Yaseen M. Arabi, MD; Ahmed A. Arifi, MD; Hanan H. Balkhy, MD; Hani Najm, MD; Abdulaziz S. Aldawood, MD; Alaa Ghabashi, MD; Hassan Hawa, MD; Adel Alothman, MB; Abdulaziz Khaldi, MD; Basel Al Raiy, MD
Acknowledgment: The authors thank the members of the Department of Clinical Nursing and the Infection Prevention and Control Program, King Abdulaziz Medical City, Riyadh, Saudi Arabia, for their assistance. They also thank the following persons: From the King Saud bin Abdulaziz University for Health Sciences, Riyadh: Sameera Johani, MD, Division of Microbiology, Pathology & Laboratory Medicine; Abdullah Ghamdi, MD, Department of Cardiac Sciences; Ghassan A. Al-Ghamdi, MD, Intensive Care Department and Assistant Professor, College of Medicine; Saqib I. Dara, MD, Intensive Care Department; Raed A. Hijazi, MD, Emergency Medicine; Olivia A. Trinidad, RRT, Edgardo Tabhan, RRT, and Charina Olay, RRT, all Respiratory Therapist I, Respiratory Services. From the King Abdulaziz Hospital, Al-Ahsa: Yusri Taha, MD, and Mohammed Ayman El Gammal, MD, Infectious Diseases, Department of Medicine and Abdulsalam Al-Aithan, MD, Pulmonary & Intensive Care Medicine. From the Imam Abdulrahman Bin Faisal Hospital, Dammam: Wafa Nasser, MD, Infection Prevention and Control Program.
Potential Conflicts of Interest: None disclosed. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2486.
Reproducible Research Statement: Study protocol, statistical code, and data set: Available from Dr. Arabi (e-mail, firstname.lastname@example.org).
Requests for Single Reprints: Yaseen M. Arabi, MD, Intensive Care Department, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Mail Code 1425, PO Box 22490, Riyadh 11426, Kingdom of Saudi Arabia; e-mail, email@example.com.
Current Author Addresses: Drs. Arabi, Aldawood, and Al Raiy: Intensive Care Department, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Mail Code 1425, PO Box 22490, Riyadh 11426, Kingdom of Saudi Arabia.
Drs. Arifi, Najm, and Khaldi: Department of Cardiac Sciences, King Saud bin Abdulaziz University for Health Sciences, Mail Code 1404, PO Box 22490, Riyadh 11426, Kingdom of Saudi Arabia.
Dr. Balkhy: Infection Prevention & Control Department, King Saud bin Abdulaziz University for Health Sciences, Mail Code 2034, PO Box 22490, Riyadh 11426, Kingdom of Saudi Arabia.
Drs. Ghabashi and Hawa: Pulmonary & Intensive Care Medicine, King Abdulaziz Hospital, Mail Code 312, PO Box 2477, Al-Ahsa 31982, Kingdom of Saudi Arabia.
Dr. Alothman: Infectious Diseases, Department of Medicine, King Saud bin Abdulaziz University for Health Sciences, Mail Code 1443, PO Box 22490, Riyadh 11426, Kingdom of Saudi Arabia.
Author Contributions: Conception and design: Y.M. Arabi, A.A. Arifi, H.H. Balkhy, H. Najm, A.S. Aldawood, A. Khaldi.
Analysis and interpretation of the data: Y.M. Arabi, A.A. Arifi, H.H. Balkhy, H. Najm, A.S. Aldawood, A. Alothman.
Drafting of the article: Y.M. Arabi, A.A. Arifi, H.H. Balkhy, A. Ghabashi, H. Hawa, B. Al Raiy.
Critical revision for important intellectual content: Y.M. Arabi, A.A. Arifi, H.H. Balkhy, H. Najm, H. Hawa, A. Alothman, B. Al Raiy.
Final approval of the article: Y.M. Arabi, A.A. Arifi, H.H. Balkhy, A.S. Aldawood, A. Ghabashi, A. Alothman, A. Khaldi.
Provision of study materials or patients: Y.M. Arabi, A.A. Arifi, H.H. Balkhy, H. Najm, A.S. Aldawood, A. Ghabashi, H. Hawa, A. Khaldi.
Statistical expertise: Y.M. Arabi.
Administrative, technical, or logistic support: Y.M. Arabi, A.S. Aldawood, B. Al Raiy.
