BACKGROUND: The 2024-2025 influenza season was the most severe in the United States (US) since 2017-2018, with co-circulation of both influenza A virus subtypes (H1N1 and H3N2). Influenza vaccine effectiveness (VE) has varied by season, setting, and patient characteristics.
METHODS: Using electronic healthcare encounter data from 7 VISION sites in 8 US states, we evaluated influenza VE against influenza-associated hospitalizations and emergency department or urgent care (ED/UC) encounters from October 2024 to April 2025 among children aged 6 months-17 years and adults aged ≥ 18 years. Using a test-negative, case-control design, we compared the odds of influenza vaccination between acute respiratory illness encounters with a positive (cases) versus negative (controls) test for influenza by molecular assay, adjusting for confounders.
RESULTS: Analyses included 108 618 encounters (5764 hospitalizations and 102 854 ED/UC encounters) among children and 309 483 encounters (76 072 hospitalizations and 233 411 ED/UC encounters) among adults. Among children across care settings, 17.0% (6097/35 765) of cases versus 29.4% (21 449/72 853) of controls were vaccinated. Among adults, 28.2% (21 832/77 477) of cases versus 44.2% (102 560/232 006) of controls were vaccinated. VE was 51% (95% confidence interval [95% CI]: 41%-60%) against influenza-associated hospitalizations and 54% (95% CI: 52%-55%) against influenza-associated ED/UC encounters among children. VE was 43% (95% CI: 41%-46%) against influenza-associated hospitalizations and 49% (95% CI: 47%-50%) against influenza-associated ED/UC encounters among adults.
CONCLUSIONS: Influenza vaccination provided protection against influenza-associated hospitalizations and ED/UC encounters among children and adults in the US during the severe 2024-2025 influenza season. These findings support influenza vaccination as an important tool to reduce influenza.