Pfizer Versus Moderna COVID-19 Vaccine Effectiveness Against Mortality: Evidence from Linked Mortality and Vaccination Records in Indiana

Objective: It is commonly believed in the public health community that the mRNA vaccines from Pfizer and Moderna were broadly similar in preventing COVID-19 mortality, with perhaps a small advantage for Moderna. We revisit this question, using a research design that controls for healthy-vaccinee bias. Methods: We studied deaths among persons aged 15 years or greater from January 2021 through December 2022 in Indiana, linked to vaccination records, using an outcome measure, namely COVID-19 Excess Mortality Percentage (CEMP), which uses non-COVID natural mortality to control for HVB. Results: We find both large healthy-vaccinee bias for both vaccines, and larger bias for Pfizervaccinees: Pfizer recipients were healthier and thus would have faced lower COVID-19 mortality without vaccination. For ages 60+, we find almost 50% higher COVID-19 remaining mortality risk (RMR) for Pfizer vaccinees receiving primary vaccination over a “core period” from 2Q2021 through 1Q2022: the average Pfizer/Moderna RMR ratio was 1.49. For ages 15–59, this ratio was 1.25, but was not statistically significant. For booster dose for ages 60+, the average Pfizer/Moderna RMR ratio was 1.34. For 2Q2022 through 4Q2022, after the major Omicron wave, we find much lower vaccine effectiveness and no significant Pfizer–Moderna difference. Conclusions: During the period with both good vaccine availability and high COVID-19 mortality (2Q-2021–1Q2022), the Moderna vaccine was associated with lower COVID-19 mortality, relative to the Pfizer vaccine. A possible explanation is the higher Moderna dose (100 μg vs. 30 for Pfizer). After that period, a high percentage of the population had natural immunity from prior COVID-19 infection; we find only small mortality gains from vaccination, with no significant Pfizer–Moderna difference. Policy Implications: Controlling for healthy-vaccinee bias, Moderna was associated with lower COVID-19 mortality, relative to Pfizer. This difference was not known in real-time due to the failure of the available studies to address healthy-vaccinee bias. Controlling for such bias is vital when making vaccination policy.