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

Gopala Koneru; Gaber El-Saber Batiha; Abdelazeem M Algammal; Mahmoud Mabrok; Sara Magdy; Shrouk Sayed; Mai E AbuElmagd; Reham Elnemr; Mahmoud M Saad; Noura H Abd Ellah; Amal Hosni; Khalid Muhammad; Helal F Hetta

doi:10.2147/IDR.S300162

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

Infect Drug Resist. 2021 Mar 23:14:1169-1184. doi: 10.2147/IDR.S300162. eCollection 2021.

Authors

Gopala Koneru¹, Gaber El-Saber Batiha², Abdelazeem M Algammal³, Mahmoud Mabrok^{4

5}, Sara Magdy⁶, Shrouk Sayed⁶, Mai E AbuElmagd⁶, Reham Elnemr⁶, Mahmoud M Saad⁶, Noura H Abd Ellah⁷, Amal Hosni⁸, Khalid Muhammad^#⁹, Helal F Hetta^#^{10

11}

Affiliations

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

^# Contributed equally.

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: BCG vaccine; COVID-19; coronavirus; trained immunity; tuberculosis.

Publication types

Review