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

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