Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers

被引：54

作者：

Pittet, Laure F. ^{[2
,5
,6
,26
,27
]}

Messina, Nicole L. ^{[2
,5
]}

Orsini, Francesca ^{[3
,4
]}

Moore, Cecilia L. ^{[3
,4
,22
,25
]}

Abruzzo, Veronica ^{[2
]}

Barry, Simone ^{[10
,11
]}

Bonnici, Rhian ^{[2
]}

Bonten, Marc ^{[28
]}

Campbell, John ^{[29
]}

Croda, Julio ^{[32
,33
,39
]}

Dalcolmo, Margareth ^{[34
,35
]}

Gardiner, Kaya ^{[2
,7
]}

Gell, Grace ^{[2
]}

Germano, Susie ^{[2
]}

Gomes-Silva, Adriano ^{[36
]}

Goodall, Casey ^{[2
]}

Gwee, Amanda ^{[2
,5
,6
]}

Jamieson, Tenaya ^{[2
]}

Jardim, Bruno ^{[37
]}

Kollmann, Tobias R. ^{[14
]}

Lacerda, Marcus V. G. ^{[37
,38
,40
]}

Lee, Katherine J. ^{[3
,4
,5
]}

Lucas, Michaela ^{[15
,16
,17
,18
]}

Lynn, David J. ^{[10
,19
]}

Manning, Laurens ^{[14
,18
,20
]}

Marshall, Helen S. ^{[12
,13
,21
]}

McDonald, Ellie ^{[2
]}

Munns, Craig F.

Nicholson, Suellen ^{[9
]}

O'Connell, Abby ^{[30
]}

de Oliveira, Roberto D. ^{[33
]}

Perlen, Susan ^{[2
]}

Perrett, Kirsten P. ^{[3
,8
]}

Prat-Aymerich, Cristina ^{[28
,41
]}

Richmond, Peter C. ^{[14
,17
,18
]}

Rodriguez-Bano, Jesus ^{[42
,43
,44
]}

dos Santos, Glauce ^{[34
]}

da Silva, Patricia V.

Teo, Jia Wei ^{[2
]}

Villanueva, Paola ^{[2
,5
,6
,33
]}

Warris, Adilia ^{[31
]}

Wood, Nicholas J. ^{[23
,24
,25
]}

Davidson, Andrew ^{[3
]}

Curtis, Nigel ^{[1
,2
,5
,6
]}

机构：

[1] Univ Melbourne, Royal Childrens Hosp Melbourne, Dept Paediat, 50 Flemington Rd, Parkville, Vic 3052, Australia

[2] Murdoch Childrens Res Inst, Infect Dis Grp, Parkville, Vic, Australia

[3] Murdoch Childrens Res Inst, Melbourne Childrens Trials Ctr, Parkville, Vic, Australia

[4] Murdoch Childrens Res Inst, Clin Epidemiol & Biostat Unit, Parkville, Vic, Australia

[5] Univ Melbourne, Dept Paediat, Parkville, Vic, Australia

[6] Royal Childrens Hosp Melbourne, Infect Dis Unit, Parkville, Vic, Australia

[7] Royal Childrens Hosp Melbourne, Res Operat, Parkville, Vic, Australia

[8] Royal Childrens Hosp Melbourne, Dept Allergy & Immunol, Parkville, Vic, Australia

[9] Royal Melbourne Hosp, Peter Doherty Inst Infect & Immun, Victorian Infect Dis Reference Lab, Parkville, Vic, Australia

[10] South Australian Hlth & Med Res Inst, Precis Med Theme, Adelaide, SA, Australia

[11] Royal Adelaide Hosp, Dept Thorac Med, Adelaide, SA, Australia

[12] Univ Adelaide, Adelaide Med Sch, Adelaide, SA, Australia

[13] Univ Adelaide, Robinson Res Inst, Adelaide, SA, Australia

[14] Telethon Kids Inst, Wesfarmers Ctr Vaccines & Infect Dis, Nedlands, WA, Australia

[15] Queen Elizabeth II Med Ctr, Dept Immunol, PathWest, Nedlands, WA, Australia

[16] Sir Charles Gairdner Hosp, Dept Immunol, Nedlands, WA, Australia

[17] Perth Childrens Hosp, Dept Immunol & Gen Paediat, Nedlands, WA, Australia

[18] Univ Western Australia, Med Sch, Perth, Australia

[19] Flinders Univ S Australia, Flinders Hlth & Med Res Inst, Bedford Pk, SA, Australia

[20] Fiona Stanley Hosp, Dept Infect Dis, Murdoch, WA, Australia

[21] Womens & Childrens Hlth Network, Vaccinol & Immunol Res Trials Unit, North Adelaide, SA, Australia

[22] Childrens Hosp Westmead, Dept Endocrinol & Diabet, Westmead, NSW, Australia

[23] Sydney Childrens Hosp Network, Westmead, NSW, Australia

[24] Natl Ctr Immunisat Res & Surveillance Vaccine Prev, Westmead, NSW, Australia

[25] Univ Sydney, Fac Med & Hlth, Sydney, Australia

[26] Univ Geneva, Fac Med, Dept Pediat Gynecol & Obstet, Infect Dis Unit, Geneva, Switzerland

[27] Univ Hosp Geneva, Geneva, Switzerland

[28] Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[29] Univ Exeter, Exeter Collaborat Acad Primary Care, Med Sch, Exeter, England

[30] Univ Exeter, Exeter Clin Trials Unit, Med Sch, Exeter, England

[31] Univ Exeter, Med Res Council, Ctr Med Mycol, Exeter, England

[32] Fundacao Oswaldo Cruz, Fiocruz Mato Grosso Sul, Campo Grande, Brazil

[33] Univ Fed Mato Grosso do Sul, Campo Grande, Brazil

[34] Fundacao Oswaldo Cruz, Helio Fraga Reference Ctr, Minist Hlth, Rio De Janeiro, Brazil

[35] Catholic Univ, Rio De Janeiro, Brazil

[36] Fundacao Oswaldo Cruz, Lab Interdisciplinar Pesquisas Med, Inst Oswaldo Cruz, Rio De Janeiro, Brazil

[37] Doctor Heitor Vieira Dourado Trop Med Fdn, Inst Clin Res Carlos Borborema, Manaus, Brazil

[38] Fundacao Oswaldo Cruz, Inst Leonidas & Maria Deane, Minist Hlth, Manaus, Brazil

[39] Yale Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA

[40] Univ Texas Med Branch, Galveston, TX USA

[41] Univ Autonoma Barcelona, Inst Invest Germans Trias & Pujol, Ctr Invest Biomed Red CIBER Enfermedades Resp, Dept Genet & Microbiol,Inst Salud Carlos III, Barcelona, Spain

[42] Hosp Univ Virgen Macarena, Div Infect Dis & Microbiol, Seville, Spain

[43] Univ Seville, Biomed Inst Seville, CSIC, Dept Med, Seville, Spain

[44] Inst Salud Carlos III, CIBER Enfermedades Infecciosas, Madrid, Spain

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2023年 / 388卷 / 17期

基金：

英国医学研究理事会; 瑞士国家科学基金会;

关键词：

TRAINED IMMUNITY; TUBERCULOSIS; STRAIN;

D O I：

10.1056/NEJMoa2212616

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundThe bacille Calmette-Guerin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19).MethodsIn 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.ResultsA 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.ConclusionsVaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo.

引用

页码：1582 / 1596

页数：15

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