A world-leading international trial examining the immune boosting benefits of the tuberculosis vaccine, BCG, has found it does not protect healthcare workers against COVID-19.
The BRACE trial at The Kids Research Institute Australia, run in partnership with Murdoch Children’s Research Institute in Melbourne, tested whether the BCG vaccine could protect healthcare workers against SARS-CoV-2 in the first six months after vaccination.
It found it didn’t reduce the risk of developing COVID-19 among those on the pandemic frontline.
BCG 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 infections in adolescents and adults. It was hoped the vaccine could be repurposed to buy crucial time in a pandemic like COVID-19 until disease-specific vaccines were developed and tested.
The study, launched at the early peak of the pandemic in April 2020, was supported by a $1.5 million donation by the Minderoo Foundation.
It involved around 2,000 WA Health staff working at Perth Children’s Hospital, Sir Charles Gairdner Hospital and Fiona Stanley Hospital. Another 2,000 healthcare workers were recruited in Victoria.
The research, published in the New England Journal of Medicine and based on the second stage of the BRACE randomised controlled trial, involved 3988 of the almost 7000 healthcare workers who signed up across 36 sites in Australia, the Netherlands, UK, Spain and Brazil.
UMC Utrecht in the Netherlands, University of Exeter in the UK and the Oswaldo Cruz Foundation in Brazil helped to oversee the international arms of the trial.
The risk of symptomatic COVID-19 was 14.7 per cent in the BCG group and 12.3 per cent in the placebo group during the first six months after joining the trial. The research could not determine whether the vaccine reduced hospitalisations or death due to the low numbers of participants with severe COVID-19.
Professor Peter Richmond, Head of the Vaccine Trials Group at the Wesfarmers Centre of Vaccines and Infectious Diseases, based at The Kids Research Institute Australia, Head of Paediatrics at The University of Western Australia and Head of Immunology at Perth Children’s Hospital was the WA lead for the study and said the state’s relatively low rates of COVID-19 infections played a crucial role in the study.
“WA was in such a unique position globally as one of the few places with close to zero COVID for the first two years of the pandemic,” he said.
As the trial evolved, the data we gathered from WA health workers was a really valuable comparison for what we were seeing in the blood samples taken from frontline staff in other parts of the world where COVID-19 was extremely prevalent.
The trial was co-ordinated in WA by Professor Richmond, The University of Western Australia Clinical Professor Michalea Lucas, UWA and The Kids Research Institute Australia infectious diseases researcher Associate Professor Laurens Manning and Head of Systems Vaccinology at The Kids Research Institute Australia, Professor Tobias Kollmann.
Murdoch Children’s and the University of Melbourne Professor Nigel Curtis, 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 analysed 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.”
Because COVID-19 vaccines had been developed and rolled out at lightning speed and healthcare workers prioritised, less participants were recruited than originally envisioned.
As a result, lower case numbers meant the team was unable to investigate whether BCG protected against hospitalisation and death from COVID-19.
“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,” Professor Curtis said.
Trials of this size and complexity usually take about eight to 12 months to organise and recruit, but BRACE was able to start within three weeks due to generous philanthropic support.
Trial data analysis is 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.