Nanomolar anti-SARS-CoV-2 Omicron activity of the host-directed TMPRSS2 inhibitor N-0385 and synergistic action with direct-acting antivirals

Antiviral Research, Journal Year: 2024, Volume and Issue: 225, P. 105869 - 105869

Published: March 26, 2024

SARS-CoV-2 Omicron subvariants with increased transmissibility and immune evasion are spreading globally alarming persistence. Whether the mutations evolution of spike (S) alter viral hijacking human TMPRSS2 for entry remains to be elucidated. This is particularly important investigate because large number diversity S reported since emergence BA.1. Here we report that a molecular determinant all clinical isolates tested in lung cells, including ancestral (BA.1, BA.2, BA.5), contemporary (BQ.1.1, XBB.1.5, EG.5.1) currently circulating BA.2.86. First, used co-transfection assay demonstrate endoproteolytic cleavage by subvariants. Second, found N-0385, highly potent inhibitor, robust inhibitor virus-like particles harbouring protein Third, show N-0385 exhibits nanomolar broad-spectrum antiviral activity against live Calu-3 cells primary patient-derived bronchial epithelial cells. Interestingly, 10-20 times more than repositioned camostat, BA.5, EG.5.1, We further shows broad synergistic clinically approved direct-acting antivirals (DAAs), i.e., remdesivir nirmatrelvir, subvariants, demonstrating potential therapeutic benefits multi-targeted treatment based on DAAs.

Language: Английский

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Padrão de circulação dos vírus influenza A/B e Vírus Sincicial Respiratório (VSR) em Fortaleza, Ceará, após a pandemia de SARS-CoV-2

HSJ., Journal Year: 2025, Volume and Issue: 15, P. e1569 - e1569

Published: Feb. 28, 2025

Objetivo: Investigar os padrões de circulação para vírus respiratórios no período janeiro 2023 a maio 2024 e descrever suas características epidemiológicas na cidade Fortaleza, partir dados obtidos por testes moleculares baseados em PCR tempo real (qPCR). Método: Foi realizado um estudo epidemiológico retrospectivo investigar infecções influenza A/B, Vírus Sincicial Respiratório (VSR) SARS-CoV-2, prevalência incidência desses Fortaleza 2024. Resultado: Houve diferença significativa distribuição casos positivos totais demanda exames entre períodos analisados (p < 0,05). Também foi observada o total causadas SARS-CoV-2 as Influenza = 0,0041) VSR 0,0012) mesmo período. Não foram verificadas diferenças estatísticas RSV nos analisados. As taxas mensais revelaram uma tendência sazonal provocadas VSR. Conclusão: A proporção detecção relação ao número resultados apresentou considerável declínio primeiro semestre 2024, com aumento detecções A/B Dessa forma, evidenciamos mudança padrão respiratórios, revelando restabelecimento do sazonalidade dos após pandemia COVID-19.

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An evaluation of barriers and facilitators to implementing multiplex rapid antigen testing for SARS-CoV-2 and influenza A and B in congregate living settings

Frontiers in Public Health, Journal Year: 2025, Volume and Issue: 13

Published: April 7, 2025

Point of care multiplex rapid antigen testing (RAT) is a tool that can be used to mitigate and respond facility-based infectious disease outbreaks. However, little known about how optimally implement this in congregate living settings (CLSs), including long term homes (LTCHs), retirement (RHs), shelters serving people experiencing homelessness. Our objective was explore the barriers facilitators implementing new device for RAT COVID-19 influenza across CLSs Greater Toronto Area, Canada. Using key informant interviews, we assessed CLSs. Qualitative coding using framework approach identify themes. We Theoretical Domains Framework (TDF) Consolidated Implementation Research (CFIR) individual contextual-level implementation. Identified were then mapped implementation strategies theoretically-rooted frameworks tools. completed 45 interviews with staff at (8 LTCHs, 4 RHs, 12 shelters) between January 2022 March 2023. Four emerged including: limited material resources implementation; insufficient capacity perform testing; complexity reluctance among adopt process. Five described training support CLSs; site-level champions; access materials perceived advantages simultaneous influenza; usability functionality device. Twenty identified through strategy mapping. Multiplex options empower CLS promptly viral respiratory The use evidence-based enhance effectiveness control outbreaks

