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Background  COVID-19 outbreaks have occurred in homeless shelters across the US, highlighting an urgent need to identify the most effective infection control strategy to prevent future outbreaks.    Methods  We developed a microsimulation model of SARS-CoV-2 transmission in a homeless shelter and calibrated it to data from cross-sectional polymerase chain reaction (PCR) surveys conducted during COVID-19 outbreaks in five homeless shelters in three US cities from March 28 to April 10, 2020. We estimated the probability of averting a COVID-19 outbreak when an exposed individual is introduced into a representative homeless shelter of 250 residents and 50 staff over 30 days under different infection control strategies, including daily symptom-based screening, twice-weekly PCR testing, and universal mask wearing.    Results  The proportion of PCR-positive residents and staff at the shelters with observed outbreaks ranged from 2.6 to 51.6%, which translated to the basic reproduction number ( R  0 ) estimates of 2.9–6.2. With moderate community incidence (~ 30 confirmed cases/1,000,000 people/day), the estimated probabilities of averting an outbreak in a low-risk ( R  0  = 1.5), moderate-risk ( R  0  = 2.9), and high-risk ( R  0  = 6.2) shelter were respectively 0.35, 0.13, and 0.04 for daily symptom-based screening; 0.53, 0.20, and 0.09 for twice-weekly PCR testing; 0.62, 0.27, and 0.08 for universal masking; and 0.74, 0.42, and 0.19 for these strategies in combination. The probability of averting an outbreak diminished with higher transmissibility ( R  0 ) within the simulated shelter and increasing incidence in the local community.    Conclusions  In high-risk homeless shelter environments and locations with high community incidence of COVID-19, even intensive infection control strategies (incorporating daily symptom screening, frequent PCR testing, and universal mask wearing) are unlikely to prevent outbreaks, suggesting a need for non-congregate housing arrangements for people experiencing homelessness. In lower-risk environments, combined interventions should be employed to reduce outbreak risk.

Comparison of infection control strategies to reduce COVID-19 outbreaks in homeless shelters in the United States: a simulation study