Characteristics of adverse events of inactivated quadrivalent influenza vaccine in healthy populations: a meta-analysis based on randomized controlled trials

Background Influenza constitutes a critical global public health issue, and quadrivalent inactivated influenza vaccine (QIV) is widely used, yet systematic analyses of its adverse events (AEs) remain lacking. This meta-analysis aimed to characterize AEs following QIV vaccination in healthy populations. Methods We searched for randomized controlled trials (RCTs) of QIV vaccination in healthy populations, extracted AE data from QIV groups, pooled incidence rates, and compared the risks of AEs between QIV and trivalent influenza vaccine (TIV) using a random-effects model. Subgroup analyses, meta-regression, and sensitivity analyses were applied to explore heterogeneity and result robustness. Publication bias was evaluated utilizing Begg's and Egger's tests. Results A total of 29 studies published from 2008 to 2025 were included, involving 28,410 participants with 8,197 reported AEs in total. The overall incidence of AEs after QIV vaccination in healthy populations was 43% (95% CI : 31%−54%), with an incidence of 27% (95% CI : 18%−37%) for local AEs and 20% (95% CI : 14%−26%) for systemic AEs. The incidence of SAEs was 0.96%. The QIV group showed significantly elevated risks of overall and local AEs relative to TIV ( P < 0.05), while no significant differences were detected in systemic AEs and SAEs between the two groups ( P > 0.05). Heterogeneity was associated with study period, study region, AE collection duration, and vaccine origin. Sensitivity analyses and publication bias analyses confirmed result stability. Conclusion This study summarizes AE incidence and features after QIV in healthy populations, supporting clinical vaccination and post-vaccination safety surveillance with exploratory data. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251233388 , identifier CRD420251233388.