BCG Vaccination to Protect Healthcare Workers Against COVID-19
BCG Vaccination to Protect Healthcare Workers Against COVID-19
Phase III, two-group multicentre, randomised controlled trial in up to 10 078 healthcare
 workers to determine if BCG vaccination reduces the incidence and severity of COVID-19 during
 the 2020 pandemic.
Healthcare workers are at the frontline of the coronavirus disease (COVID-19) pandemic. They
 will be randomised to receive a single dose of BCG vaccine or 0.9% NaCl placebo. Participants
 will be followed-up for 12 months with notification from a Smartphone application or phone
 calls (up to daily when ill) and surveys to identify and detail COVID-19 infection.
 Additional information on severe disease will be obtained from hospital medical records
 and/or government databases. Blood samples will be collected prior to randomisation and at 3,
 6, 9 and 12 months to determine exposure to severe acute respiratory syndrome coronavirus 2
 (SARS-CoV-2). Where required, swab/blood samples will be taken at illness episodes to assess
 SARS-CoV-2 infection.

 The trial includes a pre-planned meta-analysis with data from 2834 participants recruited in
 the first phase of this study, where participants were randomised to receive BCG or no BCG
 vaccine at the time of receiving influenza vaccination.
Inclusion Criteria:

 -  Over 18 years of age

 -  Healthcare worker

 -  This is defined as anyone who works in a healthcare setting or has face to face
 contact with patients.

 -  Provide a signed and dated informed consent form

 -  Australian sites only: If annual influenza vaccination is available, receiving the flu
 vaccine is an eligibility requirement. The flu vaccine will be required a minimum of 3
 days in advance of randomisation in the BRACE trial.

 -  Pre-randomisation blood collected

 Exclusion Criteria:

 -  Has any BCG vaccine contraindication

 -  Fever or generalised skin infection (where feasible, randomisation can be delayed
 until cleared)

 -  Weakened resistance toward infections due to a disease in/of the immune system

 -  Receiving medical treatment that affects the immune response or other
 immunosuppressive therapy in the last year.

 -  These therapies include systemic corticosteroids (≥20 mg for ≥2 weeks),
 non-biological immunosuppressant (also known as 'DMARDS'), biological agents
 (such as monoclonal antibodies against tumour necrosis factor (TNF)-alpha).

 -  People with congenital cellular immunodeficiencies, including specific
 deficiencies of the interferon-gamma pathway

 -  People with malignancies involving bone marrow or lymphoid systems

 -  People with any serious underlying illness (such as malignancy)

 -  NB: People with cardiovascular disease, hypertension, diabetes, and/or
 chronic respiratory disease are eligible if not immunocompromised, and if
 they meet other eligibility criteria

 -  Known or suspected HIV infection,even if they are asymptomatic or have normal
 immune function.

 -  This is because of the risk of disseminated BCG infection

 -  People with active skin disease such as eczema, dermatitis or psoriasis at or
 near the site of vaccination

 -  A different adjacent site on the upper arm can be chosen if necessary

 -  Pregnant

 -  Although there is no evidence that BCG vaccination is harmful during
 pregnancy, it is a contra-indication to BCG vaccination. Therefore, we will
 exclude women who think they could be pregnant or are planning to become
 pregnant within the next month.

 -  UK specific: Although there is no evidence that BCG vaccination is harmful
 during pregnancy, it is a contra-indication to BCG vaccination. Therefore,
 we will exclude women of childbearing potential (WOCBP) who think they could
 be pregnant.

 -  Spain specific: If the patient is female, and of childbearing potential, she
 must have a negative pregnancy test at the time of inclusion and practice a
 reliable method of birth control for 30 days after receiving the BCG
 vaccination.

 -  Another live vaccine administered in the month prior to randomisation

 -  Require another live vaccine to be administered within the month following BCG
 randomisation

 -  If the other live vaccine can be given on the same day, this exclusion
 criteria does not apply

 -  Known anaphylactic reaction to any of the ingredients present in the BCG vaccine

 -  Previous active TB disease

 -  Currently receiving long term (more than 1 month) treatment with isoniazid,
 rifampicin or quinolone as these antibiotics have activity against Mycobacterium
 bovis

 -  Previous adverse reaction to BCG vaccine (significant local reaction (abscess) or
 suppurative lymphadenitis)

 -  BCG vaccine given within the last year

 -  Have previously had a SARS-CoV-2 positive test result (positive PCR on a respiratory
 sample or a positive SARS-CoV-2 diagnostic antigen test approved by the local
 jurisdiction's public health policy)

 -  Already part of this trial, recruited at a different site/hospital.

 -  Participation in another COVID-19 prevention trial

 -  Have previously received a COVID-19-specific vaccine