We hypothesized that healthcare workers (HCWs) with high-risk exposures outside the healthcare system would have less asymptomatic coronavirus 2019 (COVID-19) disease and more symptoms than those without such exposures.

A longitudinal point prevalence study was conducted during August 17–September 4, 2020 (period 1) and during December 2–23, 2020 (period 2).

Community based teaching health system.

All HCWs were invited to participate. Among HCWs who acquired COVID-19, logistic regression models were used to evaluate the adjusted odds of asymptomatic disease using high-risk exposure outside the healthcare system as the explanatory variable. The number of symptoms between exposure groups was evaluated with the Wilcoxon rank-sum test. The risk of seropositivity among all HCS by work exposure was evaluated during both periods.

Survey and serological testing.

Seroprevalence increased from 1.9% (95% confidence interval [CI], 1.2%–2.6%) to 13.7% (95% CI, 11.9%–15.5%) during the study. Only during period 2 did HCWs with the highest work exposure (versus low exposure) have an increased risk of seropositivity (risk difference [RD], 7%; 95% CI, 1%–13%). Participants who had a high-risk exposure outside of work (compared to those without) had a decreased probability of asymptomatic disease (odds ratio [OR], 0.38; 95% CI, 0.16–0.86) and demonstrated more symptoms (median 3 [IQR, 2–6] vs 1 [IQR, 0–4]; P = .001).

Healthcare-acquired COVID-19 increases the probability of asymptomatic or mild COVID-19 disease compared to community-acquired disease. This finding suggests that infection prevention strategies (including masks and eye protection) may be mitigating inoculum and supports the variolation theory in COVID-19.