Evaluating risk factors associated with COVID-19 infections among vaccinated people early in the U.S. vaccination campaign: an observational study of five states, January–March 2021

BACKGROUND: COVID-19 vaccines are an effective tool to prevent illness due to SARS-CoV-2 infection. However, infection after vaccination still occurs. We evaluated all infections identified among recipients of either the Pfizer-BioNTech or Moderna COVID-19 vaccine in five U.S. states during January–March 2021. METHODS: Using observational data reported to CDC, we compared the incidence of SARS-CoV-2 infection among vaccinated and unvaccinated persons, and the sex, age, and vaccine product received for individuals with vaccine breakthrough infections to those of the vaccinated population using Poisson regression models. We also compared the proportion of vaccine breakthrough cases due to a SARS-CoV-2 variant of concern to data reported to CDC’s national genomic surveillance program. RESULTS: The age-adjusted incidence of reported SARS-CoV-2 infection was 97% lower among vaccinated as compared to unvaccinated persons aged ≥ 16 years (68 vs 2252 cases per 100,000 people). Vaccinated adults aged ≥ 85 years were 1.6 times (95% CI 1.3–1.9) as likely to become infected with SARS-CoV-2 than vaccinated adults aged < 65 years. Pfizer-BioNTech COVID-19 vaccine recipients were 1.4 times (95% CI 1.3–1.6) as likely to experience infection compared to Moderna COVID-19 recipients. The proportion of infections among vaccinated persons caused by SARS-CoV-2 variants of concern was similar to the proportion of circulating viruses identified as variants of concern in the five states during the same time. CONCLUSIONS: Vaccinated persons had a substantially lower incidence of SARS-CoV-2 infection compared to unvaccinated persons. Adults aged ≥ 85 years and Pfizer-BioNTech vaccine recipients had a higher risk of infection following vaccination. We provide an analytic framework for ongoing evaluation of patterns associated with SARS-CoV-2 infection among vaccinated persons using observational surveillance and immunization data. Our findings reinforce the effectiveness of COVID-19 vaccines in preventing infection in real-world settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-022-07702-x.