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BRACE FAQs

BRACE trial FAQs

Here are the answers to some common questions BRACE trial participants and supporters often ask.

Don’t see your questions answered? Email brace@mcri.edu.au.

On the frontline of novel infectious disease outbreaks like COVID-19, healthcare workers are at high risk of illness – while absenteeism due to COVID-19 exacerbates the pressure on our healthcare system. The BRACE trial began in March 2020 when the threat of the pandemic first reached Australia.

The trial was endorsed by the Director-General of the World Health Organization, Tedros Adhanom, who called for global support and assistance in the fight against COVID-19. 

The BRACE trial builds on previous studies, which showed that BCG reduces the level of virus when people are challenged with viruses. Although originally developed against tuberculosis, and still given to more than 130 million babies annually for that purpose, BCG also boosts humans’ frontline immunity, training it to respond to germs with greater intensity. Find out more about the outcomes the BRACE trial is working to determine.

The BRACE trial finished recruiting on 31 March 2021 - one year after the trial began. There are more than 30 sites across these five countries:

Australia

  • Royal Children's Hospital
  • Monash Health
  • Epworth HealthCare
  • Fiona Stanley Hospital
  • Perth Children's Hospital
  • Sir Charles Gairdner Hospital
  • Royal Adelaide Hospital
  • Women's and Children's Hospital
  • St Vincent's Hospital, Sydney
  • Prince of Wales Hospital
  • Sydney Children's Hospital, Randwick
  • The Children's Hospital at Westmead
  • Westmead Hospital

The Netherlands

  • Noord West Ziekenhuis
  • Rijnstate Hospital
  • Amphia Hospital
  • St Antonius Hospital
  • Radboud UMC
  • University hospital in Utrecht (UMCU)

Spain

  • University Hospital German Trias I Pujol
  • Mutua Terrassa University Hospital
  • University Hospital Cruces
  • Marqués de Valdecilla University Hospital
  • University Hospital Virgen Macarena

The United Kingdom

  • St Leonard’s Practice
  • Ide Lane Surgery
  • Travel Clinic
  • Royal Devon and Exeter NHS Foundation Trust
  • Teign Estuary Medical Group

Brazil

  • Federal University of Mato Grosso do Sul
  • Hospital Regional de Mato Grosso do Sul
  • CASSEMS Hospital
  • Santa Casa Hospital
  • Centro de Referência Prof Hélio Fraga
  • Centro de Estudos da Saúde do Trabalhador e Ecologia Humana
  • Fundação de Medicina Tropical Dr Heitor Vieira Dourado (FMT-HVD)

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 healthcare and community-based healthcare settings, or have face-to-face contact with patients, were invited to check their eligibility to join the BRACE trial. Trial participants had to be willing to attend recruitment and follow-up at a central recruitment site.

YES. When a COVID-19 vaccine is approved and becomes available, you can continue to participate in the BRACE trial and receive the COVID-19 vaccine. If you do receive a COVID-19-specific vaccine, we will ask you to record the name of the vaccine and the date you received it in the next 3-monthly questionnaire.

Recommendations worldwide advise against measuring serology after COVID-19-specific vaccine because this does not provide a reliable guide to an individual’s level of protection.

You will receive your individual serology regarding any detection of SARS-CoV-2 infection via email at the end of the trial.

Since the BRACE trial is investigating whether BCG vaccination protects against COVID-19, you should not participate in any other COVID-19 vaccine trial because this will make it difficult to interpret the results of both trials. It is likely that you will not be eligible for another vaccine trial if you are participating in the BRACE trial. 

It is recommended that you follow the relevant national vaccination guidelines, COVID-19-specific vaccine information sheet or wait 7 days - whichever is longest. Note that we would like you to continue in the BRACE trial after you have had a COVID-19-specific vaccine. We will continue collecting your data and samples so that we can determine the impact of BCG on all infections.

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].

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.

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.

See https://www.mcri.edu.au/BRACE

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.

Contact BRACE (brace@mcri.edu.au) for a copy of your kit instruction to be sent to you.

A general video on how to take a blood spot is available here.

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 brace@mcri.edu.au

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.

According to the trial registration website 'clinicaltrials.gov', there are approximately 20 clinical trials studying whether BCG may provide protection against COVID-19. The BRACE trial is the largest of these trials, and is designed to investigate the impact of BCG on severe COVID-19 as well as any SARS-CoV-2 infection. 

The ACTIVATE trial of BCG in the frail elderly in Greece, published in 2020 in Cell, reported that BCG had a significant beneficial effect in reducing respiratory infections.  Preliminary finding from the subsequent BCG-PRIME trial in the Netherlands suggest that BCG vaccine does not prevent COVID-19 in the frail elderly. 

Whether BCG reduces the severity of COVID-19 is still to be determined in the BCG-PRIME and other ongoing trials, including the BRACE trial. In addition, the BRACE trial and other trials continue to investigate whether BCG vaccination protects against other respiratory infections.