Incidence of adverse reactions to COVID-19 vaccination: A meta-analysis of randomized controlled trials

Objective: To systematically evaluate the incidence of adverse reactions to coronavirus disease 2019 (COVID-19) vaccination. Methods: We systematically searched PubMed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang Data, and VIP Database from the inception of each database to August 31, 2021. Randomized controlled clinical trials (RCTs) on the safety of different types of COVID-19 vaccines were retrieved and analyzed. A random or fixed-effects model was used with an odds ratio as the effect size. The quality of each reference was evaluated. The incidence of the adverse reactions of the placebo group and the vaccination group was compared. Heterogeneity and publication bias were taken care of by meta-regression and sub-group analyses. Results: A total of 13 articles were included, with 81 287 subjects. Compared with the placebo group, the vaccination group showed a higher combined risk ratio (RR) of total adverse reactions (RR=1.67, 95% CI: 1.46-1.91, P<0.01), local adverse reactions (RR=2.86, 95% CI: 2.11-3.87, P<0.01), systemic adverse reactions (RR=1.25, 95% CI: 0.92-1.72, P=0.16), pain (RR=2.55, 95% CI: 1.75-3.70, P<0.01), swelling (RR=4.16, 95% CI: 1.71-10.17, P=0.002, fever (RR=2.34, 95% CI: 1.84-2.97, P<0.01), fatigue (RR=1.36, 95% CI: 1.32-1.41, P<0.01) and headache (RR=1.22, 95% CI: 1.18-1.26, P<0.01). The subgroup analysis showed the incidence of adverse reactions of the vaccination group after injection of the three COVID-19 vaccines (inactivated viral vaccines, mRNA vaccines and adenovirus vector vaccines) was higher than that of the placebo group, and the difference between the placebo group and the vaccination group in the mRNA vaccine subgroup and the adenovirus vector vaccine subgroup was statistically significant (P<0.01). The incidence of adverse reactions after injection of COVID-19 vaccine in subgroups of different ages was significantly higher than that in the placebo group (P<0.01). Conclusions: COVID-19 vaccines have a good safety, among which adenovirus vector vaccine has the highest incidence of adverse reactions. Both adolescents and adults vaccinated with novel coronavirus vaccine have a certain proportion of adverse reactions, but the symptoms are mild and can be relieved by themselves. Our meta-analysis can help boost global awareness of vaccine safety, promote mass vaccination, help build regional and global immune barriers and effectively curb the recurrency of COVID-19.