To evaluate these risks, we enrolled 200 patient-facing HCWs between March 26 and April 8, 2020, in SARS-CoV-2 Acquisition in Frontline Healthcare Workers—Evaluation to inform Response (SAFER), a prospective cohort study in high-risk frontline HCWs in an acute National Health Service hospital trust in London. We collected nasopharyngeal swabs for RT-PCR twice per week, symptom data, and blood samples monthly for high-sensitivity serology assays (ELISA and flow cytometry for spike glycoprotein). Further methodology, study participant demographics, and the length of participation are described in the appendix. 87 (44%) of 200 HCWs had evidence of SARS-CoV-2 infec tion at any timepoint, detected either by serology or RT-PCR. Of the 200 HCWs, 181 gave a valid blood sample at two timepoints. On the basis of the composite ELISA and flow-cytometry serological results, 82 (45%) of 181 HCWs were seropositive after 1 month. 36 (20%) of 181 HCWs seroconverted during the study, and 46 (25%) of 181 HCWs were already seropositive at study entry. 42 (21%) of 200 HCWs tested positive for SARS-CoV-2 by RT-PCR in at least one swab.