The role of trained immunity in COVID-19: Lessons for the next pandemic

Mihai G Netea; Athanasios Ziogas; Christine Stabell Benn; Evangelos J Giamarellos-Bourboulis; Leo A B Joosten; Moshe Arditi; Konstantin Chumakov; Reinout van Crevel; Robert Gallo; Peter Aaby; Jos W M van der Meer

doi:10.1016/j.chom.2023.05.004

The role of trained immunity in COVID-19: Lessons for the next pandemic

Cell Host Microbe. 2023 Jun 14;31(6):890-901. doi: 10.1016/j.chom.2023.05.004.

Affiliations

¹ Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, Bonn, Germany. Electronic address: mihai.netea@radboudumc.nl.
² Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
³ Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark, Copenhagen, Denmark; Danish Institute for Advanced Study, University of Southern Denmark, Odense, Denmark.
⁴ 4(th) Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
⁵ Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
⁶ Departments of Pediatrics and Biomedical Sciences, Guerin Children's and Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, USA.
⁷ Office of Vaccines Research and Review, Food and Drug Administration, Global Virus Network Center of Excellence, Silver Spring, MD, USA.
⁸ Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁹ Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Global Virus Network, Baltimore, MD, USA.
¹⁰ Bandim Health Project, OPEN, Department of Clinical Research, University of Southern Denmark, Copenhagen, Denmark.

Abstract

Trained immunity is a long-term increase in responsiveness of innate immune cells, induced by certain infections and vaccines. During the last 3 years of the COVID-19 pandemic, vaccines that induce trained immunity, such as BCG, MMR, OPV, and others, have been investigated for their capacity to protect against COVID-19. Further, trained immunity-inducing vaccines have been shown to improve B and T cell responsiveness to both mRNA- and adenovirus-based anti-COVID-19 vaccines. Moreover, SARS-CoV-2 infection itself induces inappropriately strong programs of trained immunity in some individuals, which may contribute to the long-term inflammatory sequelae. In this review, we detail these and other aspects of the role of trained immunity in SARS-CoV-2 infection and COVID-19. We also examine the learnings from the trained immunity studies conducted in the context of this pandemic and discuss how they may help us in preparing for future infectious outbreaks.

Keywords: BCG; COVID-19; clinical trials; trained immunity; vaccines.

Publication types

Review

MeSH terms

BCG Vaccine
COVID-19*
Humans
Immunity, Innate
Pandemics / prevention & control
SARS-CoV-2
Trained Immunity
Viral Vaccines*

Substances

Viral Vaccines
BCG Vaccine