Background: Symptoms of COVID-19 including fatigue and dyspnea, may persist for weeks to months after SARS-CoV-2 infection. This study compared self-reported disability among SARS-CoV-2-positive and negative persons with mild to moderate COVID-19-like illness who presented for outpatient care before widespread COVID-19 vaccination. Methods: Unvaccinated adults with COVID-19-like illness enrolled within 10 days of illness onset at three US Flu Vaccine Effectiveness Network sites were tested for SARS-CoV-2 by molecular assay. Enrollees completed an enrollment questionnaire and two follow-up surveys (7-24 days and 2-7 months after illness onset) online or by phone to assess illness characteristics and health status. The second follow-up survey included questions measuring global health, physical function, fatigue, and dyspnea. Scores in the four domains were compared by participants SARS-CoV-2 test results in univariate analysis and multivariable Gamma regression. Results: During September 22, 2020 - February 13, 2021, 2,712 eligible adults were enrolled, 1,541 completed the first follow-up survey, and 650 completed the second follow-up survey. SARS-CoV-2-positive participants were more likely to report fever at acute illness but were otherwise comparable to SARS-CoV-2-negative participants. At first follow-up, SARS-CoV-2-positive participants were less likely to have reported fully or mostly recovered from their illness compared to SARS-CoV-2-negative participants. At second follow-up, no differences by SARS-CoV-2 test results were detected in the four domains in the multivariable model. Conclusion: Self-reported disability was similar among outpatient SARS-CoV-2-positive and -negative adults 2-7 months after illness onset.
Background Phospholipase A2 receptor-associated membranous nephropathy (PLA2R-MN) is an anti-PLA2R antibody (PLA2R-Ab) mediated autoimmune kidney disease. Although antibody titer correlates closely with disease activity, whether it can provide longer-term predictions on disease course and progression is unclear. Rituximab, a B-cell depletion therapy, has become the first-line treatment option for PLA2R-MN; however, the response to Rituximab varies among patients. Methods We developed a flow cytometry-based test that detects and quantifies PLA2R antigen-specific memory B cells (PLA2R-MBCs) in peripheral blood, the primary source for PLA2R-Ab production upon disease relapse. We applied the test to 159 blood samples collected from 28 patients with PLA2R-MN (at diagnosis, during and after immunosuppressive treatment, immunological remission, and relapse) to evaluate the relationship between circulating PLA2R-MBC levels and disease activity. Results The level of PLA2R-MBCs in healthy controls (n=56) is less than or equal to 1.5% of the total MBC compartment. High circulating PLA2R-MBC levels were detected in two patients post-Rituximab despite achieving immunologic and proteinuric remission, as well as in two patients with negative serum autoantibody but increasing proteinuria. Elimination of these cells with Rituximab improved clinical outcomes. Moreover, five patients exhibited elevated PLA2R-MBC levels before disease relapse, followed by a rapid decline to baseline when relapse became clinically evident. COVID-19 vaccination or SARS-CoV-2 infection significantly affected the dynamics of circulating PLA2R-MBCs. Conclusions This study suggests that monitoring PLA2R-MBC levels in patients with PLA2R-MN may help refine and individualize immunosuppressive therapy and predict disease course and progression. The technology and findings may also have broader applications in the clinical management of other autoimmune diseases.
Whether SARS-CoV-2 infection and COVID-19 vaccines confer exposure-dependent (“leaky”) protection against infection remains unknown. We examined the effect of prior infection, vaccination, and hybrid immunity on infection risk among residents of Connecticut correctional facilities during periods of predominant Omicron and Delta transmission. Residents with cell, cellblock, and no documented exposure to SARS-CoV-2 infected residents were matched by facility and date. During the Omicron period, prior infection, vaccination, and hybrid immunity reduced the infection risk of residents without a documented exposure (HR: 0.36 [0.25-0.54]; 0.57 [0.42-0.78]; 0.24 [0.15-0.39]; respectively) and with cellblock exposures (0.61 [0.49-0.75]; 0.69 [0.58-0.83]; 0.41 [0.31-0.55]; respectively) but not with cell exposures (0.89 [0.58-1.35]; 0.96 [0.64-1.46]; 0.80 [0.46-1.39]; respectively). Associations were similar during the Delta period and when analyses were restricted to tested residents. Although associations may not have been thoroughly adjusted due to dataset limitations, the findings suggest that prior infection and vaccination may be leaky, highlighting the potential benefits of pairing vaccination with non-pharmaceutical interventions in crowded settings.
