Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study

• Published in: Clinical infectious diseases Vol. 70; no. 9; pp. 1837 - 1844
• Main Authors: Arabi, Yaseen M, Shalhoub, Sarah, Mandourah, Yasser, Al-Hameed, Fahad, Al-Omari, Awad, Al Qasim, Eman, Jose, Jesna, Alraddadi, Basem, Almotairi, Abdullah, Al Khatib, Kasim, Abdulmomen, Ahmed, Qushmaq, Ismael, Sindi, Anees A, Mady, Ahmed, Solaiman, Othman, Al-Raddadi, Rajaa, Maghrabi, Khalid, Ragab, Ahmed, Al Mekhlafi, Ghaleb A, Balkhy, Hanan H, Al Harthy, Abdulrahman, Kharaba, Ayman, Gramish, Jawaher A, Al-Aithan, Abdulsalam M, Al-Dawood, Abdulaziz, Merson, Laura, Hayden, Frederick G, Fowler, Robert
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 15-04-2020
• Subjects: Aged; and Commentaries; Antiviral Agents - therapeutic use; Coronavirus Infections - mortality; Coronavirus Infections - therapy; Critical Illness; Female; Humans; Intensive Care Units; Interferon alpha-2 - therapeutic use; Male; Middle Aged; Middle East Respiratory Syndrome Coronavirus; Pneumonia, Viral - drug therapy; Retrospective Studies; Ribavirin - therapeutic use; RNA, Viral - blood; Saudi Arabia; Treatment Outcome; Saudi Arabia; coronavirus; ribavirin; pneumonia; interferon; Middle East respiratory syndrome
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciz544

Abstract
Background
The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders.
Methods
This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders.
Results
Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; P = .29).
Conclusions
In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.
In this observational study accounting for baseline and time-varying confounders, ribavirin and recombinant interferon (rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.