Researchers investigated the risk for COVID-19 breakthrough infection after SARS-CoV-2 vaccination among persons with or without immune dysfunction.

• From the National COVID Cohort Collaborative (N3C), data of a total of 664,722 patients who received at least 1 dose of a SARS-CoV-2 vaccine were included in this cohort study.

• A higher rate for COVID-19 breakthrough infection and worse outcomes were recorded after full or partial vaccination among persons with immune dysfunction, such as HIV infection, rheumatoid arthritis, and solid organ transplant, compared with those without immune dysfunction.

• These findings emphasize the use of nonpharmaceutical interventions (eg, mask wearing) and alternative vaccination approaches (eg, additional dose or immunogenicity testing) among persons with immune dysfunction even after full vaccination.