Predictors of SARS-CoV-2 infection following high-risk exposure: a test-negative design case-control study

Background: Non-pharmaceutical interventions (NPIs) continue to be recommended for mitigation of the ongoing COVID-19 pandemic. However, the effectiveness of NPIs in preventing SARS-CoV-2 transmission remains poorly quantified. Methods: We conducted a test-negative design case-control study enrolling cases (testing positive for SARS-CoV-2) and controls (testing negative) whose molecular SARS-CoV-2 diagnostic test results were reported to California Department of Public Health between 24 February-26 September, 2021. We used conditional logistic regression to assess predictors of case status among participants who reported contact with an individual known or suspected to have been infected with SARS-CoV-2 ("high-risk exposure") within ≤ 14 days of testing. Results: 643 of 1280 cases (50.2%) and 204 of 1263 controls (16.2%) reported high-risk exposures ≤ 14 days before testing. Adjusted odds of case status were 2.94-fold (95% confidence interval: 1.66-5.25) higher when high-risk exposures occurred with household members (vs. other contacts), 2.06-fold (1.03-4.21) higher when exposures occurred indoors (vs. not indoors), and 2.58-fold (1.50-4.49) higher when exposures lasted ≥ three hours (vs. shorter durations) among unvaccinated and partially-vaccinated individuals; excess risk associated with such exposures was mitigated among fully-vaccinated individuals. Mask usage by participants or their contacts during high-risk exposures reduced adjusted odds of case status by 48% (8-72%). Adjusted odds of case status were 68% (32-84%) and 77% (59-87%) lower for partially- and fully-vaccinated participants, respectively, than for unvaccinated participants. Benefits of mask usage were greatest when exposures lasted ≤ three hours, occurred indoors, or involved non-household contacts. Conclusions: NPIs reduced the likelihood of SARS-CoV-2 infection following high-risk exposure. Vaccine effectiveness was substantial for partially and fully vaccinated persons.