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

Author:

Arabi Yaseen M1,Shalhoub Sarah23,Mandourah Yasser4,Al-Hameed Fahad5,Al-Omari Awad6,Al Qasim Eman1,Jose Jesna1,Alraddadi Basem78,Almotairi Abdullah9,Al Khatib Kasim10,Abdulmomen Ahmed11,Qushmaq Ismael7,Sindi Anees A12,Mady Ahmed1314,Solaiman Othman15,Al-Raddadi Rajaa16,Maghrabi Khalid15,Ragab Ahmed17,Al Mekhlafi Ghaleb A18,Balkhy Hanan H19,Al Harthy Abdulrahman13,Kharaba Ayman20,Gramish Jawaher A21,Al-Aithan Abdulsalam M22,Al-Dawood Abdulaziz1,Merson Laura23,Hayden Frederick G2324,Fowler Robert25

Affiliation:

1. Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia

2. Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada

3. King Fahad Armed Forces Hospital, Jeddah

4. Military Medical Services, Ministry of Defense, Prince Sultan Military Medical City, Riyadh

5. Department of Intensive Care, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Jeddah

6. Department of Intensive Care, College of Medicine, Alfaisal University, Dr Sulaiman Al-Habib Group Hospitals, Riyadh

7. Department of Medicine, King Faisal Specialist Hospital and Research Center, Jeddah

8. Department of Medicine, University of Jeddah

9. Department of Critical Care Medicine, King Fahad Medical City, Riyadh

10. Intensive Care Department, Al-Noor Specialist Hospital, Makkah

11. Department of Critical Care Medicine, King Saud University, Riyadh

12. Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University, Jeddah

13. Intensive Care Department, King Saud Medical City, Riyadh, Saudi Arabia

14. Tanta University Hospitals, Egypt

15. Intensive Care Department, King Faisal Specialist Hospital and Research Center, Riyadh

16. Department of Community Medicine, Faculty of Medicine, King Abdulaziz University

17. Intensive Care Department, King Fahd Hospital, Jeddah

18. Department of Intensive Care Services, Prince Sultan Military Medical City

19. Department of Infection Prevention and Control, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh

20. Department of Critical Care, King Fahad Hospital, Ohoud Hospital, Al-Madinah

21. Pharmaceutical Care Department, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh

22. Department of Medicine, Critical Care Division, King Abdulaziz Hospital, Al Ahsa, Saudi Arabia

23. International Severe Acute Respiratory and Emerging Infection Consortium, Infectious Diseases Data Observatory, Oxford University, United Kingdom

24. Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville

25. Institute of Health Policy Management and Evaluation, University of Toronto, Department of Critical Care Medicine and Department of Medicine, Sunnybrook Hospital, Ontario, Canada

Abstract

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.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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