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Critically Ill Patients With the Middle East Respiratory Syndrome: A Multicenter Retrospective Cohort Study

Arabi, Yaseen M. MD, FCCP, FCCM1,2; Al-Omari, Awad MD3,4; Mandourah, Yasser MD, FRCP(C), FCCP, ABIM5; Al-Hameed, Fahad MD, FRCPC6; Sindi, Anees A. MBChB7; Alraddadi, Basem MD, MSc3,8; Shalhoub, Sarah MD9; Almotairi, Abdullah MBBS, FRCPC10; Al Khatib, Kasim MD, FCCP11; Abdulmomen, Ahmed MD12; Qushmaq, Ismael MD, FRCPC, FACP (IQ)8; Mady, Ahmed MD, FCCP, SFCCM13,14; Solaiman, Othman MD15; Al-Aithan, Abdulsalam M. MD16; Al-Raddadi, Rajaa MD, ABCM17; Ragab, Ahmed MD (AR)18; Al Mekhlafi, Ghaleb. A. MD, SFCCM, EDIC5; Al Harthy, Abdulrahman MD13; Kharaba, Ayman MD, FRCP(C)19; Ahmadi, Mashael Al BSc1; Sadat, Musharaf MBBS1,2; Mutairi, Hanan Al BSDH, MHA1; Qasim, Eman Al BSN, MSN1; Jose, Jesna MSc.Biostat1; Nasim, Maliha MD1; Al-Dawood, Abdulaziz MD, FRCPC, FCCP1,2; Merson, Laura BSc20; Fowler, Robert MD, MS(Epi)21,22; Hayden, Frederick G. MD, FACP23; Balkhy, Hanan H. MD, FAAP1,24

doi: 10.1097/CCM.0000000000002621
Clinical Investigations
Editor's Choice

Objectives: To describe patient characteristics, clinical manifestations, disease course including viral replication patterns, and outcomes of critically ill patients with severe acute respiratory infection from the Middle East respiratory syndrome and to compare these features with patients with severe acute respiratory infection due to other etiologies.

Design: Retrospective cohort study.

Setting: Patients admitted to ICUs in 14 Saudi Arabian hospitals.

Patients: Critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection (n = 330) admitted between September 2012 and October 2015 were compared to consecutive critically ill patients with community-acquired severe acute respiratory infection of non–Middle East respiratory syndrome etiology (non–Middle East respiratory syndrome severe acute respiratory infection) (n = 222).

Interventions: None.

Measurements and Main Results: Although Middle East respiratory syndrome severe acute respiratory infection patients were younger than those with non–Middle East respiratory syndrome severe acute respiratory infection (median [quartile 1, quartile 3] 58 yr [44, 69] vs 70 [52, 78]; p < 0.001), clinical presentations and comorbidities overlapped substantially. Patients with Middle East respiratory syndrome severe acute respiratory infection had more severe hypoxemic respiratory failure (PaO2/FIO2: 106 [66, 160] vs 176 [104, 252]; p < 0.001) and more frequent nonrespiratory organ failure (nonrespiratory Sequential Organ Failure Assessment score: 6 [4, 9] vs 5 [3, 7]; p = 0.002), thus required more frequently invasive mechanical ventilation (85.2% vs 73.0%; p < 0.001), oxygen rescue therapies (extracorporeal membrane oxygenation 5.8% vs 0.9%; p = 0.003), vasopressor support (79.4% vs 55.0%; p < 0.001), and renal replacement therapy (48.8% vs 22.1%; p < 0.001). After adjustment for potential confounding factors, Middle East respiratory syndrome was independently associated with death compared to non–Middle East respiratory syndrome severe acute respiratory infection (adjusted odds ratio, 5.87; 95% CI, 4.02–8.56; p < 0.001).

Conclusions: Substantial overlap exists in the clinical presentation and comorbidities among patients with Middle East respiratory syndrome severe acute respiratory infection from other etiologies; therefore, a high index of suspicion combined with diagnostic testing is essential component of severe acute respiratory infection investigation for at-risk patients. The lack of distinguishing clinical features, the need to rely on real-time reverse transcription polymerase chain reaction from respiratory samples, variability in viral shedding duration, lack of effective therapy, and high mortality represent substantial clinical challenges and help guide ongoing clinical research efforts.

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

2Intensive Care Department, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia.

3College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

4Department of Intensive Care, Dr Sulaiman Al-Habib Group Hospitals, Riyadh, Saudi Arabia.

5Department of Intensive Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.

6Department of Intensive Care, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Jeddah, Saudi Arabia.

7Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

8Department of Medicine, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.

9Division of Infectious Diseases, Department of Medicine, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia.

10Department of Critical Care Medicine, King Fahad Medical City, Riyadh, Saudi Arabia.

11Intensive Care Department, Al-Noor Specialist Hospital, Makkah, Saudi Arabia.

12Department of Critical Care Medicine, King Saud University, Riyadh, Saudi Arabia.

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

14Tanta University Hospitals, Tanta, Egypt.

15King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

16Intensive Care Department, King Abdulaziz Hospital, Al Ahsa, Saudi Arabia.

17Department of Research, Ministry of Health, Jeddah, Saudi Arabia.

18Intensive Care Department, King Fahd Hospital, Jeddah, Saudi Arabia.

19Department of Critical Care, King Fahad Hospital, Ohoud Hospital, Al-Madinah Al-Monawarah, Saudi Arabia.

20International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), Infectious Diseases Data Observatory, Oxford University, Oxford, United Kingdom.

21AMR Infection Control and Publications AIP/PED/HSE/HQ, Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, ON, Canada.

22Department of Critical Care Medicine and Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

23International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA.

24Department of Infection Prevention and Control, King Abdulaziz Medical City National Guard Health Affairs, Riyadh, Saudi Arabia.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

This study was approved by the institutional review boards (IRBs) of all participating centers. Informed consent was waived by the IRBs because of the retrospective nature of the study.

Dr. Arabi disclosed that he was the principal investigator on the a clinical trial for lopinavir/ritonavir and interferon in Middle East respiratory syndrome (MERS) and that he was a nonpaid consultant on antiviral active for MERS-coronavirus (CoV) for Gilead Sciences. Dr. Merson received salary support from Wellcome Trust. Dr. Hayden’s institution received funding from GlaxoSmithKline (Data Safety Monitoring Board [DSMB] member for influenza randomized controlled trial [RCT]) and Celltrion (DSMB member for influenza RCT); he received funding from World Health Organization (consultant on influenza and emerging viral infections) and the University of Alabama (Scientific Advisory Board member for National Institutes of Health-sponsored Antiviral Discovery and Development Consortium [honorarium]); he disclosed that he was a nonpaid consultant on antiviral active for MERS-CoV for Gilead Sciences; and he disclosed off-label product use of investigational antivirals for MERS (ribavirin, lopinavir/ritonavir, interferons) and corticosteroids for MERS. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: Arabi@ngha.med.sa

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