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Understanding COVID-19 Vaccine Effectiveness Against Death Using a Novel Measure: COVID Excess Mortality Percentage (WP-22-44)

Vladimir Atanasov, Paula Natalia Barreto Parra, Lorenzo Franchi, Jeffrey Whittle, John Meurer, Qian (Eric) Luo, Andy Yuan, Ruohao Zhang, and Bernard Black

Background. While vaccines against COVID-19 have saved millions of lives, it is important to understand the remaining risk to the vaccinated and the incremental benefit of additional vaccine doses. Comparisons between more and less vaccinated groups can be misleading due to selection bias, because these groups can differ in underlying health and thus COVID-19 risk. The authors study by how much COVID-19 increased mortality from natural causes, controlling for underlying health.

Methods. They conduct a retrospective analysis of all deaths in Milwaukee County, Wisconsin, linked to vaccination records, and compare the percentage increase in deaths from natural causes due to COVID-19 between unvaccinated persons and those receiving 1, 2, or 3 vaccine doses, using an outcome measure that controls for non-COVID mortality and thus for population health, over April 1, 2021-March 31, 2022. We report how vaccination affects Relative Mortality Risk (RMR, defined as COVID-19 death as a fraction of other natural deaths for vaccinated persons, relative to this fraction for the unvaccinated) by age group and time period.

Findings. RMR was higher (vaccine effectiveness was lower) than in studies that did not address selection. RMR for two-dose vaccine recipients was 15.5% during April-June 2021, 19.0% during July–September 2021, 22.9% during October–December 2021 and 36.0% during January–March 2022, corresponding to Alpha, early Delta, later Delta, and Omicron-dominant periods. A booster dose reduced RMR to 8-9%. RMR was higher for ages 60+. Selection effects were large; unvaccinated persons had over twice the risk of non-COVID natural death than the vaccinated.

Interpretation. Studies of vaccine effectiveness against mortality that do not control for underlying health will overstate effectiveness. Using a measure that controls for population health, fully vaccinated older individuals have substantial RMR, but boosters provide important protection.

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This paper is published in Vaccines.

Vladimir Atanasov, Brinkley-Mason Term Professor of Business, William & Mary

Paula Natalia Barreto Parra, Department of Economics, University of Illinois, Urbana-Champaign

Lorenzo Franchi, Post-Baccalaureate Research Fellow, Pritzker School of Law, Northwestern University

Jeffrey Whittle, Professor of Medicine, Medical College of Wisconsin

John Meurer, Professor of Pediatrics and Community Health, Medical College of Wisconsin

Qian (Eric) Luo, Assistant Research Professor, Milken Institute School of Public Health, George Washington University

Andy Yuan, Postdoctoral Scholar, Pritzker School of Law, Northwestern University

Ruohao Zhang, Assistant Professor of Data Science, Economics and Environmental Studies, Centre College

Bernard Black, Nicholas J. Chabraja Professor and IPR Associate, Northwestern University

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