Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

Science. 2020 Aug 7;369(6504):718-724. doi: 10.1126/science.abc6027. Epub 2020 Jul 13.

Abstract

Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression that suggest diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A distinct phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-β and low IFN-α production and activity), which was associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor nuclear factor-κB and characterized by increased tumor necrosis factor-α and interleukin-6 production and signaling. These data suggest that type I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Betacoronavirus / immunology*
  • Betacoronavirus / physiology
  • COVID-19
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / virology
  • Critical Illness
  • Cross-Sectional Studies
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunity, Innate
  • Inflammation
  • Interferon alpha-2 / metabolism*
  • Interferon-alpha / metabolism*
  • Interferon-beta / metabolism*
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • NF-kappa B / metabolism
  • Pandemics
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Viral Load

Substances

  • IFNA1 protein, human
  • IL6 protein, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukin-6
  • NF-kappa B
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Interferon-beta