Background: Recurring COVID-19 waves highlight the need for tools able to quantify transmission risk, and identify geographical areas at risk of outbreaks. Local outbreak risk depends on complex immunity patterns resulting from previous infections, vaccination, waning and immune escape, alongside other factors (population density, social contact patterns). Immunity patterns are spatially and demographically heterogeneous, and are challenging to capture in country-level forecast models. Methods: We used a spatiotemporal regression model to forecast subnational case and death counts and applied it to three EU countries as test cases: France, Czechia, and Italy. Cases in local regions arise from importations or local transmission. Our model produces age-stratified forecasts given age-stratified data, and links reported case counts to routinely collected covariates (test number, vaccine coverage..). We assessed the predictive performance of our model up to four weeks ahead using proper scoring rules and compared it to the European COVID-19 Forecast Hub ensemble model. Using simulations, we evaluated the impact of variations in transmission on the forecasts. We developed an open-source RShiny App to visualise the forecasts and scenarios. Results: At a national level, the median relative difference between our median weekly case forecasts and the data up to four weeks ahead was 25% (IQR: 12-50%) over the prediction period. The accuracy decreased as the forecast horizon increased (on average 24% increase in the median ranked probability score per added week), while the accuracy of death forecasts remained stable. Beyond two weeks, the model generated a narrow range of likely transmission dynamics. The median national case forecasts showed similar accuracy to forecasts from the European COVID-19 Forecast Hub ensemble model, but the prediction interval was narrower in our model. Generating forecasts under alternative transmission scenarios was therefore key to capturing the range of possible short-term transmission dynamics. Discussion: Our model captures changes in local COVID-19 outbreak dynamics, and enables quantification of short-term transmission risk at a subnational level. The outputs of the model improve our ability to identify areas where outbreaks are most likely, and are available to a wide range of public health professionals through the Shiny App we developed.
Background: Timely and informed public health responses to infectious diseases such as COVID-19 necessitate reliable information about infection dynamics. The case ascertainment rate (CAR), the proportion of infections that are reported as cases, is typically much less than one and varies with testing practices and behaviours, making reported cases unreliable as the sole source of data. The concentration of viral RNA in wastewater samples provides an alternate measure of infection prevalence that is not affected by human behaviours. Here, we investigated how these two data sources can be combined to inform estimates of the instantaneous reproduction number, R, and track changes in the CAR over time. Methods: We constructed a state-space model that we solved using sequential Monte Carlo methods. The observed data are the levels of SARS-CoV-2 in wastewater and reported case incidence. The hidden states that we estimate are R and CAR. Model parameters are estimated using the particle marginal Metropolis Hastings algorithm. Findings: We analysed data from 1 January 2022 to 31 March 2023 from Aotearoa New Zealand. Our model estimates that R peaked at 2.76 (95% CrI 2.20, 3.83) around 18 February 2022 and the CAR peaked around 12 March 2022. Accounting for reduced CAR, we estimate that New Zealand9s second Omicron wave in July 2022 was similar in size to the first, despite fewer reported cases. We estimate that the CAR in the BA.5 Omicron wave in July 2022 was approximately 50% lower than in the BA.1/BA.2 Omicron wave in March 2022. The CAR in subsequent waves around November 2022 and April 2023 was estimated to be comparable to that in the second Omicron wave. Interpretation: This work on wastewater-based epidemiology (WBE) can be used to give insight into key epidemiological quantities. Estimating R, CAR, and cumulative number of infections provides useful information for planning public health responses and understanding the state of immunity in the population. This model is a useful disease surveillance tool, improving situational awareness of infectious disease dynamics in real-time, which may be increasingly useful as intensive pandemic surveillance programmes are wound down.
