Ribavirin and Interferon Therapy for Critically Ill Patients with the Middle East Respiratory Syndrome: A multicenter observational study

Clinical Infectious Diseases
25 Jun 2019
Yaseen Arabi, Sarah Shalhoub, Yasser Mandourah, Fahad Al-Hameed, Awad Al-Omari, Eman Al Qasim, Jesna Jose, Biostat Basem Alraddadi, Abdullah Almotairi, Kasim Al Khatib, Ahmed Abdulmomen, Ismael Qushmaq, Anees A Sindi, Ahmed Mady, Othman Solaiman,
Rajaa Al-Raddadi, Khalid Maghrabi, Ahmed Ragab, Ghaleb A Al Mekhlafi, Hanan H Balkhy, Abdulrahman Al Harthy, Ayman Kharaba, Jawaher A Gramish, Abdulsalam M Al-Aithan, Abdulaziz Al-Dawood, Laura Merson, Frederick G Hayden, Robert Fowler,



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 the Middle East Respiratory Syndrome (MERS) accounting for time-varying confounders.


This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between 09/2012 and 01/2018. 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.


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 2 days (quartile 1, 3: 1, 3 days) from ICU admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN [106/144 (73.6%) compared to 126/205 (61.5%), p 0.02]. 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% CI 0.73, 1.44, p 0.87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio 0.65, 95% CI 0.30, 1.44, p 0.29).


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.


Acute respiratory distress syndrome (ARDS), coronavirus, Middle East Respiratory Syndrome (MERS), pneumonia, Ribavirininterferon


Drug clearance, critical illness, interferons, ribavirin, mortality, rna, human leukocyte interferon, Middle East Respiratory Syndrome coronavirus, Middle East Respiratory Syndrome