TY - JOUR
T1 - BCG vaccination of healthcare workers for protection against COVID-19
T2 - 12-month outcomes from an international randomised controlled trial
AU - Messina, Nicole L
AU - Pittet, Laure F
AU - McDonald, Ellie
AU - Moore, Cecilia
AU - Barry, Simone
AU - Bonten, Marc
AU - Byrne, Anthony
AU - Campbell, John
AU - Croda, Julio
AU - Croda, Mariana G
AU - Dalcolmo, Margareth
AU - de Almeida e Val, Fernando F
AU - de Oliveira, Roberto D
AU - dos Santos, Glauce
AU - Douglas, Mark W
AU - Gardiner, Kaya
AU - Gwee, Amanda
AU - Jardim, Bruno A
AU - Kollmann, Tobias
AU - Lacerda, Marcus V G
AU - Lucas, Michaela
AU - Lynn, David J
AU - Manning, Laurens
AU - Marshall, Helen
AU - O'Connell, Abby
AU - Perrett, Kirsten P
AU - Post, Jeffrey J
AU - Prat-Aymerich, Cristina
AU - Rocha, Jorge L
AU - Rodriguez-Baño, Jesus
AU - Wadia, Ushma
AU - Warris, Adilia
AU - Davidson, Andrew
AU - Curtis, Nigel
AU - the BRACE Trial Consortium Group
PY - 2024/10
Y1 - 2024/10
N2 - 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.
AB - 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.
KW - Bacille Calmette-Guérin (BCG) Vaccine
KW - Breakthrough infection
KW - COVID-19
KW - Immunity
KW - Randomised controlled trial
UR - http://www.scopus.com/inward/record.url?scp=85202210560&partnerID=8YFLogxK
U2 - 10.1016/j.jinf.2024.106245
DO - 10.1016/j.jinf.2024.106245
M3 - Article
C2 - 39127450
AN - SCOPUS:85202210560
SN - 0163-4453
VL - 89
JO - Journal of Infection
JF - Journal of Infection
IS - 4
M1 - 106245
ER -