Reproduction Number (RN-)EXCEL Model has been developed on an EXCEL sheet to provide important characteristics of COVID-19 infectious disease for practical use. The model is developed based only on observed data to predict future infection toward herd immunity threshold and until the end stage of the infection. Basic equations are simple and constructed in analogy with neutron multiplication reactions in nuclear reactor. To know the next day infection, we calculate an exponential increase in one day step with a rate obtained from nearby PCR positive infectious numbers, which are daily input in the EXCEL sheet. In a closed community, main players are non-immune holders and immune holders, where total number of immune holders derived from infection and vaccination plays an essential role. In traditional SIR model, infection behavior is characterized by the reproduction rate in differential equation where social actions such as governmental regulations or vaccinations are included as constant breaking term for infection spread. However, in actual situation these terms are time dependent and is difficult to solve by a set of differential equations. In contrast, RN-EXCEL model deals with infection by defining successive reproduction number for each time interval as inchworm that represents a clear physical picture of the virus infectivity. Using this model, a lot of predictions were made for semi-closed communities domestically and world-wide, timely for practical use.
Aim: To investigate whether polypharmacy and comorbidities conveyed more risk of adverse health outcomes following COVID-19 infection in people with type 1 diabetes (T1DM) or type 2 diabetes (T2DM). Materials and methods: The Greater Manchester Care Record (GMCR) is an integrated database of electronic health records containing data collected from 433 general practices in Greater Manchester. Baseline demographic information (age, BMI, gender, ethnicity, smoking status, deprivation index), hospital admission or death within 28 days of infection were extracted for adults (18+) diagnosed with either T1DM or T2DM. Results: For T2DM, 16 to 20 medications (p=0.01; OR [95% CI]=2.37 [1.31 to 4.32]) and > 20 medications (p=0; OR [95% CI]=3.14 [1.75 to 5.62]) were associated with increased risk of death following COVID-19 infection. Increased risk of hospital admissions in T2DM individuals was determined for 11 to 15 medications (p=0.01; OR [95% CI]=1.34 [1.06 to 1.69]) and above. This was independent of comorbidities, metabolic and demographic factors. For T1DM there was no association of polypharmacy with hospital admission. Respiratory, cardiovascular/cerebrovascular and gastrointestinal conditions were associated with increased risk of hospital admissions and deaths in T2DM (p>0.001). Conclusion: We have shown in T2DM an independent association of number of medications taken from 11 upwards with adverse health consequences following COVID-19 infection. We also found that individuals with diabetes develop comorbidities that were common across both T1DM and T2DM. This study has laid the foundation for future investigations into the way that complex pharmacological interactions may influence clinical outcomes in people with T2DM.
Knowledge on immunogenicity of the bivalent Omicron BA.4/5 vaccine in dialysis patients and the effect of a previous infection is limited. Therefore, vaccine-induced humoral and cellular immunity was analyzed in dialysis patients and immunocompetent controls with and without prior infection. In an observational study, 33 dialysis patients and 58 controls matched for age, sex and prior infection status were recruited. Specific IgG, neutralizing antibody activity and cellular immunity towards the spike-antigen from parental SARS-CoV-2 and Omicron subvariants BA.1, BA.2 and BA.4/5 were analyzed before and 13-18 days after vaccination. The bivalent vaccine led to a significant induction of IgG, neutralizing titers, and specific CD4 and CD8 T-cell levels. Neutralizing activity towards the parental strain was highest, whereas specific T-cell levels towards parental spike and Omicron subvariants did not differ indicating substantial cross-reactivity. Dialysis patients with prior infection had significantly higher spike-specific CD4 T-cell levels with lower CTLA-4 expression compared to infection-naive patients. When compared to controls, no differences were observed between individuals without prior infection. Among infected individuals, CD4 T-cell levels were higher in dialysis patients and neutralizing antibodies were higher in controls. Vaccination was overall well tolerated in both dialysis patients and controls with significantly less adverse events among dialysis patients. In conclusion, our study did not provide any evidence for impaired immunogenicity of the bivalent Omicron BA.4/5 vaccine in dialysis patients. Unlike in controls, previous infection of patients was even associated with higher levels of spike-specific CD4 T cells, which may reflect prolonged encounter with antigen during infection.
