Defective activation and regulation of type I interferon immunity is associated with increasing COVID-19 severity - Institut Pasteur Access content directly
Journal Articles Nature Communications Year : 2022

Defective activation and regulation of type I interferon immunity is associated with increasing COVID-19 severity

Jamie Sugrue
Liam Townsend
Vincent Rouilly
  • Function : Author
Olivier Schwartz
Benjamin Terrier
  • Function : Author

Abstract

Host immunity to infection with SARS-CoV-2 is highly variable, dictating diverse clinical outcomes ranging from asymptomatic to severe disease and death. We previously reported reduced type I interferon in severe COVID-19 patients preceded clinical worsening. Further studies identified genetic mutations in loci of the TLR3- or TLR7-dependent interferon-I pathways, or neutralizing interferon-I autoantibodies as risk factors for development of COVID-19 pneumonia. Here we show in patient cohorts with different severities of COVID-19, that baseline plasma interferon α measures differ according to the immunoassay used, timing of sampling, the interferon α subtype measured, and the presence of autoantibodies. We also show a consistently reduced induction of interferon-I proteins in hospitalized COVID-19 patients upon immune stimulation, that is not associated with detectable neutralizing autoantibodies against interferon α or interferon ω. Intracellular proteomic analysis shows increased monocyte numbers in hospitalized COVID-19 patients but impaired interferon-I response after stimulation. We confirm this by ex vivo whole blood stimulation with interferon-I which induces transcriptomic responses associated with inflammation in hospitalized COVID-19 patients, that is not seen in controls or non-hospitalized moderate cases. These results may explain the dichotomy of the poor clinical response to interferon-I based treatments in late stage COVID-19, despite the importance of interferon-I in early acute infection and may guide alternative therapeutic strategies.
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pasteur-03884236 , version 1 (05-12-2022)

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Nikaïa Smith, Céline Possémé, Vincent Bondet, Jamie Sugrue, Liam Townsend, et al.. Defective activation and regulation of type I interferon immunity is associated with increasing COVID-19 severity. Nature Communications, 2022, 13 (1), pp.7254. ⟨10.1038/s41467-022-34895-1⟩. ⟨pasteur-03884236⟩
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