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

• DOI: 10.1111/irv.13116
• Publication Date: 2023-03-21T09:22:33Z
• Authors: Faizah Alotaibi; Naif Khalaf Alharbi; Lindsey B. Rosen; Ayed Y. Asiri; Abdullah M. Assiri; Hanan H. Balkhy; Majed Al Jeraisy; Yasser Mandourah; Sameera AlJohani; Shmeylan Al Harbi; Hani A. Aziz Jokhdar; Ahmad M. Deeb; Ziad A. Memish; Jesna Jose; Sameeh Ghazal; Sarah Al Faraj; Ghaleb A. Al Mekh...; Nisreen Murad She...; Fatehi Elnour Elzein; Badriah M. AlMutairi; Abdulaziz Al‐Dawood; Mashan L. Abdullah; Tlili Barhoumi; Mohammed W. Alenazi; Abdulrahman Almasood; Steven M. Holland; Yaseen M. Arabi
• Keywords: Ritonavir; Interferon Type I; Humans; COVID-19; Original Articles; Lopinavir; Interferon beta-1b; Autoantibodies

AbstractBackgroundType 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).MethodsWe 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.ResultsAmong 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.ConclusionThis study demonstrates the presence of type I IFN auto‐Abs in hospitalized patients with MERS.