Introduction: The COVID-19 pandemic emerged as an unprecedented challenge for healthcare systems across the world disproportionately impacting immigrant and racialized populations. Canadian African, Caribbean, and Black (ACB) communities representing some of the most vulnerable populations in terms of their susceptibility to health risks, receipt of adequate care, and chances of recovery. The COVID-19 ACB Providers Project (CAPP 2) aims to strengthen the ability of health care providers (HCP) to address this community9s COVID-19 related healthcare needs. Informed by CAPP 1.0 Project, a mixed-method study which examined COVID-19 pandemic impact on ACB communities in Ontario (Ottawa and Toronto), this second study seeks to develop and implement educational programs on five key areas (modules) to strengthen the capacity of HCPs working with ACB populations. The five modules (topics) include: 1) COVID-19 and its impacts on health, 2) social determinants of health and health inequities, 3) critical health literacy, 4) critical racial literacy, and 5) cultural competence and safety. Methods and analysis: An implementation science approach will guide the development, implementation, and evaluation of the evidence-informed interventions. Intersectionality lens, socio-ecological model (SEM) and community-based participatory research (CBPR) frameworks will inform the research process. To ensure active stakeholder engagement, there will be a Project Advisory Committee comprised of 16 ACB community members, health providers, and partner agency representatives. Five modules will be developed: two virtual simulation games in collaboration with leading simulation experts, and three non-simulation modules. Ethics and dissemination: Ethics approval was granted by the University of Ottawa Research Ethics Board on July 18th, 2023 (H - 01- 23 - 8069). The results of this study will be disseminated in community workshops, an online learning platform, at academic conferences and in peer-reviewed publications.
The potential utility of wastewater-based epidemiology as an early warning tool has been explored widely across the globe during the COVID-19 pandemic. Early in the pandemic, methods were developed to detect the presence of SARS-CoV-2 RNA in wastewater. Since then, extensive research has been conducted to study the relationship between viral concentration in wastewater and COVID-19 cases in catchment areas of sewage treatment plants over time. However, few reports, to date, have attempted to develop predictive models for hospitalizations using SARS-CoV-2 RNA concentrations in wastewater. This study uses wastewater data to forecast hospitalizations using a linear mixed-effects model that allows for repeated measures and fixed and random effects. We use wastewater data from various treatment plants in California to predict hospitalizations at the county level assuming data from March 14, 2022, to May 21, 2023. The results suggest that wastewater data can serve as a dependable substitute for clinical data in creating robust models to predict hospitalizations. This approach can enhance our understanding of community-level transmission and its impact on hospital capacity.
The adoption of digital health technologies accelerated during Covid-19, with concerns over the equity of access due to digital exclusion. Using data from a text-based online mental health service for children and young people we explore the impact of the pandemic on service access and presenting concerns and whether differences were observed by sociodemographic characteristics in terms of access (gender, ethnicity and deprivation). We used interrupted time-series models to assess whether there was a change in the level and rate of service use during the Covid-19 pandemic (April 2020-April 2021) compared to pre-pandemic trends (June 2019-March 2020). Routinely collected data from 61221 service users were extracted for observation, those represented half of the service population as only those with consent to share their data were used. The majority of users identified as female (74%) and White (80%), with an age range between 13 and 20 years of age,. There was evidence of a sudden increase (13%) in service access at the start of the pandemic (RR 1.13 95% CI 1.02, 1.25), followed by a reduced rate (from 25% to 21%) of engagement during the pandemic compared to pre-pandemic trends (RR 0.97 95% CI 0.95,0.98). There was a sudden increase in almost all presenting issues apart from physical complaints. There was evidence of a step increase in the number of contacts for Black/African/Caribbean/Black British (38% increase; 95% CI: 1%-90%) and White ethnic groups (14% increase; 95% CI: 2%-27%) ), sudden increase in service use at the start of the pandemic for the most (58% increase; 95% CI: 1%-247%) and least (47% increase; 95% CI: 6%-204%) deprived areas. During the pandemic, contact rates decreased, and referral sources change at the start. Findings on access and service activity align with other studies observing reduced service utilization. The lack of differences in deprivation levels and ethnicity at lockdown suggests exploring equity of access to the anonymous service. The study provides unique insights into changes in digital mental health use during Covid-19 in the UK.
