Clinical Question: In older adults, does high-dose influenza vaccination result in a lower rate of hospitalizations for influenza or pneumonia compared with standard-dose regimens?
Background: Older adults are at increased risk for severe influenza complications, including hospitalization and death. Prior studies have confirmed the relative effectiveness of high-dose influenza vaccine against laboratory-confirmed influenza. However, the relative effectiveness of the high-dose vaccine against severe clinical outcomes, including hospitalizations, is less well established.
Study Design: Pragmatic, open-label, randomized, controlled trial
Setting: Galicia, Spain
Synopsis: During the 2023 to 2024 and 2024 to 2025 influenza seasons, 103,169 community-dwelling adults (ages 65 to 79) were randomized to receive either high-dose or standard-dose influenza vaccination. The primary outcome was hospitalization for influenza or pneumonia. High-dose influenza vaccine was associated with a significantly lower incidence of the primary outcome compared to the standard-dose group (absolute risk, 0.26% versus 0.34%; relative vaccine effectiveness, 23.7%; 95% CI, 6.6 to 37.7). While the absolute risk reduction was small, reflecting a low baseline event rate in this population, the protective effect was most pronounced against influenza-specific hospitalizations.
Notably, a separate Danish trial published in the same issue of the New England Journal of Medicine failed to demonstrate a statistically significant reduction in its primary composite endpoint of hospitalization for influenza or pneumonia with high-dose versus standard-dose vaccination, although influenza-specific hospitalizations were reduced.
Bottom Line: Among adults aged 65 to 79, high-dose influenza vaccination reduced hospitalizations for influenza or pneumonia compared with standard-dose vaccination.
Citation: Pardo-Seco J, et al. High-dose influenza vaccine to reduce hospitalizations. N Engl J Med. 2025;393(23):2303-2312. doi:10.1056/NEJMoa2509834.
Dr. Huang
Dr. Huang is a clinical professor of medicine in the division of hospital medicine and a physician advisor at the University of California San Diego in San Diego.