BackgroundHealth care workers (HCW) are heavily exposed to SARS-CoV-2 from the beginning of the pandemic. We aimed to analyze risk factors for SARS-CoV-2 seroconversion among HCW with a special emphasis on the respective healthcare institutions’ recommendation regarding the use of FFP-2 masks. MethodsWe recruited HCW from 13 health care institutions (HCI) with different mask policies (type IIR surgical face masks vs. FFP-2 masks) in Southeastern Switzerland (canton of Grisons). Sera of participants were analyzed for the presence of SARS-CoV-2 antibodies six months apart, after the first and during the second pandemic wave using an electro-chemiluminescence immunoassay (ECLIA, Roche Diagnostics). We captured risk factors for SARS-CoV-2 infection by using an online questionnaire at both time points. The effects of individual COVID-19 exposure, regional incidence and FFP-2 mask policy on the probability of seroconversion were evaluated with univariable and multivariable logistic regression.ResultsSARS-CoV-2 antibodies were detected in 99 of 2794 (3.5%) HCW at baseline and in 376 of 2315 (16.2%) participants six months later. In multivariable analyses the strongest association for seroconversion was exposure to a household member with known COVID-19 (aOR: 19.82, 95% CI: 8.11-48.43, p<0.001 at baseline and aOR: 8.68, 95% CI: 6.13-12.29, p<0.001 at follow-up). Significant occupational risk factors at baseline included exposure to COVID-19 patients (aOR: 2.79, 95% CI: 1.28-6.09, p=0.010) and to SARS-CoV-2 infected co-workers (aOR: 2.50, 95% CI: 1.52-4.12, p<0.001). At follow up six months later, non-occupational exposure to SARS-CoV-2 infected individuals (aOR: 2.54, 95% CI: 1.66-3.89 p<0.001) and the local COVID-19 incidence of the corresponding HCI (aOR: 1.98, 95% CI: 1.30-3.02, p=0.001) were associated with seroconversion. The healthcare institutions’ mask policy (surgical masks vs. FFP-2 masks) did not affect seroconversion rates of HCW during the first and the second pandemic wave. ConclusionContact with SARS-CoV-2 infected household members was the most important risk factor for seroconversion among HCW. The strongest occupational risk factor was exposure to COVID-19 patients. During this pandemic, with heavy non-occupational exposure to SARS-CoV-2, the mask policy of HCIs did not affect the seroconversion rate of HCWs.