A modified self-controlled case series on mortality risk following primary series doses of COVID-19 vaccines in U.S. Medicare beneficiaries aged 65 years and older.

BACKGROUND

Previous studies have attempted to perform self-controlled case series (SCCS) analyses to determine mortality risk following a primary series dose of a COVID-19 vaccine, including those conducted by the Florida Department of Health and the Vaccine Safety Datalink. We replicated these analyses to assess mortality risk post-vaccination in U.S. older adults.

METHODS

Using Medicare Fee-for-Service claims and enrollment data, we identified post-vaccination deaths among beneficiaries aged ≥65 years from December 14, 2020, to August 11, 2021. Exposures included receipt of up to 2 doses of BNT162b2 or mRNA-1273 or 1 dose of Ad26.COV2·S. We estimated brand- and dose-specific relative incidence (RI) of non-COVID-19-related mortality and 3 secondary mortality outcomes. The risk interval was the first 28 days post-vaccination, and the control interval was the remaining observation period. To account for curtailed follow-up time after death, we included beneficiaries' planned observation time and used a pseudo-likelihood method to estimate RI. Deaths among the unvaccinated were included in the SCCS model to adjust for temporal effects of vaccinations and mortality.

RESULTS

By August 11, 2021, there were 188,948 post-vaccination deaths eligible for SCCS analysis. RIs for non-COVID-19-related deaths were significantly less than 1 across all primary series doses. BNT162b2 Dose 1 and Dose 2 RI estimates were 0.63 (95% confidence interval (CI): 0.62, 0.65) and 0.67 (95% CI: 0.66, 0.68), respectively. mRNA-1273 Dose 1 and Dose 2 RI estimates were 0.52 (95% CI: 0.50, 0.53) and 0.63 (95% CI: 0.61, 0.64), respectively. Ad26.COV2·S Dose 1 RI estimate was 0.60 (95% CI: 0.55, 0.65). Similar RIs were observed for the secondary mortality outcomes.

CONCLUSIONS

We did not observe an increased risk of mortality in U.S. older adults 4 weeks following a primary series dose of a COVID-19 vaccine.