The SARS-CoV-2 exhibits similar aetiology, mode of transmission and clinical presentation as the H1N1pdm09 (a subtype of Influenza A) and Influenza A (other subtypes), and can exist as a coinfection in the same patient. It is essential to understand the coinfection dynamics of these viruses for effective management of the disease. This study examined 959 SARS-CoV-2 positive samples collected from the six states and three union territories in India from May to December 2022. The clinical data was accessed from the Integrated Health Information Platform (IHIP) and the Indian council of medical research (ICMR) COVID-19 data portal. The samples were tested for SARS-CoV-2, H1N1pdm09 and Influenza A using Reverse Transcriptase Real-Time Polymerase Chain Reaction q(RT-PCR). All 959 samples were subjected to SARS-CoV-2 whole genome sequencing (WGS) using Oxford Nanopore Next Generation Sequencing (NGS). From the 959 SARS-CoV-2 positive samples, 17.5% were co-infected with H1N1pdm09, 8.2% were co-infected with Influenza A, and 74.2% were only positive for SARS-CoV-2. The comparative analysis of viral load among the coinfected cases revealed that Influenza A and H1N1pdm09 had higher viral loads than SARS-CoV-2 in the studied samples. Out of 959 samples subjected to WGS, 815 and 144 were considered quality control (QC) passed, and QC failed, respectively, for SARS-CoV-2 variant calling. SARS-CoV-2 WGS identified 46 different variants belonging to the Omicron lineage. The SARS-CoV-2 and Influenza A coinfection group; and the SARS-CoV-2 and H1N1pdm09 coinfection group showed a higher proportion of symptomatic cases. This work demonstrates the need for coinfection analysis for the H1N1pdm09 virus, Influenza A virus and SARS-CoV-2 while studying the etiological agent in individuals with ILI/SARI symptoms. It is recommended that, in addition to determining the aetiology of ILI/SARI, an examination for H1N1pdm09 and Influenza A be conducted concurrently utilising molecular tools such as WGS and RT-PCR to understand the variant dynamics and the viral load for taking an informed decision during the patient management and treatment discourse.
Background. The purpose of this study was to evaluate whether a bivalent COVID-19 vaccine protects against COVID-19. Methods.. Employees of Cleveland Clinic in employment when the bivalent COVID-19 vaccine first became available, were included. Cumulative incidence of COVID-19 over the following weeks was examined. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with change in dominant circulating lineages over time accounted for by time-dependent coefficients. The analysis was adjusted for the pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses. Results. Among 51017 employees, COVID-19 occurred in 4034 (7.9%) during the study. In multivariable analysis, the bivalent vaccinated state was associated with lower risk of COVID-19 during the BA.4/5 dominant (HR, .71; 95% C.I., .63-.80) and the BQ dominant (HR .81; 95% C.I., .70-.95) phases, but decreased risk was not found during the XBB dominant phase (HR .96; 95% C.I., .78-.1.18). Estimated vaccine effectiveness (VE) was 29% (95% C.I., 20%-37%), 19% (95% C.I., 5%-30%), and 5% (95% C.I., -18%-22%), during the BA.4/5, BQ, and XBB dominant phases, respectively. Risk of COVID-19 also increased with time since most recent prior COVID-19 episode and with the number of vaccine doses previously received. Conclusions. The bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 while the BA.4/5 lineages were the dominant circulating strains, afforded less protection when the BQ lineages were dominant, and effectiveness was not demonstrated when the XBB lineages were dominant.
