Pre-existing Autoantibodies Neutralizing High Concentrations of Type I Interferons in Almost 10% of COVID-19 Patients Admitted to Intensive Care in Barcelona

J Clin Immunol. 2021 Nov;41(8):1733-1744. doi: 10.1007/s10875-021-01136-x. Epub 2021 Sep 27.

Abstract

Background: It is important to predict which patients infected by SARS-CoV-2 are at higher risk of life-threatening COVID-19. Several studies suggest that neutralizing auto-antibodies (auto-Abs) against type I interferons (IFNs) are predictive of critical COVID-19 pneumonia.

Objectives: We aimed to test for auto-Abs to type I IFN and describe the main characteristics of COVID-19 patients admitted to intensive care depending on whether or not these auto-Abs are present.

Methods: Retrospective analysis of all COVID-19 patients admitted to an intensive care unit (ICU) in whom samples were available, from March 2020 to March 2021, in Barcelona, Spain.

Results: A total of 275 (70.5%) out of 390 patients admitted to ICU were tested for type I IFNs auto-antibodies (α2 and/or ω) by ELISA, being positive in 49 (17.8%) of them. Blocking activity of plasma diluted 1/10 for high concentrations (10 ng/mL) of IFNs was proven in 26 (9.5%) patients. Almost all the patients with neutralizing auto-Abs were men (92.3%). ICU patients with positive results for neutralizing IFNs auto-Abs did not show relevant differences in demographic, comorbidities, clinical features, and mortality, when compared with those with negative results. Nevertheless, some laboratory tests (leukocytosis, neutrophilia, thrombocytosis) related with COVID-19 severity, as well as acute kidney injury (17 [65.4%] vs. 100 [40.2%]; p = 0.013) were significantly higher in patients with auto-Abs.

Conclusion: Auto-Abs neutralizing high concentrations of type I IFNs were found in 9.5% of patients admitted to the ICU for COVID-19 pneumonia in a hospital in Barcelona. These auto-Abs should be tested early upon diagnosis of SARS-CoV-2 infection, as they account for a significant proportion of life-threatening cases.

Keywords: COVID-19; SARS-CoV-2; acute kidney injury; auto-antibodies; type I interferons.

Publication types

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

MeSH terms

  • Aged
  • Antibodies, Neutralizing / blood*
  • Autoantibodies / blood*
  • COVID-19 / immunology*
  • Female
  • Humans
  • Intensive Care Units
  • Interferon Type I / immunology*
  • Male
  • Middle Aged
  • Retrospective Studies
  • SARS-CoV-2*

Substances

  • Antibodies, Neutralizing
  • Autoantibodies
  • Interferon Type I