Antiviral treatment was associated with lower risks of all-cause hospitalization, intensive care unit admission, and mortality among nonhospitalized patients with laboratory-confirmed influenza in a multicenter retrospective cohort study.
Researchers evaluated outcomes among patients with influenza using a global electronic health record database. After propensity score matching, 426,275 patients who received antiviral therapy within 2 days of diagnosis were compared with an equal number of untreated patients.
Hospitalization occurred in 1.54% of antiviral-treated patients compared with 1.70% of untreated patients (risk ratio [RR], 0.91). Emergency department visits occurred in 3.54% vs 4.41% (RR, 0.80). Intensive care unit (ICU) admission occurred in 0.09% vs 0.10% (RR, 0.84), and mortality in 0.02% vs 0.04% (RR, 0.60). Absolute risk reductions were 1.56 per 1,000 patients for hospitalization and 0.15 per 1,000 for mortality.
The retrospective cohort study used the TriNetX global network, which includes electronic health record data from more than 177 million patients across 150 health care organizations, with data extracted from 2014 through 2025. Patients were excluded if they required hospitalization within 2 days of diagnosis or had outcome events or influenza-related complications during the peri-diagnosis period. Outcomes were assessed from 3 to 30 days following diagnosis.
Antiviral exposure included oseltamivir, laninamivir, zanamivir, peramivir, and baloxavir initiated within 2 days of diagnosis.
Subgroup analyses showed consistent reductions in hospitalization among adult patients (RR, 0.91) and pediatric patients (RR, 0.79). Regionally, reductions were observed in North America (RR, 0.88) and Asia-Pacific (RR, 0.46). By influenza type, the association was present for type A (RR, 0.89) but not statistically significant for type B.
Oseltamivir was associated with fewer events across all secondary outcomes, whereas baloxavir was associated with fewer primary outcome events (RR, 0.28) but not with ICU admission or mortality. No statistically significant reductions in primary or secondary outcomes were observed for zanamivir, laninamivir, or peramivir.
In sensitivity analyses, lower hospitalization risk was observed when the treatment window was limited to the same day as diagnosis (RR, 0.82). Among patients aged 2 to 64 years without high-risk comorbidities, fewer outcome events were reported for hospitalization (RR, 0.76), emergency department visits (RR, 0.68), and ICU admission (RR, 0.48).
The researchers noted several limitations, including potential unmeasured confounding despite propensity score matching, incomplete documentation of symptoms and vaccination status, possible immortal time bias, and the inability to establish causality. Differences in antiviral administration routes may also have influenced outcomes.
“Antiviral treatment was negatively associated with hospitalization, ICU admission, and mortality. The results need to be interpreted with caution, given limitations,” wrote lead study researcher Taito Kitano, DrPH, of Nara Prefecture General Medical Center in Japan, and colleagues.
Kitano reported receiving research funding from the Japan Foundation for Pediatric Research and bioMérieux. Shinya Tsuzuki reported funding from the Japan Society for the Promotion of Science, Japan Science and Technology Agency, Ministry of Health, Labour and Welfare, and Japan Institute for Health Security, as well as honoraria from Gilead Sciences. Sayaka Yoshida reported a grant from Tauns Laboratories.
Source: BMC Medicine