Background Omicron-containing bivalent boosters are available worldwide. Results of a large, randomized, active-controlled study are presented. Methods This phase 3, randomized, observer-blind, active-controlled trial in the United Kingdom evaluated the immunogenicity and safety of 50-μg doses of omicron-BA.1- monovalent mRNA-1273.529 and bivalent mRNA-1273.214 booster vaccines compared with 50-μg mRNA-1273 administered as boosters in individuals ≥16 years. Participants had previously received 2 doses of any authorized/approved Covid-19 vaccine with or without an mRNA vaccine booster. Safety and immunogenicity were primary objectives; immunogenicity was assessed in all participants, with analysis conducted based on prior infection status. Incidence of Covid-19 post-boost was a secondary (mRNA-1273.214) or exploratory (mRNA-1273.529) objective. Results In part 1 of the study, 719 participants received mRNA-1273.529 (n=362) or mRNA-1273 (n=357); in part 2, 2813 received mRNA-1273.214 (n=1418) or mRNA-1273 (n=1395). Median durations (months [interquartile range]) between the most recent Covid-19 vaccine and study boosters were similar in the mRNA-1273.529 (4.0 [[3.6-4.7]) and mRNA-1273 (4.1 [3.5-4.7]) (part 1), and mRNA-1273.214 (5.5 [4.8-6.2] and mRNA-1273 (5.4 [4.8-6.2]) groups (part 2). Both mRNA-1273.529 and mRNA-1273.214 elicited superior neutralizing antibody responses against omicron BA.1 with geometric mean ratios (99% CI) of 1.68 (1.45-1.95) and 1.53 (1.41-1.67) compared to mRNA-1273 at day 29 post-boost. Although the study was not powered to assess relative vaccine efficacy, the incidence rates/1000 person years (95% CI) of Covid-19 were numerically lower with mRNA-1273.529 (670.5 [528.3-839.3]) than mRNA-1273 (769.3 [615.4-950.1]) and mRNA-1273.214 (633.0 [538.1-739.7]) than mRNA-1273 (711.6 [607.5-828.5]). Sequence analysis in part 2 showed that this was driven by lower incidence of Covid-19 in the mRNA-1273.214 cohort with BA.2 and BA.4 sublineages but not BA.5 sublineages. All study boosters were well-tolerated. Conclusion The bivalent omicron BA.1 containing booster elicited superior neutralizing antibody responses against omicron BA.1 with acceptable safety results consistent with the BA.1 monovalent vaccine. Incidence rates for Covid-19 were numerically lower in participants who received mRNA-1273.214 compared to the original booster vaccine mRNA-1273, driven by the BA.2 and BA.4 sublineages.
Age-associated B cells (ABCs) accumulate with age, as well as in individuals with a range of immunological dyscrasias. These include patients with cancer treated with immune checkpoint blockade and patients with inborn errors of immunity. In this study, we sought to determine whether ABCs found in all these conditions are similar, and whether they enhance or detract from the response to COVID-19 vaccination. We use single cell RNA sequencing to show that ABCs arising from distinct aetiologies have common transcriptional profiles and may be subdivided according to the expression of genes associated with different immune functions, such as the autoimmune regulator (AIRE). Next, we perform detailed longitudinal profiling of the COVID-19 vaccination response in patients and controls. We show that high pre-vaccination ABC frequency correlates with decreased levels of antigen-specific memory B cells, and reduced magnitude and longevity of neutralising capacity against SARS-CoV-2 virus. Potentially contributing to this, ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes. This could contribute to diminished vaccine responses either directly as result of inhibitory signalling or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may therefore serve as a biomarker identifying individuals at risk of a suboptimal response to COVID-19 vaccination.
