BCG Revaccination for Healthcare Workers

This project is part of the EDCTP2 programme supported by the European Union

Project abstract

Morbidity and mortality attributable to COVID-19 is devastating global health systems and economies. Bacillus Calmette Guérin (BCG) vaccination has been in use for many decades to prevent severe forms of tuberculosis in children. Studies have also shown a combination of improved long-term innate or trained immunity (through epigenetic reprogramming of myeloid cells) and adaptive responses after BCG vaccination, which leads to non-specific protective effects in adults. Observational studies have shown that countries with routine BCG vaccination programs have significantly less reported cases and deaths of COVID-19, but such studies are prone to significant bias and need confirmation. To date, in the absence of direct evidence, WHO does not recommend BCG for the prevention of COVID-19. This project aims to investigate in a timely manner whether and why BCG-revaccination can reduce infection rate and/or disease severity in health care workers during the SARS- CoV-2 outbreak in South Africa.

These objectives will be achieved with a blinded, randomised controlled trial of BCG revaccination versus placebo in exposed front-line staff in hospitals in Cape Town. Observations will include the rate of infection with COVID-19 as well as the occurrence of mild, moderate, or severe ambulatory respiratory tract infections, hospitalisation, need for oxygen, mechanical ventilation, or death. HIV-positive individuals will be excluded. Safety of the vaccines will be monitored. A secondary endpoint is the occurrence of latent or active tuberculosis. Initial sample size and follow-up duration is at least 500 workers and 52 weeks. Statistical analysis will be model-based and ongoing in real time with frequent interim analyses and optional increases of both sample size or observation time, based on the unforeseeable trajectory of the South African COVID-19 epidemic, available funds and recommendations of an independent data and safety monitoring board. The study will be supported by a novel 3D lung organoid model of SARS-CoV-2 infection system that can mimic the cascade of immunological events after SARS-CoV-2 infection to determine and analyse the contribution of cellular components to the impact of BCG revaccination in this study.

Given the immediate threat of the SARS-CoV-2 epidemic the trial has been designed as a pragmatic study with highly feasible endpoints that can be continuously measured. This allows for the most rapid identification of a beneficial outcome that would lead to immediate dissemination of the results, vaccination of the control group and outreach to the health authorities to consider BCG vaccination for all qualifying health care workers.

Coordinator

1. Task Foundation-NPC, South Africa (Professor Andreas Henri Diacon)

Beneficiaries

2. Uppsala universitet, Sweden (Ulrika Simonsson)

3. Stichting Katholieke Universiteit- Radboudumc (RUMC), Netherlands (Reinout van Crevel)

4. Fundación Instituto de Investigación Sanitaria Aragón, Spain (Santiago Ramon-Garcia)

Media

*Not all media included in list

Date Media Publisher Topic Link
9 Apr 2020 Online Business Insider South Africa Hundreds of SA doctors and nurses may soon get a TB vaccine to see if it helps against Covid-19 https://www.businessinsider.co.za/500-sa-doctors-and-nurses-may-soon-get-a-tb-vaccine-to-see-if-it-helps-against-covid-19-2020-4
25 Apr 2020 Online/ print Weekend Argus Cape Town trial begins next week – can BCG shot prevent Covid-19 infection? https://www.iol.co.za/weekend-argus/news/cape-town-trial-begins-next-week-can-bcg-shot-prevent-covid-19-infection-47187565
4 May 2020 Online Health24 South Africa starts coronavirus trial of TB vaccine https://www.health24.com/Medical/Infectious-diseases/Coronavirus/south-africa-starts-coronavirus-trial-of-tb-vaccine-20200504
5 May 2020 Online Businesstech South Africa begins Covid-19 BCG vaccine trial https://businesstech.co.za/news/government/395166/south-africa-begins-covid-19-bcg-vaccine-trial/
6 May 2020 Online Matie Media Clinical trial at Tygerberg Hospital could be a ‘game changer’ for Covid-19 https://www.matiemedia.org/clinical-trial-at-tygerberg-hospital-could-be-a-game-changer-for-covid-19/?fbclid=IwAR0NUjDtPuOqvNoXhDXtftuPPXuD30Hw-cQsvnq8Y0O5975fL87XTNmQydA
6 May 2020 TV interview SABC News Researchers conducting COVID-19 BCGvaccine trial https://www.youtube.com/watch?v=RJ6CrevSz_0
8 May 2020 Online (video) The South Africa Watch: An exclusive look at South Africa’s COVID-19 BCGvaccine trial https://www.thesouthafrican.com/news/does-bcg-vaccine-prevent-covid-19-medical-trial-video/
13 May 2020 Online Medical Brief BCG vaccine COVID-19 trial starts on SA healthcare workers https://www.medicalbrief.co.za/archives/bcg-vaccine-covid-19-trial-starts-on-sa-healthcare-workers/
19 May 2020 Online Reuters South Africa BCGbooster trials seek low-cost weapon against COVID-19 https://uk.reuters.com/article/us-health-coronavirus-safrica-vaccine/south-africa-bcg-booster-trials-seek-low-cost-weapon-against-covid-19-idUKKBN22V15I
5 Jun 2020 Online DW Scientists test BCG vaccine against Coronavirus https://www.dw.com/en/scientists-test-bcg-vaccine-against-coronavirus/av-53702556

 

Online presentations

Date of presentation Event Name Consortium Rep Topic Link
28 Apr 2020 Tygerberg ICU review Caryn Upton BCG for COVID-19 NA
22 Oct 2020 The Union Conference Andreas Diacon Global Community Advisory Board: BCG for SARS-Cov-2 in HCW Pending
22 Oct 2020 The Union Conference Andreas Diacon Discussion on COVID-19: Is There a Role for the 100-year-old BCGVaccine? Pending

 

Face-to-face presentations

Date of presentation Event Name Consortium Rep Topic Link
TBA

 

Publications

Date published Journal Lead Author Title Link
TBA

BCG Covid-19 trial video explanation

Link to news article on vaccine trial can be found here

For media or press interview enquires, please complete the contact form below.