BCG vaccination to prevent COVID19 in healthcare workers. The international BRACE clinical trial

Conference:

SAPC ASM 2021 - virtual

Talk Code:

3B.6

Presenter:

John Campbell

Twitter:

@profjcampbell

Co-authors:

Campbell, J Quinne, L Warris, A O’Connell, A Fletcher, E Rhodes, S Curtis, N

Author institutions:

University of Exeter; Exeter Clinical Trials Unit; Murdoch Clinical Research Institute, Melbourne , Australia

Problem

BCG vaccination, introduced 100 years ago, is safe, cheap, and widely available. 4 Billion doses have been administered - currently 120 million annually. Routine BCG administration stopped in the UK in 2005. Evidence from a range of studies identifies a range of 'potent' off-target effects for BCG including anti-viral effects against a range of Corona-like viruses. As part of a large global collaboration, we investigated the hypothesis that BCG may reduce the incidence and severity of COVID19 amongst healthcare workers in Australia, UK, Netherlands, Spain, and Brazil.

Approach

International collaboration led from Melbourne, Australia. 1:1 Randomized controlled clinical trial of standard Danish-strain BCG vaccination (0.1 ml intradermal) versus 0.1ml intradermal saline placebo. Joint primary-outcomes at 6 months follow up - incidence of COVID19 confirmed using routine PCR testing of individuals becoming symptomatic during follow-up, and severity of COVID19 (COVID disease and work absenteeism, admission, or death). Wide range of secondary outcomes including COVID-related, non-COVID-related (eg Herpes Simplex recurrence, upper respiratory infection), work absenteeism, immunological outcomes. Recruitment is from a broad range of hospital and community healthcare settings including carehomes, community pharmacy, ambulance, and nurse settings. Online follow-up using REDCAP for 1 year, with blood testing and questionnaire review at 0,3,6,9,12 months.

Findings

Recruitment is ongoing (>6600 at 23 February 2021), including 175 from southwest UK settings. UK recruitment with a target of 1000 participants started in early October 2020 and stopped 28 January 2021. We latterly encountered a challenging recruitment environment as COVID19-specific vaccines became available and were rapidly and successfully promoted within our target population. Recruitment is ongoing elsewhere. Interim analysis planned after 100 'severe' COVID events documented in trial. We will report on the challenges and complexities of setting up and securing funding for this trial in the current UK context and report the UK baseline recruitment profile.

Consequences

BCG may have important potential against original SARSCoV2, variant SARSCoV2, and as-yet-unknown future pandemic viral agents

Submitted by:

John L. Campbell

Funding acknowledgement:

Murdoch Clinical Research Institute (Bill and Melinda Gates Foundation) Peter Sowerby Foundation