Post Covid-19 condition (PCC), long COVID-19 syndrome and post-acute sequelae of SARS-CoV-2 (PASC) all refer to a constellation of symptoms that are unresolved long after the acute phase of the viral infection. The severity of symptoms varies from mild and tolerable to severe and debilitating 1, 2. Due to the evolving nature of the SARS-CoV-2 pandemic, treatment protocols for the acute illness are also in a constant state of evolution. Due to the infancy of long COVID-19 syndrome, there is a lack of evidence-based treatment protocols to treat or at the very least attenuate the symptoms of long COVID-19. Current treatment regimens include homeopathic medicine, system focused treatments by specialists, infusion therapies, hyperbaric oxygenation, and polypharmacy. Most of these treatments have partial efficacy at best and place a substantial financial burden on the patients. The physiological, psychological, and societal impact of long COVID-19 cannot be approached casually and must govern the intensity with which the healthcare community approaches treatment of long COVID-19 syndrome. In this 41-patient cohort study from a chronic pain management practice in Colorado, the use of either unilateral or bilateral stellate ganglion block (SGB) was explored to manage symptoms associated with long COVID-19 syndrome. Results indicated that a substantial proportion of patients (86%) experienced a significant reduction of their symptoms following SGB treatment, while 61% achieved a reduction in all their symptoms.
A Study to Evaluate the Safety and Immunogenicity of an (Omicron Subvariant) COVID-19 Vaccine Booster Dose in Previously Vaccinated Participants and Unvaccinated Participants. - Condition: COVID-19
Interventions: Biological: XBB.1.5 Vaccine (Booster); Biological: XBB.1.5 Vaccine (single dose)
Sponsor: Novavax
Not yet recruiting
EFFECT OF COGNITIVE BEHAVIORAL THERAPY ON DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH POST COVID-19 - Condition: Post-COVID-19 Syndrome
Intervention: Behavioral: rehacom
Sponsor: Cairo University
Enrolling by invitation
Intradermal Administration of a COVID-19 mRNA Vaccine in Elderly - Conditions: Vaccination; Infection; COVID-19
Intervention: Biological: Comirnaty
Sponsor: Radboud University Medical Center
Not yet recruiting
Immunogenicity and Safety of AdCLD-CoV19-1 OMI as a Booster: A SARS-CoV-2 (COVID-19) Preventive Vaccine in Healthy Volunteers - Conditions: COVID-19; Vaccines
Interventions: Biological: AdCLD-CoV19-1 OMI; Biological: Comirnaty Bivalent 0.1mg/mL (tozinameran and riltozinameran)
Sponsor: Cellid Co., Ltd.
Not yet recruiting
Using Text Messages to Boost COVID-19 Vaccine Booking Rate - Conditions: Vaccination Hesitancy; COVID-19
Interventions: Behavioral: Behavioural science-informed text messages; Behavioral: Control
Sponsors: The Behavioural Insights Team; Public Health England; Department of Health and Social Care; NHS England and NHS Improvement
Completed
Ivermectin to Prevent SARS-CoV-2 (COVID-19) Hospitalisation in Subjects Over 50 - Conditions: COVID-19; SARS-CoV-2
Interventions: Drug: Ivermectin; Drug: Placebo
Sponsor: Insud Pharma
Terminated
Methylprednisolone in Patients With Cognitive Deficits in Post-COVID-19 Syndrome (PCS) - Condition: Post-COVID-19 Syndrome
Intervention: Drug: Methylprednisolone
Sponsor: Charite University, Berlin, Germany
Not yet recruiting
Hyperbaric on Pulmonary Functions in Post Covid -19 Patients. - Condition: Post COVID-19 Patients
Interventions: Device: hyperbaric oxygen therapy; Device: breathing exercise; Drug: medical treatment
Sponsor: Cairo University
Completed
Dietary Intervention to Mitigate Post-Acute COVID-19 Syndrome - Conditions: Post-Acute COVID-19 Syndrome; Fatigue
Interventions: Other: Dietary intervention to mitigate Post-Acute COVID-19 Syndrome; Other: Attention Control
Sponsor: University of Maryland, Baltimore
Not yet recruiting
A Phase II Trial to Evaluate the Safety and Immunogenicity of BIMERVAX® When Coadministered With Seasonal Influenza Vaccine (SIIV) in Adults Older Than 65 Years of Age Fully Vaccinated Against COVID-19 - Conditions: SARS CoV 2 Infection; Influenza, Human
Interventions: Biological: BIMERVAX; Biological: SIIV
Sponsor: Hipra Scientific, S.L.U
Not yet recruiting
Pulmonary Artery Pressure in COVID-19 Survivors - Condition: Pulmonary Hypertension Secondary
Intervention: Diagnostic Test: right heart catheterization (RHC).
