OBJECTIVES: Moderately to severe immunocompromised (IC) individuals are among the most vulnerable for COVID-19. IC individuals comprise approximately 3% of the US population but account for an estimated 44% of breakthrough COVID-19 hospitalizations. Previous studies have shown that IC individuals were better protected with two doses of mRNA-1273 compared with 2 doses of BNT162b2 (primary series). The objective of this study was to compare the real-world effectiveness of the third dose of mRNA-1273 versus BNT162b2 in the US.

METHODS: A retrospective cohort study using HealthVerity claims data from December 2020 to August 2022 was conducted. IC individuals who completed a primary vaccination series were followed from 14 days after receipt of their third dose of COVID-19 vaccine (mRNA-1273 or BNT162b2) until receipt of another COVID-19 vaccine, outcome(s) occurring, end of continuous enrollment or end of data cut. Inverse probability of treatment weighting (IPTW) was applied to adjust for baseline measurement confounding. Comparative vaccine effectiveness against medically attended COVID-19 infection and hospitalization was estimated based on rate differences (RDs) between the 2 vaccine groups.

RESULTS: Preliminary results show that IC individuals who received mRNA-1273 as their third dose (n=52,943) had lower crude rates of medically attended COVID-19 (166 vs 179 per 1000 person-years) and COVID-19 hospitalization (7.9 vs 10.0 per 1000 person-years) compared with those who received BNT162b2 (n=60,084). After IPTW, people who received a third dose of mRNA-1273 had statistically lower rate of medically attended COVID-19 (RD=-7.5; 95% CI: -14.3, -0.6) and COVID-19 hospitalizations (RD=-2.3; 95% CI: -3.8, -0.8) compared with their BNT162b2 counterparts.

CONCLUSIONS: Similar to prior experience with the primary series, these real-world effectiveness results demonstrate that IC individuals were better protected with a third dose of mRNA-1273 compared to BNT162b2. As COVID-19 disease burden remains high in the IC, these individuals should follow recommended vaccination guidance for the fall 2023/2024 season.