Innate immune and inflammatory responses to SARS-CoV-2: Implications for COVID-19

Cell Host Microbe. 2021 Jul 14;29(7):1052-1062. doi: 10.1016/j.chom.2021.05.004. Epub 2021 May 17.


COVID-19 can result in severe disease characterized by significant immunopathology that is spurred by an exuberant, yet dysregulated, innate immune response with a poor adaptive response. A limited and delayed interferon I (IFN-I) and IFN-III response results in exacerbated proinflammatory cytokine production and in extensive cellular infiltrates in the respiratory tract, resulting in lung pathology. The development of effective therapeutics for patients with severe COVID-19 depends on our understanding of the pathological elements of this unbalanced innate immune response. Here, we review the mechanisms by which SARS-CoV-2 both activates and antagonizes the IFN and inflammatory response following infection, how a dysregulated cytokine and cellular response contributes to immune-mediated pathology in COVID-19, and therapeutic strategies that target elements of the innate response.

Keywords: SARS-CoV-2; coronavirus; cytokines; immune antagonism; immune evasion; inflammatory; innate immunity; interferon.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • COVID-19 / immunology*
  • COVID-19 Drug Treatment
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Immune Evasion
  • Immunity, Innate / immunology*
  • Interferon Lambda
  • Interferon Type I / metabolism
  • Interferons / metabolism
  • Interferons / therapeutic use*
  • Kinetics
  • SARS-CoV-2 / immunology*


  • Anti-Inflammatory Agents
  • Cytokines
  • Interferon Type I
  • Interferons
  • Interferon Lambda