ABSTRACT Introduction The nirmatrelvir/ritonavir (PAXLOVIDTM) is an antiviral blocking the replication of SARS-CoV-2. Early treatment with this antiviral has showed to reduce COVID-19 hospitalization and death in unvaccinated outpatients with mild-to-moderate COVID-19 and high risk of progression to severe disease with variants before Omicron. However, the current epidemiological context and the level of immunity in the population (vaccination and/or natural infection) have evolved considerably since the disclosure of these results. Thus, real-world evidence studies in vaccinated outpatients with lineage and sublineage of the variant are needed. Objective To assess whether nirmatrelvir/ritonavir treatment reduces the risk of COVID-19-associated hospitalization among Québec outpatients with mild-to-moderate COVID-19 at high risk of progression to severe disease in a real-world context, regardless of vaccination status and circulating variants, in the province of Québec. Methods This was a retrospective cohort study of SARS-CoV-2-infected outpatients who received nirmatrelvir/ritonavir between March 15 and August 15, 2022, using data from the Québec provincial clinico-administrative databases. Outpatients treated with nirmatrelvir/ritonavir were compared to unexposed ones. The treatment group was matched with controls using propensity-score matching in a ratio of 1:1. The outcome was COVID-19-associated hospitalization occurring within 30 days following the index date. Poisson regression with robust error variance was used to estimate the relative risk of hospitalization among the treatment group compared to the control group. Results A total of 16,601 and 242,341 outpatients were eligible to be included in the treatment (nirmatrelvir/ritonavir) and control groups respectively. Among treated outpatients, 8,402 were matched to controls. Regardless of vaccination status, nirmatrelvir/ritonavir-treated outpatient status was associated with a 69% reduced relative risk of COVID-19-associated hospitalization (RR: 0.31 [95% CI: 0.28; 0.36]). The effect was more pronounced in outpatients without a complete primary vaccination course (RR: 0.04 [95% CI: 0.03; 0.06]), while treatment with nirmatrelvir/ritonavir was not associated with benefit when outpatients with a complete primary vaccination course were considered (RR: 0.93 [95% CI: 0.78; 1.08]) Subgroups analysis among outpatients with a primary vaccination course showed that nirmatrelvir/ritonavir treatment was associated with a significant decrease in relative risk of hospitalization in severely immunocompromised outpatients (RR: 0.66 [95% CI: 0.50; 0.89]) and in outpatients aged 70 years and older (RR: 0.50 [95% CI: 0.34; 0.74]) when the last dose of the vaccine was received more than six months before. Conclusions Among SARS-CoV-2 infected outpatients at high risk for severe COVID-19 during Omicron BA.2 and BA.4/5 surges, treatment with nirmatrelvir/ritonavir was associated with a significant reduced relative risk of COVID-19-associated hospitalization. This effect was observed in outpatients with incomplete primary vaccination course and in outpatients who were severely immunocompromised. Except for severely immunocompromised outpatients, no evidence of benefit was found in any category of outpatient with a complete primary vaccination course whose last dose of COVID-19 vaccine was received within six months.
Abstract Importance: Consistent, evidence-based communication is critical to building trust and maintaining credibility of public health agencies. Objective: To identify any significant changes in the mainstream media9s presentation of public health advice for flu prevention before and after the COVID-19 pandemic. Design, Setting, and Participants: A systematic search in Factiva of top ten U.S. newspapers by circulation, using two search periods, 2018-2019 and 2021-2022. Articles with flu prevention advice were identified, abstracted for media outlet, reporter, date. Articles were coded for the specific advice provided. Main Measure(s): Number of recommendations for flu prevention, frequency of each recommendation; percent of recommendations aligned with CDC guidelines for each period. Changes in frequency of each recommendation. Differences determined using 2-proportion Z-tests, p-value 0.05 significance. Results: 128 articles with 244 recommendations for pre-COVID period; 122 articles with 296 recommendations post-COVID. 96.3% of recommendations in alignment with CDC guidelines pre-COVID. 63.9% of recommendations in alignment with CDC during post-COVID timeframe. Percentage of articles with advice to mask for flu increased by 1,494.8% (p=<0.00001). 14.5% decline in percentage of articles advising flu vaccine (p=0.002). 495.5% increase in percentage of articles recommending social distancing (p=0.001). 1,368.9% increase in percentage articles recommending increased ventilation (p=0.0004). Advice to cover cough/sneeze declined by 52.8% (p=0.041); advice to disinfect surfaces declined by 76.7% (p=0.038). Conclusions and Relevance: Expert advice on flu prevention as presented in top 10 U.S. newspapers changed significantly during the COVID-19 pandemic. The strategies discussed more frequently are not currently recommended by CDC. This is relevant information for public health leaders as they address ongoing issues of trust and credibility.
