Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

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Bastard P., Gervais A., Taniguchi M., Saare L., Särekannu K., Voyer T. L., ...More

Journal of Experimental Medicine, vol.221, no.2, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 221 Issue: 2
  • Publication Date: 2024
  • Doi Number: 10.1084/jem.20231353
  • Journal Name: Journal of Experimental Medicine
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Veterinary Science Database, Nature Index
  • Keywords: COVID-19, Immunodeficiency, Infectious disease and host defense, Innate immunity and inflammation
  • Open Archive Collection: AVESIS Open Access Collection
  • Ankara Yıldırım Beyazıt University Affiliated: Yes

Abstract

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7–9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2–5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6–35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1–9.6]) of IFN-ω and/or IFN-α2.