An international study carried out in various countries on the benefits of the immunological booster provided by the anti-tuberculosis vaccine, BCG, revealed that it does not protect health workers against Covid-19. The Brace study, led by the Murdoch Children’s Research Institute and published last Wednesday (April 26) on the New England Journal of Medicine, tested whether the immunizer might be able to protect health workers in the first six months after vaccination. In Brazil, it was led by Fiocruz.

The BCG vaccine was originally developed to prevent tuberculosis, and it is administered to more than 130 million newborns every year. The Brace study was developed based on a previous research that showed that BCG increases innate immunity, the kind that is non-specific regarding pathogens, in children. The research showed it protected adolescents and adults against respiratory infections. It was expected that the vaccine could be temporarily repositioned until specific vaccines for the disease could be developed and tested.

The results presented in the New England Journal of Medicine are part of the second phase of a randomized study involving 3,988 of the almost 7,000 health workers enrolled in 36 places in Australia, the Netherlands, the United Kingdom, Spain, and Brazil. The Utrecth Medical Center (the Netherlands), the University of Exeter (United Kingdom) and Fiocruz helped with research supervision in their countries.

The risk of developing symptomatic Covid-19 was 14.7% in the group vaccinated with BCG and 12.3% in the group that was given placebo, in the six months of follow-up after their inclusion in the study. The research was not able to determine whether the immunizer reduced hospitalizations or deaths, due to the low number of participants with severe Covid-19.

Professor Nigel Curtis of the Murdoch Institute and of the University of Melbourne, lead researcher in the study, explained that the slightly higher observation of symptomatic Covid-19 in the group immunized with BCG can be explained by a stronger immune response induced by the vaccine. 

“When we analyzed the immune cells of our health workers, we observed that the BCG vaccine altered their immune response to Covid-19”, he said. “Symptoms are a reflection of the immune system working hard to fight the virus. A stronger response induced by BCG could be beneficial, as it kills the virus more quickly and protects against progression into a more severe form of the disease. There is some evidence of this happening in participants of the study who are above 60 years of age; Covid-19 symptoms seem to be milder in the group vaccinated with BCG”.

In Brazil, researchers Julio Croda, of Fiocruz Mato Grosso do Sul, Margareth Dalcomo, of the Sergio Arouca National School of Public Health (Ensp/Fiocruz), and Marcus Lacerda, of Fiocruz Amazônia, participated in the study, which involved health workers from Campo Grande, Rio de Janeiro and Manaus. Croda explained that most cases of symptomatic Covid-19 in the study were reported in Brazil.

“This shows the heavy burden of the disease in Brazil during the pandemic. Although the BCG vaccine does not protect against symptomatic Covid-19, we will be using the data to analyze whether it protects health workers against latent tuberculosis infection. This is an open issue, especially for populations at a high risk of contracting the disease”, he said.

According to Nigel Curtis, all Covid-19 vaccines were developed rapidly, and health workers were the priority targets of vaccination campaigns. As a consequence, less participants were recruited than was originally expected. With less cases, the team was not able to investigate whether the BCG vaccine protected against hospitalization and death.

A study led by the Murdoch Institute published on Clinical & Translational Immunology last year, using blood samples from participants of the Brace study, also showed that the BCG vaccine in fact provided a consistent immune response with protection against severe Covid-19.

Professor John Campbel of the University of Exeter, who led the research in the United Kingdom, said the study was an important opportunity to test the potential of the BCG vaccine. “The discoveries raise important issues on how the BCG vaccine can change the course of different viral diseases and allow us to develop a more thorough understanding of whether the vaccine can provide protection against a series of infections beyond its main target, which is tuberculosis”, he said.

According to the researchers, data analysis is still ongoing and additional results on the effects of BCG are expected to be released by the end of the year, including the impact of the vaccine on other infections, such as respiratory diseases and responses to the Covid-19 vaccine. The research team also uses the participants’ blood samples to try to discover biomarkers for the risk of Covid-19.