The BRACE trial results found that BCG vaccination did not reduce the likelihood of COVID-19 in the first 6-months after joining the trial.

In the 3988 participants in Stage 2 of the trial, the risk of symptomatic COVID-19 was 14.7% in the BCG group and 12.3% in the placebo group during the first six months after joining the trial. This difference was not statistically significant. Any effect on hospitalisation or death could not be assessed as there were too few of these events.

There were some differences in the effect of BCG on the length of reported episodes of COVID-19
according to age and comorbidities (other health problems).

The trial comprised two stages. In Stage 1, participants were recruited only in Victoria and Western Australia, and in both states, there was very low COVID-19 exposure during the trial period. Before seeing the results, it was therefore decided to analysis COVID-19 outcomes in Stage 2 only.

COVID-19 occurred more frequently in the BCG group although this difference was not large. The reason for this difference is not clear, but one possibility is that BCG caused a stronger immune response to SARS-CoV-2 and therefore more symptoms (as symptoms are caused by the body’s immune response to the virus). Further studies are ongoing using samples from participants to try and answer this question.

The results analysed to date from BRACE only apply to COVID-19. We are still analysing results for other infections. It is possible that BCG has a different effect on non-COVID infections as previous studies have reported beneficial effects of BCG on other infections.

We were unable to reach the planned 10,000 participants that was necessary to look at those outcomes. This was due to a combination of very low COVID-19 in Stage 1 (in Australia) and recruitment ending early due to availability of COVID-19-specific vaccines.

This is being investigated as a sub-study of the BRACE trial. The BCOS (BRACE COVID-19-Specific vaccine) sub-study will look at whether BCG vaccine, by boosting the immune system, improved the response to Pfizer, AstraZeneca and CoronaVac vaccines.

You can find further details of the trial and the results at:

• BRACE trial page 
• ClinicalTrials.gov
• Primary Outcome Publication
• Your study site Principal Investigator/study doctor
• Contact the BRACE trial via email:  show email address

Yes, we are still analysing the extensive data collected in the BRACE trial. We are looking at a number of
other outcomes, including the effect of BCG vaccination on:

• COVID-19 episodes over 12 months, including break-through infections
• COVID-19 vaccine responses
• Fever and respiratory illnesses
• Herpes virus (cold sore) recurrences

Your blood samples were tested for SARS-CoV-2 antibodies to help identify episodes of COVID-19. They are also being used in ongoing laboratory projects to investigate: the immune response to BCG vaccination, biomarkers (risk factors) for COVID-19 and factors influencing COVID-19 vaccine responses.

The results show that BCG vaccination does not reduce the risk of COVID-19 in adults. We were unable to assess the effect of BCG on the most severe outcomes of COVID-19, as we did not have enough participants to look at hospitalisations or deaths from COVID-19 in the trial. It is possible, for example, that the stronger immune response caused by BCG vaccination increases the likelihood of symptoms but also leads to faster clearance of the virus and consequently lowers the risk of hospitalisation or death.

The BRACE trial findings only apply to the effect of BCG vaccination on COVID-19 in adults. The off-target effects of BCG vaccination might depend on the age at which it is given (it seems to be more effective in infancy). BCG vaccination might also only protect against some infections (animal studies show BCG protects only against some viruses).

Recent reports confirm the beneficial ‘off-target’ effects of BCG in other settings, particularly infants in high-mortality settings, and ongoing research is investigating the underlying immunological mechanisms.

Over the past five to 10 years, Professor Nigel Curtis and researchers at the Murdoch Children’s Research Institute have been looking at the effect of BCG vaccine on the immune system in babies, with promising results. See: Prevention of infant eczema by neonatal Bacillus Calmette-Guérin vaccination: The MIS BAIR randomized controlled trial and Neonatal BCG Vaccination Reduces Interferon-γ Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial.

Our Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) continues to investigate
whether BCG could help reduce allergies, eczema, infections and asthma in infants and children.

