Background Given the reduced immune response to vaccines in older populations, this study aimed to evaluate the efficacy of COVID-19 vaccinations and its impact on breakthrough infection, hospital admission, and mortality in the elderly. Methods We carried out a systemic review and meta-analysis where MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials were queried to identify relevant literature. We included randomized controlled trials (RCTs), non-randomized trials, prospective, observational cohort, and case–control studies assessing breakthrough infection, hospital admission, and mortality after coronavirus 2 (SARS-CoV-2) vaccination in the elderly (≥ 60 years old). Results Overall, 26 studies were included in this meta-analysis. Compared with the unvaccinated group, the vaccinated group showed a decreased risk of SARS-CoV-2 infection after 28–34 (relative risk [RR] = 0.42, 95% confidence interval [CI] 0.37–0.49) and 35–60 days (RR = 0.49, 95% CI 0.37–0.62). There was a step-wise increase in efficacy with additional doses with the two-dose group experiencing decreased risk of breakthrough infection (RR = 0.37, 95% CI 0.32–0.42), hospital admissions (RR = 0.25, 95% CI 0.14–0.45), disease severity (RR = 0.38, 95% CI 0.20–0.70), and mortality (RR = 0.21, 95% CI 0.14–0.32) compared with those receiving one or no doses. Similarly three-dose and four-dose vaccine groups also showed a decreased risk of breakthrough infection (3-dose: RR = 0.14, 95% CI 0.10–0.20; 4-dose RR = 0.46, 95% CI 0.4–0.53), hospital admissions (3-dose: RR = 0.11, 95% CI 0.07–0.17; 4-dose: RR = 0.42, 95% CI 0.32–0.55), and all-cause mortality (3-dose: RR = 0.10, 95% CI 0.02–0.48; 4-dose: RR = 0.48, 95% CI 0.28–0.84) Subgroup analysis found that protection against mortality for vaccinated vs. unvaccinated groups was similar by age (60–79 years: RR = 0.59; 95% CI, 0.47–0.74; ≥ 80 years: RR = 0.76; 95% CI, 0.59–0.98) and gender (female: RR = 0.66; 95% CI, 0.50–0.87, male: (RR = 0.58; 95% CI, 0.44–0.76), and comorbid cardiovascular disease (CVD) (RR = 0.69; 95% CI, 0.52–0.92) or diabetes (DM) (RR = 0.59; 95% CI, 0.39–0.89. Conclusions Our pooled results showed that SARS-CoV-2 vaccines administered to the elderly is effective in preventing prevent breakthrough infection, hospitalization, severity, and death. What’s more, increasing number of vaccine doses is becoming increasingly effective. Supplementary Information The online version contains supplementary material available at 10.1007/s11606-023-08254-9.
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