Effectiveness, Safety, and Immunogenicity of a Second COVID-19 Vaccine Booster in the Elderly: A Systematic Review and Meta-Analysis Protocol.

BACKGROUND/AIMS: Older adults remain highly vulnerable to severe COVID-19 outcomes due to immunosenescence and comorbidities. Although booster vaccination strategies have reduced hospitalizations and mortality, evidence regarding the effectiveness, safety, and immunogenicity of a second COVID-19 vaccine booster dose in older adults remains fragmented. This systematic review and meta-analysis protocol aims to critically evaluate the available evidence from randomized and nonrandomized clinical trials (NRCTs) regarding the effectiveness, safety, and immunogenicity of the second COVID-19 vaccine booster in older adults worldwide.

METHODS

A systematic review of clinical trials will be conducted using PubMed/MEDLINE, EMBASE, Cochrane Library, Web of Science, Scopus, and LILACS, without restrictions on publication date or language. Eligible studies will include randomized controlled trials and NRCTs involving older adults aged ≥ 60 years who received a second COVID-19 vaccine booster dose. Primary outcomes will include measures related to effectiveness, safety, and/or immunogenicity. Study selection will follow PRISMA-2020 guidelines. Risk of bias will be assessed using RoB 2 and ROBINS-I tools, while certainty of evidence will be evaluated using the GRADE approach.

RESULTS

A narrative synthesis will be performed, and meta-analysis will be conducted whenever methodologically appropriate.

CONCLUSION

This review will provide comprehensive evidence regarding second COVID-19 booster doses in older adults and may support evidence-based public health strategies and vaccination policies for high-risk populations.

TRIAL REGISTRATION: PROSPERO registration number: CRD42025644411.