Trained Immunity: A Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection

Cell. 2020 May 28;181(5):969-977. doi: 10.1016/j.cell.2020.04.042. Epub 2020 May 4.


SARS-CoV-2 infection is mild in the majority of individuals but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed "trained immunity," by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections through epigenetic, transcriptional, and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole-microorganism vaccines may represent an important tool for reducing susceptibility to and severity of SARS-CoV-2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • BCG Vaccine / immunology
  • Betacoronavirus / physiology*
  • Clinical Trials as Topic
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / pathology
  • Coronavirus Infections / physiopathology
  • Coronavirus Infections / transmission
  • Humans
  • Immunity, Innate* / drug effects
  • Immunomodulation*
  • Lung / immunology
  • Lung / pathology
  • Lymphopenia / pathology
  • Middle East Respiratory Syndrome Coronavirus / physiology
  • Pandemics
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / physiopathology
  • Pneumonia, Viral / transmission
  • SARS Virus / physiology*
  • Severe Acute Respiratory Syndrome / immunology
  • Severe Acute Respiratory Syndrome / pathology
  • Virus Replication


  • BCG Vaccine

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2