease in time to intervention among patients with STEMI (14%; p<0.01) during the early COVID-19 pandemic. Conclusions: We found that the number of patient with STEMI and NSTEMI was consistent during the COVID-19 pandemic and that no time delays in patient response and intervention occurred. However, the door-to-balloon time among patients with STEMI significantly reduced during the early COVID-19 pandemic, which could be attributed to reduced emergency care utilization during the early pandemic.
While the standard regimen of the BNT162b2 mRNA vaccine includes two doses administered three weeks apart, some public health authorities decided to space them, raising concerns about vaccine efficacy. Here, we analyzed longitudinal humoral responses including antibody binding, Fc-mediated effector functions and neutralizing activity against the D614G strain but also variants of concern and SARS-CoV-1 in a cohort of SARS-CoV-2 naive and previously infected individuals, with an interval of sixteen weeks between the two doses. While the administration of a second dose to previously infected individuals did not significantly improve humoral responses, we observed a significant increase of humoral responses in naive individuals after the 16-weeks delayed second shot, achieving similar levels as in previously infected individuals. Our results highlight strong vaccine-elicited humoral responses with an extended interval BNT162b2 vaccination for naive individuals.
Protection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains the efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines. We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class five months earlier on average. After controlling for time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between groups. Thus, a dichotomy exists between humoral and cellular responses elicited by the two SARS- CoV-2 vaccine classes. Our results have implications for the need of booster doses in vaccinated subjects and might explain the dichotomy reported between the waning protection from symptomatic infection by SARS-CoV-2 vaccination and its persisting efficacy in preventing hospitalization and death.
Background: All-cause excess mortality (the number of deaths that exceed projections in any period) has been widely reported during the Covid-19 pandemic. Whether excess mortality has occurred during the Delta wave is less well understood. Methods: We performed an observational study using data from the Massachusetts Department of Health. Five years of US Census population data and CDC mortality statistics were applied to a seasonal autoregressive integrated moving average (sARIMA) model to project the number of expected deaths for each week of the pandemic period, including the Delta period (starting in June 2021, extending through August 28th 2021, for which mortality data are >99% complete). Weekly Covid-19 cases, Covid-19-attributed deaths, and all-cause deaths are reported. County-level excess mortality during the vaccine campaign are also reported, with weekly rates of vaccination in each county that reported 100 or more all-cause deaths during any week included in the study period. Results: All-cause mortality was not observed after March 2021, by which time over 75% of persons over 65 years of age in Massachusetts had received a vaccination. Fewer deaths than expected (which we term 9deficit mortality9) occurred both during the summer of 2020, the spring of 2021 and during the Delta wave (beginning June 13, 2021 when Delta isolates represented >10% of sequenced cases). After the initial wave in the spring of 2020, more Covid-19-attributed deaths were recorded that all-cause excess deaths, implying that Covid-19 was misattributed as the underlying cause, rather than a contributing cause of death in some cases. Conclusion: In a state with high vaccination rates, excess mortality has not been recorded during the Delta period. Deficit mortality has been recorded during this period.
Understanding the rate and clinical features associated with vaccine breakthrough infections (VBT) is of critical public health importance. Recent evidence on VBT in Barnstable County, Massachusetts, has prompted guidance on masking for vaccinated individuals in areas of high community-level transmission. Additional data is needed to better understand the prevalence and rate of VBT infections. Using detailed disease investigation data from Washoe County, Nevada we sought to assess the rate of symptomatic infection and serious illness among VBT cases compared to non- vaccinated individuals with COVID-19. From February 12 - July 29, 2021, the Washoe County Health District identified and traced 6,128 out of 6,399 reported cases across the sample period. 338 (5.5%) of all cases were identified as breakthrough infections, and 289 (86%) vaccinated individuals had symptomatic infections. Severe clinical outcomes were infrequent with 17 hospitalizations (5% of VBT) and no deaths. Cycle threshold values were not statistically different between vaccinated and unvaccinated individuals.
Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV) - Condition: COVID-19
Interventions: Drug: Favipiravir; Drug: Monoclonal antibodies; Drug: Ivermectin; Other: No treatment; Drug: Remdesivir
Sponsor: University of Oxford
Not yet recruiting
Safety and Immunogenicity Study of AdCLD-CoV19-1: A COVID-19 Preventive Vaccine in Healthy Volunteers - Condition: Covid19
Intervention: Biological: AdCLD-CoV19-1
Sponsor:
Cellid Co., Ltd.
