The BCG Vaccine and COVID-19: Seeking Answers in the BRACE Trial

BCG vaccine, commonly given to over 130 million infants worldwide annually as tuberculosis prevention, is now being tested in the BRACE trial to assess its effectiveness in guarding against COVID-19 during the early stages of the pandemic (1^✔ ✔Trusted Source
Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers

Go to source). The lack of evidence regarding the efficacy of the BCG vaccine for COVID-19 led to the World Health Organization's decision not to endorse its use during the early stages of the pandemic.

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BCG Vaccine's Promise in Fighting COVID-19

Hence, to address this uncertainty, the BRACE trial was initiated in March 2020, aiming to test the protective effect of the BCG vaccine against COVID-19 when no specific vaccines for the coronavirus were available.

This double-blind, placebo-controlled trial involved 3,988 healthcare workers, a highly exposed group, across 36 centers and hospitals in Australia, Brazil, the UK, the Netherlands, and Spain.

It was led by the Murdoch Children's Research Institute (MCRI) in Melbourne and brought to Europe with the support of the Bill & Melinda Gates Foundation and coordinated by the University Medical Centre (UMC) in Utrecht.

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Germans Trias i Pujol's involvement in the BRACE trial

In the fall of 2020, the Germans Trias i Pujol University Hospital (HUGTiP), along with five other Spanish hospitals, joined the clinical trial. This Can Ruti institution contributed 46 participants who underwent regular check-ups every three months, with a survey and a blood sample collection.

The final visits concluded in July 2021, marking the end of a 12-month follow-up period which was adhered to by 95% of the participants.

The Germans Trias i Pujol University Hospital and Research Institute (IGTP) collaborated on this project, which had a strong multidisciplinary component.

The trial involved the Pulmonology and Preventive Medicine services, and the Hospital Pharmacy and Multipurpose Clinical Research (UPIC) units at HUGTiP, in conjunction with the Innovation in Respiratory Infections and Tuberculosis Diagnosis research group at IGTP.

"This is a large size, international trial that highlights the importance of testing proposed interventions through carefully designed randomized trials, even in the midst of a pandemic. The hypothesis was worth to be evaluated in such a critical situation while maintaining a rigorous methodology. The setting up was quite challenging, spanning five countries across three continents. Both the data and samples collected are very important in terms of allowing a better understanding of BCG response." explains Dr. Cristina Prat-Aymerich, co-leader of an IGTP research group dedicated to tuberculosis and head of the Respiratory and Mycobacterial Infection section in the Microbiology service at HUGTiP, currently on leave from this position and working in UMC Utrecht, the Netherlands.

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The BCG Vaccine did not Reduce COVID-19 Risk

The recent study published in the New England Journal of Medicine, one of the world's leading medical science journals (impact factor: 176.082), analyses the results of the second stage of the trial.

Researchers found that BCG vaccination did not reduce the incidence of COVID-19. It increased the risk of symptomatic disease during the first six months following enrolment in the trial, which was 14.7% in the BCG group compared to 12.3% in the placebo group, a difference deemed not statistically significant.

The increase in symptomatic COVID-19 among those vaccinated with BCG could be due to a stronger immune response to the virus, but it is unclear whether this had any impact on protection against severe cases or re-infections. Interestingly, older participants who were vaccinated had shorter illness durations, hinting at potentially more efficient virus clearance.

No Clear Evidence of Protection against Life-Threatening COVID-19

Recruitment for the trial was stopped prematurely and the follow-up period was reduced, which affected the number of episodes recorded.

Consequently, the lack of significant difference between the studied groups could be caused by the trial not being powerful enough to detect a real effect - a phenomenon sometimes referred to as a 'type 2 error' in statistics.

Dr.Antoni Rosell, clinical director of the Thorax Institute at HUGTiP, states that "very few people in the trial were hospitalized or died, so the trial could not test whether BCG reduced the risk of severe types of COVID-19. This is partly due to the earlier-than-expected availability of COVID-19 vaccines (with health care workers prioritized) leading to recruitment stopping before the target number was reached as well as shorter follow-up period."

Despite the Negative Results, the Trial remains Valuable for Future Research

Although the BCG vaccine did not protect against symptomatic COVID-19, this research provides valuable insights into the immune response to the virus and the potential benefits and drawbacks of repurposing existing vaccines.

Dr.José Domínguez, co-leader of an IGTP research group, is positive about the future. "There remains strong evidence that BCG protects against tuberculosis and has important beneficial effects against other infections in infants. The trial allowed to further explore the safety of revaccination in adults and soon will be reported whether BCG protected against infections other than SARS-CoV-2".

The BRACE Trial Consortium Group will continue to analyze data and will share further results on the impact of the BCG vaccine on other infections and the effect on COVID-19 vaccine responses later this year.

Reference:

1. Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers - (https://www.nejm.org/doi/10.1056/NEJMoa2212616)

Source-Eurekalert