COVID-19 Vaccination Effectiveness Against Infection or Death in a National U.S. Health Care System : A Target Trial Emulation Study

Abstract

Background: Little is known about real-world COVID-19 vaccine effectiveness (VE) in racially and ethnically diverse, elderly populations with high comorbidity burden.

Objective: To determine the effectiveness of messenger RNA COVID-19 vaccines.

Design: Target trial emulation study comparing newly vaccinated persons with matched unvaccinated controls.

Setting: U.S. Department of Veterans Affairs health care system.

Participants: Among persons receiving care in the Veterans Affairs health care system (n = 5 766 638), those who received at least 1 dose of the Moderna or Pfizer-BioNTech COVID-19 vaccine from 11 December 2020 to 25 March 2021 (n = 2 099 871) were matched to unvaccinated controls in a 1:1 ratio according to demographic, clinical, and geographic characteristics.

Intervention: Follow-up for SARS-CoV-2 infection or SARS-CoV-2-related death, defined as death within 30 days of infection, began after the vaccination date or an identical index date for the matched unvaccinated controls and continued until up to 30 June 2021.

Measurements: Vaccine effectiveness against SARS-CoV-2 infection or SARS-CoV-2-related death.

Results: Vaccinated and unvaccinated groups were well matched; both were predominantly male (92.9% vs. 93.4%), had advanced age (mean, 68.7 years in both groups), had diverse racial and ethnic distribution (for example, Black: 17.3% vs. 17.0%, Hispanic: 6.5% vs. 6.1%), and had substantial comorbidity burden. Vaccine effectiveness 7 or more days after the second vaccine dose was 69% (95% CI, 67% to 70%) against SARS-CoV-2 infection and 86% (CI, 82% to 89%) against SARS-CoV-2-related death and was similar when follow-up was extended to 31 March versus 30 June. Vaccine effectiveness against infection decreased with increasing age and comorbidity burden.

Limitation: Predominantly male population and lack of data on SARS-CoV-2 variants.

Conclusion: In an elderly, diverse, high-comorbidity population, COVID-19 VE against infection was substantially lower than previously reported, but VE against death was high. Complementary infection mitigation efforts remain important for pandemic control, even with vaccination.

Primary funding source: U.S. Department of Veterans Affairs.

Visual Abstract.. COVID-19 Vaccination Effectiveness Against Infection or Death.

In a target trial emulation study that included nearly 6 million predominately male patients receiving care in the U.S. Department of Veterans Affairs health care system, those receiving messenger RNA vaccines against SARS-CoV-2 were matched 1:1 to unvaccinated controls according to demographic, clinical, and geographic characteristics and followed for SARS-CoV-2 infection or SARS-CoV-2–related death to determine vaccine efficacy.

Appendix Figure.. Distribution of baseline characteristics and propensity scores in vaccinated and unvaccinated persons before and after matching.

BMI = body mass index; CAN = Care Assessment Need score. Top. Absolute standardized mean differences and variance ratios of baseline characteristics between vaccinated and unvaccinated persons for the raw and matched data show balance after matching. Bottom. Probability distribution (kernel density) of propensity score between vaccinated and unvaccinated persons for the raw and matched data show balance after matching.

Figure.. Kaplan–Meier curve with 95% confidence bands showing cumulative incidence (%) of SARS-CoV-2 infection and SARS-CoV-2–related death in persons who received COVID-19 vaccination versus matched unvaccinated controls, with number at risk and cumulative number of infections or deaths shown at 28-d intervals.

The slight separation in Kaplan–Meier curves between days 0 and 7 is likely related to the standard screening questions before vaccination and postponing vacination in persons who feel sick, including those who may have COVID-19, hence resulting in an artificially slightly lower rate of infection and death in vaccinated persons immediately after vaccination (incident infections or deaths within 0 to 14 d after vaccination were not used in any of the analyses). Top. SARS-CoV-2 infection. Bottom. SARS-CoV-2–related death.