Publication Date
1-1-2025
Journal
Open Forum Infectious Diseases
DOI
10.1093/ofid/ofaf007
PMID
39872813
PMCID
PMC11770274
PubMedCentral® Posted Date
1-16-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
BCG vaccine, COVID-19, DNA methylation, innate training, epigenetics
Abstract
BACKGROUND: The BCG vaccine induces trained immunity, an epigenetic-mediated increase in innate immune responsiveness. Therefore, this clinical trial evaluated if BCG-induced trained immunity could decrease coronavirus disease 2019 (COVID-19)-related frequency or severity.
METHODS: A double-blind, placebo-controlled clinical trial of healthcare workers randomized participants to vaccination with BCG TICE or placebo (saline). Enrollment included 529 healthcare workers randomized to receive BCG or placebo. Primary analysis evaluated COVID-19 disease frequency, while secondary analysis evaluated coronavirus immunity in a subset of participants. Study enrollment ceased early in December 2020 following introduction of COVID-19-specific vaccines.
RESULTS: Study enrollment was halted early, prior to reaching the targeted recruitment, and was not powered to detect a decrease in COVID-19 frequency. Symptomatic COVID-19 occurred in 21 of 263 and 10 of 266 participants in the BCG and placebo arms, respectively (
CONCLUSIONS: Due to early study closure, the study was not powered to evaluate COVID-19 frequency. Secondary analysis demonstrated that 12 months following vaccination, BCG increased coronavirus vaccine immunity compared to those who did not receive BCG. This increase in COVID-19 vaccine immunity correlated with BCG-induced DNA methylation changes.
Included in
COVID-19 Commons, Digestive System Diseases Commons, Epidemiology Commons, Gastroenterology Commons, Health Services Research Commons, Hepatology Commons, Influenza Humans Commons, Influenza Virus Vaccines Commons, Medical Sciences Commons, Pediatrics Commons
