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BackgroundPersonal protective equipment (PPE) and social distancing are designed to mitigate risk of occupational SARS-CoV-2 infection in hospitals. Why healthcare workers nevertheless remain at increased risk is uncertain.MethodsWe conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using nasopharyngeal PCR testing and immunoassays for IgG antibodies. A positive result by either modality determined a composite outcome. Risk-factors for Covid-19 were investigated using multivariable logistic regression.Results1083/9809(11.0%) staff had evidence of Covid-19 at some time and provided data on potential risk-factors. Staff with a confirmed household contact were at greatest risk (adjusted odds ratio [aOR] 4.63 [95%CI 3.30-6.50]). Higher rates of Covid-19 were seen in staff working in Covid-19-facing areas (21.2% vs. 8.2% elsewhere) (aOR 2.49 [2.00-3.12]). Controlling for Covid-19-facing status, risks were heterogenous across the hospital, with higher rates in acute medicine (1.50 [1.05-2.15]) and sporadic outbreaks in areas with few or no Covid-19 patients. Covid-19 intensive care unit (ICU) staff were relatively protected (0.46 [0.29-0.72]). Positive results were more likely in Black (1.61 [1.20-2.16]) and Asian (1.58 [1.34-1.86]) staff, independent of role or working location, and in porters and cleaners (1.93 [1.25-2.97]). Contact tracing around asymptomatic staff did not lead to enhanced case identification. 24% of staff/patients remained PCR-positive at ≥6 weeks post-diagnosis.ConclusionsIncreased Covid-19 risk was seen in acute medicine, among Black and Asian staff, and porters and cleaners. A bundle of PPE-related interventions protected staff in ICU.