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

Autor: Messina NL; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia., Pittet LF; 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., McDonald E; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia., Moore C; Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia., Barry S; 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., Bonten M; 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., Byrne A; 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., Campbell J; Exeter Collaboration for Academic Primary Care, University of Exeter Medical School, Exeter, United Kingdom., Croda J; 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., Croda MG; Universidade Federal de Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil., Dalcolmo M; Centro de Referência Professor Hélio Fraga, ENSP/FIOCRUZ (Fundação Oswaldo Cruz), Rio de Janeiro, Brazil., de Almeida E Val FF; Tropical Medicine Foundation Dr Heitor Vieira Dourado, Manaus, Brazil., de Oliveira RD; State University of Mato Grosso do Sul, Dourados, Brazil; Post Graduate Program in Health Sciences, Federal University of Grande Dourados, Dourados, Brazil., Dos Santos G; Centro de Referência Professor Hélio Fraga, ENSP/FIOCRUZ (Fundação Oswaldo Cruz), Rio de Janeiro, Brazil., Douglas MW; 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., Gardiner K; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Research Operations, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia., Gwee A; 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., Jardim BA; Institute of Clinical Research Carlos Borborema, Doctor Heitor Vieira Dourado Tropical Medicine Foundation, Manaus, Brazil., Kollmann T; Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia, Australia., Lacerda MV; 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., Lucas M; 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., Lynn DJ; 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., Manning L; 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., Marshall H; The University of Adelaide and the Women's and Children's Health Network, Adelaide, SA, Australia., O'Connell A; Exeter Clinical Trials Unit, University of Exeter, Exeter, United Kingdom., Perrett KP; 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., Post JJ; 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., Prat-Aymerich C; 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., Rocha JL; Helio Fraga Reference Center, Oswaldo Cruz Foundation Ministry of Health, Curicica, Brazil., Rodriguez-Baño J; 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., Wadia U; 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., Warris A; Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom; Department of Infectious Diseases, Great Ormond Street Hospital, London, United Kingdom., Davidson A; Melbourne Children's Trial Centre, Murdoch Children's Research Institute, Parkville, Victoria, Australia., Curtis N; 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. Electronic address: nigel.curtis@rch.org.au.
Jazyk: angličtina
Zdroj: The Journal of infection [J Infect] 2024 Oct; Vol. 89 (4), pp. 106245. Date of Electronic Publication: 2024 Aug 08.
DOI: 10.1016/j.jinf.2024.106245
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The trial is financially supported by the Foundations listed in the Funding section. Authors disclose funding support over the past 36 months: National Health and Medical Research Council (NHMRC) Ideas Grant (NM), NHMRC Investigator Grant (NC), Melbourne Children’s Clinician-Scientist Fellowship Grant (KPP). Outside of the submitted work, JCr has received grants or contracts from Sanofi, MSD & CEPI; payment or honoraria for presentations from Pfizer and participates on Latin American data safety monitoring/advisory boards for mRNA-1273 (Modern/Zodiac), RSV maternal vaccine (Pfizer), Qdenga vaccine (Takeda) and Nirmatrelvir/Ritonavir-Paxlovid (Pfizer). KG is a member of the Royal Children’s Hospital (RCH) Human Research Ethics Committee (the primary ethics committee providing approval for the BRACE trial) and Director of Research Operations at RCH; she abstained from all discussion, voting, approval and review related to the BRACE trial. All other authors declare no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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