System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Randomized Controlled Trial Clinical Trial, Phase III Multicenter Study Ppublish 6 citations

PubMed: 39127450 DOI: 10.1016/j.jinf.2024.106245

BCG vaccination of healthcare workers for protection against COVID-19: 12-month outcomes from an international randomised controlled trial.

J Infect 89(4):106245

Authors: Nicole L Messina, Laure F Pittet, Ellie McDonald, Cecilia Moore, Simone Barry, Marc Bonten, Anthony Byrne, John Campbell, Julio Croda, Mariana G Croda, Margareth Dalcolmo, Fernando F de Almeida E Val, Roberto D de Oliveira, Glauce Dos Santos, Mark W Douglas, Kaya Gardiner, Amanda Gwee, Bruno A Jardim, Tobias Kollmann, Marcus Vg Lacerda, Michaela Lucas, David J Lynn, Laurens Manning, Helen Marshall, Abby O'Connell, Kirsten P Perrett, Jeffrey J Post, Cristina Prat-Aymerich, Jorge L Rocha, Jesus Rodriguez-Baño, Ushma Wadia, Adilia Warris, Andrew Davidson, Nigel Curtis

Affiliations

  • Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
  • Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Immunology, Vaccinology, Rheumatology and Infectious Diseases Unit, Geneva and University Hospitals and Faculty of Medicine, Geneva, Switzerland.
  • Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
  • Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
  • Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia; Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
  • Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, the Netherlands; European Clinical Research Alliance on Infectious Diseases, Utrecht, Netherlands.
  • St Vincent's Hospitals, Darlinghurst, New South Wales, Australia; Partners In Health, Socios En Salud, Peru; Thoracic Society of Australia & New Zealand (NSW/ACT Branch), Australia.
  • Exeter Collaboration for Academic Primary Care, University of Exeter Medical School, Exeter, United Kingdom.
  • Fiocruz Mato Grosso do Sul, Fundação Oswaldo Cruz, Campo Grande, Mato Grosso do Sul, Brazil; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA; Universidade Federal de Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil.
  • Universidade Federal de Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil.
  • Centro de Referência Professor Hélio Fraga, ENSP/FIOCRUZ (Fundação Oswaldo Cruz), Rio de Janeiro, Brazil.
  • Tropical Medicine Foundation Dr Heitor Vieira Dourado, Manaus, Brazil.
  • State University of Mato Grosso do Sul, Dourados, Brazil; Post Graduate Program in Health Sciences, Federal University of Grande Dourados, Dourados, Brazil.
  • Storr Liver Centre, The Westmead Institute for Medical Research, The University of Syndey at Westmead Hospital, Westmead, New South Wales, Australia; Centre for Infectious Diseases and Microbiology, Sydney Infectious Diseases Institute, The University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia.
  • Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Research Operations, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
  • Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia; Antimicrobials Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
  • Institute of Clinical Research Carlos Borborema, Doctor Heitor Vieira Dourado Tropical Medicine Foundation, Manaus, Brazil.
  • Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia, Australia.
  • Institute of Clinical Research Carlos Borborema, Doctor Heitor Vieira Dourado Tropical Medicine Foundation, Manaus, Brazil; Instituto Leônidas & Maria Deane, Oswaldo Cruz Foundation Ministry of Health, Manaus, Brazil; University of Texas Medical Branch, Galveston, TX, USA.
  • Department of Immunology, Pathwest, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia; Department of Immunology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; Department of Immunology, Perth Children's Hospital, Nedlands, Western Australia, Australia; School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
  • Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia; Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia.
  • Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia, Australia; School of Medicine, University of Western Australia, Perth, Western Australia, Australia; Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.
  • The University of Adelaide and the Women's and Children's Health Network, Adelaide, SA, Australia.
  • Exeter Clinical Trials Unit, University of Exeter, Exeter, United Kingdom.
  • Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Population Allergy Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Allergy and Immunology, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
  • Department of Infectious Diseases, Prince of Wales Hospital, Randwick, New South Wales, Australia; School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
  • Helio Fraga Reference Center, Oswaldo Cruz Foundation Ministry of Health, Curicica, Brazil.
  • Division of Infectious Diseases and Microbiology, Department of Medicine, Hospital Universitario Virgen Macarena, University of Seville, Biomedicines Institute of Seville-Consejo Superior de Investigaciones Científicas, Seville, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carloss III, Madrid, Spain.
  • Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia, Australia; School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
  • Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom; Department of Infectious Diseases, Great Ormond Street Hospital, London, United Kingdom.
  • Melbourne Children's Trial Centre, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
  • Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.

Abstract

OBJECTIVES

Bacille Calmette-Guérin (BCG) vaccine has immunomodulatory effects that may provide protection against unrelated infectious diseases. We aimed to determine whether BCG vaccination protects adults against COVID-19.

DESIGN

Phase III double-blind randomised controlled trial.

SETTING

Healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom during the COVID-19 pandemic.

PARTICIPANTS

3988 healthcare workers with no prior COVID-19 and no contraindication to BCG.

INTERVENTION

Randomised 1:1 using a web-based procedure to receive a single 0.1 mL intradermal dose of BCG-Denmark (BCG group, n = 1999) or saline (placebo group, n = 1989).

MAIN OUTCOME MEASURES

Difference in incidence of (i) symptomatic and (ii) severe COVID-19 during the 12 months following randomisation in the modified intention to treat (mITT) population (confirmed SARS-CoV-2 naïve at inclusion).

RESULTS

Of the 3988 participants randomised, 3386 had a negative baseline SARS-CoV-2 test and were included in the mITT population. The 12-month adjusted estimated risk of symptomatic COVID-19 was higher in the BCG group (22.6%; 95% confidence interval [CI] 20.6 to 24.5%) compared with the placebo group (19.6%; 95% CI 17.6 to 21.5%); adjusted difference +3.0% points (95% CI 0.2 to 5.8%; p = 0.04). The 12-month adjusted estimated risk of severe COVID-19 (mainly comprising those reporting being unable to work for ≥3 consecutive days) was 11.0% in the BCG group (95% CI 9.5 to 12.4%) compared with 9.6% in the placebo group (95% CI 8.3 to 11.1%); adjusted difference +1.3% points (95% CI -0.7 to 3.3%, p = 0.2). Breakthrough COVID-19 (post COVID-19 vaccination) and asymptomatic SARS-CoV-2 infections were similar in the two groups. There were 18 hospitalisations due to COVID-19 (11 in BCG group, 7 in placebo group; adjusted hazard ratio 1.56, 95% CI 0.60 to 4.02, p = 0.4) and two deaths due to COVID-19, both in the placebo group.

CONCLUSIONS

Compared to placebo, vaccination with BCG-Denmark increased the risk of symptomatic COVID-19 over 12 months among healthcare workers and did not decrease the risk of severe COVID-19 or post-vaccination breakthrough COVID-19.

TRIAL REGISTRATION

ClinicalTrials.gov NCT04327206.

MeSH

Bacterial Infections, Vaccines, Vaccination, Covid-19, Work, Health Personnel, Communicable Diseases

Cited by