Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Science. 2020 Oct 23;370(6515):eabd4585. doi: 10.1126/science.abd4585. Epub 2020 Sep 24.

Abstract

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / blood
  • Asymptomatic Infections
  • Autoantibodies / blood*
  • Betacoronavirus
  • COVID-19
  • Case-Control Studies
  • Coronavirus Infections / immunology*
  • Critical Illness
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Interferon Type I / immunology*
  • Interferon alpha-2 / immunology*
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / immunology*
  • SARS-CoV-2

Substances

  • Antibodies, Neutralizing
  • Autoantibodies
  • Immunoglobulin G
  • Interferon Type I
  • Interferon alpha-2
  • interferon omega 1