Influenza Activity and Estimated Vaccine Effectiveness During the 2025-2026 Influenza Season.

IMPORTANCE

Antigenically drifted influenza A(H3N2) J.2.4.1 (subclade K) viruses predominated during the 2025-2026 Northern Hemisphere influenza season.

OBJECTIVE

To describe influenza activity and burden, characterize subclade K, evaluate susceptibility to influenza antivirals and postinfluenza vaccination antibodies, and estimate vaccine effectiveness.

DESIGN, SETTING, AND

PARTICIPANTS

This surveillance study used multiple data sources, including (1) national surveillance of influenza-positive respiratory specimens collected by approximately 300 clinical laboratories and 100 public health laboratories from October 1, 2025, through March 14, 2026, a subset of which were further characterized; (2) serologic data of people who received 2025-2026 influenza vaccines; (3) influenza admissions data from the Influenza Hospitalization Surveillance Network (ie, 10% of US population) and the associated estimates of US burden; and (4) test-negative, case-control vaccine effectiveness estimates from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network.

EXPOSURES: Influenza infection, hospitalization, and vaccination.

MAIN OUTCOMES AND MEASURES: Outcomes included influenza virus type, subtype, and clade; antiviral susceptibility; immunogenicity; influenza-associated outpatient and emergency department visits, hospitalizations, and mortality; estimated influenza illnesses, hospitalizations, and death; and estimated vaccine effectiveness.

RESULTS

As of March 14, 2026, of the 55 318 influenza-positive respiratory specimens tested by public health laboratories, most (50 291 specimens [90.9%]) were influenza A, of which 40 779 (81.1%) were subtyped and 35 801 (87.8%) were A(H3N2). Of the 1754 characterized A(H3N2) viruses, most (1626 specimens [92.7%]) were subclade K. Postinfluenza vaccination neutralizing geometric mean antibody titers against subclade K were reduced 1.62 (95% CI, 1.29-2.02)-fold compared with the vaccine virus. All 1729 tested A(H3N2) viruses were sensitive to antivirals. Of the 27 881 recorded influenza hospitalizations, 15 426 (54.7%) were among female patients, and 15 051 (54.0%) were among patients aged 65 years or older. The estimated cumulative influenza-associated hospitalization rate was 80.0 per 100 000 which would correlate with estimates of between 28 000 000 to 49 000 000 illnesses, 360 000 to 740 000 hospitalizations, and 22 000 to 74 000 deaths in the US during the 2025-2026 season. Adjusted interim vaccine effectiveness estimates against influenza-associated emergency department or urgent care encounters and hospitalizations were 35% (95% CI, 33%-38%) and 27% (95% CI, 21%-34%), respectively.

CONCLUSIONS AND RELEVANCE: This surveillance study found that while antigenically drifted viruses predominated and caused substantial morbidity and mortality, influenza vaccines were associated with a reduced risk of influenza among those who were vaccinated, and recommended antivirals remained effective.