COVID-19 mRNA Vaccines Linked to Higher Adverse Event Risk vs Traditional Vaccines

FONTANA, CA – JUNE 02: Syringes wait to be filled with the Moderna COVID-19 Vaccine at Auto Club Speedway in Fontana during San Bernardino County”u2019s first “u201csuper site”u201d to distribute the vaccine Tuesday, Feb. 2, 2021. The site was giving out 3,500 first doses of the vaccine. (Photo by Will Lester/MediaNews Group/Inland Valley Daily Bulletin via Getty Images)
Researchers evaluated the occurrence of adverse events following COVID-19 vaccination with mRNA- and vector-based vaccines, inactivated vaccines, DNA vaccines, and protein subunit vaccines.

Although the risk for adverse events (AEs) was increased for mRNA-based COVID-19 vaccines compared with traditional vaccines, the efficacy and benefits of mRNA vaccination exceeded that of the associated risks, according to a study in International Immunopharmacology.

Researchers conducted a meta-analysis to evaluate the safety of several types of COVID-19 vaccines. They searched the PubMed and ISI databases through May 2022 for studies that assessed the efficacy and safety of COVID-19 vaccination; studies that lacked a control group were excluded from the analysis. Included studies assessed the incidence of AEs following vaccination on the basis of COVID-19 vaccination status.

A total of 19 studies were included in the meta-analysis, of which 6 assessed inactivated COVID-19 vaccines, 5 assessed mRNA vaccines, 3 assessed viral vector vaccines, 1 assessed DNA vaccines, and 4 assessed protein subunit vaccines.

In the pooled analysis, the risk for any AE following COVID-19 vaccination was most increased for mRNA-based vaccines (risk ratio [RR], 2.01; 95% CI, 1.82-2.23), followed by viral vector-based vaccines (RR, 1.65; 95% CI, 1.31-2.32) and inactivated vaccines (RR, 1.46; 95% CI, 1.19-1.78).

In regard to the risk systemic AEs following vaccination, the risk was significantly increased for mRNA-based vaccines (RR, 1.53; 95% CI, 1.08-2.16) and protein subunit vaccines (RR, 1.62; 95% CI, 1.39-1.89), with a decreased risk observed for DNA vaccines (RR, 0.72; 95% CI, 0.34-1.55). Although inactivated vaccines also were associated with an increased risk for systemic AEs, the risk was not statistically significant (RR, 1.13; 95% CI, 0.79-1.61).

The most common systemic AEs following vaccination included fever, fatigue, and headache. For studies that assessed mRNA-based COVID-19 vaccination, the risk for fever (RR, 8.35), headache (RR, 1.89), and fatigue (RR, 1.95) was significantly increased among patients who were vaccinated vs those in the control group. Although an increased risk for these reactions was observed in patients who received either inactivated or viral vector-based vaccines, the risk did not significantly differ compared with those in the respective control groups.

Compared with any other vaccine type, mRNA-based vaccines were associated with the most significantly increased risk for local AEs (RR 4.96; 95% CI, 4.02-6.11), followed by protein subunit vaccines (RR, 4.09; 95% CI, 2.63-6.35). Stratified by individual local AEs, mRNA-based vaccines were associated with a significantly increased risk for pain (RR 5.39; 95% CI, 4.26- 6.82), erythema (RR 7.65; 95% CI, 3.94-14.86), and swelling (RR 10.6; 95% CI, 4.52-24.88).

Limitations were high heterogeneity among some of the included studies, the inability to conduct subgroup analyses for all individual AEs, and the small sample size of studies that assessed vector-based vaccines and protein subunit vaccines.

“At the present moment the benefits of all types of vaccines approved by the World Health Organization still outweigh the risks… and vaccination… is highly recommended,” the researchers concluded.


Kouhpayeh H, Ansari H. Adverse events following COVID-19 vaccination: a systematic review and meta-analysis. Int Immunopharmacol. Published online May 30, 2022. doi: 10.1016/j.intimp.2022.108906