ABSTRACT
Background Comparative effectiveness of COVID-19 vaccines across patient subgroups is poorly understood and essential to precisely target vaccination strategies. Methods We used the US Department of Veterans Affairs COVID-19 Shared Data Resource to identify veterans who utilize VA healthcare and had no documented SARS-CoV-2 infection before December 11, 2020. Using a test-negative case-control design (TND), we used conditional logistic regression with adjustment for covariates to estimate vaccine effectiveness (VE) over time for Veterans who received two doses of mRNA vaccines or one dose of Ad26.Cov2.S. Results We identified 4.8 million veterans with a mean age of 64 years, of whom 58% had at least one chronic disease. Vaccine effectiveness for symptomatic infections, hospitalizations, and ICU admission or death declined over time and varied by the type of vaccine (P < 0.01). VE estimates against symptomatic infection during months 1 and 7 for mRNA-1273 compared to BNT162b2 were 89.7% (CI 84.4-93.0) and 57.3% (CI 48.4-64.7) vs. 81.6% (CI 75.9-85.9) and 22.5% (CI 7.2-35.2) for individuals <65 years and 78.4% (CI: 71.1-83.9) and 36.2% (CI 27.7-43.6) vs. 66.3% (CI 55.7-74.4) and -23.3% (CI -40.5, -8.2) in subjects ≥ 65 years;Against hospitalization 92.0% (76.1-97.3) and 83.1% (CI 66.8-91.4) vs. 85.6% (CI 72.6-92.4) and 57.0% (CI 31.2-73.2) in subjects <65 years, and 66.1%(CI 45.3-79.0) and 64.7%(CI 55.2-72.3) vs. 61.0% (CI 41.3-74.2) and 1.7% (CI -22.0-20.8) in those ≥65 years;Against ICU admission or death in subjects < 65 years of age 89.2% (CI 49.5-97.7) and 84.4% (CI 59.0-94.1). vs. 87.6% (CI 61.0-96.1) and 66.4% (CI 7.7-87.8), and 75.4% (CI 51.7-87.5) and 73.8 (CI 62.9-81.5) vs. 67.4% (CI 32.6-84.3) and 29.3% (CI 2.3-48.9) in subjects ≥65 years of age, respectively (interaction P < 0.01 for all comparisons). Similarly, mRNA-1273 was more effective than BNT162b2 in veterans with more than one chronic disease. Conclusions mRNA-1273 was more effective than BNT162b2 in older veterans and those with chronic diseases.