Yaseen M Arabi1, Awad Al-Omari, Yasser Mandourah, Fahad Al-Hameed, Anees A Sindi, Basem Alraddadi, Sarah Shalhoub, Abdullah Almotairi, Kasim Al Khatib, Ahmed Abdulmomen, Ismael Qushmaq, Ahmed Mady, Othman Solaiman, Abdulsalam M Al-Aithan, Rajaa Al-Raddadi, Ahmed Ragab, Ghaleb A Al Mekhlafi, Abdulrahman Al Harthy, Ayman Kharaba, Mashael Al Ahmadi, Musharaf Sadat, Hanan Al Mutairi, Eman Al Qasim, Jesna Jose, Maliha Nasim, Abdulaziz Al-Dawood, Laura Merson, Robert Fowler, Frederick G Hayden, Hanan H Balkhy. 1. 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.
Abstract
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.
OBJECTIVES: To describe patient characteristics, clinical manifestations, disease course including viral replication patterns, and outcomes of critically illpatients 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 illpatients 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 illpatients 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 infectionpatients 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.
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