The Murdoch Children’s Research Institute in Melbourne, Australia, has announced its infectious disease researchers are preparing to roll-out a multi-center randomised controlled clinical trial of the BCG vaccine against COVID-19.
Below, we answer some common questions that have arisen since the announcement.
The BRACE trial will be recruiting in June at:
- Royal Children's Hospital (from 29th June)
- Women's & Children's Hospital, Adelaide
- The Children's Hospital at Westmead
Enrolment is now closed at Monash Medical Centre, Epworth Hospital and in Western Australia.
Further participating sites are likely to be announced in the Netherlands and Spain.
The trial is designed to see if the BCG vaccine can protect healthcare workers who are likely to be exposed to SARS-CoV-2. All healthcare workers who work in a healthcare setting or have face-to-face contact with patients are invited to check your eligibility to join the BRACE trial. Interested healthcare workers must be willing to attend recruitment and follow-up at a central recruitment site.
No. You will be randomly allocated to receive or not receive BCG vaccination.
A placebo vaccine is something that looks exactly like a real vaccine, but contains no active ingredients. In this study, the placebo is an injection that looks exactly like the BCG vaccine, but contains only saline.
Sometimes, people have a response to a vaccine or treatment, regardless of what it is. This is called the placebo effect. It is triggered by the person's belief in the benefit from the intervention and their expectation of feeling better, rather than the treatment itself.
Using a placebo means that the results of our trial are not influenced by participants knowing whether or not they have been given BCG. Everyone will be given an injection of either BCG or placebo.
We will not tell participants if they are being given a placebo until the trial is finished. Once the trial is over, we will contact participants in the trial to let them know which group they were in.
The vaccine will be administered by the BRACE study team in the left shoulder.
Yes. We need to follow up both the BCG-vaccinated and non-BCG-vaccinated groups, so that we can compare outcomes between the 2 groups.
It is uncertain to what extent BCG given years earlier still has protective off-target effects. You can therefore still take part in the trial.
Yes. There is some evidence that BCG's beneficial off-target effects against infection can be enhanced by a further BCG vaccination in those who have received it in the past.
Yes, but the normal reaction at the injection site may occur earlier and be more pronounced.
Local skin lesions (ulceration and discharge) are more frequent in adults who have had a previous BCG vaccine than in those who have never had BCG vaccine before.
However, the risk of severe armpit lymph gland infection or disseminated BCG has not been found to be more common in adults who have had previous BCG vaccine.
No. You are not eligible if you've been treated for TB disease.
Yes. If you have previously had a positive Mantoux tuberculin skin test (TST) or TB blood test (IGRA) but have not required treatment for TB disease, then you are eligible for the trial.
The normal reaction at the injection site may occur earlier and be more pronounced.
Local skin lesions (ulceration and discharge) are more frequent in adults who have previously been exposed to TB.
However, the risk of severe armpit lymph gland infection or disseminated BCG has not been found to be more common in adults who have had previous BCG vaccine or previous TB exposure.
Studies suggest that the beneficial off-target effects of BCG vaccination are evident with days or weeks of vaccination. These effects have been shown to persist up to 12 months in adults.
No, BCG vaccination is a live vaccine and thus it is not recommended in pregnancy. If there is a chance you may be pregnant, discrete pregnancy testing will be made available for any potential participants on the day of vaccination.
Pregnancy should be avoided for 28 days after receiving a live vaccine such as BCG .
1. Kroger AT, Duchin J, Vázquez M. General best practice guidelines for immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP). https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html. Accessed on March 22, 2020.
Randomised trials which compare outcomes in those who receive the vaccine and those who do not are the only way to be certain if a preventative measure such as this works. Over 10,000 healthcare workers will be recruited from hospitals around the world for the trial. Half will receive the vaccine and the other half won’t.
Healthcare workers in the BRACE trial will record their health and any symptoms using a dedicated custom-made smartphone app. Results cannot be expected until sufficient participants have been exposed to the SARS-CoV-2 virus. The first planned interim analysis will be at around three months but the trial will run for at least a year.
If the trial is successful, should BCG be used worldwide for treating coronavirus among any kind of population – kids, elderly people?
If the trial shows BCG vaccination is effective against this respiratory viral infection, it could be used as a preventive measure in high-risk populations, such as healthcare workers and the elderly.
The purpose of the BRACE trial is to find out whether BCG vaccination reduces the severity of COVID-19.
The BCG vaccine is still given to over 130 million babies each year globally to protect them against tuberculosis (TB). This vaccine also has so-called ‘off-target’ effects, separate to its protective effects against TB. These off-target effects boost the frontline immune system (innate immunity). Previous small studies suggest that the beneficial off-target effects of BCG vaccination might protect against a diverse range of pathogens including respiratory viruses.
We hypothesise that the off-target effects of BCG vaccination will reduce the symptom severity and impact of COVID-19 in healthcare workers.
This remains a hypothesis only. The only way to determine if the off-target effects of BCG vaccination on immunity include protection against SARS-CoV-2 is through randomised clinical trials such as the BRACE trial.
The beneficial off-target effects of BCG vaccination on immunity are not specific to SARS-CoV-2. In the trial, we will also be able to determine whether the vaccine protects against other infections.
It is unlikely that the off-target effects of BCG given many years earlier remain protective against COVID-19. The best way for everyone to protect themselves is by frequent and thorough hand-washing, social distancing, and, for healthcare workers, personal protection equipment (PPE). The WHO has highlighted that the non-peer reviewed pre-print studies suggesting that childhood BCG vaccination is protective might be misleading. Such ecological studies are prone to significant bias from many confounders, including differences in national demographics and disease burden, testing rates for COVID-19 virus infections, and the stage of the pandemic in each country.
Yes, the supply of BCG for this trial is separate from the medical supply, with enough stock for both.
Similar trials are underway in many countries. Are these independent researches or are you cooperating with the specialists from other countries?
We are actively collaborating with researchers around the world and will be sharing our results to find a definitive answer as fast as possible.
We welcome inquiries to collaborate on the trial via email to email@example.com
We strongly recommend that BCG in relation to protecting against COVID-19 should only be used in randomised clinical trials.
Philanthropic support has been received from The Royal Children’s Hospital Foundation, Sarah and Lachlan Murdoch, The Minderoo Foundation, Calvert-Jones Foundation, the National Australia Bank (NAB), South Australian Government, and individual philanthropists. The Bill and Melinda Gates Foundation has provided further funding to expand the BRACE trial to over 10,000 participants by including sites overseas.