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BackgroundProtecting healthcare workers (HCW) from Coronavirus Disease-19 (COVID-19) is critical to preserve the functioning of healthcare systems. We therefore assessed seroprevalence and identified risk factors for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) seropositivity in this population. MethodsBetween June 22nd and August 15th 2020, HCW from institutions in Northern/Eastern Switzerland were screened for SARS-CoV-2 antibodies. We recorded baseline characteristics, non-occupational and occupational risk factors. We used pairwise tests of associations and multivariable logistic regression to identify factors associated with seropositivity. FindingsAmong 4664 HCW from 23 healthcare facilities, 139 (3%) were seropositive. Non-occupational exposures independently associated with seropositivity were contact with a COVID-19-positive household (adjusted OR=54, 95%-CI: 31-97) and stay in a COVID-19 hotspot (aOR=2{middle dot}2, 95%-CI: 1{middle dot}1-3{middle dot}9). Blood group 0 vs. non-0 (aOR=0{middle dot}4, 95%-CI: 0{middle dot}3-0{middle dot}7), active smoking (aOR=0{middle dot}5, 95%-CI: 0{middle dot}3-0{middle dot}9) and living with children <12 years (aOR=0{middle dot}3, 95%-CI: 0{middle dot}2-0{middle dot}6) were associated with decreased risk. Occupational risk factors were close contact to COVID-19 patients (aOR=2{middle dot}8, 95%-CI: 1{middle dot}5-5{middle dot}5), exposure to COVID-19-positive co-workers (aOR=2{middle dot}0, 95%-CI: 1{middle dot}2-3{middle dot}1), poor knowledge of standard hygiene precautions (aOR=2{middle dot}0, 95%-CI: 1{middle dot}3-3{middle dot}2), and frequent visits to the hospital canteen (aOR=1{middle dot}9, 95%-CI: 1{middle dot}2-3{middle dot}1). InterpretationLiving with COVID-19-positive households showed by far the strongest association with SARS-CoV-2 seropositivity. We identified several potentially modifiable risk factors, which might allow mitigation of the COVID-19 risk among HCW. The lower risk among those living with children, even after correction for multiple confounders, is remarkable and merits further study. FundingSwiss National Sciences Foundation, Federal Office of Public Health, Cantonal Health Department St.Gallen

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