Effect of Current-Season-Only Versus Continuous Two-Season Influenza Vaccination on Mortality in Older Adults: A Propensity-Score-Matched Retrospective Cohort Study

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.

Keywords: cardio-cerebral vascular diseases; influenza vaccination; mortality; older adults; survival analysis.

Figure 1

Inclusion process for research subjects during the 2017–2018 and 2018–2019 influenza seasons.

Figure 2

Kaplan–Meier curves of influenza vaccination and all-cause survival probability. (a) During the 2017–2018 influenza season, the all-cause survival probability was higher in the influenza-vaccinated group compared to the unvaccinated group (p < 0.001); (b) during the 2018–2019 influenza season, the all-cause survival probability was higher in the influenza-vaccinated group compared to the unvaccinated group (p < 0.001); (c) the all-cause survival probability was higher in those who were only vaccinated in 2018–2019 compared to those who were vaccinated in two continuous seasons in 2017–2018 and 2018–2019 (p = 0.017).

Figure 3

Cumulative incidence function curves for influenza vaccination and cardio-cerebral vascular disease (CCVD) mortality after accounting for competing risks of death from other causes. (a) During the 2017–2018 influenza season, the cumulative incidence of CCVD mortality was lower in the influenza-vaccinated group compared to the unvaccinated group after accounting for the competing risk of mortality from other causes (p < 0.001); (b) during the 2018–2019 influenza season, the cumulative incidence of CCVD mortality was lower in the influenza-vaccinated group compared to the unvaccinated group after accounting for the competing risk of mortality from other causes (p < 0.001); (c) after accounting for the competing risk of mortality from other causes, there was no significant difference in the cumulative incidence of CCVD mortality between those who were vaccinated in two continuous seasons in 2017–2018 and 2018–2019 and those who were vaccinated only in 2018–2019 (p = 0.130).