2025-2026 Flu Season: Reduced Vaccine Match May Lead to Increased Transmission and Severity, Experts Warn

Several recent reports suggest the 2025–26 influenza season in the United States may carry higher-than-usual risk, driven in part by the emergence of a mutated H3N2 subclade K variant and signals of reduced vaccine match. Influenza activity in the US remains low nationally but is increasing, primarily among children, with H3N2 accounting for approximately 72% of subtyped influenza A viruses as of mid-November, according to CDC surveillance data.¹

The H3N2 Subclade K Impact So Far This Season

The variant H3N2 subclade K carries 7 mutations in key positions of the hemagglutinin protein relative to the 2025–26 northern hemisphere vaccine strain, and has been detected globally.¹ Between May and November 2025, subclade K accounted for 33% of all H3N2 sequences deposited in the Global Initiative on Sharing All Influenza Data (GISAID) worldwide, and 47% in the European Union and European Economic Area, according to the European Centre for Disease Prevention and Control.² The variant has been detected in Japan, the United Kingdom, and Canada, where it has driven early-season influenza activity.²

Real-world vaccine effectiveness data from the UK provide critical early insights.³ In England, where subclade K has dominated the early 2025–26 season, vaccine effectiveness against influenza-related emergency department attendance and hospital admission was 72–75% in children and adolescents under 18 years, and 32–39% in adults, according to a preprint published by the UK Health Security Agency.³ These figures fall within typical ranges for seasonal influenza vaccine effectiveness, which generally runs between 30% and 60%, though the durability of this protection as the season progresses remains uncertain, according to the agency preprint.³

US Influenza Season Update

In the US, surveillance data through mid-November showed seasonal influenza activity remains low but is increasing, with 71.9% of subtyped influenza A viruses identified as H3N2.⁴ The CDC has not published detailed subclade information in its FluView reports, though early genomic sequencing from the US indicates that approximately half of H3N2 viruses analyzed are subclade K.⁴ Limited national surveillance during the recent federal government shutdown created data gaps that have since been partially addressed as reporting resumed.⁴

From a public health perspective, the 2025–26 vaccine was formulated before subclade K emerged and targets the earlier J.2 reference strain.³ Post-infection ferret antisera raised against the northern hemisphere 2025–26 vaccine strains showed reduced reactivity to subclade K viruses, aligning with World Health Organization reports.³ Several influenza researchers note that this constitutes antigenic "drift" rather than a full "shift," yet even drift with reduced vaccine match can lead to higher incidence and severity.

This is the Year for a Flu Shot

"If there's ever a year to get a flu vaccine, this is the year," Scott Hensley, PhD, a microbiologist and influenza vaccine scientist at the University of Pennsylvania told STAT News last week,⁵ emphasizing that historical data from seasons with vaccine mismatch, such as 2014–15, show vaccination can still reduce rates of hospitalization or severe disease even when effectiveness against infection is lower.⁵

Clinical manifestations of subclade K infection remain consistent with typical influenza—fever, cough, myalgias, and fatigue—but the variant's apparent increased transmissibility or immune-escape potential may contribute to larger caseloads or more hospitalizations in vulnerable populations.⁴ The 2024–25 US influenza season was classified as high severity overall and for all age groups, marking the first high-severity season since 2017–18. While consecutive severe seasons are uncommon, epidemiologists note that H3N2-dominant seasons have historically correlated with greater severity of illness in older adults and lower overall vaccine effectiveness.⁴

The CDC estimates that there have been at least 41 million illnesses so far this season and, based on data from FluSurv-NET, the cumulative hospitalization rate for this season is the highest observed since the 2010-2011 season, with 540,000 recorded to date. There have been 23,000 influenza-related deaths this season.⁴

Action Steps for Primary Care

For practicing clinicians and particularly for primary care clinicians, there are a number of action steps you can take as the respiratory virus season continues:

• Encourage immunization for all patients 6 months of age and older per CDC recommendations, even in a year of uncertain vaccine match. Vaccination remains the primary defense against severe disease, hospitalization, and death from influenza.
• Maintain vigilance for earlier-than-usual seasonal onset, especially in older adults, children, and immunocompromised patients. H3N2-predominant seasons typically cause more severe illness in these populations.
• When influenza is suspected in patients at high risk of complications, consider prompt antiviral treatment, even before test results, as timely therapy remains a key intervention consistent with CDC guidance.
• Advise everyone on non-vaccine preventive measures: hand hygiene for at least 20 seconds, avoiding large indoor gatherings when symptomatic, and considering masks in crowded public indoor settings for high-risk individuals.
• Be aware that reduced vaccine effectiveness against infection does not necessarily indicate reduced effectiveness against severe outcomes. Even partial protection significantly reduces healthcare burden and mortality risk.

References

1. Weekly US Influenza Surveillance Report: key updates for week 46, ending November 15, 2025. Centers for Disease Control and Prevention. November 21, 2025. Accessed November 24, 2025. https://www.cdc.gov/fluview/surveillance/2025-week-46.html
2. European Centre for Disease Prevention and Control. Threat Assessment Brief – Assessing the risk of influenza for the EU/EEA in the context of increasing circulation of A(H3N2) subclade K – 20 November 2025. ECDC: Stockholm; 2025. Accessed November 24, 2025. https://www.ecdc.europa.eu/en/publications-data/threat-assessment-brief-assessing-risk-influenza-november-2025
3. Kirsebom FCM, Thompson C, Talts T, et al. Early influenza virus characterisation and vaccine effectiveness in England in autumn 2025, a period dominated by influenza A(H3N2) subclade K. Euro Surveill. 2025;30(46):pii=2500854. doi:10.2807/1560-7917.ES.2025.30.46.2500854
4. Weekly US Influenza Surveillance Report: key updates for week 46, ending November 15, 2025. Centers for Disease Control and Prevention. Nov. 21, 2025. Accessed November 24, 2025. https://www.cdc.gov/fluview/surveillance/2025-week-46.html
5. Branswell H. Is a bad flu season on the way? Experts see reason to be anxious. STATNews. November 20, 2025. Accessed November 24, 2025. https://www.statnews.com/2025/11/20/flu-season-2025-vaccinations-still-helpful-h3n2-subclade-k
6. Influenza (Flu). Centers for Disease Control and Prevention. Accessed November 24, 2025. https://www.cdc.gov/fluview/surveillance/2025-week-10.html