Comptes Rendus Biologies (Feb 2021)

Insufficient type I IFN immunity underlies life-threatening COVID-19 pneumonia

  • Bastard, Paul,
  • Zhang, Qian,
  • Cobat, Aurélie,
  • Jouanguy, Emmanuelle,
  • Zhang, Shen-Ying,
  • Abel, Laurent,
  • Casanova, Jean-Laurent

DOI
https://doi.org/10.5802/crbiol.36
Journal volume & issue
Vol. 344, no. 1
pp. 19 – 25

Abstract

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We established the COVID Human Genetic Effort (www.covidhge.com) to discover the human genetic and immunological bases of the vast interindividual clinical variability between humans infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that about 3% of patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia were ill because of inborn errors of genes controlling type I interferon (IFN)-dependent immunity (which controls influenza virus), and at least 10% of patients with life-threatening COVID-19 pneumonia had neutralizing auto-Abs against some of the 17 individual type I IFNs. These findings indicate that impaired type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 13% of patients. These discoveries pave the way for further research into unexplained severe cases, and provide a rationale for preventing and treating the disease in individuals at risk, with recombinant type I IFNs.

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