Because of the large number of infected individuals, an estimate of the future burdens of the long-term consequences of SARS-CoV-2 infection is needed. This systematic review examined associations between SARS-CoV-2 infection and incidence of categories of and selected chronic conditions, by age and severity of infection (inpatient vs. outpatient/mixed care). MEDLINE and EMBASE were searched (Jan 1, 2020 to Oct 4, 2022) and reference lists scanned. We included observational studies from high-income OECD countries with a control group adjusting for sex and comorbidities. Identified records underwent a two-stage screening process. Two reviewers screened 50% of titles/abstracts, after which DistillerAI acted as second reviewer. Two reviewers then screened the full texts of stage one selections. One reviewer extracted data and assessed risk of bias; results were verified by another. Random-effects meta-analysis estimated pooled hazard ratios (HR). GRADE assessed certainty of the evidence. Twenty-five studies were included. Among the outpatient/mixed SARS-CoV-2 care group, there is high certainty of a small-to-moderate increase (i.e., HR 1.26 to 1.99) among adults ≥65 years of any cardiovascular condition, and of little-to-no difference (i.e., HR 0.75 to 1.25) in anxiety disorders for individuals <18, 18-64, and ≥65 years old. Among 18-64 and ≥65 year-olds receiving outpatient/mixed care there are probably (moderate certainty) large increases (i.e., HR ≥2.0) in encephalopathy, interstitial lung disease, and respiratory failure. After SARS-CoV-2 infection, there is probably an increased risk of diagnoses for some chronic conditions; whether the magnitude of risk will remain stable into the future is uncertain.
Importance: Removing the epidemic waves and reducing the instability level of an endemic critical point of COVID-19 dynamics are fundamental to the control of COVID-19 in the US. Objective: To develop new mathematic models and investigate when and how will the COVID-19 in the US be evolved to endemic. Design, Setting, and Participants: To solve the problem of whether mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic, we defined a set of nonlinear ordinary differential equations as a mathematical model of transmission dynamics of COVID-19 with vaccination. Multi-stability analysis was conducted on the data for the daily reported new cases of infection from January 12, 2021 to December 12, 2022 across 50 states in the US using the developed dynamic model of COVID-19 and limit cycle theory. Main Outcomes and Measures: Eigenvalues and the reproduction number under the disease-free equilibrium point and endemic equilibrium point were used to assess the stability of the disease-free equilibrium point and endemic equilibrium point. Both analytic analysis and numerical methods were used to determine the instability level of new cases of COVID-19 in the US under the different types of equilibrium points and to investigate how the system moves back and forth between stable and unstable states of the system and how the pandemic COVD-19 will evolve to endemic in the US. Results: Multi-stability analysis identified two types of critical equilibrium points, disease-free endemic equilibrium points in the COVID-19 transmission dynamic system. The transmissional, recovery, vaccination rates and vaccination effectiveness during the major transmission waves of COVID-19 across 50 states in the US were estimated. These parameters in the model varied over time and across the 50 states. The eigenvalues and the reproduction numbers R0 and R0end in the disease-free equilibrium point and endemic equilibrium point were estimated to assess stability and classify equilibrium points. They also varied from state to state. The impacts of the transmission and vaccination parameters on the stability of COVID-19 were simulated, and stability attractor regions of these parameters were found and ranked for all 50 states in the US. The US experienced five major epidemic waves, endemic equilibrium points of which across 50 states were all in unstable states. However, the combination of re-infection and vaccination (hybrid immunity) may provide strong protection against COVID-19 infection, and stability analysis showed that these unstable equilibrium points were toward stable points. Theoretical analysis and real data analysis showed that additional epidemic waves may be possible in the future, but COVID-19 across all 50 sates in the US is rapidly moving toward stable endemicity. Conclusions and Relevance: Both stability analysis and observed epidemic waves in the US indicated that the pandemic might not end with the disappearance of the virus. However, after enough people gained immune protection from vaccination and from natural infection, COVID-19 would become an endemic disease, as the stability analysis showed. Educating the population about multiple epidemic waves of the transmission dynamics of COVID-19 and designing optimal vaccine rollout are crucial for controlling the pandemic of COVID-19 and its evolving to endemic.
