Publication date: May 23, 2025

The global impact of COVID-19, caused by SARS-CoV-2, has extended beyond acute infection, with Post-Acute COVID-19 Syndrome (PACS) affecting an estimated 10% of recovered individuals. PACS manifests a range of debilitating symptoms, including fatigue, cognitive impairment, and gastrointestinal issues. While vaccination has proven effective in mitigating severe COVID-19 outcomes, the role of booster doses in preventing PACS remains unclear. This study aimed to evaluate whether COVID-19 booster vaccinations reduce the incidence and severity of PACS in individuals with prior SARS-CoV-2 infection. A systematic review and meta-analysis were conducted in adherence to PRISMA guidelines. Databases PubMed, Embase, and Cochrane were searched for peer-reviewed studies published in English from January 2020-August 2023. Inclusion criteria encompassed RCTs, prospective cohort studies, and case-control studies comparing PACS prevalence between booster recipients and non-recipients. Risk of bias was assessed using the Joanna Briggs Institute appraisal tool. Data synthesis included pooled prevalence estimates and narrative analyses. Of 849 identified studies, 22 met inclusion criteria, with 12 providing complete data for meta-analysis. Among 38,718 participants, a trend toward lower PACS prevalence was observed in booster recipients (RR: 0. 66; 95%-CI: 0. 41 – 1. 09), though heterogeneity (I^2 = 98%) limited statistical significance. Risk of bias analysis classified most studies as low or moderate risk, with two high-risk studies reporting higher PACS rates in boosted individuals. This study suggests a potential protective effect of booster vaccinations against PACS, though findings were not statistically significant. Further research with larger, standardized cohorts is essential to validate these observations and guide vaccination strategies.

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