The interferon landscape along the respiratory tract impacts the severity of COVID-19

Cell. 2021 Sep 16;184(19):4953-4968.e16. doi: 10.1016/j.cell.2021.08.016. Epub 2021 Aug 19.

Abstract

Severe coronavirus disease 2019 (COVID-19) is characterized by overproduction of immune mediators, but the role of interferons (IFNs) of the type I (IFN-I) or type III (IFN-III) families remains debated. We scrutinized the production of IFNs along the respiratory tract of COVID-19 patients and found that high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity. Production of specific IFN-III, but not IFN-I, members denotes patients with a mild pathology and efficiently drives the transcription of genes that protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In contrast, compared to subjects with other infectious or noninfectious lung pathologies, IFNs are overrepresented in the lower airways of patients with severe COVID-19 that exhibit gene pathways associated with increased apoptosis and decreased proliferation. Our data demonstrate a dynamic production of IFNs in SARS-CoV-2-infected patients and show IFNs play opposing roles at distinct anatomical sites.

Keywords: COVID-19; SARS-CoV-2; Type I IFN; Type III IFN; airways; dendritic cell; epithelial cell; interferon; lung; pattern recognition receptor.

Publication types

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

MeSH terms

  • Age Factors
  • Aging / pathology
  • COVID-19 / genetics
  • COVID-19 / immunology
  • COVID-19 / pathology*
  • Epithelial Cells / pathology
  • Epithelial Cells / virology
  • Gene Expression Regulation
  • Humans
  • Interferons / genetics
  • Interferons / metabolism*
  • Leukocytes / pathology
  • Leukocytes / virology
  • Lung / pathology
  • Lung / virology
  • Respiratory Distress Syndrome / pathology
  • Respiratory Distress Syndrome / virology
  • Respiratory System / virology*
  • Severity of Illness Index*
  • Viral Load

Substances

  • Interferons