Background: To characterize interferences between Streptococcus pneumoniae and SARS-CoV-2 we investigated the longitudinal patterns of viral infection and pneumococcal carriage in households infected with SARS-CoV-2. Methods: SARS-CoV-2 and pneumococcus were detected with quantitative molecular methods in saliva from members of eighty participating households. Samples were collected between October 2020 and January 2021 from n=197 adults and n=118 children of which n=176 adults and n=98 children had a complete set of ten samples collected within 42 days since enrolment. Time-dependent Cox models were used to evaluate the associations between SARS-CoV-2 and pneumococcal carriage. Results: In the entire cohort, cumulative pneumococcal carriage and SARS-CoV-2 infection rates were 58% and 65%, respectively. Pneumococcal abundances were associated with an increased risk of SARS-CoV-2 infection (HR 1.14, 95% CI, 1.01-1.29, P=0.04) and delayed clearance of SARS-CoV-2 infection (HR 0.90, 95% CI, 0.82-0.99, P=0.03). Elevated viral loads were observed among pneumococcal carriers and individuals with high overall bacterial 16S abundances, however, there were no longitudinal differences in viral loads in linear mixed-effects models. Individuals with high 16S abundances displayed delayed viral clearance (HR 0.65, 95% CI 0.55-0.78, P<0.0001). Conclusions: Although we found insufficient evidence for a strong impact of SARS-CoV-2 infection on pneumococcal carriage. Results from the current study suggest that pneumococcal carriers may have an increased risk of SARS-CoV-2 infection and high pneumococcal abundances and 16S abundances may be associated with elevated viral loads and delayed clearance of SARS-CoV-2 infection.
MG Granules Improve COVID-19 Efficacy and Safety of Convalescent Exercise Tolerance - Condition: COVID-19
Intervention: Drug: Manzi Guben granules
Sponsors: Second Affiliated Hospital, School of Medicine, Zhejiang University; The First Affiliated Hospital of Zhejiang Chinese Medical University; Hangzhou Hospital of Traditional Chinese Medicine; Suzhou Hospital of Traditional Chinese Medicine
Not yet recruiting
Effects of Pilates in Patients With Post- -COVID-19 Syndrome: Controlled and Randomized Clinical Trial - Condition: COVID-19
Intervention: Procedure: Pilates Exercises
Sponsor: Michele de Aguiar Zacaria
Recruiting
Heterologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine in Children 12-17 Years of Age - Condition: COVID-19
Intervention: Biological: SARS-CoV-2 subunit protein recombinant vaccine
Sponsors: PT Bio Farma; Faculty of Medicine Universitas Padjadjaran
Not yet recruiting
Exercise Training Six-Months After Discharge in Post-COVID-19 Syndrome - Condition: COVID-19 Pneumonia
Intervention: Other: Aerobic exercise and strength training
Sponsor: Ukbe Sirayder
Completed
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone) - Condition: Covid19
Interventions: Drug: Fluticasone; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm A (Ivmermectin 400) - Condition: Covid19
Interventions: Drug: Ivermectin; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
Improving Adherence to COVID-19 Prevention Behaviours: Test of Persuasive Messages - Condition: COVID-19
Intervention: Behavioral: Persuasive Appeal
Sponsor: University of Calgary
Completed
Counter-Regulatory Hormonal and Stress Systems in Patients With COVID-19 - Condition: COVID-19
Intervention: Diagnostic Test: Blood sampling
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Completed
Exploratory Efficacy of N-Acetylcysteine in Patients With History of COVID-19 - Condition: COVID-19
Interventions: Drug: N-Acetylcysteine; Drug: Placebo
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Active, not recruiting
A Specific miRNA Encoded by SARS-CoV-2 as a Diagnostic Tool to Predict Disease Severity in COVID-19 Patients - Condition: COVID-19
Intervention: Diagnostic Test: miRNA analysis in plasma
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Completed
Study for Efficacy and Safety Assessment of the Drug RADAMIN®VIRO for COVID-19 Postexposure Prophylaxis - Condition: COVID-19
Interventions: Drug: Double-Stranded RNA sodium salt; Drug: Placebo
Sponsor: Promomed, LLC
Completed
CONFIDENCE: a Multicomponent Clinic-based Intervention to Promote COVID-19 Vaccine Intention and Uptake Among Diverse Youth and Adolescents - Condition: COVID-19 Vaccination
