Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 23, 2024

Abstract Viral clearance, antibody response and the mutagenic effect of molnupiravir has not been elucidated in at-risk populations. Non-hospitalised participants within 5 days SARS-CoV-2 symptoms randomised to receive (n = 253) or Usual Care 324) were recruited study viral dynamics on whole genome sequence from 1437 genomes. Molnupiravir accelerates load decline, but virus is detectable by Day most cases. At 14 (9 post-treatment), associated with significantly higher persistence lower anti-SARS-CoV-2 spike titres compared Care. Serial sequencing reveals increased mutagenesis treatment. Persistence RNA at group transition mutations following treatment cessation. viability similar both groups post-molnupiravir treated samples cultured up 9 post cessation The current 5-day course too short. Longer courses should be tested reduce risk potentially transmissible molnupiravir-mutated variants being generated. Trial registration: ISRCTN30448031

Язык: Английский

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SARS-CoV-2 evolution on a dynamic immune landscape

Nature, Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Abstract Since the onset of pandemic, many SARS-CoV-2 variants have emerged, exhibiting substantial evolution in virus’ spike protein 1 , main target neutralizing antibodies 2 . A plausible hypothesis proposes that virus evolves to evade antibody-mediated neutralization (vaccine- or infection-induced) maximize its ability infect an immunologically experienced population 1,3 Because viral infection induces antibodies, may thus navigate on a dynamic immune landscape is shaped by local history. Here we developed comprehensive mechanistic model, incorporating deep mutational scanning data 4,5 antibody pharmacokinetics and regional genomic surveillance data, predict variant-specific relative number susceptible individuals over time. We show this quantity precisely matched historical variant dynamics, predicted future dynamics explained global differences dynamics. Our work strongly suggests ongoing pandemic continues shape immunity, which determines variant’s transmit, defining fitness. The model can be applied any region utilizing allows contextualizing risk assessment provides information for vaccine design.

Язык: Английский

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Assessing changes in incubation period, serial interval, and generation time of SARS-CoV-2 variants of concern: a systematic review and meta-analysis

BMC Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Сен. 29, 2023

Abstract Background After the first COVID-19 wave caused by ancestral lineage, pandemic has been fueled from continuous emergence of new SARS-CoV-2 variants. Understanding key time-to-event periods for each emerging variant concern is critical as it can provide insights into future trajectory virus and help inform outbreak preparedness response planning. Here, we aim to examine how incubation period, serial interval, generation time have changed lineage different variants concern. Methods We conducted a systematic review meta-analysis that synthesized estimates (both realized intrinsic) Alpha, Beta, Omicron SARS-CoV-2. Results Our study included 280 records obtained 147 household studies, contact tracing or studies where epidemiological links were known. With variant, found progressive shortening analyzed periods, although did not find statistically significant differences between subvariants. BA.1 had shortest pooled period (3.49 days, 95% CI: 3.13–4.86 days), BA.5 interval (2.37 1.71–3.04 (2.99 2.48–3.49 days). Only one estimate intrinsic was available subvariants: 6.84 days (95% CrI: 5.72–8.60 days) BA.1. The highest investigated period. also observed shorter compared across lineages. When pooling lineages, considerable heterogeneities ( I 2 > 80%; refers percentage total variation due heterogeneity rather than chance), possibly resulting populations (e.g., deployed interventions, social behavior, demographic characteristics). Conclusions supports importance conducting investigations monitor changes in transmission patterns. findings highlight time, which lead epidemics spread faster, with larger peak incidence, harder control. consistently suggesting feature potential pre-symptomatic transmission. These observations are instrumental plan waves.

Язык: Английский

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Zoonosis and zooanthroponosis of emerging respiratory viruses

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 13

Опубликована: Янв. 5, 2024

Lung infections in Influenza-Like Illness (ILI) are triggered by a variety of respiratory viruses. All human pandemics have been caused the members two major virus families, namely Orthomyxoviridae (influenza A viruses (IAVs); subtypes H1N1, H2N2, and H3N2) Coronaviridae (severe acute syndrome coronavirus 2, SARS−CoV−2). These acquired some adaptive changes known intermediate host including domestic birds (IAVs) or unknown (SARS-CoV-2) following transmission from their natural reservoirs (e.g. migratory bats, respectively). Verily, these substitutions facilitated crossing species barriers to infect humans phenomenon that is as zoonosis. Besides, aided variant strain transmit horizontally other contact non-human animal pets wild animals (zooanthroponosis). Herein we discuss main zoonotic reverse-zoonosis events occurred during last influenza A/H1N1 SARS-CoV-2. We also highlight impact interspecies pandemic on evolution possible prophylactic therapeutic interventions. Based information available presented this review article, it important close monitoring viral zoonosis reverse strains within One-Health One-World approach mitigate unforeseen risks, such resistance limited

Язык: Английский

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A unifying model to explain frequent SARS-CoV-2 rebound after nirmatrelvir treatment and limited prophylactic efficacy

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 28, 2024

Abstract In a pivotal trial (EPIC-HR), 5-day course of oral ritonavir-boosted nirmatrelvir, given early during symptomatic SARS-CoV-2 infection (within three days symptoms onset), decreased hospitalization and death by 89.1% nasal viral load 0.87 log relative to placebo in high-risk individuals. Yet, nirmatrelvir/ritonavir failed as post-exposure prophylaxis trial, frequent rebound has been observed subsequent cohorts. We develop mathematical model capturing viral-immune dynamics nirmatrelvir pharmacokinetics that recapitulates loads from this another clinical (PLATCOV). Our results suggest nirmatrelvir’s vivo potency is significantly lower than vitro assays predict. According our model, maximally potent agent would reduce the approximately 3.5 logs at 5 days. The identifies earlier initiation shorter treatment duration are key predictors post-treatment rebound. Extension 10 for Omicron variant vaccinated individuals, rather increasing dose or dosing frequency, predicted incidence significantly.