Sponsor: Mansoura University Hospital
Enrolling by invitation
Preliminary Efficacy of a Technology-based Physical Activity Intervention for Older Korean Adults During the COVID-19 Pandemic - Conditions: Cardiovascular Health; Physical Function
Intervention: Behavioral: Golden Circle
Sponsor: University of Illinois at Urbana-Champaign
Completed
Supported Employment COVID-19 Rapid Testing for PWID - Condition: Health Behavior
Intervention: Behavioral: Supported Employment
Sponsor: University of Oregon
Not yet recruiting
Study of Tixagevimab/Cilgavimab and Regdanvimab Efficacy for Treatment of COVID-19 - Condition: Coronavirus Infections
Interventions: Drug: tixagevimab/cilgavimab 150+150 mg; Drug: tixagevimab/cilgavimab 300+300 mg; Drug: regdanvimab
Sponsors: City Clinical Hospital No.52 of Moscow Healthcare Department; Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
Active, not recruiting
Playing Games to Learn About Children’s Vaccines Project - Conditions: HPV; COVID-19; Vaccine-Preventable Diseases
Intervention: Behavioral: vaccination games
Sponsor: Michigan State University
Recruiting
De novo design of bioactive phenol and chromone derivatives for inhibitors of Spike glycoprotein of SARS-CoV-2 in silico - This work presents the synthesis of 12 phenol and chromone derivatives, prepared by the analogs, and the possibility of conducting an in silico study of its derivatives as a therapeutic alternative to combat the SARS-CoV-2, pathogen responsible for COVID-19 pandemic, using its S-glycoprotein as a macromolecular target. After the initial screening for the ranking of the products, it was chosen which structure presented the best energy bond with the target. As a result, derivative 4 was submitted…
Endothelial FoxM1 reactivates aging-impaired endothelial regeneration for vascular repair and resolution of inflammatory lung injury - Aging is a major risk factor of high incidence and increased mortality of acute respiratory distress syndrome (ARDS). Here, we demonstrated that persistent lung injury and high mortality in aged mice after sepsis challenge were attributable to impaired endothelial regeneration and vascular repair. Genetic lineage tracing study showed that endothelial regeneration after sepsis-induced vascular injury was mediated by lung resident endothelial proliferation in young adult mice, whereas this…
Forodesine and Riboprine Exhibit Strong Anti-SARS-CoV-2 Repurposing Potential: In Silico and In Vitro Studies - Lately, nucleos(t)ide antivirals topped the scene as top options for the treatment of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Targeting the two broadly conserved SARS-CoV-2 enzymes, RNA-dependent RNA polymerase (RdRp) and 3’-to-5’ exoribonuclease (ExoN), together using only one shot is a very successful new tactic to stop SARS-CoV-2 multiplication irrespective of the SARS-CoV-2 variant type. Herein, the current…
Anticancer pan-ErbB inhibitors reduce inflammation and tissue injury and exert broad-spectrum antiviral effects - Targeting host factors exploited by multiple viruses could offer broad-spectrum solutions for pandemic preparedness. Seventeen candidates targeting diverse functions emerged in a screen of 4,413 compounds for SARS-CoV-2 inhibitors. We demonstrated that lapatinib and other approved inhibitors of the ErbB family receptor tyrosine kinases suppress replication of SARS-CoV-2, Venezuelan equine encephalitis virus (VEEV), and other emerging viruses with a high barrier to resistance. Lapatinib…
Pyronaridine tetraphosphate is an efficacious antiviral and anti-inflammatory active against multiple highly pathogenic coronaviruses - The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to be one of the largest dangers to human health around the world. The need for effective antiviral and anti-inflammatory treatments is still extremely high as newly emerging variants threaten the efficacy of currently used treatment options. Many compounds are effective at inhibiting SARS-CoV-2 infection in vitro but fail to recapitulate that efficacy in vivo….
