From the Infectious Diseases Group (L.F.P., N.L.M., V.A., R.B., K.G., G.G., S.G., C.G., A.G., T.J., E.M., S.P., J.W.T., P.V., N.C.), Melbourne Children's Trials Centre (F.O., C.L.M., K.J.L., K.P.P., A.D.), and the Clinical Epidemiology and Biostatistics Unit (F.O., C.L.M., K.J.L.), Murdoch Children's Research Institute, the Department of Paediatrics, University of Melbourne (L.F.P., N.L.M., A.G., K.J.L., K.P.P., P.V., N.C.), the Infectious Diseases Unit (L.F.P., A.G., P.V., N.C.), Research Operations (K.G.), and the Department of Allergy and Immunology (K.P.P.), Royal Children's Hospital Melbourne, and the Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity (S.N.), Parkville, VIC, Precision Medicine Theme, South Australian Health and Medical Research Institute (S.B., D.J.L.), the Department of Thoracic Medicine, Royal Adelaide Hospital (S.B.), and Adelaide Medical School and Robinson Research Institute, University of Adelaide (H.S.M.), Adelaide, SA, Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute (T.R.K., L.M., P.C.R.), the Department of Immunology, PathWest, Queen Elizabeth II Medical Centre (M.L.), the Department of Immunology, Sir Charles Gairdner Hospital (M.L.), and the Department of Immunology and General Paediatrics, Perth Children's Hospital (M.L., P.C.R.), Nedlands, WA, the University of Western Australia Medical School, Perth (M.L., L.M., P.C.R.), Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA (D.J.L.), the Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, WA (L.M.), the Vaccinology and Immunology Research Trials Unit, Women's and Children's Health Network, North Adelaide, SA (H.S.M.), the Department of Endocrinology and Diabetes, Children's Hospital at Westmead (C.F.M.), Sydney Children's Hospitals Network (N.J.W.), and the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Disease (N.J.W.), Westmead, NSW, and the Faculty of Medicine and Health, University of Sydney, Sydney (C.F.M., N.J.W.) - all in Australia; the Infectious Diseases Unit, Department of Pediatrics, Gynecology, and Obstetrics, Faculty of Medicine, University of Geneva and University Hospitals of Geneva, Geneva (L.F.P.); the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands (M.B., C.P.-A.); Exeter Collaboration for Academic Primary Care (J. Campbell) and Exeter Clinical Trials Unit (A.O.), University of Exeter Medical School, and the Medical Research Council Centre for Medical Mycology, University of Exeter (A.W.) - both in Exeter, United Kingdom; Fiocruz Mato Grosso do Sul, Fundação Oswaldo Cruz (J. Croda), and Universidade Federal de Mato Grosso do Sul (J. Croda, R.D.O., P.V.S.), Campo Grande, Helio Fraga Reference Center, Oswaldo Cruz Foundation Ministry of Health (M.D., G.S.), Catholic University (M.D.), and Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (A.G.-S.), Rio de Janeiro, and the Institute of Clinical Research Carlos Borborema, Doctor Heitor Vieira Dourado Tropical Medicine Foundation (B.J., M.V.G.L.), and Instituto Leônidas and Maria Deane, Oswaldo Cruz Foundation Ministry of Health (M.V.G.L.), Manaus - all in Brazil; the Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT (J. Croda); University of Texas Medical Branch, Galveston (M.V.G.L.); and Institut d'Investigació Germans Trias i Pujol, Departament de Genètica i Microbiologia, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias, Instituto de Salud Carlos III, Badalona, Barcelona (C.P.-A.), the Division of Infectious Diseases and Microbiology, Hospital Universitario Virgen Macarena, and the Department of Medicine, University of Seville, Biomedicines Institute of Seville-Consejo Superior de Investigaciones Científicas, Seville (J.R.-B.), and CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid (J.R.-B.) - all in Spain.
N Engl J Med. 2023 Apr 27;388(17):1582-1596. doi: 10.1056/NEJMoa2212616.
The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19).
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.
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.
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.).
卡介苗（BCG）疫苗具有免疫调节的“非靶向”作用，据推测这些作用可以预防 2019 年冠状病毒病（COVID-19）。
在这项国际、双盲、安慰剂对照试验中，我们将卫生保健工作者随机分配接种卡介苗-丹麦疫苗或生理盐水安慰剂，并随访 12 个月。主要结局为 6 个月时的有症状 COVID-19 和重症 COVID-19；主要分析包括改良意向治疗人群，该人群限于基线时严重急性呼吸综合征冠状病毒 2 检测阴性的参与者。
共有 3988 名参与者接受了随机分组；由于 COVID-19 疫苗的供应，在计划样本量达到之前，提前停止了招募。改良意向治疗人群包括 84.9%的随机分组参与者：BCG 组 1703 人，安慰剂组 1683 人。BCG 组 6 个月时有症状 COVID-19 的估计风险为 14.7%，安慰剂组为 12.3%（风险差 2.4 个百分点；95%置信区间 [CI]，-0.7 至 5.5；P=0.13）。BCG 组 6 个月时重症 COVID-19 的风险为 7.6%，安慰剂组为 6.5%（风险差 1.1 个百分点；95%CI，-1.2 至 3.5；P=0.34）；大多数符合 COVID-19 重症定义的参与者虽未住院，但至少连续 3 天无法工作。在使用更不保守的删失规则的补充和敏感性分析中，风险差异相似，但置信区间较窄。每组各有 5 例 COVID-19 住院病例（包括安慰剂组 1 例死亡）。BCG 组与安慰剂组相比，任何 COVID-19 发作的风险比为 1.23（95%CI，0.96 至 1.59）。未发现安全性问题。
与安慰剂相比，接种卡介苗-丹麦疫苗并未降低卫生保健工作者 COVID-19 的风险。（由比尔及梅琳达·盖茨基金会等资助；BRACE 临床试验.gov 编号，NCT04327206）。
