COVID-19 Vaccine Effectiveness Against Mortality in the Omicron Period: Evidence from Linked Mortality and Vaccination Records

Document Type

Journal Article

Publication Date

12-11-2025

Journal

Vaccines

Volume

13

Issue

12

DOI

10.3390/vaccines13121235

Keywords

COVID Excess Mortality Percentage; COVID-19; COVID-19 mortality; cause of death; healthy vaccinee bias; hybrid immunity; vaccine effectiveness; waning vaccine effectiveness

Abstract

OBJECTIVE: This study aimed to assess COVID-19 vaccine effectiveness against death (VE), controlling for healthy vaccinee bias. METHODS: We link all adult deaths through year-end 2022 in the State of Indiana, U.S.A., to vaccination records and identify which deceased received primary vaccination (measured as either one or two initial doses) and which received one or two booster doses. We measure COVID-19 mortality with the COVID Excess Mortality Percentage (CEMP). CEMP is calculated, for a group defined by various characteristics (age, sex, time period), as COVID-19 deaths divided by non-COVID natural deaths. The CEMP outcome measure accounts for healthy vaccinee bias by using non-COVID natural mortality to control for differences in population health. RESULTS: We find a large healthy vaccinee bias. Controlling for this bias, we find substantial VE for primary vaccination and the first booster dose during the first five vaccine-available calendar quarters, from 1Q2021 through 1Q2022 (end of Omicron infection wave). However, over 2Q-4Q2022, we find no evidence for primary-vaccination VE, and find moderate but statistically insignificant booster VE, which largely wanes by 4Q2022. CONCLUSIONS: It is known that by 2Q2022, most people had natural immunity from prior COVID-19 infection. Thus, our results for 2Q-4Q2022 largely reflect comparing hybrid (infection plus vaccination) immunity to infection-only immunity. In this period, we find negligible mortality benefit from primary vaccination, and moderate but waning benefit from a booster dose. POLICY IMPLICATIONS: Controlling for healthy vaccinee bias is crucial when estimating VE. We found limited VE against COVID-19 mortality over 2Q-4Q2022, but lacked data for more recent periods.

Department

Health Policy and Management

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