Longitudinal viral shedding and antibody response characteristics of men with acute infection of monkeypox virus: a prospective cohort study

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 27, 2024

Abstract Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and environmental fomites 77 acute MPXV infections (HIV co-infection: N = 42) were collected every two to three days used detection DNA, surface protein specific antibodies neutralizing titers. Skin lesions show 100% positivity rate followed by rectum (88.16%), saliva (83.78%) oropharynx (78.95%). Positivity decreases rapidly after 7 post symptom onset (d.p.o), while the maintain a similar skin lesions. Viral are among lesions, oropharynx, with peak at about 6 d.p.o. In contrast, viral levels in beginning decrease thereafter. 52.66% fomite swabs positive highest (69.89%) air-conditioning air outlets. High seropositivity A29L (100%) H3L (94.74%) detected, correlation between IgG endpoint titers only found A29L. Most indexes HIV Non-HIV participants, rectitis associated higher loads rectum.

Language: Английский

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How robust are estimates of key parameters in standard viral dynamic models?

PLoS Computational Biology, Journal Year: 2024, Volume and Issue: 20(4), P. e1011437 - e1011437

Published: April 16, 2024

Mathematical models of viral infection have been developed, fitted to data, and provide insight into disease pathogenesis for multiple agents that cause chronic infection, including HIV, hepatitis C, B virus. However, acute infections or during the stage infections, load data are often collected after symptoms develop, usually around peak load. Consequently, we frequently lack in initial phase growth, i.e., when pre-symptomatic transmission events occur. Missing may make estimating time infectious period, parameters dynamic models, such as cell rate, difficult. having extra information, average load, improve robustness estimation. Here, evaluated estimates key model prior is missing, know values some and/or from Although sensitive quality amount available particularly pre-peak, other important understanding pathogenesis, loss rate infected cells, less sensitive. Viral infectivity production affecting fits. Fixing their literature can help estimate remaining pre-peak missing limited. We find a growth underestimates by several days, leading shorter predicted phase. On hand, knowing (e.g., epidemiological data) fixing it results good dynamical even absence early data. While ways approximate our also suggest these available, needed more precisely.

Language: 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, Journal Year: 2025, Volume and Issue: 97(1)

Published: Jan. 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.

Language: Английский

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The impact of remdesivir on SARS-CoV-2 evolution in vivo

JCI Insight, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

The impact of remdesivir on SARS-CoV-2 diversity and evolution in vivo has remained unclear. In this single-center, retrospective cohort study, we assessed diversification over time a hospitalized patients who did or not receive remdesivir. Whole genome sequencing was performed 98 paired specimens collected from 49 before after administration. Genetic divergence between significantly different what observed the drug. However, when comparing minority variants, several positions showed preferential treatment, which were associated with variants concern. Most notably, administration resulted strong selection for nonsynonymous mutation nsp12, G671S, previously enhanced viral fitness. This same found enriched second 143 inpatients compared to controls. Only one other implicated resistance (nsp12:V792I) be preferentially selected These data suggest that replicative fitness may presence antiviral therapy as an indirect means overcome selective pressure.

Language: Английский

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Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

ABSTRACT In a subset of SARS-CoV-2-infected individuals treated with the antiviral nirmatrelvir-ritonavir, virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used mathematical model to describe longitudinal viral load dynamics 51 20 whom rebounded. Target cell preservation, either by robust innate immune response or initiation N-R near time symptom onset, coupled incomplete clearance, appears be main factor leading rebound. Moreover, occurrence is likely influenced treatment relative progression infection, earlier treatments higher chance A comparison an untreated cohort suggests that early nirmatrelvir-ritonavir may associated delay in onset adaptive response. Nevertheless, our demonstrates extending course 10-day regimen greatly diminish people mild-to-moderate COVID-19 and who at high risk severe disease. Altogether, results suggest some individuals, standard 5-day starting around completely eliminate virus. Thus, after ends, can if effective has fully developed. These findings on role target preservation clearance also offer possible explanation for other SARS-CoV-2. IMPORTANCE Nirmatrelvir-ritonavir initial reduction followed once stopped. show timing influence stops growth preserves cells but lead full adequately developed, remaining Our provide insights into help develop better strategies minimize possibility.

Language: Английский

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Transarterial Chemoembolization for Patients With Hepatocellular Carcinoma Using Miriplatin Without the Need for Hydration

Clinical and Translational Science, Journal Year: 2025, Volume and Issue: 18(3)

Published: March 1, 2025

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, with a rising incidence. The therapeutic choice for HCC transarterial chemoembolization (TACE). While standard protocol of TACE adopts cisplatin, application cisplatin needs hydration before and after procedure to alleviate adverse effects on kidney function. Miriplatin, lipophilic platinum complex, enables omission periprocedural compared cisplatin-based TACE. This study aimed compare survival benefit between miriplatin-based Briefly, retrospective cohort in single hospital was designed. Patients complicated by vascular invasion or distant metastasis were excluded. Background variability adjusted using propensity score matching; then, overall rates Gehan-Breslow-Wilcoxon test. As result, miriplatin administered 166 120 patients procedures. After adjusting baseline characteristics including age, sex, tumor burden, functional hepatic reserve, year, HbA1c, pair 99-patient cohorts generated. Overall survivals did not differ significantly, despite poorer serum creatinine at (0.89 vs. 0.74 mg/dL, p < 0.0001) fewer being prepared through prehydration (18 38 ones, = 0.0025) group than group. median time 1490 days 1,830 (p 0.4022; ratio 0.814; 95% confidence interval 0.546-1.215). In conclusion, will who cannot tolerate perioperative hydration.

