Comparison of Moderna versus Pfizer-BioNTech COVID-19 vaccine outcomes: A target trial emulation study in the U.S. Veterans Affairs healthcare system.

Background: mRNA COVID-19 vaccines manufactured by Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) have been shown to be efficacious but have not been compared in head-to-head clinical trials. Methods: We designed this observational study to emulate a target trial of COVID-19 vaccination by BNT162b2 versus mRNA-1273 among persons who underwent vaccination in the national U.S. Veterans Affairs (VA) healthcare system from 11/12/2020 to 25/03/2021 using combined VA and Medicare electronic health records. We identified the best matching mRNA-1273 recipient(s) for each BNT162b2 recipient, using exact/coarsened-exact matching (calendar week, VA integrated service network, age buckets and Charlson comorbidity index buckets) followed by propensity score matching. Vaccine recipients were followed from the date of first vaccine dose until 25/08/2021 for the development of SARS-CoV-2 infection, SARS-CoV-2-related hospitalization or SARS-CoV-2-related death. Findings: Each group included 902,235 well-matched vaccine recipients, followed for a mean of 192 days, during which 16,890 SARS-CoV-2 infections, 3591 SARS-CoV-2-related hospitalizations and 381 SARS-CoV-2-related deaths were documented. Compared to BNT162b2, mRNA-1273 recipients had significantly lower risk of SARS-CoV-2 infection (adjusted hazard ratio [aHR] 0.736, 95% CI 0.696-0.779) and SARS-CoV-2-related hospitalization (aHR 0.633, 95% CI 0.562-0.713), which persisted across all age groups, comorbidity burden categories and black/white race. The differences between mRNA-1273 and BNT162b2 in risk of infection or hospitalization were progressively greater when the follow-up period was longer, i.e. extending to March 31, June 30 or August 25, 2021. These differences were more pronounced when we analyzed separately the outcomes that occurred during the follow-up period from July 1 to August 25, 2021 when the Delta variant became predominant in the U.S. (aHR for infection 0.584, 95% CI 0.533-0.639 and aHR for hospitalization 0.387, 95% 0.311-0.482). SARS-CoV-2-related deaths were less common in mRNA-1273 versus BNT162b2 recipients (168 versus 213) but this difference was not statistically significant (aHR 0.808, 95% CI 0.592-1.103). Interpretation: In conclusion, although absolute rates of infection, hospitalization and death in both vaccine groups were low regardless of the vaccine received, our data suggests that compared to BNT162b2, vaccination with mRNA-1273 resulted in significantly lower rates of SARS-CoV-2-infection and SARS-CoV-2-related hospitalization. These differences were greater with longer follow-up time since vaccination and even more pronounced in the Delta variant era. Funding: U.S. Department of Veterans Affairs, grant numbers COVID19-8900-11 and C19 21-278.