Risk of SARS-CoV-2 Among Ontario Healthcare Workers: A Comparison of Test-negative and Cohort Study Designs in a Heterogeneous Reason-for-testing Population

OBJECTIVE: Differential reason-for-testing may bias test-negative estimates. This study aimed to estimate healthcare worker SARS-CoV-2 risk, with adjustment for healthcare-seeking behavior and unmeasured reason-for-testing. METHODS: A total of 1.2-million workers in Ontario, Canada, were followed for SARS-CoV-2 polymerase chain reaction tests from February 2020 to December 2021. Hazard ratios (HRs) were used to estimate SARS-CoV-2 risk in healthcare workers versus non-healthcare workers based on the overall and test-negative subcohort. Unmeasured reason-for-testing was examined through probabilistic bias analyses. RESULTS: In the test-negative subcohort, healthcare and non-healthcare workers had a similar risk of SARS-CoV-2. However, healthcare workers had an increased risk in the symptomatic-adjusted (HR: 1.15, 95% confidence interval: 1.03-1.40) and asymptomatic-adjusted (HR: 2.83, 95% confidence interval: 1.08-9.07) models. CONCLUSIONS: Future test-negative studies should account for potential bias from varying symptomatic and asymptomatic testing groups and may consider using probabilistic bias analysis methods when reason-for-testing data is missing.