Language: Английский

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Impact of the COVID-19 pandemic and COVID-19 downgrade on non-COVID-19 respiratory diseases in Japan

Public Health, Journal Year: 2025, Volume and Issue: 243, P. 105719 - 105719

Published: April 14, 2025

A worldwide decrease in the incidence of respiratory diseases during coronavirus disease (COVID-19) pandemic has been reported, largely due to non-pharmaceutical interventions (NPIs). However, impact lifting NPIs remains unclear. In Japan, were lifted rather drastically when COVID-19 was downgraded on May 8, 2023. This study aimed evaluate and its downgrade non-COVID-19 using nationwide databases. Retrospective cohort study. Monthly hospitalisation prescription rates between January 2017 October 2023 collected from JMDC insurance claims database covering 16,485,812 insured individuals. The monthly mortality Japan an open data source published by Ministry Health, Labour Welfare Japan. Interrupted time series analyses seasonal autoregressive integrated moving average models performed. While for such as pneumonia, asthma, aspiration pneumonia decreased pandemic, a step increase hospitalisations these prescriptions anti-asthma drugs observed following downgrade. impacted all age groups; however, more pronounced children aged 0-5 years. Although no immediate increased immediately after downgrading COVID-19, presumably because older people less affected than children.

Language: Английский

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Multi-omic profiling reveals early immunological indicators for identifying COVID-19 Progressors

Clinical Immunology, Journal Year: 2023, Volume and Issue: 256, P. 109808 - 109808

Published: Oct. 16, 2023

We sought to better understand the immune response during immediate post-diagnosis phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by identifying molecular associations with longitudinal disease outcomes. Multi-omic analyses identified differences in cell composition, cytokine levels, and subset-specific transcriptomic epigenomic signatures between individuals on a more serious trajectory (Progressors) as compared those milder course (Non-progressors). Higher levels multiple cytokines were observed Progressors, IL-6 showing largest difference. Blood monocyte subsets also skewed, comparative decrease non-classical CD14-CD16+ intermediate CD14+CD16+ monocytes. In lymphocytes, CD8+ T effector memory cells displayed gene expression signature consistent stronger activation Progressors. These early stage observations could serve basis for development prognostic biomarkers risk interventional strategies improve management COVID-19. BACKGROUND: Much literature post-SARS-CoV-2 infection has been post-acute phases infection. TRANSLATIONAL SIGNIFICANCE: found at time points approximately 160 participants. multi-omic progressing needing significant medical intervention non-progressors. widespread evidence state increased inflammation associated progression, supported range epigenomic, transcriptomic, proteomic signatures. The we support other findings later biomarker or inform strategies.

Language: Английский

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Burden of human metapneumovirus infections among children with acute respiratory tract infections attending a Tertiary Care Hospital, Kathmandu

BMC Pediatrics, Journal Year: 2023, Volume and Issue: 23(1)

Published: Aug. 7, 2023

Acute respiratory infections (ARIs) are one of the most common causes mortality and morbidity worldwide. Every year millions children suffer from viral tract (RTIs) ranging mild to severe illnesses. Human Metapneumovirus (HMPV) is among frequent viruses responsible for RTIs. However, HMPV their severity have not been explored yet in Nepal.Therefore, study was focused on other potential etiologies or co-infections using multiplex PCR attending Kanti Children's Hospital assessed clinical characteristics as well found co-infections. A hospital-based cross-sectional designed a convenience sampling method used enroll less than 15 years with flu-like symptoms both outpatients inpatients departments over three months period.HMPV infection (13.3%) predominant different ARIs Hospital. The more prevalent age group (21.8%). Cough fever were features present all infected followed by rhinorrhea, sore throat, wheezing. HMPV-positive diagnosed pneumonia (42.9%), bronchiolitis (28.5%), upper (14.3%), asthma (14.3%). prevalence high late winter (14.3%) early spring (13.5%).This provides baseline information associated co-infection differential diagnosis based molecular methods also comparison presentations syndromes.

