Association of antiviral use for influenza among non-severe cases with subsequent hospitalization and mortality

BACKGROUND: Evidence regarding a preventive impact of antiviral medication for influenza on hospitalization or mortality among non-severe cases is scarce. The objective of this study was to assess the association between the use of antiviral medications in non-hospitalized patients with influenza and their subsequent hospitalization and mortality. METHODS: This multi-center retrospective cohort study used TriNetX, a global database to assess the clinical impact of antiviral medications (oseltamivir, laninamivir, zanamivir, peramivir, and baloxavir) for influenza among non-hospitalized patients. The outcomes included hospitalization, emergency department visit, intensive care unit (ICU) admission, and mortality between 3 and 30 days following influenza diagnosis with the 2-day window period between diagnosis and antiviral administration. Propensity score matching with a 1:1 ratio was conducted to estimate the risk ratio (RR). RESULTS: A total of 1,016,581 patients with influenza were identified. After matching, 426,275 patients from each cohort were compared. The antiviral-treated group was associated with lower risks of hospitalization (RR 0.91; 95% confidence interval 0.85-0.95; p < 0.001); emergency department visits (RR 0.80; 95% CI 0.79-0.82; p < 0.001), ICU admission (RR 0.84; 95% CI 0.73-0.97; p = 0.016); and mortality (RR 0.60; 95% CI 0.47-0.77; p < 0.001). The sensitivity analysis revealed that the statistical significance in hospitalization was maintained by replacing the 2-day window period with 0 days (RR 0.82; 95% CI 0.79-0.84; p < 0.001). The sensitivity analysis limited to those aged 2 to 64 years without any high-risk comorbidities in the antiviral-treated group compared to the antiviral-untreated group showed fewer outcome events for hospitalization (RR 0.76; 95% CI 0.68-0.85; p < 0.001); ED visit (RR 0.68; 95% CI 0.65-0.71; p < 0.001); and ICU admission (RR 0.48; 95% CI 0.30-0.78; p = 0.002). CONCLUSIONS: Antiviral treatment was negatively associated with hospitalization, ICU admission, and mortality. The results need to be interpreted with caution, given limitations.