Identification of Promising Sulfonamide Chalcones as Inhibitors of SARS-CoV-2 3CLpro through Structure-Based Virtual Screening and Experimental Approaches - 3CL^(pro) is a viable target for developing antiviral therapies against the coronavirus. With the urgent need to find new possible inhibitors, a structure-based virtual screening approach was developed. This study recognized 75 pharmacologically bioactive compounds from our in-house library of 1052 natural product-based compounds that satisfied drug-likeness criteria and exhibited good bioavailability and membrane permeability. Among these compounds, three promising sulfonamide chalcones were…
TGF-β1 inhibition of ACE2 mediated by miRNA uncovers novel mechanism of SARS-CoV-2 pathogenesis - SARS-CoV-2 utilizes receptor binding domain (RBD) of spike glycoprotein to interact with angiotensin-converting enzyme 2 (ACE2). Decreased cell surface density of ACE2 contributes to mortality during COVID-19. Studies published early during the pandemic reported that people with cystic fibrosis (PwCF) treated with the high efficiency CFTR modulators ETI (elexacaftor-tezacaftor-ivacaftor) had higher ACE2 levels and milder COVID-19 symptoms, compared to people without CF. Subsequent studies did…
WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by various disabling symptoms including exercise intolerance and is diagnosed in the absence of a specific cause, making its clinical management challenging. A better understanding of the molecular mechanism underlying this apparent bioenergetic deficiency state may reveal insights for developing targeted treatment strategies. We report that overexpression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3),…
Endogenous and Therapeutic 25-hydroxycholesterols May Worsen Early SARS-CoV-2 Pathogenesis in Mice - Oxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-hydroxycholesterol (25HC), a product of activity of cholesterol-25-hydroxylase (CH25H) upon cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against SARS-CoV-2. However, 25HC can also amplify inflammation and be converted by CYP7B1 to 7α,25HC, a lipid with chemoattractant activity via the G protein-coupled receptor, EBI2/GPR183. Here, using in vitro studies and two…
Design of a bifunctional pan-sarbecovirus entry inhibitor targeting the cell receptor and viral fusion protein - Development of highly effective antivirals that are robust to viral evolution is a practical strategy for combating the continuously evolved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inspired by viral multistep entry process, we here focus on developing a bispecific SARS-CoV-2 entry inhibitor, which acts on the cell receptor angiotensin converting enzyme 2 (ACE2) and viral S2 fusion protein. First, we identified a panel of diverse spike (S) receptor-binding domains (RBDs) and…
A novel robust inhibitor of papain-like protease (PLpro) as a COVID-19 drug - Regarding the significance of SARS-CoV-2, scientists have shown considerable interest in developing effective drugs. Inhibitors for PLpro are the primary strategies for locating suitable COVID-19 drugs. Natural compounds comprise the majority of COVID-19 drugs. Due to limitations on the safety of clinical trials in cases of COVID, computational methods are typically utilized for inhibition studies. Whereas papain is highly similar to PLpro and is entirely safe, the current study aimed to examine…
Growth media affects susceptibility of air-lifted human nasal epithelial cell cultures to SARS-CoV2, but not Influenza A, virus infection - Primary differentiated human epithelial cell cultures have been widely used by researchers to study viral fitness and virus-host interactions, especially during the COVID19 pandemic. These cultures recapitulate important characteristics of the respiratory epithelium such as diverse cell type composition, polarization, and innate immune responses. However, standardization and validation of these cultures remains an open issue. In this study, two different expansion medias were evaluated and the…
Protegrin-2, a potential inhibitor for targeting SARS-CoV-2 main protease Mpro - CONCLUSIONS: Our in silico and experimental studies identified Protegrin-2 as a potent inhibitor of M^(pro) that could be pursued further towards drug development against COVID-19 infection.
Real-world effectiveness of mRNA COVID-19 vaccines in the elderly during the Delta and Omicron variants: Systematic review - CONCLUSION: Because of the natural diminishing effectiveness of the vaccine, the need for booster dose to restore its efficacy is vital. From a research perspective, the use of highly heterogeneous outcome measures inhibits the comparison, contrast, and integration of the results which makes data pooling across different studies problematic. While pharmaceutical intervention like vaccination is important to fight an epidemic, utilizing common outcome measurements or carrying out studies with…
A pan-coronavirus peptide inhibitor prevents SARS-CoV-2 infection in mice by intranasal delivery - Coronaviruses (CoVs) have brought serious threats to humans, particularly severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which continually evolves into multiple variants. These variants, especially Omicron, reportedly escape therapeutic antibodies and vaccines, indicating an urgent need for new antivirals with pan-SARS-CoV-2 inhibitory activity. We previously reported that a peptide fusion inhibitor, P3, targeting heptad repeated-1 (HR1) of SARS-CoV-2 spike (S) protein, could…