Using BCG Vaccine to Enhance Nonspecific Protection of Health Care Workers During the COVID-19 Pandemic: A Randomized Controlled Trial.

Background: The BCG (Bacillus Calmette-Guérin) vaccine can induce nonspecific protection against unrelated infections. We aimed to test the effect of BCG on absenteeism and health of Danish health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic.
Methods: A single-blinded randomized controlled trial included 1221 HCWs from 9 Danish hospitals. Participants were randomized 1:1 to standard dose BCG or placebo. Primary outcome was days of unplanned absenteeism. Main secondary outcomes were incidence of COVID-19, all-cause hospitalization, and infectious disease episodes.
Results: There was no significant effect of BCG on unplanned absenteeism. Mean number of days absent per 1000 workdays was 20 in the BCG group and 17 in the placebo group (risk ratio, 1.23; 95% credibility interval, 0.98-1.53). BCG had no effect on incidence of COVID-19 or all-cause hospitalization overall. In secondary analyses BCG revaccination was associated with higher COVID-19 incidence (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.07-5.71), but also reduced risk of hospitalization (HR, 0.28; 95% CI, .09-.86). The incidence of infectious disease episodes was similar between randomization groups (HR, 1.09; 95% CI, .96-1.24).
Conclusions: In this relatively healthy cohort of HCWs, there was no overall effect of BCG on any of the study outcomes.
Clinical Trials Registration: NCT0437329 and EU Clinical Trials Register (EudraCT number 2020-001888-90).
Competing Interests: Potential conflicts of interests . T. B. reports grants or contracts from Novo Nordisk, Simonsen, Lundbeck, Kai, Erik and Susanna Olesen's Charitable Found, GSK, Pfizer, Boehringer Ingelheim, Gilead Sciences, MSD, Pentabase, Roche, Novartis, Kancera AB, Janssen, and Astra Zeneca; consulting fees from GSK and Pfizer; honoraria for lectures from GSK, Pfizer, Gilead Sciences, Boehringer Ingelheim, Abbvie, and Astra Zeneca; and donation of trial medication from Eli Lilly. P. E. K. reports participation on Data Safety Monitoring Board or Advisory Board on trials “Specific and non-specific effects of measles and BCG vaccines for mother and child (MATVAC)”, “Evaluating the effectiveness of different BCG strains in Guinea-Bissau: A randomized trial of the impact on neonatal hospital admissions”, and “BCG vaccine to reduce unplanned absenteeism due to COVID-19 illness of health care workers in Guinea-Bissau and Mozambique. A multi-center single-blinded randomized controlled trial (BCG-COVID-RCT)”, and “A randomized trial of providing BCG vaccination immediately to neonates admitted to the intensive care unit in Guinea-Bissau: Effect on mortality”. C. W. reports honoraria for a lecture from Novartis; and participation on the Advisory Board on COVID-19 Treatments, Danish government. I. S. J. reports honoraria from Pfizer for being chairman for the European Congress of Clinical Microbiology and Infectious Diseases 2023 COVID-19 symposium. M. G. N. reports to be scientific founder and have stock in TTxD and Lemba. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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