Incidence of adverse reactions to COVID-19 vaccination: A metaanalysis of randomized controlled trials
Authors: Xin-Xin Wu1#, Jin-Jian Yao2#, Jin Qian3,4, Qi-Feng Huang3,5, Tang Deng3,5, Shuang-Qin Xu3,5, Hang-Fei Wang3,5, Qi Li3,5, Ji-Chao Peng1 , Yang Yi3,5, Nan Li3,5, Yue Huang3,5, Xiao-Ran Liu1,3,5
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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 81287 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
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.