Influenza vaccines reduce severe disease safely

Recent evidence supports annual influenza vaccination to reduce severe illness without new safety concerns.
*Systematic review of mixed intervention studies; Level 2 (OCEBM).

Citation

Senerth E, Sheikholeslamian SM, Sivakumaran K, et al. Influenza Vaccine Effectiveness and Safety for the 2026-2027 Respiratory Season. JAMA. Published September 2, 2026. doi:10.1001/jama.2026.18126

Background

Influenza continues to cause many hospitalizations and deaths in the United States, especially among older adults and people with medical risks. This review updated recent evidence on influenza vaccine benefits and harms.

Patients

Human populations, including older adults, adults, pregnant patients and their infants, children, young adults, and immunocompromised persons. Excluded studies included modeling studies, abstracts, preprints, reviews, commentaries, and case series with fewer than 10 participants.

Intervention

United States–licensed seasonal influenza vaccines, including standard-dose, high-dose, adjuvanted, recombinant, cell-based, and messenger ribonucleic acid vaccines.

Control

No vaccination, another vaccine formulation, or standard-dose influenza vaccine.

Outcome

Influenza illness, hospitalization, death, serious adverse events, and reactions limiting daily activities.

Follow-up Period

Studies were published August 2025 to June 2026; included data from 2015 to 2026.

Results

Population Outcome Key finding
Older adults Influenza hospitalization 31.0% lower risk (95% CI 21.0% to 39.0%).
Older adults Influenza death 29.0% to 65.8% lower risk (95% CI 16.0% to 40.0%; 54.6% to 76.9%).
Children and adolescents Influenza death 80.0% lower risk (95% CI 75.0% to 84.0%).
Infants of vaccinated pregnant patients Laboratory-confirmed influenza 44.4% lower risk (95% CI 31.4% to 54.9%).
Older adults High-dose versus standard-dose hospitalization 43.6% relative improvement (95% CI 27.5% to 56.3%).
Adults aged 50 years or older Messenger ribonucleic acid vaccine reactions limiting activities RR 6.36 (95% CI 4.34 to 9.32); NNH about 19.

CI = confidence interval; RR = risk ratio; NNH = number needed to harm.

No increased risk of serious adverse events was found, including Guillain-Barré syndrome, stroke, anaphylaxis, or febrile seizures. Standard-dose vaccine is an available current treatment comparator.

Limitations

Few studies had low risk of bias. Results varied by season, vaccine type, population, and setting. Several estimates came from observational studies, so unmeasured differences between vaccinated and unvaccinated people may remain.

Funding

Philanthropic support; no pharmaceutical industry funding.

Clinical Application

Continue recommending annual influenza vaccination, prioritizing older adults, children, pregnant patients, and high-risk groups; consider high-dose vaccine for older adults.