Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

Cell. 2020 May 28;181(5):1036-1045.e9. doi: 10.1016/j.cell.2020.04.026. Epub 2020 May 15.

Abstract

Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.

Keywords: COVID-19; Coronavirus; IL6; SARS-CoV-2; chemokines; ferret; interferon; transcriptomics; virus-host interactions.

Publication types

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

MeSH terms

  • Animals
  • Betacoronavirus / physiology*
  • Cells, Cultured
  • Chemokines / genetics
  • Chemokines / immunology
  • Coronavirus Infections / genetics
  • Coronavirus Infections / immunology*
  • Disease Models, Animal
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate
  • Inflammation / virology
  • Interferons / genetics
  • Interferons / immunology
  • Pandemics
  • Pneumonia, Viral / genetics
  • Pneumonia, Viral / immunology*
  • RNA Viruses / classification
  • RNA Viruses / immunology*
  • Transcription, Genetic

Substances

  • Chemokines
  • Interferons

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2