Abstract
BACKGROUND/OBJECTIVES: This study evaluated the impact of influenza vaccination on mortality using real-world data and compared the effect of current-season-only vaccination versus continuous two-season vaccination. METHODS: The 2017-2019 data from the Center for Disease Control and Prevention of Shenzhen, Guangdong, China, included 880,119 individuals aged ≥65 years. The participants were divided into vaccinated and unvaccinated groups and matched using propensity scores with a 1:4 nearest-neighbor approach. Vaccinated individuals were further divided into current-season-only and continuous two-season vaccination groups, matched 1:1. Cox's multivariable proportional hazards regression models were used to assess the effect of vaccination on all-cause mortality, with Firth's penalized likelihood method applied to correct for a few events. The Fine-Gray competing risk models were used to assess the effect of vaccination on cardio-cerebral vascular disease (CCVD) mortality. Sensitivity analyses, including caliper matching, a nested case-control design, and Poisson's regression, were performed to test the robustness of the results. RESULTS: Influenza vaccination reduced all-cause mortality by 39% (HR = 0.61, 95% CI: 0.47-0.80) and 55% (HR = 0.45, 95% CI: 0.33-0.60) in 2017-2018 and 2018-2019, respectively. Current-season-only vaccination showed stronger protective effects than continuous two-season vaccination (HR = 0.56, 95% CI: 0.31-0.99). Influenza vaccination reduced CCVD mortality by 46% (HR = 0.54, 95% CI: 0.34-0.84) in 2018-2019. The results were consistent across the sensitivity analyses. CONCLUSIONS: Influenza vaccination was associated with a reduced risk of all-cause and CCVD mortality in older adults, underscoring the importance of routine influenza vaccination in older populations. Stronger effects were observed for current-season-only vaccination, warranting further research to confirm the association and explore mechanisms.