The tuberculosis vaccine BCG was not protective against COVID-19 infections in healthcare workers, according to the results of an international trial in the New England Journal of Medicine.
The study was based on results from the second stage of the BCG Vaccination to Reduce the Impact of COVID-19 in Healthcare Workers (BRACE) trial, which involved 3,988 of almost 7,000 healthcare workers who signed up to participate across 36 sites in Australia, the Netherlands, the United Kingdom, Spain, and Brazil.
The goal of the BRACE trial was to see if the BCG vaccine could offer protection to healthcare workers during the first months of the COVID-19 pandemic, because the vaccine has a history of being broadly protective against respiratory infections in infants and adults.
The hope was BCG could act as a stop-gap vaccine until COVID-specific vaccines were made available. Participants in the second stage of the trial (recruitment from May 2020 through April 2021) were separated into two groups, 1,703 in the BCG group and 1,683 in the placebo group.
Participants were mostly women (73.7%), with an average age of 42 years. A large proportion of the participants were enrolled in Brazil (64.4%).
The participants were followed for 12 months, with primary outcomes assessed at 6 months, which included the incidence of symptomatic COVID-19 and the incidence of severe COVID-19 by 6 months after randomization.
BCG participants had more symptomatic COVID-19
The risk of symptomatic COVID-19 was 14.7% in the BCG group and 12.3% in the placebo group during the first 6 months of the trial.
There were five hospitalizations due to COVID-19 in each group (including one death in the placebo group). Severe COVID-19 occurred in 75 participants in the BCG group (7.6%) and in 61 participants in the placebo group (6.5%).
Because such low numbers of study participants and severe COVID-19 cases, researchers could not determine whether the vaccine reduced hospitalizations or deaths.
The study authors said the BCG vaccine may have primed the immune system to react more strongly to COVID-19 infection.
"In theory, an increased risk of symptomatic Covid-19 could be explained by a BCG-induced stronger immune response. BCG-vaccinated participants in the BRACE trial had more activated and effector T cells in response to in vitro SARS-CoV-2 stimulation than controls," the authors said. "These effects might result in more rapid clearance of SARS-CoV-2, leading to a shorter illness."
Study author Nigel Curtis, PhD said in a press release on the study that this effect was seen to some degree in older study participants.
There was some evidence of this in trial participants over the age of 60, in whom COVID-19 symptoms were shorter in the BCG-vaccinated group.
"Symptoms reflect the immune system working hard to fight the virus," Curtis said. "A stronger response induced by BCG could be beneficial in killing the virus more rapidly and protecting against progression to more severe disease. There was some evidence of this in trial participants over the age of 60, in whom COVID-19 symptoms were shorter in the BCG-vaccinated group."
Of note, 75% of all trial participants had previously been given the BCG vaccine. That factor and the speedy rollout of COVID-19 vaccines led to lower-than-expected enrollment in the study.
Despite those limitations, co-study author John Campbell, PhD, of the University of Exeter said the trial represented an important opportunity to test the potential of the BCG vaccine.
"The findings raise important questions about how BCG can modify the course of different viral illnesses and allows us to develop a fuller understanding of whether the vaccine can provide protection against a range of infections other than its main target, tuberculosis," he said.
