Can BCG vaccine protect against COVID-19 via trained immunity and tolerogenesis?

Bioessays. 2021 Mar;43(3):e2000200. doi: 10.1002/bies.202000200. Epub 2020 Nov 9.

Abstract

As the number of infections and mortalities from the SARS-CoV-2 pandemic continues to rise, the development of an effective therapy against COVID-19 becomes ever more urgent. A few reports showing a positive correlation between BCG vaccination and reduced COVID-19 mortality have ushered in some hope. BCG has been suggested to confer a broad level of nonspecific protection against several pathogens, mainly via eliciting "trained immunity" in innate immune cells. Secondly, BCG has also been proven to provide benefits in autoimmune diseases by inducing tolerogenicity. Being an acute inflammatory disease, COVID-19 requires a therapy that induces early priming of anti-viral immune responses and regulates aberrant hyperactivity of innate-immune cells. Here, we hypothesize that BCG can offer reliable spatiotemporal protection from COVID-19 by triggering trained immunity and tolerogenesis, through multiple cellular pathways. We propose further research on BCG-mediated immunoprotection, especially in vulnerable individuals, as a strategy to halt the progress of the SARS-CoV-2 pandemic. Also see the video abstract here https://youtu.be/P2D2RXfq6Vg.

Keywords: BCG; COVID-19; SARS-CoV-2; epigenetic reprogramming; innate immune cells; regulatory T cells; trained immunity.

Publication types

  • Review

MeSH terms

  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology
  • BCG Vaccine / therapeutic use*
  • COVID-19 / immunology
  • COVID-19 / pathology
  • COVID-19 / prevention & control*
  • COVID-19 / virology
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / pathology
  • Cytokine Release Syndrome / prevention & control*
  • Cytokine Release Syndrome / virology
  • Cytokines / genetics
  • Cytokines / immunology
  • Gene Expression Regulation
  • Humans
  • Immune Tolerance / drug effects*
  • Immunity, Innate / drug effects*
  • Immunologic Memory / drug effects
  • Pathogen-Associated Molecular Pattern Molecules / immunology
  • Pathogen-Associated Molecular Pattern Molecules / metabolism
  • RNA, Viral / genetics
  • RNA, Viral / immunology
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / virology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / virology
  • Vaccination / methods

Substances

  • BCG Vaccine
  • Cytokines
  • Pathogen-Associated Molecular Pattern Molecules
  • RNA, Viral