bcg vaccination to protect healthcare workers against covid-19

Conditions: Coronavirus Disease 2019 (COVID-19); Respiratory Illness; Corona Virus Infection; COVID-19

Summary: 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 stage 1 of this study, where participants were randomised to receive bcg or no bcg vaccine at the time of receiving influenza vaccination.

Eligibility criteria:
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