Influenza vaccine effectiveness according to frailty status in adults aged ≥ 50 years: a systematic review and meta-analysis.

Authors

Henrique Pott, Shelly A McNeil, Melissa K Andrew

Published in

BMC infectious diseases. Jul 11, 2026. Epub Jul 11, 2026.

Abstract

Older adults with influenza have an elevated risk of adverse clinical outcomes. Influenza vaccine effectiveness (VE) is generally lower in this age group due to several factors. Frailty has been identified as a potential modifier of VE, but the literature on this topic is fragmented.
A systematic review of studies evaluating frailty and influenza VE in adults aged ≥ 50 years. Databases were searched from inception to September 2025. The primary outcomes were laboratory-confirmed influenza (LCI), influenza-related hospitalization, and influenza-associated mortality. Random-effects models with restricted maximum likelihood estimation and Hartung-Knapp adjustment were applied when pooling was appropriate. Effect sizes were reported as odds ratios (ORs) with 95% confidence intervals (CIs).
Eight studies with 262,952 pooled participants were included. The prevalence of frailty ranged from 14.3% to 36.4%, with a pooled estimate of 24.3% (95% CI, 19.0%-30.4%; I²=99.8%). Four test-negative studies were pooled for LCI cases. Vaccination was associated with reduced odds of LCI (pooled OR, 0.53; 95% CI, 0.37-0.76; I²=4.0%), with a 95% prediction interval of 0.30-0.96. Stratified analyses showed pooled ORs of 0.43 (95% CI, 0.24-0.75) and 0.66 (95% CI, 0.35-1.25) in non-frail and frail individuals, respectively; no statistically significant effect modification was detected (p = 0.10). Hospitalization and mortality outcomes were not pooled because of heterogeneity. The certainty of evidence was low for LCI and very low for other outcomes.
Influenza vaccination protected against LCI across frailty strata, though study heterogeneity requires cautious interpretation, and estimates were less precise for frail individuals. The elevated risk of adverse clinical outcomes in this age group supports immunization, and current data do not justify withholding vaccination.

PMID:
42436428
Bibliographic data and abstract were imported from PubMed on 12 Jul 2026.

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