SARS-CoV-2 virus spike antibodies are produced by the body’s immune system following either:

1. SARS-CoV-2 infection (COVID-19); and/or
2. Vaccination with a spike-targeting COVID-19 vaccine, such as:
   • AstraZeneca-Oxford (ChAdOx1-S)
   • Pfizer-BioNTech (BNT162b2)
   • Moderna (mRNA-1273)
   • Johnson & Johnson (Ad26.COV2.S)
3. Vaccination with a whole-inactivated virus COVID-19 vaccine, such as:
   • Sinovac-CoronaVac

SARS-CoV-2 virus nucleocapsid antibodies are produced by the body’s immune system following either:

1. SARS-CoV-2 infection (COVID-19); and/or
2. Vaccination with a whole-inactivated virus COVID-19 vaccine, such as:
   • Sinovac-CoronaVac (but not spike-targeting COVID-19 vaccines)

Yes, there will be an impact on the serology test as most COVID-19 vaccines are spike-targeting COVID19 vaccines. Most BRACE samples were tested for SARS-CoV-2 nucleocapsid antibody to ensure SARSCoV-2 antibodies produced by the body’s immune system were following SARS-CoV-2 infection only.

• Stage 1 participants:
  • Baseline, 3-month and 6-month serology:
    • SARS-CoV-2 antibodies to spike protein were tested
• 9-month and 12-month serology:
  • VIC participants who had not received COVID-19 vaccination
    • SARS-CoV-2 antibodies to spike protein were tested
  • VIC participants who had received COVID-19 vaccination
    • SARS-CoV-2 antibodies to nucleocapsid protein were tested

Stage 2 participants:

• Baseline, 3-month, 6-month, 9-month and 12-month results:
  • All participants, regardless of COVID-19 vaccination status, except those vaccinated with Sinovac-CoronaVac (some participants in Brazil only)
    • SARS-CoV-2 antibodies to nucleocapsid protein were tested
  • Participants vaccinated with Sinovac-CoronaVac (some participants in Brazil only)
    • As it is not possible to distinguish between antibodies created in response to a SARSCoV-2 infection (COVID-19) and the Sinovac-CoronaVac vaccine, postvaccination serology results will not be provided.

• SARS-CoV-2 ‘antibody positive’:
  • SARS-CoV-2 virus antibodies were detected in your blood suggesting you had a SARS-CoV-2 infection (COVID-19) at some point before this blood sample was taken.
  • The latest global recommendations advise that SARS-CoV-2 serology results do not provide a reliable guide to an individual’s level of protection against COVID-19.
• SARS-CoV-2 ‘antibody negative’:
  • SARS-CoV-2 virus antibodies were not detected in your blood suggesting you had not had a SARS-CoV-2 infection (COVID-19) before this blood sample was taken.
• SARS-CoV-2 ‘unable to determine’:
  • For some participants there was insufficient volume of blood in their blood draw for testing, or a technical issue in the testing occurred, which meant the lab was unable to determine a clear result.
• SARS-CoV-2 ‘sample taken after Sinovac-CoronaVac vaccination’:
  • If you received Sinovac-CoronaVac, it is not possible to distinguish between antibodies created in response to a SARS-CoV-2 infection or the Sinovac-CoronaVac vaccine, therefore you will not receive post-vaccination serology results.

The relationship between SARS-CoV-2 antibody results (serology) and protective immunity against COVID-19 is currently uncertain. Positive serology does not guarantee protection against COVID-19.

The latest global recommendations advise that SARS-CoV-2 serology results do not provide a reliable guide to an individual’s level of protection against COVID-19.

For Victoria participants

If you are a Stage 1 participant from Victoria, you will receive your baseline, 3-month and 6-month serology results once the six-month primary outcomes have been announced.

For Western Australian participants

If you are a Stage 1 participant from Western Australia, you will not receive serology results.

The Trial Steering Committee, along with site Principal Investigators in Western Australia, determined that serology testing would not be done for all Stage 1 participants due to the low level of COVID-19 community transmission at the time of the trial.

For study purposes only, a small proportion of Western Australian blood samples will be screened to confirm the expected negative results of SARS-CoV-2 antibodies.

You will receive your baseline, 3-month and 6-month serology results once the six-month primary outcomes have been announced. You will receive your 9-month and 12-month serology results once the data has been analysed for the 12-month outcomes in mid-2023.

You should delete the app after your final 12-month blood visit, which can be up to 42 days after your 12-month milestone post vaccination.

On the frontline of novel infectious disease outbreaks like COVID-19, healthcare workers are at high risk of illness–while absenteeism because of 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 Director-General of the World Health Organization, Tedros Adhanom, who called for global support and assistance in the fight against COVID-19, endorsed the trial. 

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 over 130 million babies annually for that purpose, BCG also boosts humans’ frontline immunity, training it to respond to germs with greater intensity.

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 Medial Group/Glendevon Medical Practice

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 attend recruitment and follow-up at a central recruitment site.

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 World Health Organisation (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. 

• WHO - Bacille Calmette-Guérin (BCG) vaccination and COVID-19