ABSTRACT
Evaluations of vaccine effectiveness (VE) are important to monitor as coronavirus disease 2019 (COVID-19) vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, the VE of messenger RNA vaccines against COVID-19 was 91% (95% confidence interval, 83%-95%) for full vaccination and 75% (55%-87%) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.