All-cause mortality within seven days of COVID-19 vaccination: A matched cohort and self-controlled case series study...

We evaluated 7-day all-cause mortality after COVID-19 vaccination in a large population-based cohort.

Using the Vaccine Integrated Platform of Lombardy Region (Italy), we compared mortality rates of individuals who received a first vaccine dose between 27 December 2020 and 28 February 2022 with unvaccinated individuals, matched by sex, age, residence health district and Covid Vulnerability Score. The Cox regression model estimated the association between vaccination and 7-day mortality risk. Moreover, a modified self-controlled case series (SCCS) design allowed a within-person comparison of mortality rates between risk intervals (Days 0-7 after first dose, second dose, and booster dose) and the control interval outside vaccination. Mortality rate ratios (MRRs) and 95% CI were estimated.

The cohort study included 7,612,244 exposed at least to the first vaccine dose, matched to as many controls. Overall, 717 and 3070 deaths occurred among vaccinated and controls, corresponding to mortality rates of 13.5 and 62.8 deaths per 1,000,000 person-days, respectively. Vaccination was associated with reduced 7-days mortality risk (HR: 0.21, 95% CI 0.19-0.23). The SCCS study included 127,122 all-cause deaths during the study period. MRRs after administration of first, second, and booster doses were 0.46 (95% CI 0.43-0.49), 0.53 (95% CI 0.50-0.57), and 0.61 (95% CI 0.57-0.65), respectively.

Mortality rates were lower during the short-term interval following vaccine administration compared to unexposed periods. Our findings support the conclusion that the benefits of COVID-19 vaccination outweigh the risks, despite potential for serious adverse effects.