ABSTRACT
infection, infections, TTxD.
FOUNDER, INFECTIONS, INFECTION, CORONAVIRUS, SEVERE ACUTE RESPIRATORY SYNDROME
Present address: Thijs ten Doesschate, Department of Internal Medicine, Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, Netherlands.Present address: Axel B. Janssen, Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.The authors declare a conflict of interest. C.H.V.W. reports research grants from DaVolterra, bioMérieux, and LimmaTech and consultancy fees from MSD and Sanofi-Pasteur, in the last 36 months (unrelated to the work in this manuscript, payments to institution). H.L. reports a research grant from Takeda, and consultancy fees from Takeda, Sobi, Novartis, and GSK, in the last 36 months (unrelated to the work in this manuscript, payments to institution). L.M.V. reports consulting fees from MSD in the last 36 months (unrelated to the work in this manuscript, payments to institution). M.J.M.B. reports research grants from Janssen Vaccines, Novartis, CureVac, and Merck, Advisory Board memberships of Spherecydes, Pfizer, MSD, Novartis and AstraZeneca, and DSMB membership of Sanofi, in the last 36 months (unrelated to the work in this manuscript, payments to institution). M.G.N. is scientific founder and scientific advisory board member of Trained Therapeutix Discovery (TTxD) and scientific founder of Lemba Therapeutics, has obtained research grants from GSK Biologicals, TTxD, and Ono Pharma, and consultancy fees from TTxD. J.H.H.M.V.D.W. reports payments for meeting attendance from the Dutch Ministry of Health and Sports and the Netherlands Organisation for Health Research and Development (ZonMw) in the last 36 months (unrelated to the work in this manuscript, payments to institution). All other authors declare no competing interests.Bacillus Calmette-Guerin (BCG) vaccination has been hypothesized to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severity, and/or duration via trained immunity induction. Health care workers (HCWs) in nine Dutch hospitals were randomized to BCG or placebo vaccination (1:1) in March and April 2020 and followed for 1 year. They reported daily symptoms, SARS-CoV-2 test results, and health care-seeking behavior via a smartphone application, and they donated blood for SARS-CoV-2 serology at two time points. A total of 1,511 HCWs were randomized and 1,309 analyzed (665 BCG and 644 placebo). Of the 298 infections detected during the trial, 74 were detected by serology only. The SARS-CoV-2 incidence rates were 0.25 and 0.26 per person-year in the BCG and placebo groups, respectively (incidence rate ratio, 0.95; 95% confidence interval, 0.76 to 1.21; 