BCG vaccination to reduce the impact of COVID-19 in healthcare workers: Protocol for a randomised controlled trial (BRACE trial)

• Published in: BMJ open Vol. 11; no. 10; p. e052101
• Main Authors: Jamieson, Tenaya, Manning, Laurens, Richmond, Peter, Agius, Sophie, Barbosa, Adelita Agripina, Anderson, Jeremy, Almajano, Francisco Arnaiz, Azzopardi, Kristy, Gutierrez, Ana Belen, Bergant, Nikki, Bijllaardt, Wouter, Garcia, Pilar Bohedo, Boon, Anne, Brophy, Clare, Bucholc, Jess, Burrell, Emma, Byrne, Bridie, Catterick, Helen, Chan, Joyce, Cobbledick, Annie, Corbett, Mary, Dalton, Karen, Oliveira, Adriely de, Dixon, Rachel, Eden, Georgina, Ewe, Krist, Freitas, Thamires, Furtado, Ana Carolina, Oliveira, Maria Gabriela, Gamage, Dinusha, Ganpat, Radhika, Gifford, Alison, Ginsberg, Ann, Glenn, Penny, Godinho, Vanessa, Rico, Claudia González, Hall, Richard, Andrade, Paulo Henrique, Herrmann, Susan, Kandasamy, Rama, Karunanayake, Anushka, Korman, Tony, Lagunday, Renier, Lalich, Debbie, Lieschke, Katherine, Santos, Karla Lopes, Malley, Richard, Barriocanal, Ana Maria, Pereira, Rosa Maria, Marins, Adriana, Tadokoro, Mariana Mayumi, McDonald, Fiona, Molina, Gemma, Molina, Barbara, Moyle, Will, Newman, Georgina, Noonan, Fran, Oppedisano, Frances, Orsini, Francesca, Group, Orygen, Owens, Rosie, Pandine, Girlene, Pell, Casey, Pereira, Gabrielle, Post, Jeffrey, Prajitno, Endriaen, Queiroz, Evelyn, Ramos, Pedro, Fernandes, Iara Rodrigues, Santos, Daniel, Santos, Tilza, Shave, Margaret, Baena, Adrian Siles, Silva, Rafaela, Silva, Juliana, Singh, Ronita, Chaves, Marciléia Soares, Stevens, Natalie, Studham, Josephine, Subbarao, Kanta, Suiker, Astrid, Taks, Esther, Oever, Jaap ten, Tsuha, Daniel, Uffing, Marlot, Valero, Olga, Veen, Sigrid van, Waal, Marije van, van Leusen, J.H., van Onzenoort, H., Vasconcelos, Adria, Vega, Noelia, Velagapudi, Sunitha, Ortega, Rosario Vigo, Wadia, Ushma, Wallace, Rachael, Warren, Ruth, Watts, Emma, Xie, Ivy, Young, Angela
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 28.10.2021; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Protocol
• Subjects: BCG Vaccine; Coronaviruses; COVID-19; COVID-19 vaccines; Data collection; Disease; Health Personnel; Herpes viruses; Humans; Illnesses; Immunology; Infections; Infectious Diseases; Influenza; Medical personnel; microbiology; Mortality; Multicenter Studies as Topic; Pandemics; Pathogens; Randomized Controlled Trials as Topic; Respiratory diseases; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Treatment Outcome; Tropical diseases; Tuberculosis; Vaccination; virology; Denmark; Australia; COVID-19; microbiology; virology; immunology; infectious diseases
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2021-052101

IntroductionBCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19.Methods and analysisThis international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections.Ethics and disseminationEthical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system.Trial registrationClinicalTrials.gov NCT04327206