Evaluation of the safety profile of COVID-19 vaccines: a rapid review

BMC Med. 2021 Jul 28;19(1):173. doi: 10.1186/s12916-021-02059-5.


Background: The rapid process of research and development and lack of follow-up time post-vaccination aroused great public concern about the safety profile of COVID-19 vaccine candidates. To provide comprehensive overview of the safety profile of COVID-19 vaccines by using meta-analysis technique.

Methods: English-language articles and results posted on PubMed, Embase, Web of Science, PMC, official regulatory websites, and post-authorization safety surveillance data were searched through June 12, 2021. Publications disclosing safety data of COVID-19 candidate vaccines in humans were included. A meta-analysis of proportions was performed to estimate the pooled incidence and the pooled rate ratio (RR) of safety outcomes of COVID-19 vaccines using different platforms.

Results: A total of 87 publications with safety data from clinical trials and post-authorization studies of 19 COVID-19 vaccines on 6 different platforms were included. The pooled rates of local and systemic reactions were significantly lower among inactivated vaccines (23.7%, 21.0%), protein subunit vaccines (33.0%, 22.3%), and DNA vaccines (39.5%, 29.3%), compared to RNA vaccines (89.4%, 83.3%), non-replicating vector vaccines (55.9%, 66.3%), and virus-like particle vaccines (100.0%, 78.9%). Solicited injection-site pain was the most common local reactions, and fatigue and headache were the most common systemic reactions. The frequency of vaccine-related serious adverse events was low (< 0.1%) and balanced between treatment groups. Vaccine platforms and age groups of vaccine recipients accounted for much of the heterogeneity in safety profiles between COVID-19 vaccines. Reporting rates of adverse events from post-authorization observational studies were similar to results from clinical trials. Crude reporting rates of adverse events from post-authorization safety monitoring (passive surveillance) were lower than in clinical trials and varied between countries.

Conclusions: Available evidence indicates that eligible COVID-19 vaccines have an acceptable short-term safety profile. Additional studies and long-term population-level surveillance are strongly encouraged to further define the safety profile of COVID-19 vaccines.

Keywords: Novel coronavirus diseases 2019; Review; Safety profile; Severe acute respiratory syndrome coronavirus 2; Vaccine.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Aged
  • Aged, 80 and over
  • BNT162 Vaccine
  • COVID-19 Vaccines / adverse effects
  • COVID-19*
  • ChAdOx1 nCoV-19
  • Humans
  • Middle Aged
  • SARS-CoV-2
  • Vaccines* / adverse effects


  • COVID-19 Vaccines
  • Vaccines
  • reluscovtogene ralaplasmid
  • ChAdOx1 nCoV-19
  • BNT162 Vaccine