Recruiting
A Post-Exposure Prophylaxis Study of PF-07321332/Ritonavir in Adult Household Contacts of an Individual With Symptomatic COVID-19 - Condition: COVID-19
Interventions: Drug: PF-07321332; Drug: Placebo for PF-07321332; Drug: Placebo for Ritonavir; Drug: Ritonavir
Sponsor: Pfizer
Not yet recruiting
Factors Influencing the COVID-19 Vaccine Immune Response According to Age and Presence or Not of a Past History of COVID-19 - Condition: Covid19
Interventions: Biological: COVID-19 vaccine Pfizer (2 doses); Biological: COVID-19 vaccine Pfizer (1 dose); Biological: COVID-19 mRNA Vaccine Moderna (2 doses); Biological: COVID-19 mRNA Vaccine Moderna (1 dose)
Sponsors: Centre Hospitalier Universitaire de Saint Etienne; Sanofi Pasteur, a Sanofi Company; Bioaster
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
TThe Safety and Efficacy of SCTV01C in Population Aged ≥18 Years Previously Vaccinated With Inactivated COVID-19 Vaccine.Healthy Population Aged ≥18 Years Previously Vaccinated With Inactivated COVID-19 Vaccine. - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01C; Other: Placebo
Sponsor: Sinocelltech Ltd.
Not yet recruiting
The Safety and Efficacy of SCTV01C in Population Aged ≥18 Years Previously Vaccinated With Inactivated COVID-19 Vaccine.Healthy Population Aged ≥18 Years Previously Vaccinated With Adenovirus Vectored or mRNA COVID-19 Vaccine. - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01C; Other: Placebo
Sponsor: Sinocelltech Ltd.
Not yet recruiting
Heterologous Prime-boost Immunization With an Aerosolised Adenovirus Type-5 Vector-based COVID-19 Vaccine (Ad5-nCoV) After Priming With an Inactivated SARS-CoV-2 Vaccine - Condition: COVID-19
Interventions: Biological: inactive SARS-CoV-2 vaccine (Vero cell); Biological: Low dose aerosolized Ad5-nCoV; Biological: High dose aerosolized Ad5-nCoV
Sponsor: Jiangsu Province Centers for Disease Control and Prevention
Recruiting
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
Combined Antihistaminics Therapy in COVID 19 Patients - Condition: Covid19
Interventions: Drug: Loratadine; Drug: Famotidine
Sponsors: Ain Shams University; Nasr City Insurance Hospital
Not yet recruiting
Relate to the Virus That Causes COVID-19, Known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - Condition: Covid19
Intervention: Other: Rapid antigen testing kit
Sponsors:
Mahidol University; Yuvabadhana foundation; Zero COVID Thailand
Not yet recruiting
Prevention and Treatment of Patient Before, During, and After Covid-19 Infection - Condition: Covid19
Intervention: Drug: AntiCov-220
Sponsor:
Nguyen Thi Trieu, MD
Active, not recruiting
Test to Stay in School: COVID-19 Testing Following Exposure in School Communities - Condition: Covid19
Intervention: Other: COVID-19 Testing
Sponsor:
Duke University
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
The Suppressor of Cytokine Signalling family of proteins and their potential impact on COVID-19 disease progression - The family of Suppressor of Cytokine Signalling (SOCS) proteins plays pivotal roles in cytokine and immune regulation. Despite their key roles, little attention has been given to the SOCS family as compared to other feedback regulators. To date, SOCS proteins have been found to be exploited by viruses such as herpes simplex virus (HSV), hepatitis B virus (HBV), hepatitis C virus (HCV), Zika virus, respiratory syncytial virus (RSV), Ebola virus, influenza A virus (IAV) and SARS-CoV, just to name…
Increasing Preparedness for Extreme Events using Plausibility-Based Scenario Planning: Lessons from COVID-19 - A striking feature of COVID-19 is many countries’ low level of preparedness for it, despite pandemics being a known threat. This raises a question as to the reasons for this underpreparedness. While preparedness should have better reflected pandemics’ long-run inevitability and potentially catastrophic impact, government-planning horizons are short term, and the attentiveness of policymakers is bounded and subject to multiple demands. Preparedness is therefore affected by the fundamental…
Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants - The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is therefore paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, and Delta, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human…
Synthetic lethality-based prediction of anti-SARS-CoV-2 targets - Novel strategies are needed to identify drug targets and treatments for the COVID-19 pandemic. The altered gene expression of virus-infected host cells provides an opportunity to specifically inhibit viral propagation via targeting the synthetic lethal (SL) partners of such altered host genes. Pursuing this antiviral strategy, here we comprehensively analyzed multiple in vitro and in vivo bulk and single-cell RNA-sequencing datasets of SARS-CoV-2 infection to predict clinically relevant…
The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells - The COVID-19 pandemic, caused by SARS-CoV-2 coronavirus, is a global health issue with unprecedented challenges for public health. SARS-CoV-2 primarily infects cells of the respiratory tract via Spike glycoprotein binding to angiotensin-converting enzyme (ACE2). Circadian rhythms coordinate an organism’s response to its environment and can regulate host susceptibility to virus infection. We demonstrate that silencing the circadian regulator Bmal1 or treating lung epithelial cells with the…
Inhibitory effect of honokiol on furin-like activity and SARS-CoV-2 infection - The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a pandemic and has caused damage to the lives of the people and economy of countries. However, the therapeutic reagents against SARS-CoV-2 remain unclear. The spike (S) protein of SARS-CoV-2 contains a cleavage motif at the S1/S2 boundary, known to be cleaved by furin. As cleavage is essential for S protein activation and viral entry, furin was selected as the target…
Assessment of the binding interactions of SARS-CoV-2 spike glycoprotein variants - Severe acute respiratory syndrome-associated coronavirus 2 is a major global health issue and is driving the need for new therapeutics. The surface spike protein, which plays a central role in virus infection, is currently the target for vaccines and neutralizing treatments. The emergence of novel variants with multiple mutations in the spike protein may reduce the effectiveness of neutralizing antibodies by altering the binding activity of the protein with angiotensin- converting enzyme 2…
The utilization of hydroxychloroquine to reduce the main signs and symptoms of COVID-19 patients, a cross-sectional study - CONCLUSION: The recommendation of this study is to utilize HCQ to all subjects with asymptomatic COVID-19 infection providing that these subjects are within the inclusion criteria of this study. There was no adverse drug reaction observed for HCQ on daily follow-up. ECG could be done after starting loading dose not before.