Intervention: Behavioral: CONFIDENCE
Sponsors: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC; Baystate Health
Not yet recruiting
Cognitive Rehabilitation for People With Cognitive Covid19 - Condition: Long Covid19
Intervention: Behavioral: Cognitive rehabilitation
Sponsors: University College, London; Bangor University; St George’s University Hospitals NHS Foundation Trust; University of Brighton; University Hospital Southampton NHS Foundation Trust; Greater Manchester Mental Health NHS Foundation Trust
Recruiting
MGC Health COVID-19 & Flu A+B Home Multi Test Usability Study - Conditions: COVID-19; Influenza A; Influenza B
Interventions: Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test; Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test (2 to 13 y/o)
Sponsors: Medical Group Care, LLC; CSSi Life Sciences
Recruiting
Washing COVID-19 Away With a Hypertonic Seawater Nasal Irrigation Solution - Condition: SARS-CoV2 Infection
Intervention: Other: Hypertonic seawater solution
Sponsor: Larissa University Hospital
Completed
Anakinra-An Interleukin-1 Receptor Antagonist for COVID-19 - BACKGROUND: Coronavirus disease (COVID-19) caused by SARS-CoV-2 virus caused a global pandemic in 2019. There are limited pharmacologic options available. The Food and Drug Administration initiated an emergency use authorization process to expedite pharmacologic agents to treat COVID-19. There are several agents available through the emergency use authorization process, ritonavir-boosted nirmatrelvir, remdesivir, and baricitinib. Anakinra is an interleukin (IL)-1 receptor antagonist that…
New Potential Anti-SARS-CoV-2 and Anti-cancer Therapies of Chitosan Derivatives and its Nanoparticles: Preparation and Characterization - Chitosan (CS) is a biopolymer and has reactive amine/hydroxyl groups facilitated its modifications. The purpose of this study is improvement of (CS) physicochemical properties and its capabilities as antiviral and antitumor through modification with 1-(2-oxoindolin-3-ylidene)thiosemicarbazide (3A) or 1-(5-fluoro-2-oxoindolin-3-ylidene)thiosemicarbazide (3B) via crosslinking of poly(ethylene glycol)diglycidylether (PEGDGE) using microwave-assisted as green technique gives (CS-I) and (CS-II)…
Broad learning solution for rapid diagnosis of COVID-19 - COVID-19 has put all of humanity in a health dilemma as it spreads rapidly. For many infectious diseases, the delay of detection results leads to the spread of infection and an increase in healthcare costs. COVID-19 diagnostic methods rely on a large number of redundant labeled data and time-consuming data training processes to obtain satisfactory results. However, as a new epidemic, obtaining large clinical datasets is still challenging, which will inhibit the training of deep models. And a…
Sulfated polysaccharides as multi target molecules to fight COVID 19 and comorbidities - The majority of research to combat SARS-CoV-2 infection exploits the adaptive immune system, but innate immunity, the first line of defense against pathogenic microbes, is equally important in understanding and controlling infectious diseases. Various cellular mechanisms provide physiochemical barriers to microbe infection in mucosal membranes and epithelia, with extracellular polysaccharides, particularly sulfated polysaccharides, being among the most widespread and potent extracellular and…
Computational framework to understand the clinical stages of COVID-19 and visualization of time course for various treatment strategies - COVID-19 is known to be regulated by multiple factors such as delayed immune response, impaired T cell activation, elevated levels of pro-inflammatory cytokines affecting the disease severity. Clinical management of the disease remains challenging due to interplay of various factors as drug candidates may elicit different responses depending on stage of the disease. In this context, we propose a computational framework which provides insights into the interaction between viral infection and…
The detectable anti-interferon-γ autoantibodies in COVID-19 patients may be associated with disease severity - CONCLUSION: Our results would add COVID-19 to the list of diseases with the presence of neutralizing anti-IFN-γ autoAbs. Anti-IFN-γ autoantibodies positivity is a potential predictor of severe/critical COVID-19.
