Apr 28: BCG vaccine does not protect against COVID-19 in healthcare workers

Apr 28: BCG vaccine does not protect against COVID-19 in healthcare workers

A world-leading international trial into the immune boosting benefits of the tuberculosis vaccine, BCG, has found it does not protect healthcare workers against COVID-19. The BRACE trial to test whether the BCG vaccine could protect healthcare workers against SARS-CoV-2 in the first six months after vaccination found it didn’t reduce the risk of developing COVID-19 among those on the pandemic frontline.

The BCG vaccine was originally developed to prevent tuberculosis and is still given to over 130 million babies worldwide each year for that purpose. The BRACE trial was built on previous research, which showed BCG also boosted ‘front-line’ immunity in infants and protected against respiratory tract infections in adolescents and adults. It was hoped the vaccine could be repurposed to buy crucial time early in the corona pandemic until disease-specific vaccines were developed and tested. The research, published in the New England Journal of Medicine, involved 3,988 healthcare workers who signed up across 36 sites in Australia, Europe and South America. UMC Utrecht coordinated the European part of the trial.

Stronger immune response

The risk of symptomatic COVID-19 was 14.7 percent in the BCG group and 12.3 percent in the placebo group during the first six months after joining the trial. The research could not determine whether the vaccine reduced hospitalizations or death due to the low numbers of participants with severe COVID-19. Prof. Nigel Curtis (Murdoch Children’s Research Institute and the University of Melbourne), chief principal investigator of BRACE, said symptomatic COVID-19 being observed slightly more frequently in the BCG group might be explained by stronger immune responses induced by the vaccine: “When we analyzed the immune cells from our healthcare workers, we saw that the BCG vaccine altered the immune response to COVID-19,” he said. “Symptoms reflect the immune system working hard to fight the virus. 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.”

Professor Curtis said because COVID-19 vaccines had been developed and rolled out at lightning speed and healthcare workers prioritized, less participants were recruited than originally envisioned. As a result, lower case numbers meant the team was unable to investigate whether BCG protected against hospitalization and death from COVID-19, he said. A previous published last year using blood samples from BRACE participants, also showed that the BCG vaccine did provide an immune response consistent with protection against severe COVID-19.

Importance of large-scale trials

Trials of this size and complexity normally took about eight to 12 months to organize and recruit, but BRACE was able to start within three weeks due to the dedicated researchers and support teams at the study sites, together with generous philanthropic support. Prof. Marc Bonten, coordinator of the European arm of the BRACE trial: “This trial highlights the importance of large-scale randomized controlled trials to test hypotheses and evaluate the effectiveness of new or repurposed drugs or vaccines”.

Prof. Marc Bonten

Further analyses ongoing

Trial data analysis is still ongoing with further results on the effect of BCG expected later this year, including the impact of the vaccine on other infections, such as respiratory illnesses and the effect on COVID-19 vaccine responses. The trial team is also using blood samples collected from participants to discover biomarkers for COVID-19 risk.


Pittet LF, Messina NL, Orsini F, Moore CL, Abruzzo V, Barry S, Bonnici R, Bonten M, Campbell J, Croda J, Dalcolmo M, Gardiner K, Gell G, Germano S, Gomes‐Silva A, Goodall C, Gwee A, Jamieson T, Jardim B, Kollmann TR, Lacerda MVG, Lee KJ, Lucas M, Lynn DJ, Manning L, Marshall HS, McDonald E, Munns CF, Nicholson S, O’Connell A, de Oliveira RD, Perlen S, Perrett KP, Prat‐Aymerich C, Richmond PC, Rodriguez‐Baño J, dos Santos G, da Silva PV, Teo JW, Villanueva P, Warris A, Wood NJ, Davidson A, Curtis N, for the BRACE Trial Consortium Group. Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers. New England Journal of Medicine 2023;388:1582-96. DOI: https://10.1056/NEJMoa2212616

Working at UMC Utrecht





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