Understanding COVID-19 Vaccine Effectiveness Against Death Using a Novel Measure: COVID Excess Mortality Percentage

COVID-19 vaccines have saved millions of lives and prevented countless adverse patient disease outcomes. Understanding the long-term effectiveness of these vaccines is imperative to developing recommendations for precautions and booster doses. Comparisons between more and less vaccinated groups may be misleading due to selection bias, as these groups may differ in underlying health status and thus risk of adverse COVID-19 outcomes. We study all adult deaths over April 1, 2021-June 30, 2022 in Milwaukee County, Wisconsin, linked to vaccination records, use mortality from other natural causes to proxy for underlying health, and report relative COVID-19 mortality risk (RMR) for vaccinees versus the unvaccinated, using a novel outcome measure that controls for selection effects. This measure, COVID Excess Mortality Percentage (CEMP) uses the non-COVID natural mortality rate (Non-Covid-NMR) as a measure of population risk of COVID mortality without vaccination. We validate this measure during the pre-vaccine period (r = 0.97) and demonstrate that selection effects are large, with Non-Covid-NMRs for two-dose vaccinees less than half those for the unvaccinated, and Non-COVID NMRs still lower for three dose (booster) recipients. Progressive waning of two-dose effectiveness is observed, with relative mortality risk (RMR) for two-dose vaccinees aged 60 + versus the unvaccinated of 11% during April-June 2021, rising steadily to 36% during the Omicron period (January-June, 2022). Notably, a booster dose reduced RMR to 10-11% for ages 60+. Boosters thus provide important additional protection against mortality.