CDK4/6 inhibitor palbociclib promotes SARS-CoV-2 cell entry by down-regulating SKP2 dependent ACE2 degradation - Coronavirus disease 2019 (COVID-19) outbreak has become a global pandemic. CDK4/6 inhibitor palbociclib was reported to be one of the top-scored repurposed drugs to treat COVID-19. As the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry, expression level of angiotensin-converting enzyme 2 (ACE2) is closely related to SARS-CoV-2 infection. In this study, we demonstrated that palbociclib and other methods could arrest cells in G0/G1 phase and up-regulate ACE2 mRNA…
Qimai Feiluoping decoction inhibits mitochondrial complex I-mediated oxidative stress to ameliorate bleomycin-induced pulmonary fibrosis - CONCLUSION: It concludes that QM treatment could treat PF by inhibiting mitochondrial complex I-mediated mitochondrial oxidated stress injury, which could offer new insights into the pharmacological mechanisms of QM in the clinical application of PF patients.
Protein nanopore reveals the renin-angiotensin system crosstalk with single-amino-acid resolution - The discovery of crosstalk effects on the renin-angiotensin system (RAS) is limited by the lack of approaches to quantitatively monitor, in real time, multiple components with subtle differences and short half-lives. Here we report a nanopore framework to quantitatively determine the effect of the hidden crosstalk between angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) on RAS. By developing an engineered aerolysin nanopore capable of single-amino-acid resolution,…
Identification of global inhibitors of cellular glycosylation - Small molecule inhibitors of glycosylation enzymes are valuable tools for dissecting glycan functions and potential drug candidates. Screening for inhibitors of glycosyltransferases are mainly performed by in vitro enzyme assays with difficulties moving candidates to cells and animals. Here, we circumvent this by employing a cell-based screening assay using glycoengineered cells expressing tailored reporter glycoproteins. We focused on GalNAc-type O-glycosylation and selected the GalNAc-T11…
SARS-CoV-2 omicron variants are susceptible in vitro to Artemisia annua hot water extracts - CONCLUSIONS: A. annua hot-water extracts (tea infusions) continue to show efficacy against SARS-CoV-2 and its rapidly evolving variants and deserve greater attention as a possible cost-effective therapeutic.
In silico analysis of dietary polyphenols and their gut microbial metabolites suggest inhibition of SARS-CoV-2 infection, replication, and host inflammatory mediators - The outcome of SARS-CoV-2 infection ranges from asymptomatic to severe COVID-19 and death resulting from an exaggerated immune response termed cytokine storm. Epidemiological data have associated consumption of a high-quality plant-based diet with decreased incidence and severity of COVID-19. Dietary polyphenols and their microbial metabolites (MMs) have anti-viral and anti-inflammatory activities. Autodock Vina and Yasara were used in molecular docking and dynamics studies to investigate…
Hypochlorous acid inactivates oral pathogens and a SARS-CoV-2-surrogate - CONCLUSIONS: HOCl solution (45-60 ppm) is still effective against oral pathogens and SAR-CoV-2 surrogate viruses even in the presence of saliva and after passing through the dental unit water line. This study indicates that the HOCl solution can be used as therapeutic water or mouthwash and may ultimately reduce the risk of airborne infection in dental practice.
Targeting ACE2-BRD4 crosstalk in colorectal cancer and the deregulation of DNA repair and apoptosis - ACE2 overexpression in colorectal cancer patients might increase susceptibility to SARS-CoV-2 infection. We report that knockdown, forced overexpression, and pharmacologic inhibition in human colon cancer cells targeted ACE2-BRD4 crosstalk to mediate marked changes in DNA damage/repair and apoptosis. In colorectal cancer patients for whom high ACE2 plus high BRD4 expression is predictive of poor survival, pan-BET inhibition would need to consider proviral/antiviral actions of different BET…
Bidirectional and persistent immunomodulation of Astragalus polysaccharide as an adjuvant of influenza and recombinant SARS-CoV-2 vaccine - Respiratory viral infections, such as coronavirus disease of 2019 (COVID-19) and influenza, cause significant morbidity and mortality and have become a worldwide public health concern with tremendous economic and societal burdens. Vaccination is a major strategy for preventing infections. However, some new vaccines have an unmet need for impairing responses in certain individuals, especially COVID-19 vaccines, despite ongoing vaccine and adjuvant research. Here, we evaluated the effectiveness of…