Flu vaccination modestly reduced severe outcomes

The 2025–2026 flu vaccine modestly reduced flu-related emergency visits and hospitalizations among U.S. veterans.
*Target trial emulation cohort study; Level 2b (OCEBM).

Citation

Xie Y, Choi T, Al-Aly Z. Effectiveness of the 2025–2026 seasonal influenza vaccine among U.S. veterans: an observational study. eClinicalMedicine. 2026;100:104183. doi:10.1016/j.eclinm.2026.104183

Background

Flu vaccine benefit varies each season, especially when circulating virus strains differ from vaccine strains. The 2025–2026 season was dominated by a changed influenza A(H3N2) strain, raising concern about reduced protection.

Patients

1,401,492 participant-trials among U.S. Veterans Affairs users with in-person primary care visits from September 15, 2025, to February 28, 2026. Exclusions included recent flu vaccination, recent flu infection, end-of-life or long-term care, advanced illness, recent emergency care or hospitalization, acute illness at the visit, and high predicted short-term hospitalization or death risk.

Intervention

Receipt of the 2025–2026 seasonal flu vaccine at the primary care visit.

Control

No seasonal flu vaccine at that visit or during follow-up.

Outcome

Primary: composite of flu-associated emergency department visit or hospitalization. Components were also analyzed separately.

Follow-up Period

Median 175 days, through May 7, 2026.

Results

Outcome Vaccine effectiveness Absolute risk difference NNT
Emergency visit or hospitalization (primary) 21.95% (95% CI 16.08 to 27.65) 4.94 fewer per 10,000 (95% CI 3.47 to 6.49 fewer) 2,024
Emergency visit 22.25% (95% CI 16.38 to 27.94) 5.01 fewer per 10,000 (95% CI 3.53 to 6.55 fewer) 1,996
Hospitalization 31.84% (95% CI 14.77 to 46.27) 1.08 fewer per 10,000 (95% CI 0.44 to 1.82 fewer) 9,259

CI = confidence interval; NNT = number needed to treat.

Analyses estimated per-protocol effects. The control was not current recommended preventive care. Emergency visits largely drove the composite result.

Limitations

Observational design leaves possible residual bias. Veterans were mostly older men, limiting generalizability. Vaccines or outcomes outside Veterans Affairs care may have been missed. Absolute individual benefit was small despite population-level value.

Funding

U.S. Department of Veterans Affairs; no funder role; unpaid Pfizer consulting reported.

Clinical Application

Continue offering seasonal flu vaccination; protection was modest but clinically relevant, especially for preventing severe flu outcomes during mismatch seasons.