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

• Type of Material: Article
• Authors: Faizah Alotaibi, King Saud bin Abdulaziz University for Health Sciences; Naif K Alharbi, King Saud bin Abdulaziz University for Health Sciences; Lindsey B Rosen, National Institute of Allergy and Infectious Diseases (NIAID); Ayed Y Asiri, Prince Mohammed Bin Abdulaziz Hospital; Abdullah M Assiri, Ministry of Health Saudi Arabia; Hanan H Balkhy, Organisation Mondiale de la Santé; Majed Al Jeraisy, King Saud bin Abdulaziz University for Health Sciences; Yasser Mandourah, Prince Sultan Military Medical City; Sameera AlJohani, King Saud bin Abdulaziz University for Health Sciences; Shmelyan Al Harbi, King Saud bin Abdulaziz University for Health Sciences; Hani Aziz A Jokhdar, Ministry of Health Saudi Arabia; Ahmad M Deeb, King Saud bin Abdulaziz University for Health Sciences; Ziad Memish, Emory University; Jesna Jose, King Saud bin Abdulaziz University for Health Sciences; Sameeh Ghazal, Prince Mohammed Bin Abdulaziz Hospital; Sarah Al Faraj, Prince Sultan Military Medical City; Ghaleb A Al Mekhlafi, Prince Sultan Military Medical City; Nisreen Murad Sherbeeni, Prince Sultan Military Medical City; Fatehi Elnour Elzein, Prince Sultan Military Medical City; Badriah M AlMutairi, King Saud bin Abdulaziz University for Health Sciences; Abdulaziz Al-Dawood, King Saud bin Abdulaziz University for Health Sciences; Mashan L Abdullah, King Saud bin Abdulaziz University for Health Sciences; Tlili Barhoumi, King Saud bin Abdulaziz University for Health Sciences; Mohammed W Alenazi, King Saud bin Abdulaziz University for Health Sciences; Abdurahman Almasood, King Saud bin Abdulaziz University for Health Sciences; Steven M Holland, National Institute of Allergy and Infectious Diseases (NIAID); Yaseen M Arabi, King Saud bin Abdulaziz University for Health Sciences
• Language: English
• Date: 2023-03-01
• Publisher: John Wiley & Sons Ltd.
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/irv.13116
• Title of Journal or Parent Work: Influenza and other Respiratory Viruses
• Volume: 17
• Issue: 3
• Start Page: e13116
• End Page: e13116
• Keywords: COVID-19; Lopinavir; Humans; auto‐abs; MIRACLE trial; Autoantibodies; Interferon beta-1b; MERS; ICU; Ritonavir; Interferon Type I; Type I IFNs
• Research Categories: Health Sciences, Public Health; Health Sciences, Medicine and Surgery

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.