High-dose flu vaccine reduces hospitalizations

In adults 65 years or older, high-dose influenza vaccine reduced hospitalizations but not mortality.
*Systematic review and meta-analysis of randomized trials; Level 1.

Citation

Skaarup KG, Lassen MCH, Hosseini K, et al. High-Dose vs Standard-Dose Influenza Vaccines in Older Adults: A Meta-Analysis. JAMA Network Open. 2026;9(5):e2614620. doi:10.1001/jamanetworkopen.2026.14620

Background

Older adults have weaker immune responses to standard influenza vaccine and higher risk of severe influenza complications. High-dose vaccine contains more antigen and may improve protection against serious illness.

Patients

605,098 randomized participants, mainly adults 65 years or older; trials included general older adults, nursing home residents, and one cardiovascular disease population. Pandemic-season trials were excluded.

Intervention

High-dose inactivated influenza vaccine.

Control

Standard-dose inactivated influenza vaccine, an available current treatment.

Outcome

Hospitalization for influenza, laboratory-confirmed influenza, pneumonia or influenza, cardiorespiratory disease, any cause, and death from any cause.

Follow-up Period

At least 1 influenza season; some trials followed multiple seasons.

Results

Outcome Relative reduction with high-dose vaccine Number needed to vaccinate
Influenza hospitalization 38.5% lower 2,429
Laboratory-confirmed influenza hospitalization 31.2% lower 2,075
Pneumonia or influenza hospitalization 11.5% lower 1,216
Cardiorespiratory hospitalization 7.5% lower 479
All-cause hospitalization 3.3% lower 335

Death from any cause was not significantly reduced. All data were analyzed by intention to treat.

Limitations

Results were dominated by large Danish and Spanish trials, and all studies were in Western Europe or North America. Effects vary by influenza season. Absolute benefits were modest for influenza-specific hospitalizations despite strong relative reductions. Some outcomes showed possible small-study effects.

Funding

Sanofi SA funded; employees coauthored, creating potential bias.

Clinical Application

Prefer high-dose influenza vaccine for adults 65 or older when available, primarily to reduce hospitalization rather than mortality.