Type I and III interferon responses in SARS-CoV-2 infection

Exp Mol Med. 2021 May;53(5):750-760. doi: 10.1038/s12276-021-00592-0. Epub 2021 May 6.


Coronavirus disease 2019 (COVID-19), the current pandemic disease, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Type I and III interferons (IFNs) are innate cytokines that are important in the first-line defense against viruses. Similar to many other viruses, SARS-CoV-2 has evolved mechanisms for evading the antiviral effects of type I and III IFNs at multiple levels, including the induction of IFN expression and cellular responses to IFNs. In this review, we describe the innate sensing mechanisms of SARS-CoV-2 and the mechanisms used by SARS-CoV-2 to evade type I and III IFN responses. We also discuss contradictory reports regarding impaired and robust type I IFN responses in patients with severe COVID-19. Finally, we discuss how delayed but exaggerated type I IFN responses can exacerbate inflammation and contribute to the severe progression of COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • COVID-19 / genetics
  • COVID-19 / immunology*
  • Gene Expression Regulation
  • Humans
  • Immune Evasion*
  • Immunity, Innate*
  • Inflammation / genetics
  • Inflammation / immunology
  • Interferon Lambda
  • Interferon Type I / genetics
  • Interferon Type I / immunology*
  • Interferons / genetics
  • Interferons / immunology*
  • SARS-CoV-2 / immunology*


  • Interferon Type I
  • Interferons
  • Interferon Lambda