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BCG Vaccine-Induced Trained Immunity and COVID-19: Protective or Bystander?

Authors Koneru G, Batiha GES, Algammal AM, Mabrok M, Magdy S, Sayed S, AbuElmagd ME, Elnemr R, Saad MM, Abd Ellah NH, Hosni A, Muhammad K, Hetta HF

Received 2 January 2021

Accepted for publication 24 February 2021

Published 23 March 2021 Volume 2021:14 Pages 1169—1184


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Suresh Antony

Gopala Koneru,1 Gaber El-Saber Batiha,2 Abdelazeem M Algammal,3 Mahmoud Mabrok,4,5 Sara Magdy,6 Shrouk Sayed,6 Mai E AbuElmagd,6 Reham Elnemr,6 Mahmoud M Saad,6 Noura H Abd Ellah,7 Amal Hosni,8 Khalid Muhammad,9,* Helal F Hetta10,11,*

1Department of Medicine, Division of Gastroenterology and Hepatology, Rutger New Jersey Medical School, Rutgers University, New Brunswick, NJ, 07103, USA; 2Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicines, Damanhour University, Damanhur, 22511, Egypt; 3Department of Bacteriology, Immunology, and Mycology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt; 4Department of Fish Diseases and Management, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt; 5Fish Infectious Diseases Research Unit (FID RU), Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand; 6Faculty of Medicine, Assiut University, Assiut, 71515, Egypt; 7Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt; 8Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt; 9Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates; 10Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt; 11Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA

*These authors contributed equally to this work

Correspondence: Khalid Muhammad; Helal F Hetta Email [email protected]; [email protected]

Abstract: In late 2019, a new virulent coronavirus (CoV) emerged in Wuhan, China and was named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This virus spread rapidly, causing the coronavirus disease-2019 (COVID-19) pandemic. Bacillus Calmette–Guérin (BCG) is a live attenuated tuberculosis (TB) vaccine, associated with induction of non-specific cross-protection against unrelated infections. This protection is a memory-like response in innate immune cells (trained immunity), which is caused by epigenetic reprogramming via histone modification in the regulatory elements of specific genes in monocytes. COVID-19 related epidemiological studies showed an inverse relationship between national BCG vaccination policies and COVID-19 incidence and death, suggesting that BCG may induce trained immunity that could confer some protection against SARS-CoV-2. As this pandemic has put most of Earth’s population under quarantine, repurposing of the old, well-characterized BCG may ensure some protection against COVID-19. This review focuses on BCG-related cross-protection and acquisition of trained immunity, as well as the correlation between BCG vaccination and COVID-19 incidence and mortality.

Keywords: COVID-19, BCG vaccine, coronavirus, trained immunity, tuberculosis

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