SARS-CoV-2 Vaccine Effectiveness in a High-Risk National Population in a Real-World Setting

Ann Intern Med. 2021 Oct;174(10):1404-1408. doi: 10.7326/M21-1577. Epub 2021 Jul 20.


Background: With the emergency use authorization of multiple vaccines against SARS-CoV-2 infection, data are urgently needed to determine their effectiveness in a real-world setting.

Objective: To evaluate the short-term effectiveness of vaccines in preventing SARS-CoV-2 infection.

Design: Test-negative case-control study using conditional logistic regression.

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

Participants: All veterans who had testing for SARS-CoV-2 infection between 15 December 2020 and 4 March 2021 and no confirmed infection before 15 December 2020.

Intervention: SARS-CoV-2 vaccination with either the BNT-162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine as part of routine clinical care.

Measurements: Effectiveness of vaccination against confirmed SARS-CoV-2 infection.

Results: Among 54 360 persons who tested positive and 54 360 propensity score-matched control participants, the median age was 61 years, 83.6% were male, and 62% were White. Median body mass index was 31 kg/m2 among those who tested positive and 30 kg/m2 among those who tested negative. Among those who tested positive, 9800 (18.0%) had been vaccinated; among those who tested negative, 17 825 (32.8%) had been vaccinated. Overall vaccine effectiveness 7 or more days after the second dose was 97.1% (95% CI, 96.6% to 97.5%). Effectiveness was 96.2% (CI, 95.5% to 96.9%) for the Pfizer-BioNTech BNT-162b2 vaccine and 98.2% (CI, 97.5% to 98.6%) for the Moderna mRNA-1273 vaccine. Effectiveness remained above 95% regardless of age group, sex, race, or presence of comorbidities.

Limitations: Predominantly male population; lack of data on disease severity, mortality, and effectiveness by SARS-CoV-2 variants of concern; and short-term follow-up.

Conclusion: Currently used vaccines against SARS-CoV-2 infection are highly effective in preventing confirmed infection in a high-risk population in a real-world setting.

Primary funding source: None.

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273
  • Aged
  • BNT162 Vaccine
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines*
  • Case-Control Studies
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Pandemics / prevention & control
  • Risk Factors
  • SARS-CoV-2
  • Veterans Health Services
  • Veterans*


  • COVID-19 Vaccines
  • 2019-nCoV Vaccine mRNA-1273
  • BNT162 Vaccine