BackgroundMany patients are avoiding essential care for fear of contracting Covid-19 in healthcare settings. However, the incidence of nosocomial Covid-19 infection in U.S. acute care hospitals is unknown.MethodsWe conducted an observational study of all patients admitted to Brigham and Women’s Hospital in Boston, Massachusetts between March 7 (when the first Covid-19 patient was admitted) and May 30, 2020. During this period, a comprehensive infection control program was implemented including dedicated Covid-19 units with airborne infection isolation rooms, personal protective equipment (PPE) in accordance with CDC recommendations, PPE donning and doffing monitors, universal masking, restriction of visitors, and liberal RT-PCR testing of symptomatic and asymptomatic patients. We reviewed the medical records of all patients who tested positive for SARS-CoV-2 by RT-PCR on hospital day 3 or later or within 14 days of hospital discharge to determine whether infection was community or hospital-acquired based on timing of RT-PCR tests, clinical course, and exposures.ResultsOver the 12-week period, 9,149 patients were admitted, in whom 7,394 SARS-CoV-2 RT-PCR tests were performed and 697 Covid-19 cases were confirmed, translating into a total 8,656 days of Covid-19-related care (Figure). The inpatient Covid-19 census peaked at 171 on April 21. Twelve of the 697 Covid-19 patients (1.7%) were first diagnosed by RT-PCR on hospital day 3 or later (median 4 days, range 3–15 days). Of these, only one was deemed hospital-acquired and was most likely acquired from his pre-symptomatic spouse who was visiting daily and diagnosed with Covid-19 before visitor restrictions were implemented. Amongst 8,370 non-Covid-19 patients discharged through June 17, 11 (0.1%) subsequently tested positive within 14 days (median time to diagnosis 6 days, range 1–14). Only one was deemed likely to have been hospital-acquired, albeit with no known exposures.Figure. Timeline of implementation of major infection control policies and cumulative number of hospitalized COVID-19 cases (total and hospital-onset) ConclusionNosocomial Covid-19 infection was exceedingly rare during the height of the pandemic in a hospital with rigorous infection control measures. Our findings may inform practices in other institutions and provide reassurance to patients regarding the safety of receiving care in acute care hospitals.Disclosures All Authors: No reported disclosures