Effectiveness of Covid-19 vaccines against symptomatic and asymptomatic SARS-CoV-2 infections in an urgent care setting

•mRNA VE against infection declined during periods of delta variant predominance.•High effectiveness of mRNA vaccines in 12–15 year old children in delta period.•Prior infection with pre-delta strains were as protective as full vaccination.•Hybrid immunity provides best protection against infection.•mRNA-1273 vaccine marginally more effective compared to BNT162b2 against infection. It is critical to monitor changes in vaccine effectiveness against COVID-19 outcomes for various vaccine products in different population subgroups. We conducted a retrospective study in patients ≥12 years who underwent testing for SARS-CoV-2 virus from April 14 through October 25, 2021, at urgent care centers in the New York metropolitan area. Patients self-reported vaccination status at the time of testing. We used a test-negative design to estimate vaccine effectiveness (VE) by comparing odds of a positive test for SARS-CoV-2 infection among vaccinated (n = 474,805), partially vaccinated (n = 87,834), and unvaccinated (n = 369,333) patients, adjusted for demographic factors and calendar time. VE against symptomatic infection after 2 doses of mRNA vaccine was 96% (95% Confidence Interval: 95%, 97%) in the pre-delta period and reduced to 79% (95% CI: 77%, 81%) in the delta period. In the delta period, VE for 12–15-year-olds (85%; [95% CI: 81%, 88%]) was higher compared to older age groups (