BCG Against Covid-19 for Prevention and Amelioration of Severity Trial (BAC to the PAST)

Summary

The purpose of this study is to assess the efficacy of Bacille Calmette-Guérin (BCG) vaccination compared to placebo in reducing severe Covid-19 disease among elderly residents of skilled nursing facilities. The investigators hypothesize that BCG vaccination can reduce severity of Covid-19 disease. Patients who are residents of participating long-term care facilities (LTCFs), with the ability to understand and cooperate with study procedures, who agree to participate in the study will be randomly assigned to receive BCG vaccination or a placebo. Participants will be followed for up to twelve months to assess severity of Covid-19 outcomes.

Timeline

Start

2021-09

Primary completion

2022-05

Completion

2022-07

Outcome

Outcome not reported

Stopped: “At this time it has been decided by the study team the the study will no longer take place in the United States.”

Publications

• Background Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.
• Background Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994.
• Background Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, Ma K, Xu D, Yu H, Wang H, Wang T, Guo W, Chen J, Ding C, Zhang X, Huang J, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 26;368:m1091. doi: 10.1136/bmj.m1091.
• Background Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, Lee M. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. 2020 Apr 28;323(16):1612-1614. doi: 10.1001/jama.2020.4326.
• Background Cao J, Tu WJ, Cheng W, Yu L, Liu YK, Hu X, Liu Q. Clinical Features and Short-term Outcomes of 102 Patients with Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis. 2020 Jul 28;71(15):748-755. doi: 10.1093/cid/ciaa243.
• Background Basu-Ray I, Almaddah NK, Vaqar S, Soos MP. Cardiac Manifestations of Coronavirus (COVID-19). 2024 Feb 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK556152/
• Background Danzi GB, Loffi M, Galeazzi G, Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: a random association? Eur Heart J. 2020 May 14;41(19):1858. doi: 10.1093/eurheartj/ehaa254. No abstract available.
• Background Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, Chen H, Ding X, Zhao H, Zhang H, Wang C, Zhao J, Sun X, Tian R, Wu W, Wu D, Ma J, Chen Y, Zhang D, Xie J, Yan X, Zhou X, Liu Z, Wang J, Du B, Qin Y, Gao P, Qin X, Xu Y, Zhang W, Li T, Zhang F, Zhao Y, Li Y, Zhang S. Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. N Engl J Med. 2020 Apr 23;382(17):e38. doi: 10.1056/NEJMc2007575. Epub 2020 Apr 8.
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• Background de Bree LCJ, Marijnissen RJ, Kel JM, Rosendahl Huber SK, Aaby P, Benn CS, Wijnands MVW, Diavatopoulos DA, van Crevel R, Joosten LAB, Netea MG, Dulos J. Bacillus Calmette-Guerin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice. Front Immunol. 2018 Apr 30;9:869. doi: 10.3389/fimmu.2018.00869. eCollection 2018.
• Background Kulkarni S, Mukherjee S, Pandey A, Dahake R, Padmanabhan U, Chowdhary AS. Bacillus Calmette-Guerin Confers Neuroprotection in a Murine Model of Japanese Encephalitis. Neuroimmunomodulation. 2016;23(5-6):278-286. doi: 10.1159/000452171. Epub 2017 Feb 17.
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• Background Niobey FM, Duchiade MP, Vasconcelos AG, de Carvalho ML, Leal Mdo C, Valente JG. [Risk factors for death caused by pneumonia in children younger than 1 year old in a metropolitan region of southeastern Brazil. A case- control study]. Rev Saude Publica. 1992 Aug;26(4):229-38. doi: 10.1590/s0034-89101992000400004. Portuguese.
• Background Hollm-Delgado MG, Stuart EA, Black RE. Acute lower respiratory infection among Bacille Calmette-Guerin (BCG)-vaccinated children. Pediatrics. 2014 Jan;133(1):e73-81. doi: 10.1542/peds.2013-2218. Epub 2013 Dec 30.
• Background de Castro MJ, Pardo-Seco J, Martinon-Torres F. Nonspecific (Heterologous) Protection of Neonatal BCG Vaccination Against Hospitalization Due to Respiratory Infection and Sepsis. Clin Infect Dis. 2015 Jun 1;60(11):1611-9. doi: 10.1093/cid/civ144. Epub 2015 Feb 27.
• Background Chisti MJ, Salam MA, Ahmed T, Shahid AS, Shahunja KM, Faruque AS, Bardhan PK, Hossain MI, Islam MM, Das SK, Huq S, Shahrin L, Huq E, Chowdhury F, Ashraf H. Lack of BCG vaccination and other risk factors for bacteraemia in severely malnourished children with pneumonia. Epidemiol Infect. 2015 Mar;143(4):799-803. doi: 10.1017/S0950268814001368. Epub 2014 Jun 3.
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• Background Stensballe LG, Ravn H, Birk NM, Kjaergaard J, Nissen TN, Pihl GT, Thostesen LM, Greisen G, Jeppesen DL, Kofoed PE, Pryds O, Sorup S, Aaby P, Benn CS. BCG Vaccination at Birth and Rate of Hospitalization for Infection Until 15 Months of Age in Danish Children: A Randomized Clinical Multicenter Trial. J Pediatric Infect Dis Soc. 2019 Jul 1;8(3):213-220. doi: 10.1093/jpids/piy029.
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• Background Abdallah AM, Hill-Cawthorne GA, Otto TD, Coll F, Guerra-Assuncao JA, Gao G, Naeem R, Ansari H, Malas TB, Adroub SA, Verboom T, Ummels R, Zhang H, Panigrahi AK, McNerney R, Brosch R, Clark TG, Behr MA, Bitter W, Pain A. Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations. Sci Rep. 2015 Oct 21;5:15443. doi: 10.1038/srep15443.
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• Background Guerin N, Teulieres L, Noba A, Schlumberger M, Bregere P, Chauvin P. Comparison of the safety and immunogenicity of the lyophilized Merieux seed and the World Health Organization working reference BCG vaccines in school-aged children in Senegal. Vaccine. 1999 Jan;17(2):105-9. doi: 10.1016/s0264-410x(98)00186-8.
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• Background Gallagher, J., C. Watson, and M. Ledwidge, Association of Bacille Calmette-Guérin (BCG), Adult Pneumococcal and Adult Seasonal Influenza Vaccines with Covid-19 Adjusted Mortality Rates in Level 4 European countries. medRxiv, 2020: p. 2020.06.03.20121624.
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• Background Totura AL, Whitmore A, Agnihothram S, Schafer A, Katze MG, Heise MT, Baric RS. Toll-Like Receptor 3 Signaling via TRIF Contributes to a Protective Innate Immune Response to Severe Acute Respiratory Syndrome Coronavirus Infection. mBio. 2015 May 26;6(3):e00638-15. doi: 10.1128/mBio.00638-15.
• Background Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available.
• Background Netea MG, Dominguez-Andres J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LAB, van der Meer JWM, Mhlanga MM, Mulder WJM, Riksen NP, Schlitzer A, Schultze JL, Stabell Benn C, Sun JC, Xavier RJ, Latz E. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020 Jun;20(6):375-388. doi: 10.1038/s41577-020-0285-6. Epub 2020 Mar 4.
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