BCG Vaccination to Protect Healthcare Workers Against COVID-19

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