Comparative COVID-19 Vaccine Effectiveness Over Time in Veterans

BACKGROUND: Comparative effectiveness of coronavirus disease 2019 (COVID-19) vaccines across patient subgroups is poorly understood and essential to precisely targeting vaccination strategies. METHODS: We used the US Department of Veterans Affairs COVID-19 Shared Data Resource to identify veterans who utilize VA health care and had no documented severe acute respiratory syndrome coronavirus 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 2 doses of mRNA vaccines or 1 dose of Ad26.Cov2.S. RESULTS: We identified 4.8 million veterans with a mean age of 64 years, of whom 58% had ≥1 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 with BNT162b2 were 89.7% (95% CI, 84.4%–93.0%) and 57.3% (95% CI, 48.4%–64.7%) vs 81.6% (95% CI, 75.9%–85.9%) and 22.5% (95% CI, 7.2%–35.2%) for individuals age <65 years and 78.4% (95% CI, 71.1%–83.9%) and 36.2% (95% CI, 27.7%–43.6%) vs 66.3% (95% CI, 55.7%–74.4%) and −23.3% (95% CI, −40.5% to −8.2%) in subjects age ≥65 years; against hospitalization 92.0% (95% CI, 76.1%–97.3%) and 83.1% (95% CI, 66.8%–91.4%) vs 85.6% (95% CI, 72.6%–92.4%) and 57.0% (95% CI, 31.2%–73.2%) in subjects age <65 years and 66.1% (95% CI, 45.3%–79.0%) and 64.7% (95% CI, 55.2%–72.3%) vs 61.0% (95% CI, 41.3%–74.2%) and 1.7% (95% CI, −22.0% to 20.8%) in those age ≥65 years; against ICU admission or death 89.2% (95% CI, 49.5%–97.7%) and 84.4% (95% CI, 59.0%–94.1%) vs 87.6% (95% CI, 61.0%–96.1%) and 66.4% (95% CI, 7.7%–87.8%) in subjects age <65 years and 75.4% (95% CI, 51.7%–87.5%) and 73.8 (95% CI, 62.9%–81.5%) vs 67.4% (95% CI, 32.6%–84.3%) and 29.3% (95% CI, 2.3%–48.9%) in subjects age ≥65 years, respectively (P(interaction) < .01 for all comparisons). Similarly, mRNA-1273 was more effective than BNT162b2 in veterans with >1 chronic disease. CONCLUSIONS: mRNA-1273 was more effective than BNT162b2 in older veterans and those with chronic diseases.