Journal Article

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

Alharbi, Naif Khalaf, AlJohani, Sameera, Assiri, Abdullah M., Holland, Steven M., Rosen, Lindsey B., Balkhy, Hanan H., Jokhdar, Hani A. Aziz, Mandourah, Yasser, Jose, Jesna, Abdullah, Mashan L., Alenazi, Mohammed W., Sherbeeni, Nisreen Murad, Alotaibi, Faizah, Al Faraj, Sarah, AlMutairi, Badriah M., Al‐Dawood, Abdulaziz, Ghazal, Sameeh, Asiri, Ayed Y., Al Mekhlafi, Ghaleb A., Deeb, Ahmad M., Elzein, Fatehi Elnour, Barhoumi, Tlili, Almasood, Abdulrahman, Al Harbi, Shmeylan, Al Jeraisy, Majed, Memish, Ziad A., Arabi, Yaseen M.

2023

Overview

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.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Antiretroviral drugs / Antiviral drugs / Autoantibodies / auto‐abs / Clinical trials / Comorbidity / Coronaviruses / COVID-19 / Health services / Humans / ICU / IgG antibody / Immunoglobulin G / Interferon / Interferon beta-1b - therapeutic use / Interferon Type I / Lopinavir / Lopinavir - therapeutic use / MERS / Middle East respiratory syndrome / MIRACLE trial / Mortality / Original / Patients / Respiratory diseases / Risk factors / Ritonavir / Ritonavir - therapeutic use / Type I IFNs / Viruses