the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) Study has detected and investigated SARS-CoV-2 reinfections in the United Kingdom; after vaccine rollout, SIREN was adapted to monitor vaccine effectiveness (1-5). As the United Kingdom, like other countries, adapts to the postacute phase of the pandemic and reduced testing availability (6,7), SIREN has an ongoing function in national surveillance. SIREN informs the UK pandemic response by real-time monitoring of emerging variants and determining national rates of primary infection and reinfection. We describe SIREN's surveillance strategy and characterize emergence of Omicron subvariants during successive waves within the study.The Study SIREN is a large, multicenter, prospective cohort study of >44,000 UK healthcare workers from 135 secondary care health organizations. SIREN is led by the UK Health Security Agency in collaboration with Public Health Wales, Public Health Scotland, and the Public Health Agency Northern Ireland (1). Participants were initially followed for 12 months and had an option to extend to 24 months. Participants completed an initial enrollment survey regarding demographic and occupational data, then completed follow-up surveys every other week regarding symptoms, vaccination status, and occupational, household, and community SARS-CoV-2 exposures. Participants underwent PCR testing every 2 weeks and serologic testing monthly for the first

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