Type I interferon autoantibodies in hospitalized patients with Middle East respiratory syndrome and association with outcomes and treatment effect of interferon beta-1b in MIRACLE clinical trial

Influenza Other Respir Viruses. 2023 Mar 21;17(3):e13116. doi: 10.1111/irv.13116. eCollection 2023 Mar.

Abstract

Background: Type I interferons (IFNs) are essential antiviral cytokines induced upon respiratory exposure to coronaviruses. Defects in type I IFN signaling can result in severe disease upon exposure to respiratory viral infection and are associated with worse clinical outcomes. Neutralizing autoantibodies (auto-Abs) to type I IFNs were reported as a risk factor for life-threatening COVID-19, but their presence has not been evaluated in patients with severe Middle East respiratory syndrome (MERS).

Methods: We evaluated the prevalence of type I IFN auto-Abs in a cohort of hospitalized patients with MERS who were enrolled in a placebo-controlled clinical trial for treatment with IFN-β1b and lopinavir-ritonavir (MIRACLE trial). Samples were tested for type I IFN auto-Abs using a multiplex particle-based assay.

Results: Among the 62 enrolled patients, 15 (24.2%) were positive for immunoglobulin G auto-Abs for at least one subtype of type I IFNs. Auto-Abs positive patients were not different from auto-Abs negative patients in age, sex, or comorbidities. However, the majority (93.3%) of patients who were auto-Abs positive were critically ill and admitted to the ICU at the time of enrollment compared to 66% in the auto-Abs negative patients. The effect of treatment with IFN-β1b and lopinavir-ritonavir did not significantly differ between the two groups.

Conclusion: This study demonstrates the presence of type I IFN auto-Abs in hospitalized patients with MERS.

Keywords: ICU; MERS; MIRACLE trial; Type I IFNs; auto‐abs.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies
  • COVID-19*
  • Humans
  • Interferon Type I*
  • Interferon beta-1b / therapeutic use
  • Lopinavir / therapeutic use
  • Ritonavir / therapeutic use

Substances

  • Ritonavir
  • Lopinavir
  • Interferon beta-1b
  • Interferon Type I
  • Autoantibodies