Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine in Reducing Mortality Among Older Adults: A Real-World Retrospective Cohort Study in Guangzhou, China

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Abstract
Objectives: To evaluate the real-world effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in reducing all-cause, pneumonia-related, and chronic obstructive pulmonary disease (COPD)-related mortality in adults aged ≥60 years. Methods: In this retrospective cohort study using existing health surveillance data, individuals aged ≥60 years on 1 January 2020 were followed until 31 August 2025 and classified by PPSV23 vaccination status. Propensity score matching (PSM) at a 1:1 ratio balanced sex, age, regional distribution, urbanization level and influenza vaccination status. Time-dependent Cox proportional hazards models estimated hazard ratios (HR) and vaccine effectiveness (VE), defined as (1 − HR) × 100%. Subgroup, negative control (mortality from traffic accidents), and E-value sensitivity analyses were performed. Results: After PSM, 453,500 individuals were included, with a mean follow-up of 5.61 years. All-cause mortality was 3.93 per 1000 person-years in vaccinated versus 9.57 in unvaccinated individuals. PPSV23 vaccination reduced all-cause mortality (VE = 43.1%, 95% CI: 41.2–45.0%), pneumonia-related mortality (VE = 46.2%, 95% CI: 39.6–52.1%), and COPD-related mortality (VE = 33.5%, 95% CI: 20.9–44.2%) (all p < 0.001). In a cause-specific decomposition, pneumonia- and COPD-related deaths together explained only 14.9% of the absolute reduction in all-cause deaths, whereas circulatory diseases and malignant tumors accounted for 36.8% and 31.9%, respectively. Among those also vaccinated against influenza, VE was 48.0% and 38.2% for pneumonia- and COPD-related mortality, respectively. For COPD-related mortality, the benefit was greater in men (VE = 42.3%) and in those aged ≥70 years (70–79 years, VE = 45.6%; ≥80 years, VE = 52.0%). PPSV23 was not associated with the negative control outcome (p = 0.247); E-values (1.98–2.44) indicated robustness to unmeasured confounding. Conclusions: PPSV23 vaccination was associated with significantly lower all-cause, pneumonia-related, and COPD-related mortality among elderly individuals aged ≥60 years. However, the observed association with all-cause mortality should be interpreted cautiously. Continued promotion of PPSV23 vaccination and advocacy for combined influenza–pneumococcal vaccination strategies are recommended.
Funding Information
  • Key Project of Medicine Discipline of Guangzhou (2025–2027-11)
  • Basic and Applied Research Project of Guangzhou (2024A04J4504)
  • Basic and Applied Research Project of Guangzhou (2025A03J3694)
  • Guangzhou Municipal Health Science and Technology Project (20241A011066)
  • Guangzhou Municipal Health Science and Technology Project (20251A011057)
  • Guangzhou Municipal Health Science and Technology Project (20251A011055)
  • Guangdong Medical Science and Technology Project (B2025342)

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