Oseltamivir Treatment vs Supportive Care for Seasonal Influenza Requiring Hospitalization.

Importance: Current guidelines recommend oseltamivir treatment for all patients hospitalized with influenza, but this guidance is based on suboptimal evidence. Objective: To evaluate outcomes associated with oseltamivir treatment when compared with supportive care for severe seasonal influenza requiring hospitalization. Design, Setting, and Participants: This retrospective cohort study using target trial emulation included adult patients admitted to hospital with influenza from 30 hospitals in Ontario, Canada, from January 2015 to June 2023. Data were analyzed from November 2024 to March 2025. Exposure: Oseltamivir treatment on hospital day 0 or 1 vs supportive care without oseltamivir. Main Outcome and Measures: The primary outcome was in-hospital mortality. Secondary outcomes included time to being discharged alive and readmission within 30 days. Overlap weighting of propensity scores was used to balance covariates, and a competing risk model was used to compare time to being discharged alive. Results: Of 11 073 patients (mean [SD] age, 72.6 [16.8] years; 5793 female [52.3%]), there were 7632 patients (68.9%) and 3441 patients (31.1%) in the oseltamivir and supportive care groups, respectively. In hospital, 268 patients (3.5%) and 168 patients (4.9%) in the oseltamivir and supportive care groups died, respectively, with an adjusted risk difference of -1.8% (95% CI, -2.8% to -0.9%; P < .001). The oseltamivir treatment group was more likely to be discharged alive (adjusted subdistribution hazard ratio, 1.20; 95% CI, 1.15 to 1.25; P < .001). After discharge, 645 patients (8.5%) and 336 patients (9.8%) were readmitted in the oseltamivir and supportive care groups, respectively, with an adjusted risk difference of -1.5% (95% CI, -2.8% to -0.2%; P = .02). Conclusions and Relevance: In this cohort study of patients hospitalized with influenza, oseltamivir treatment was associated with a lower in-hospital mortality risk, earlier discharge, and lower readmission rate, supporting evidence for the current guideline recommendation of oseltamivir treatment for severe influenza. Clinical trials are needed to definitively answer this question.