Multi-level inhibition of coronavirus replication by chemical ER stress - Coronaviruses (CoVs) are important human pathogens for which no specific treatment is available. Here, we provide evidence that pharmacological reprogramming of ER stress pathways can be exploited to suppress CoV replication. The ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types including primary differentiated human bronchial epithelial cells, (partially) reverses the virus-induced translational shut-down,…
22-Hydroxyhopane, a novel multitargeted phytocompound against SARS-CoV-2 from Adiantum latifolium Lam - The present pandemic disease COVID-19 demands an urgent need for more efficient antiviral drugs against SARS-CoV-2. 22-Hydroxyhopane is a bioactive triterpenoid compound with antibacterial activity, present in the leaves of Adiantum latifolium. In this study, molecular docking method revealed strong binding affinity of the compound for ten proteins essential for SARS-CoV-2 multiplication in host cells, including seven nonstructural proteins, two structural proteins and one receptor protein, with…
SARS-CoV-2 Nsp5 Demonstrates Two Distinct Mechanisms Targeting RIG-I and MAVS To Evade the Innate Immune Response - Newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic with astonishing mortality and morbidity. The high replication and transmission of SARS-CoV-2 are remarkably distinct from those of previous closely related coronaviruses, and the underlying molecular mechanisms remain unclear. The innate immune defense is a physical barrier that restricts viral replication. We report here that the SARS-CoV-2 Nsp5 main protease targets RIG-I and mitochondrial…
Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective - In Covid-19, systemic disturbances may progress due to development of cytokine storm and dysregulation of and plasma osmolarility due to high release of pro-inflammatory cytokines and neuro-hormonal disorders. Arginine vasopressin (AVP) which is involve in the regulation of body osmotic system, body water content, blood pressure and plasma volume, that are highly disturbed in Covid-19 and linked with poor clinical outcomes. Therefore, this present study aimed to find the potential association…
Enzyme inhibition as a potential therapeutic strategy to treat COVID-19 infection - With the emergence of the third infectious and virulent coronavirus within the past two decades, it has become increasingly important to understand how the virus causes infection. This will inform therapeutic strategies that target vulnerabilities in the vital processes through which the virus enters cells. This review identifies enzymes responsible for SARS-CoV-2 viral entry into cells (ACE2, Furin, TMPRSS2) and discuss compounds proposed to inhibit viral entry with the end goal of treating…
Inhibition of the RNA-dependent RNA Polymerase of the SARS-CoV-2 by Short Peptide Inhibitors - The rapid proliferation of SARS-CoV-2 in COVID-19 patients has become detrimental to their lives. However, blocking the replication cycle of SARS-CoV-2 will help in suppressing the viral loads in patients, which would ultimately help in the early recovery. To discover such drugs, molecular docking, MD-simulations, and MM/GBSA approaches have been used herein to examine the role of several short ionic peptides in inhibiting the RNA binding site of the RNA-dependent RNA polymerase (RdRp). Out of…
The natural stilbenoid (-)-hopeaphenol inhibits cellular entry of SARS-CoV-2 USA-WA1/2020, B.1.1.7 and B.1.351 variants - Antivirals are urgently needed to combat the global SARS-CoV-2/COVID-19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding of the viral spike receptor binding domain (RBD) to the host ACE2 receptor may be effective inhibitors of SARS-CoV-2 cell entry. Here we screened 512 pure compounds derived from natural products using a high-throughput RBD/ACE2 binding assay and identified (-)-hopeaphenol, a…
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
一种检测新型冠状病毒的引物探针组合及其应用 - 本发明提供了一种检测新型冠状病毒的引物探针组合及其应用，所述检测新型冠状病毒的引物探针组合包括特异性扩增并检测2019‑nCoV的ORF1ab基因、核壳蛋白N基因和刺突蛋白S基因N501Y突变位点的特异性引物对和探针。本发明还提供了一种检测新型冠状病毒的试剂盒及其以非疾病诊断和/或治疗为目的的使用方法。本发明所述检测新型冠状病毒的引物探针组合具有良好的特异性与灵敏度，配合优化后的检测体系，可以对待测样本进行快速准确的检测，并可以对整个实验流程进行监控，降低假阳性以及假阴性检测结果的出现概率，具有重要的意义。 - 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