BackgroundEarly evaluations of healthcare professional (HCP) COVID-19 risk occurred during insufficient personal protective equipment and disproportionate testing, contributing to perceptions of high patient-care related HCP risk. We evaluated HCP COVID-19 seropositivity after accounting for community factors and coworker outbreaks.MethodsPrior to universal masking, we conducted a single-center retrospective cohort plus cross-sectional study. All HCP (1) seen by Occupational Health for COVID-like symptoms (regardless of test result) or assigned to (2) dedicated COVID-19 units, (3) units with a COVID-19 HCP outbreak, or (4) control units from 01/01/2020 to 04/15/2020 were offered serologic testing by an FDA-authorized assay plus a research assay against 67 respiratory viruses, including 11 SARS-CoV-2 antigens. Multivariable models assessed the association of demographics, job role, comorbidities, care of a COVID-19 patient, and geocoded socioeconomic status with positive serology.ResultsOf 654 participants, 87 (13.3%) were seropositive; among these 60.8% (N = 52) had never cared for a COVID-19 patient. Being male (OR 1.79, CI 1.05–3.04,p = 0.03), working in a unit with a HCP-outbreak unit (OR 2.21, CI 1.28–3.81,p p = 0.05), and ethnically Latino (OR 2.10, CI 1.12–3.96,p = 0.02) were positively-associated with COVID-19 seropositivity, while working in dedicated COVID-19 units was negatively-associated (OR 0.53, CI = 0.30–0.94,p = 0.03). The research assay identified 25 additional seropositive individuals (78 [12%] vs. 53 [8%],p ConclusionsPrior to universal masking, HCP COVID-19 risk was dominated by workplace and community exposures while working in a dedicated COVID-19 unit was protective, suggesting that infection prevention protocols prevent patient-to-HCP transmission.Article summaryPrior to universal masking, HCP COVID-19 risk was dominated by workplace and community exposures while working in a dedicated COVID-19 unit was protective, suggesting that infection prevention protocols prevent patient-to-HCP transmission.