Estimating the population effectiveness of interventions against COVID-19 in France: A modelling study

Epidemics, Год журнала: 2024, Номер 46, С. 100744 - 100744

Опубликована: Фев. 2, 2024

Non-pharmaceutical interventions (NPIs) and vaccines have been widely used to manage the COVID-19 pandemic. However, uncertainty persists regarding effectiveness of these due data quality issues, methodological challenges, differing contextual factors. Accurate estimation their effects is crucial for future epidemic preparedness. To address this, we developed a population-based mechanistic model that includes impact NPIs on SARS-CoV-2 transmission hospitalization rates. Our statistical approach estimated all parameters in one step, accurately propagating uncertainty. We fitted comprehensive epidemiological France from March 2020 October 2021. With same model, simulated scenarios vaccine rollout. The first lockdown was most effective, reducing by 84% (95% confidence interval (CI) 83-85). Subsequent lockdowns had diminished (reduction 74% (69-77) 11% (9-18), respectively). A 6 pm curfew more effective than at 8 (68% (66-69) vs. 48% (45-49) reduction), while school closures reduced 15% (12-18). In scenario without before November 2021, predicted 159,000 or 194% prediction (PI) 74-424) deaths 1,488,000 340% (136-689) hospitalizations. If available after 100 days, over 71,000 (16,507-204,249) 384,000 (88,579-1,020,386) hospitalizations could averted. results highlight substantial NPIs, including curfews, controlling also demonstrate value days objective Coalition Epidemic Preparedness Innovations (CEPI) initiative availability.

Язык: Английский

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Serodynamics: a primer and synthetic review of methods for epidemiological inference using serological data

Epidemics, Год журнала: 2024, Номер 49, С. 100806 - 100806

Опубликована: Ноя. 30, 2024

We present a review and primer of methods to understand epidemiological dynamics identify past exposures from serological data, referred as serodynamics. discuss processing interpreting data prior fitting serodynamical models, approaches for estimating trends exposures, ranging serocatalytic models applied binary serostatus more complex incorporating quantitative antibody measurements immunological understanding. Although these are seemingly disparate, we demonstrate how they derived within common mathematical framework. Finally, key areas methodological development improve scientific discovery public health insights in seroepidemiology.

Язык: Английский

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BioNTech/Pfizer (BNT162b2) COVID-19 mRNA vaccine: manufacturing, immunogenicity, efficacy and safety

Prospects in Pharmaceutical Sciences, Год журнала: 2025, Номер 23(1), С. 31 - 46

Опубликована: Фев. 5, 2025

The investigation into the Pfizer vaccine for Coronavirus (COVID-19) is a vital area of study, especially given ongoing global pandemic. safety, efficacy, and overall credibility remain contentious issues. This research seeks to deliver thorough unbiased examination vaccine's production process, its functional mechanism, immunogenic properties. It also presents latest scientific findings concerning safety efficacy based on recent clinical trials. analysis conducted with impartiality, ensuring that data outcomes are reported without prejudice. BNT162b2 nucleoside-modified mRNA formulated lipid nanoparticles, designed encode spike protein SARS-CoV-2, which stimulates an immune response in those vaccinated. Pfizer-BioNTech COVID-19 incorporates advanced cap 1 analog, specific 5′ UTR region derived from human α-globin gene, optimized downstream Kozak consensus sequence. sequence has been enhanced by introducing N1-methyl-Ψ, substituting all uridines, including stop codons. 3′-UTR includes sequences amino-terminal enhancer split mitochondrial 12S rRNA, alongside 30-mer poly(A) tail 10-nucleotide linker, together improve extend expression. As May 30, 2024, U.S. National Library Medicine (Clinicaltrials.gov) lists 1,314 trials globally related vaccines, 135 specifically focusing BNT162b2, most Phase II III. Numerous have confirmed effectiveness no major adverse effects majority studies. Access reliable information public awareness informed vaccination decisions, emphasizing importance update medical literature, as evaluated across various age groups against new SARS-CoV-2 variants.

