Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies

Hum Vaccin Immunother. 2023 Aug 1;19(2):2230828. doi: 10.1080/21645515.2023.2230828.


Self-controlled case series (SCCS) is a novel study design uniquely equipped to ethically quantify the safety of vaccination. We sought out to perform a meta-analysis on all SCCS assessing mortality associated with COVID-19 vaccination in the immediate post-vaccination period. We included SCCS investigating the safety of COVID-19 vaccination and reporting all-cause and cardiac-related mortality. Three SCCS were located, totaling approximately 750,000 patients. The pooled hazard ratio (HR) revealed no significant association of COVID-19 vaccination with all-cause mortality (HR = 0.89, 95% CI [0.71, 1.10], p = .28). Regarding cardiac-related mortality, the pooled HR suggests that COVID-19 vaccination is associated with an increased risk of cardiac-related mortality (HR = 1.06, 95% CI [1.02, 1.11], p = .007). Subgroup analysis showed that the male gender is significantly associated with an increased incidence of cardiac-related deaths (HR = 1.09, 95% CI [1.02, 1.15], p = .006). In conclusion, COVID-19 vaccination may be associated with a small increase in cardiac-related mortality, especially among males. Prospero Prospective Registration Number: CRD42022372256.

Keywords: COVID19 vaccination; all-cause mortality; cardiac mortality; mRNA vaccination; meta-analysis; self controlled case series.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • COVID-19 Vaccines* / adverse effects
  • COVID-19* / prevention & control
  • Humans
  • Male
  • Prospective Studies
  • Research Design
  • Vaccination / adverse effects


  • COVID-19 Vaccines

Grants and funding

The author(s) reported that there is no funding associated with the work featured in this article.