Language: Английский

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The use of wastewater surveillance to estimate SARS-CoV-2 fecal viral shedding pattern and identify time periods with intensified transmission

BMC Public Health, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 24, 2025

Wastewater-based surveillance is an important tool for monitoring the COVID-19 pandemic. However, it remains challenging to translate wastewater SARS-CoV-2 viral load infection number, due unclear shedding patterns in and potential differences between variants. We utilized comprehensive data estimates of prevalence (i.e., source shedding) available New York City (NYC) characterize fecal pattern over multiple waves. collected measurements NYC during August 31, 2020 – 29, 2023 (N = 3794 samples). Combining with (number infectious individuals including those not detected as cases), we estimated time-lag, duration, per-infection rate ancestral/Iota, Delta, Omicron variants, separately. also developed a procedure identify occasions intensified transmission. Models suggested likely starts around same time lasts slightly longer than respiratory tract shedding. Estimated was highest ancestral/Iota variant wave, at 1.44 (95% CI: 1.35 1.53) billion RNA copies per day (measured by RT-qPCR), decreased 20% 50-60% Delta wave period, respectively. identified 200 which exceeded expected level any city's 14 sewersheds. These anomalies disproportionally occurred late January, April—early May, early August, from late-November late-December, frequencies exceeding expectation assuming random occurrence (P < 0.05; bootstrapping test). may be useful understanding changes underlying help quantify transmission severity time. have demonstrated that can support identification periods potentially

Language: Английский

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A Modular Mathematical Model of the Immune Response for Investigating the Pathogenesis of Infectious Diseases

Viruses, Journal Year: 2025, Volume and Issue: 17(5), P. 589 - 589

Published: April 22, 2025

The COVID-19 pandemic highlighted the importance of mathematical modeling for understanding viral infection dynamics and accelerated its application into immunological research. Collaborative efforts among international research groups yielded a wealth experimental data, which facilitated model development validation. This study focuses on developing modular immune response, capturing interactions between innate adaptive immunity, with an to SARS-CoV-2 infection. was validated using data from middle-aged individuals moderate progression, including measurements load in upper lower airways, serum antibodies, CD4+ CD8+ T cells, interleukin-6 levels. Parameter optimization sensitivity analysis were performed improve accuracy. Additionally, identifiability conducted assess whether sufficient reliable parameter estimation. verified simulates moderate, severe, critical progressions measured lung epithelium damage, load, IL-6 levels as key indicators disease severity. We also series validation scenarios correctly reproduces biologically relevant behaviors under various conditions, such immunity hyperactivation, co-infection HIV, interferon administration therapeutic strategy. developed component Digital Twin project represents general module that integrates both immunity. It can be utilized further or serve foundation studying other infectious diseases, provided are available.

Language: Английский

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Review: The Landscape of Antiviral Therapy for COVID-19 in the Era of Widespread Population Immunity and Omicron-Lineage Viruses

Clinical Infectious Diseases, Journal Year: 2023, Volume and Issue: 78(4), P. 908 - 917

Published: Nov. 9, 2023

Abstract The goals of coronavirus disease 2019 (COVID-19) antiviral therapy early in the pandemic were to prevent severe disease, hospitalization, and death. As these outcomes have become infrequent age widespread population immunity, objectives shifted. For general population, COVID-19–directed should decrease symptom severity duration minimize infectiousness, for immunocompromised individuals, reduce persistent infection. increased recognition virologic rebound following ritonavir-boosted nirmatrelvir (NMV/r) lack randomized controlled trial data showing benefit acute respiratory syndrome 2 (SARS-CoV-2) infection standard-risk, vaccinated individuals remain major knowledge gaps. Here, we review selected agents immunomodulators currently available or late-stage clinical trials use outpatients. We do not antibody products, convalescent plasma, systemic corticosteroids, IL-6 inhibitors, Janus kinase that Food Drug Administration approval emergency authorization are appropriate

Language: Английский

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Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution.

The Journal of Infectious Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 12, 2024

Abstract Background Efforts are underway to support the development of novel mucosal coronavirus disease 2019 (COVID-19) vaccines. However, there is limited consensus about complementary role immunity in progression and how evaluate immunogenicity This study investigated oral antibody responses viral clearance COVID-19 symptom duration. Methods Participants with polymerase chain reaction (PCR)–confirmed severe acute respiratory syndrome 2 (SARS-CoV-2) infection provided fluid for testing SARS-CoV-2 multiplex assays, nasal swabs reverse-transcription PCR, information at up 8 follow-ups from April 2020 February 2022. Results High moderate anti-spike (S) secretory IgA (SIgA) postinfection was associated significantly faster resolution across age groups effect sizes equivalent prior vaccine time infection. Those high anti-S SIgA cleared virus 14 (95% confidence interval [CI], 10–18) days recovered 9–10 CI, 6–14) earlier. Delayed higher IgG longer recovery. Experiencing symptoms &gt;4 weeks lower anti–receptor-binding domain 15–30 after onset (P &lt; .001). Conclusions Robust early appears recovery symptoms. research underscores importance harmonizing immune response assays new

Language: Английский

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