Язык: Английский

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A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B

PLoS Computational Biology, Год журнала: 2025, Номер 21(5), С. e1012322 - e1012322

Опубликована: Май 6, 2025

Chronic hepatitis B virus (HBV) infection is strongly associated with increased risk of liver cancer and cirrhosis. While existing treatments effectively inhibit the HBV life cycle, viral rebound frequently occurs following treatment interruption. Consequently, functional cure rates chronic remain low there interest in a novel modality, capsid assembly modulators (CAMs). Here, we develop multiscale mathematical model CAM infection. By fitting to participant data from phase I trial first-generation vebicorvir, estimate drug’s dose-dependent effectiveness identify physiological mechanisms that drive observed biphasic decline DNA RNA, mechanistic differences between HBeAg-positive negative Finally, demonstrate analytically numerically relative change RNA more accurately reflects antiviral than DNA.

Язык: Английский

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Negative associations of age and lifestyle factors with the antibody response to the COVID-19 vaccine BNT162b2 in health workers from Spain

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 30, 2025

Introduction Despite the high efficacy of anti-coronavirus disease 2019 (COVID-19) BNT162b2 vaccine (Comirnaty ® , Pfizer-BioNTech), variability in antibody titers following vaccination has been described. However, little is known about risk factors that are associated with a poorer response to vaccine. Methodology We studied determinants humoral anti-COVID-19 200 healthcare workers followed up for 2 years. Serum samples were tested anti-spike immunoglobulin G (IgG) levels and neutralizing against selected severe acute respiratory syndrome coronavirus (SARS-CoV-2) variants at different time points after primary booster vaccinations. Anthropometric data clinical lifestyle information also collected. Statistical analyses consisted linear logistical regressions point estimations Mann–Whitney, Friedman, generalized estimating equations repeated measures. Results After vaccination, percentage seroconverted individuals peaked 5 weeks but declined 1 year; however, they remained administration. first dose vaccine, negative associations IgG age ( β = −0.01, 95%CI −0.03 −0.003), smoking habit −1.08, −1.70 −0.46), alcohol consumption −1.43, −2.20 −0.65) found. With regard retained stepwise multivariate model: anti-Delta antibodies hip circumference (OR 1.07, 1.01–1.12, p 0.008), anti-Delta-K 1.06, 1.01–1.11, 0.007), anti-Omicron Mediterranean diet score 0.74, 0.58–0.96, 0.023). Conclusion Lifestyle habits had an association

Язык: Английский

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Neutralizing Antibody Levels as a Correlate of Protection Against SARS‐CoV‐2 Infection: A Modeling Analysis

Clinical Pharmacology & Therapeutics, Год журнала: 2023, Номер 115(1), С. 86 - 94

Опубликована: Окт. 5, 2023

Although anti‐severe acute respiratory syndrome‐coronavirus 2 antibody kinetics have been described in large populations of vaccinated individuals, we still poorly understand how they evolve during a natural infection and this impacts viral clearance. For that purpose, analyzed the both load neutralizing levels prospective cohort individuals with alpha variant. Using mathematical model, show progressive increase antibodies leads to shortening half‐life infected cells infectious particles. We estimated activity reached 90% its maximal level within 11 days after symptom onset could reduce circulating virus by 6‐fold factor, thus playing key role achieve rapid conducted simulation study predict more general context protection conferred pre‐existing neutralization titers, due either vaccination or prior infection. predicted activity, as measured 50% effective dose > 10 3 , 46% risk having detectable standard polymerase chain reaction assays 98% above threshold infectiousness. Our model shows be used define correlates against transmission.

