Flu vaccines retained benefit during drifted H3N2 season

Clinical takeaway: Continue recommending influenza vaccination and prompt antiviral treatment for eligible patients, even when circulating strains have drifted from vaccine components. During the 2025-2026 season, vaccination still reduced influenza-related emergency, urgent care, and hospital encounters, and circulating viruses remained susceptible to recommended antivirals.

The 2025-2026 US influenza season was moderately severe overall and high severity among children, driven largely by antigenically drifted influenza A(H3N2) viruses.

Researchers analyzed US influenza data from September 2025 through March 2026, including national laboratory surveillance, viral genetic and antigenic characterization, vaccine immunogenicity, hospitalization surveillance, disease burden estimates, antiviral susceptibility testing, and interim vaccine effectiveness data.

Among influenza-positive specimens tested by public health laboratories, 90.9% were influenza A. Of subtyped influenza A viruses, 87.8% were A(H3N2). Most genetically characterized A(H3N2) viruses belonged to subclade K, a drifted strain that differed antigenically from the 2025-2026 vaccine reference virus.

The drift had measurable effects on vaccine-induced antibody responses. Postvaccination neutralizing antibody titers against subclade K were reduced compared with the vaccine virus. Even so, vaccination was still associated with lower risk of medically attended influenza.

Interim vaccine effectiveness against any influenza was 35% for influenza-associated emergency department or urgent care encounters and 27% for influenza-associated hospitalizations. Effectiveness against emergency or urgent care visits was similar in children and adults, at 37% and 34%, respectively. Against hospitalization, estimated effectiveness was 47% among children and 27% among adults.

The season caused substantial morbidity and mortality. Through March 14, 2026, FluSurv-NET recorded 27,881 laboratory-confirmed influenza-associated hospitalizations. The cumulative hospitalization rate was 80.0 per 100,000 people, the third highest at that point in the season since 2010-2011. Adults aged 65 years and older had the highest hospitalization rate, followed by children younger than 5 years.

Based on surveillance data, CDC estimated that the season had caused 28 million to 49 million influenza illnesses, 360,000 to 740,000 hospitalizations, and 22,000 to 74,000 deaths in the US by mid-March 2026.

Antiviral susceptibility remained reassuring. All tested A(H3N2) viruses, including subclade K viruses, were susceptible to oseltamivir, peramivir, zanamivir, and baloxavir. A small number of A(H1N1)pdm09 and B/Victoria viruses showed reduced susceptibility to specific antivirals, but recommended antivirals remained effective overall.

The authors noted that influenza activity could continue beyond the study period and that estimates may change as additional data accrue. They emphasized that vaccination and antiviral recommendations remain in effect while influenza continues to circulate, particularly for hospitalized patients, those with severe or complicated illness, and patients at higher risk for complications.

Source: Azziz-Baumgartner E, et al. 2026 June 17. JAMA Netw Open. Influenza activity and estimated vaccine effectiveness during the 2025-2026 influenza season