Language: Английский

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Outcomes of COVID-19 and Influenza in Cerebral Palsy Patients Hospitalized in the United States: Comparative Study of a Nationwide Database

Viruses, Journal Year: 2024, Volume and Issue: 16(8), P. 1284 - 1284

Published: Aug. 12, 2024

Patients with cerebral palsy (CP) are particularly vulnerable to respiratory infections, yet comparative outcomes between COVID-19 and influenza in this population remain underexplored. Using the National Inpatient Sample from 2020–2021, we performed a retrospective analysis of hospital data for adults CP diagnosed either or influenza. The study aimed compare these infections provide insights into their impact on population. We assessed in-hospital mortality, complications, length stay (LOS), hospitalization costs, discharge dispositions. Multivariable logistic regression propensity score matching were used adjust confounders, enhancing analytical rigor our study. cohort comprised 12,025 patients—10,560 1465 patients had higher mortality rate (10.8% vs. 3.1%, p = 0.001), an adjusted odds ratio 3.2 (95% CI: 1.6–6.4). They also experienced extended LOS by average 2.7 days. substantially increases health burden hospitalized compared influenza, as evidenced rates, longer stays, increased costs. These findings highlight urgent need tailored strategies effectively manage reduce high-risk group.

Language: Английский

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Risk factors for death associated with severe influenza in children and the impact of the COVID-19 pandemic on clinical characteristics

Frontiers in Pediatrics, Journal Year: 2023, Volume and Issue: 11

Published: Sept. 12, 2023

To summarize the clinical features of severe influenza in children and high-risk factors for influenza-related deaths to raise awareness among pediatricians.A retrospective study manifestations, laboratory tests, diagnosis treatment 243 with admitted Shenzhen Children's Hospital from January 2009 December 2022 was conducted. Univariate logistic regression analysis Boruta were also performed identify potentially critical characteristics associated death, clinically significant used further multivariate analysis. Subject receiver operating characteristic (ROC) curves applied assess efficacy death-related independent risk predict death influenza.There 169 male 74 female patients influenza, a median age 3 years 2 months 77.4% under six. There 46 cases (18.9%) group. The most common pathogen Influenza A virus (IAV) (81.5%). complication group influenza-associated acute necrotizing encephalopathy (ANE [52.2%]). Severe decreased significantly during COVID-19 pandemic, 5 years, high predominance neurological symptoms such as ANE (P = 0.001), being H3N2 < 0.001). D-dimer, respiratory distress syndrome (ARDS), (ANE) death. Furthermore, ROC showed that combined had early diagnostic value deaths.Neurological disorders are more after pandemic. infection can cause serious multisystem complications ARDS ANE, D-dimer has predictive determination prognosis influenza.

Language: Английский

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COVID-19 waves in an urban setting 2020–2022: an electronic medical record analysis

Frontiers in Public Health, Journal Year: 2024, Volume and Issue: 12

Published: Jan. 29, 2024

Background Global and national surveillance efforts have tracked COVID-19 incidence clinical outcomes, but few studies compared comorbid conditions outcomes across each wave of the pandemic. We analyzed data from registry a large urban healthcare system to determine associations between presenting comorbidities during Methods for all inpatients outpatients with March 2020 through September 2022 ( N = 44,499). Clinical were death, hospitalization, intensive care unit (ICU) admission. Demographic overall wave. Unadjusted multivariable logistic regressions performed explore age, sex, race, ethnicity, comorbidities, mortality. Results Waves 2 3 (Alpha Delta variants) associated greater hospitalizations, ICU admissions, mortality than other variants. Chronic pulmonary disease was most common condition age groups waves. Mortality rates higher in older patients decreased later In every wave, renal disease, congestive heart failure, cerebrovascular diabetes, chronic disease. Multivariable analysis found that liver significantly mortality, admission, diabetes hospitalization Conclusion The is valuable resource identify risk factors outcomes. Our findings may inform stratification planning based on conditions.

Language: Английский

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Influenza-Associated Outcomes and Healthcare Utilization by Race and Ethnicity in the USA: a Retrospective Cohort Study Using the National Inpatient Sample Database

Journal of Racial and Ethnic Health Disparities, Journal Year: 2024, Volume and Issue: unknown

Published: March 27, 2024

Language: Английский

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