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

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.