Язык: Английский

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Modulation of T-Cell-Dependent Humoral Immune Response to Influenza Vaccine by Multiple Antioxidant/Immunomodulatory Micronutrient Supplementation

Vaccines, Год журнала: 2024, Номер 12(7), С. 743 - 743

Опубликована: Июль 4, 2024

Notwithstanding prevalence gaps in micronutrients supporting immune functions, the significance of their deficits/supplementation for efficacy vaccines is underinvestigated. Thus, influence supplementation combining vitamins C and D, zinc, selenium, manganese, N-acetyl cysteine on correlates/surrogates protection conferred by a quadrivalent influenza vaccine (QIV) mice was investigated. The starting 5 days before first two QIV injections given 28 apart increased serum titres total neutralizing IgG against each four strains from QIV. Accordingly, frequencies germinal center B cells, follicular CD4+ T helper (Th) IL-21-producing Th cells secondary lymphoid organs (SLOs). Additionally, improved already response to second injection augmenting not only antibody production, but also IgG2a response, which important virus clearance, through favoring Th1 differentiation as indicated (IFN-γ)/Th2 (IL-4) signature cytokine level ratio upon restimulation SLO cell cultures. This most likely partly reflected antioxidant action supplement splenic redox status analyses. study provides solid scientific background further research aimed at repurposing use this safe inexpensive micronutrient combination improve vaccine.

Язык: Английский

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Prediction of long-term humoral response induced by the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo vaccine against Ebola

npj Vaccines, Год журнала: 2023, Номер 8(1)

Опубликована: Ноя. 8, 2023

The persistence of the long-term immune response induced by heterologous Ad26.ZEBOV, MVA-BN-Filo two-dose vaccination regimen against Ebola has been investigated in several clinical trials. Longitudinal data on IgG-binding antibody concentrations were analyzed from 487 participants enrolled six Phase I and II trials conducted EBOVAC1 EBOVAC2 consortia. A model based ordinary differential equations describing dynamics antibodies short- long-lived antibody-secreting cells (ASCs) was used to humoral 7 days after second a follow-up period 2 years. Using population-based approach, we first assessed robustness model, which originally estimated data, all data. Then longevity identified factors that influence these dynamics. We half-life ASC at least 15 years found an geographic region, sex, age dynamics, with longer Europeans women higher production younger participants.

Язык: Английский

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Vaccine and antiviral drug promise for preventing post-acute sequelae of COVID-19, and their combination for its treatment

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Авг. 9, 2024

Introduction Most healthy individuals recover from acute SARS-CoV-2 infection, whereas a remarkable number continues to suffer unexplained symptoms, known as Long COVID or post-acute COVID-19 syndrome (PACS). It is therefore imperative that methods for preventing and treating the onset of PASC be investigated with utmost urgency. Methods A mathematical model immune response vaccination viral infection SARS-CoV-2, incorporating memory cells, was developed. Results discussion Similar our previous model, persistent observed by residual virus in host, implying possibility chronic inflammation delayed recovery tissue injury. Pre-infectious antiviral medication administered during can reduce load; however, they show no beneficial effects infection. Therefore, impact these treatments on PASC, which has been clinically observed, mainly attributed their role severe damage caused infections. For patients cause an immediate rapid increase load, followed temporary decrease over approximately one year. The former effectively suppressed coadministration medications, indicating this combination promising treatment PASC.

Язык: Английский

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Ensemble modeling of SARS-CoV-2 immune dynamics in immunologically naïve rhesus macaques predicts that potent, early innate immune responses drive viral elimination

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 7, 2024

Introduction An unprecedented breadth of longitudinal viral and multi-scale immunological data has been gathered during SARS-CoV-2 infection. However, due to the high complexity, non-linearity, multi-dimensionality, mixed anatomic sampling, possible autocorrelation available immune data, it is challenging identify components innate adaptive response that drive elimination. Novel mathematical models analytical approaches are required synthesize contemporaneously cytokine, transcriptomic, flow cytometry, antibody response, load into a coherent story control, ultimately discriminate drivers mild versus severe Methods We investigated dataset describing innate, specific T cell, responses in lung early late stages infection immunologically naïve rhesus macaques. used multi-model inference ensemble modeling from ecology weather forecasting compare combine various competing models. Results discussion Model outputs suggest plays crucial role controlling infection, while CD4+ cells correspond later elimination, anti-spike IgG antibodies do not impact dynamics. Among numerous genes potentially contributing we identified IFI27 as most closely linked decline. A 90% knockdown our validated model resulted ~10-fold increase peak Our approach provides novel methodological framework for future analyses similar complex, non-linear multi-component immunologic sets.

Язык: Английский

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