Язык: Английский

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Defining the Critical Requisites for Accurate Simulation of SARS‐CoV‐2 Viral Dynamics: Patient Characteristics and Data Collection Protocol

Journal of Medical Virology, Год журнала: 2025, Номер 97(1)

Опубликована: Янв. 1, 2025

ABSTRACT Mathematical models of viral dynamics are crucial in understanding infection trajectories. However, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) load data often includes limited sparse observations with significant heterogeneity. This study aims to: (1) understand the impact patient characteristics shaping temporal trajectory and (2) establish a collection protocol (DCP) to reliably reconstruct individual We collected longitudinal for SARS‐CoV‐2 Delta Omicron variants from 243 patients Singapore (2021–2022). A model was calibrated using patients' age, symptom presence, vaccination status. accessed associations between these aspects linear regression models. evaluated accuracy estimation under different simulated DCPs by varying numbers, test frequencies, intervals. Older unvaccinated individuals had longer shedding duration due lower cell death rates. Higher peak loads were found older, symptomatic, vaccinated individuals, earlier peaks younger individuals. Symptom presence resulted shorter time diagnosis. To accurately estimate dynamics, more frequent tests, intervals, larger samples required. For 500 patients, 21‐day follow‐up measurements every 3 days an 8‐day daily optimal variants, respectively. Patient significantly impacted dynamics. Our analytic approach recommended can enhance preparedness response emerging pathogens beyond SARS‐CoV‐2.

Язык: Английский

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Testing-isolation interventions will likely be insufficient to contain future novel disease outbreaks

Mathematical Biosciences, Год журнала: 2025, Номер unknown, С. 109432 - 109432

Опубликована: Март 1, 2025

Язык: Английский

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flepiMoP: The evolution of a flexible infectious disease modeling pipeline during the COVID-19 pandemic

Epidemics, Год журнала: 2024, Номер 47, С. 100753 - 100753

Опубликована: Март 2, 2024

The COVID-19 pandemic led to an unprecedented demand for projections of disease burden and healthcare utilization under scenarios ranging from unmitigated spread strict social distancing policies. In response, members the Johns Hopkins Infectious Disease Dynamics Group developed flepiMoP (formerly called COVID Scenario Modeling Pipeline), a comprehensive open-source software pipeline designed creating simulating compartmental models infectious transmission inferring parameters through these models. framework has been used extensively produce short-term forecasts longer-term scenario at state county level in US, other countries various geographic scales, more recently seasonal influenza. this paper, we highlight how evolved throughout address changing epidemiological dynamics, new interventions, shifts policy-relevant model outputs. As reached mature state, provide detailed overview flepiMoP's key features remaining limitations, thereby distributing its documentation as flexible powerful tool researchers public health professionals rapidly build deploy large-scale complex any pathogen demographic setup.

Язык: Английский

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The Asymptomatic Proportion of SARS‐CoV‐2 Omicron Variant Infections in Households: A Systematic Review

Influenza and Other Respiratory Viruses, Год журнала: 2024, Номер 18(7)

Опубликована: Июль 1, 2024

ABSTRACT Understanding the clinical spectrum of SARS‐CoV‐2 infection, including asymptomatic fraction, is important as individuals are still able to infect other and contribute ongoing transmission. The WHO Unity Household transmission investigation (HHTI) protocol provides a platform for prospective systematic collection high‐quality clinical, epidemiological, serological virological data from confirmed cases their household contacts. These can be used understand key severity transmissibility parameters—including proportion—in relation local epidemic context help inform public health response. We aimed estimate proportion Omicron variant infections in Unity‐aligned HHTIs. conducted review meta‐analysis alignment with PRISMA 2020 guidelines registered our on PROSPERO (CRD42022378648). searched EMBASE, Web Science, MEDLINE bioRxiv medRxiv 1 November 2021 22 August 2023. identified 8368 records, which 98 underwent full text review. only three studies extraction, substantial variation study design corresponding estimates proportion. As result, we did not generate pooled or I 2 metric. limited number quality that highlights need improved preparedness response capabilities facilitate robust HHTI implementation, analysis reporting, better national, regional global risk assessments policymaking.

Язык: Английский

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Best practices for estimating and reporting epidemiological delay distributions of infectious diseases

PLoS Computational Biology, Год журнала: 2024, Номер 20(10), С. e1012520 - e1012520

Опубликована: Окт. 28, 2024

Epidemiological delays are key quantities that inform public health policy and clinical practice. They used as inputs for mathematical statistical models, which in turn can guide control strategies. In recent work, we found censoring, right truncation, dynamical bias were rarely addressed correctly when estimating these biases large enough to have knock-on impacts across a number of use cases. Here, formulate checklist best practices reporting epidemiological delays. We also provide flowchart practitioners based on their data. Our examples focused the incubation period serial interval due importance outbreak response modeling, but our recommendations applicable other The recommendations, literature experience delay distributions during responses, help improve robustness utility reported estimates guidance evaluation downstream transmission models or analyses.

Язык: Английский

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