Mild COVID-19 despite autoantibodies against type I IFNs in autoimmune polyendocrine syndrome type 1

J Clin Invest. 2021 Jul 15;131(14):e150867. doi: 10.1172/JCI150867.


Autoantibodies against IFN-α and IFN-ω (type I IFNs) were recently reported as causative for severe COVID-19 in the general population. Autoantibodies against IFN-α and IFN-ω are present in almost all patients with autoimmune polyendocrine syndrome type 1 (APS-1) caused by biallelic deleterious or heterozygous dominant mutations in AIRE. We therefore hypothesized that autoantibodies against type I IFNs also predispose patients with APS-1 to severe COVID-19. We prospectively studied 6 patients with APS-1 between April 1, 2020 and April 1, 2021. Biobanked pre-COVID-19 sera of APS-1 subjects were tested for neutralizing autoantibodies against IFN-α and IFN-ω. The ability of the patients' sera to block recombinant human IFN-α and IFN-ω was assessed by assays quantifying phosphorylation of signal transducer and activator of transcription 1 (STAT1) as well as infection-based IFN-neutralization assays. We describe 4 patients with APS-1 and preexisting high titers of neutralizing autoantibodies against IFN-α and IFN-ω who contracted SARS-CoV-2, yet developed only mild symptoms of COVID-19. None of the patients developed dyspnea, oxygen requirement, or high temperature. All infected patients with APS-1 were females and younger than 26 years of age. Clinical penetrance of neutralizing autoantibodies against type I IFNs for severe COVID-19 is not complete.

Keywords: COVID-19; Immunology; Innate immunity.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIRE Protein
  • Adolescent
  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • COVID-19 / complications*
  • COVID-19 / immunology*
  • Female
  • Humans
  • In Vitro Techniques
  • Interferon Type I / antagonists & inhibitors*
  • Interferon Type I / immunology*
  • Interferon-alpha / antagonists & inhibitors
  • Interferon-alpha / immunology
  • Male
  • Polyendocrinopathies, Autoimmune / complications*
  • Polyendocrinopathies, Autoimmune / genetics
  • Polyendocrinopathies, Autoimmune / immunology*
  • SARS-CoV-2* / immunology
  • SARS-CoV-2* / physiology
  • Severity of Illness Index
  • Transcription Factors / genetics
  • Virus Replication / immunology
  • Young Adult


  • Antibodies, Neutralizing
  • Autoantibodies
  • Interferon Type I
  • Interferon-alpha
  • Transcription Factors
  • interferon omega 1

Grants and funding

to MAM