COVID-19 Vaccine Adverse Events by Country Income Level: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract

PurposeTo synthesize evidence on the incidence of COVID-19 vaccine-related adverse events across countries by income level.DesignSystematic review and meta-analysis of randomized trials.SettingStudies published 2020-2025, retrieved from EMBASE, PubMed/MEDLINE, and Scopus.SampleEleven trials with 7841 participants; seven from high-income and four from upper-middle-income countries.MeasuresIncidence per 100 vaccinated. Countries by income: low (≤$1145), lower-middle ($1146-4515), upper-middle ($4516-14,005), high (>$14,005). Inter-reviewer agreement assessed by kappa (0.684). Risk of bias evaluated with Cochrane RoB 2.AnalysisMantel-Haenszel random-effects models estimated relative risks (RR) with 95% confidence intervals. Heterogeneity assessed by I². Subgroup analyses by income and dose.ResultsAEFI incidence was consistently higher in high-income vs upper-middle-income countries, especially after dose 2. Injection-site pain (68.1 vs 26.3 per 100), headache (45.7 vs 14.1), myalgia (42.5 vs 9.2), and fatigue (33.8 vs 11.4) were most common. Meta-analyses showed higher pooled RR in high-income settings: any AEFI after dose 1, RR = 1.83 (95% CI: 1.39-2.42); local, RR = 3.15; systemic, RR = 2.05. After dose 2, overall RR reached 2.94; local, 4.37; systemic, 2.48. All subgroup differences were significant.ConclusionHigher-income countries showed a greater incidence of mostly mild adverse events, particularly after the second dose. mRNA vaccines had the highest rates. Findings reveal income-based disparities and inform equitable post-vaccination monitoring.