AbstractObjective:Evidence-based infection control strategies are needed for healthcare workers (HCWs) following high-risk exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). In this study, we evaluated the negative predictive value (NPV) of a home-based 7-day infection control strategy.Methods:HCWs advised by their infection control or occupational health officer to self-isolate due to a high-risk SARS-CoV-2 exposure were enrolled between May and October 2020. The strategy consisted of symptom-triggered nasopharyngeal SARS-CoV-2 RNA testing from day 0 to day 7 after exposure and standardized home-based nasopharyngeal swab and saliva testing on day 7. The NPV of this strategy was calculated for (1) clinical coronavirus disease 2019 (COVID-19) diagnosis from day 8–14 after exposure, and for (2) asymptomatic SARS-CoV-2 detected by standardized nasopharyngeal swab and saliva specimens collected at days 9, 10, and 14 after exposure. Interim results are reported in the context of a second wave threatening this essential workforce.Results:Among 30 HCWs enrolled, the mean age was 31 years (SD, ±9), and 24 (80%) were female. Moreover, 3 were diagnosed with COVID-19 by day 14 after exposure (secondary attack rate, 10.0%), and all cases were detected using the 7-day infection control strategy: the NPV for subsequent clinical COVID-19 or asymptomatic SARS-CoV-2 detection by day 14 was 100.0% (95% CI, 93.1%–100.0%).Conclusions:Among HCWs with high-risk exposure to SARS-CoV-2, a home-based 7-day infection control strategy may have a high NPV for subsequent COVID-19 and asymptomatic SARS-CoV-2 detection. Ongoing data collection and data sharing are needed to improve the precision of the estimated NPV, and here we report interim results to inform infection control strategies in light of a second wave threatening this essential workforce.