Purpose: Healthcare workers (HCW) have been an essential societal resource to face the COVID-19 pandemic. Early in the pandemic, they were at increased risk of contracting SARS-CoV-2 infection. We established a longitudinal cohort of HCW in an acute care hospital and four long-term care facilities in Ontario, Canada to follow the incidence of SARS-CoV-2 infection, the immune response to infection and/or vaccination, and the occupational, household and community factors related to their risk of infection. Participants Two hundred participants were recruited between November 2020 and July 2021. They completed a baseline survey, monthly surveillance data for 9-12 months, a post-Omicron-wave survey, and provided blood samples for anti-SARS-CoV2 antibody measurements. We collected data on host-related factors (humoral response to vaccines and SARS-CoV-2 infection) and environmental factors ( social contact history, occupational, household and community conditions) to establish the main determinants of risk of SARS-CoV-2 infection. Findings : Here, we describe the cohort demographics, occupational characteristics, SARS-CoV-2 vaccination status and COVID-19 infection risk during the cohort follow-up. Analyses: The data from this cohort of HCW allows analyses on 1) the risk factors for SARS-CoV-2 infection, 2) the impact of the Omicron variant on the risk of infection; 3) the relationship between humoral responses and SARS-CoV-2 infection/vaccination and, 4) their relationship of SARS-CoV-2 infection and the community, household and healthcare facility-related exposures.