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

Clinical Infectious Diseases

Published

25 Jun 2019

Authors

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,

DOI

https://doi.org/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 the 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 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.

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 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).

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.

Keywords

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

Topic:

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

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