Skip to main content

Modeling viral #shedding and #symptom #outcomes in #oseltamivir-treated experimental #influenza infection

Abstract

Influenza remains a global public health concern, and although the antiviral drug oseltamivir is widely used to treat infections, questions regarding its actual antiviral efficacy and clinical benefits remain. Here, we evaluated the effects of oseltamivir on viral shedding dynamics in the context of experimental influenza infection. We analyzed individual participant data, including viral load, time to symptom alleviation, and laboratory test measurements, obtained from three publicly available clinical trials involving experimental infections with influenza A and B viruses. We applied mathematical modeling and estimated parameters using a nonlinear mixed-effects model to capture viral infection dynamics. Our analysis revealed that, compared with placebo groups, the oseltamivir-treated groups tended to have lower values in terms of viral load area under the curve, duration of infection, peak viral titer, and time to peak; however, most of these differences were not significant; and no dose-dependent effects were observed. Moreover, there was no significant correlation between time to symptom alleviation and viral load. Some laboratory test parameters showed opposing correlations with symptom-related and viral load-related outcomes. These findings are consistent with distinct mechanisms underlying the symptom-alleviating effects of oseltamivir and its antiviral activity. Our findings suggest that the availability of individual-level data for public use is essential because it enables the evaluation of mechanisms in clinical trials and the development of more appropriate outcome measures.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.05.02.651873v1

____

Comments

Popular posts from this blog

#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

{Excerpt} A novel reassortant Oropouche virus (OROV) lineage (with medium [M], large [L], and small [S] RNA segments : M1L2S2) has driven Brazil's largest and most geographically widespread OROV epidemic , expanding beyond the endemic Amazon basin to establish local transmission across multiple Brazilian states and other previously unaffected Latin American countries . The rapid spread of this lineage underscores its evolutionary potential and reinforces its significance as a public health threat .1 Similar to chikungunya and Zika viruses, expanding arboviruses can exhibit unexpected clinical and epidemiological shifts , including vertical transmissions , neuroinvasive effects, and potentially fatal outcomes.2–4 Although OROV typically causes self-limited febrile illness, accumulating clinical and experimental evidence suggests neurotropic potential .5 This Correspondence describes the first confirmed case of neuroinvasive OROV infection caused by the emergent M1L2S2 lineage in ext...

No evidence of immune #exhaustion after repeated #SARS-CoV-2 #vaccination in vulnerable and healthy populations

Abstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion , which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada . Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was...

Chimeric #hemagglutinin and #M2 #mRNA #vaccine for broad #influenza subtype protection

Abstract Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics , developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy , we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs , as well as highly pathogenic avian influenza . Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies , T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries . In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells . Moreover, Fluaxe immuniza...