Importance: Effectiveness of mRNA vaccinations in a diverse older population with high comorbidity is unknown.
Objectives: To describe the scope of the COVID-19 vaccination rollout among US veterans, and to estimate mRNA COVID-19 vaccine effectiveness (VE) as measured by rates of SARS-CoV-2 infection.
Design, setting, and participants: This matched test-negative case-control study was conducted using SARS-CoV-2 test results at Veterans Health Administration sites from December 14, 2020, to March 14, 2021. Vaccine coverage was estimated for all veterans. VE against SARS-CoV-2 infection and COVID-19-related hospitalization and death were estimated using electronic health records from veterans who routinely sought care at a VHA facility and had a test result positive for SARS-CoV-2 (cases) or negative for SARS-CoV-2 (controls). Cases and controls were matched on time of test and geographic region. Data were analyzed from May to July 2021.
Exposures: Vaccination status, defined as unvaccinated, partially vaccinated (≥14 days after first dose until second dose), or fully vaccinated (≥14 days after second dose), at time of test.
Main outcomes and measures: The main outcome of interest was a positive result for SARS-CoV-2 on a polymerase chain reaction or antigen test. Secondary outcomes included COVID-19-related hospitalization and death, defined by discharge data and proximity of event to positive test result. VE was estimated from odds ratios for SARS-CoV-2 infection with 95% CIs.
Results: Among 6 647 733 veterans included (3 350 373 veterans [50%] aged ≥65 years; 6 014 798 [90%] men and 632 935 [10%] women; 461 645 Hispanic veterans of any race [7%], 1 102 471 non-Hispanic Black veterans [17%], and 4 361 621 non-Hispanic White veterans [66%]), 1 363 180 (21%) received at least 1 COVID-19 vaccination by March 7, 2021. In this period, during which the share of SARS-CoV-2 variants Alpha, Epsilon, and Iota had started to increase in the US, estimates of COVID-19 VE against infection, regardless of symptoms, was 95% (95% CI, 93%-96%) for full vaccination and 64% (95% CI, 59%-68%) for partial vaccination. Estimated VE against COVID-19-related hospitalization for full vaccination was 91% (95% CI 83%-95%); there were no deaths among veterans who were fully vaccinated. VE against infection was similar across subpopulations (non-Hispanic Black, 94% [95% CI, 88%-97%]; Hispanic [any race], 83% [95% CI, 45%-95%]; non-Hispanic White, 92% [95% CI 88%-94%]; rural, 94% [95% CI, 89%-96%]; urban, 93% 95% CI, 89%-95%]).
Conclusions and relevance: For veterans of all racial and ethnic subgroups living in urban or rural areas, mRNA vaccination was associated with substantially decreased risk of COVID-19 infection and hospitalization, with no deaths among fully vaccinated veterans.