TY - JOUR
T1 - Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers
AU - Pittet, Laure F.
AU - Messina, Nicole L.
AU - Orsini, Francesca
AU - Moore, Cecilia L.
AU - Abruzzo, Veronica
AU - Barry, Simone
AU - Bonnici, Rhian
AU - Bonten, Marc
AU - Campbell, John
AU - Croda, Julio
AU - Dalcolmo, Margareth
AU - Gardiner, Kaya
AU - Gell, Grace
AU - Germano, Susie
AU - Gomes-Silva, Adriano
AU - Goodall, Casey
AU - Gwee, Amanda
AU - Jamieson, Tenaya
AU - Jardim, Bruno
AU - Kollmann, Tobias R.
AU - Lacerda, Marcus V.G.
AU - Lee, Katherine J.
AU - Lucas, Michaela
AU - Lynn, David J.
AU - Manning, Laurens
AU - Marshall, Helen S.
AU - McDonald, Ellie
AU - Munns, Craig F.
AU - Nicholson, Suellen
AU - O'Connell, Abby
AU - De Oliveira, Roberto D.
AU - Perlen, Susan
AU - Perrett, Kirsten P.
AU - Prat-Aymerich, Cristina
AU - Richmond, Peter C.
AU - Rodriguez-Baño, Jesus
AU - Dos Santos, Glauce
AU - Da Silva, Patricia V.
AU - Teo, Jia Wei
AU - Villanueva, Paola
AU - Warris, Adilia
AU - Wood, Nicholas J.
AU - Davidson, Andrew
AU - Curtis, Nigel
N1 - Funding Information:
Supported by grants from the Bill and Melinda Gates Foundation (INV-017302), the Minderoo Foundation (COV-001), the Royal Children’s Hospital Foundation (2020-1263 BRACE Trial), the Australian National Health and Medical Research Council (1194694, to Dr. Gwee; 1127984, to Dr. Lee; 2008911, to Dr. Perrett; 1155066, to Dr. Marshall; and 1197117, to Dr. Curtis), the Swiss National Science Foundation (P2GEP3_178155, to Dr. Pittet), EMBL Australia (to Dr. Lynn), and the U.K. Medical Research Council (MR/N006364/2, to Dr. Warris) and by Sarah and Lachlan Murdoch , Health Services Union NSW , the Peter Sowerby Foundation , SA Health , the Insurance Advisernet Foundation , the NAB Foundation , the Calvert-Jones Foundation , the Modara Pines Charitable Foundation , the UHG Foundation , Epworth HealthCare , and individual donors. The Murdoch Children’s Research Institute leads the BRACE trial across 36 sites in five countries; it is supported by the Victorian Government Operational Infrastructure Support Programme.
Publisher Copyright:
© 2023 Massachusetts Medical Society.
PY - 2023/4/27
Y1 - 2023/4/27
N2 - Background The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target"effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19). Methods In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline. Results A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], -0.7 to 5.5; P=0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, -1.2 to 3.5; P=0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified. Conclusions Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, NCT04327206.).
AB - Background The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target"effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19). Methods In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline. Results A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], -0.7 to 5.5; P=0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, -1.2 to 3.5; P=0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified. Conclusions Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, NCT04327206.).
KW - Coronavirus
KW - Global Health
KW - Infectious Disease
KW - Infectious Disease General
KW - Vaccines
UR - http://www.scopus.com/inward/record.url?scp=85156154969&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2212616
DO - 10.1056/NEJMoa2212616
M3 - Article
C2 - 37099341
AN - SCOPUS:85156154969
SN - 0028-4793
VL - 388
SP - 1582
EP - 1596
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 17
ER -