Collection and assembly of data: Y.M. Arabi, A.A. Arifi, H.H. Balkhy, A.S. Aldawood, A. Ghabashi, H. Hawa, A. Khaldi, B. Al Raiy.
Since September 2012, 170 confirmed infections with Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization, including 72 deaths. Data on critically ill patients with MERS-CoV infection are limited.
To describe the critical illness associated with MERS-CoV.
3 intensive care units (ICUs) at 2 tertiary care hospitals in Saudi Arabia.
12 patients with confirmed or probable MERS-CoV infection.
Presenting symptoms, comorbid conditions, pulmonary and extrapulmonary manifestations, measures of severity of illness and organ failure, ICU course, and outcome are described, as are the results of surveillance of health care workers (HCWs) and patients with potential exposure.
Between December 2012 and August 2013, 114 patients were tested for suspected MERS-CoV; of these, 11 ICU patients (10%) met the definition of confirmed or probable cases. Three of these patients were part of a health care–associated cluster that also included 3 HCWs. One HCW became critically ill and was the 12th patient in this case series. Median Acute Physiology and Chronic Health Evaluation II score was 28 (range, 16 to 36). All 12 patients had underlying comorbid conditions and presented with acute severe hypoxemic respiratory failure. Most patients (92%) had extrapulmonary manifestations, including shock, acute kidney injury, and thrombocytopenia. Five (42%) were alive at day 90. Of the 520 exposed HCWs, only 4 (1%) were positive.
The sample size was small.
MERS-CoV causes severe acute hypoxemic respiratory failure and considerable extrapulmonary organ dysfunction and is associated with high mortality. Community-acquired and health care–associated MERS-CoV infection occurs in patients with chronic comorbid conditions. The health care–associated cluster suggests that human-to-human transmission does occur with unprotected exposure.
Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen with a clinical spectrum that is not yet fully delineated.
Twelve hospitalized patients found to have MERS-CoV infection all required intensive care, including mechanical ventilation. Underlying comorbid disease was present in all patients. Extrapulmonary involvement was common. Various treatments were tried. Mortality was high. Three cases were nosocomially acquired, and 1 health care worker was among the case patients.
A small case series may not be representative of all patients presenting to hospitals with MERS-CoV infection.
Additional information on optimal management of MERS-CoV infection is urgently needed.
Map of the Kingdom of Saudi Arabia showing the 2 study hospitals, the number of suspected and confirmed MERS-CoV infections in patients, and the number of HCWs screened and cases confirmed in HCWs.
ICU 1 is located in Al-Ahsa and ICU 2 and ICU 3 in Riyadh. HCW = health care worker; ICU = intensive care unit; KAH = King Abdulaziz Hospital; KAMC = King Abdulaziz Medical City; MERS-CoV = Middle East respiratory syndrome coronavirus; UAE = United Arab Emirates.
Study flow diagram.
HCW = health care worker; ICU = intensive care unit; MERS-CoV = Middle East respiratory syndrome coronavirus.
* Cases described in this report.
Table 1. Characteristics of Patients With Confirmed or Probable Middle East Respiratory Syndrome Coronavirus Infection
Appendix Table 1. Individual-Patient Characteristics and Primary Therapies During the Intensive Care Unit Stay
Appendix Table 2. Physiologic and Laboratory Variables on Day 1 and During the ICU Stay
Appendix Table 3. SOFA Score, by Study Day
Timeline of the clinical course of the study patients.
The beginning of the solid lines refers to the onset of MERS-CoV symptoms. The different line colors indicate the 3 different intensive care units (ICU 1 in Al-Ahsa and ICU 2 and ICU 3 in Riyadh). The dashed line indicates the time in the hospital before the onset of MERS-CoV symptoms in patients with health care–associated infection. Patient G was still in the hospital as of 9 January 2014. ICU = intensive care unit; MERS-CoV = Middle East respiratory syndrome coronavirus.
Chest radiographs from the 12 patients with Middle East respiratory syndrome coronavirus infection on the day of intubation, demonstrating airspace disease that ranged from lobular to bilateral lung involvement.
Computed tomography images from 3 patients, showing bilateral airspace disease.
Table 2. Physiologic and Laboratory Variables of Patients on Days 1, 3, 7, and 14
Results of sequential real-time polymerase chain reaction.
The red circles indicate a positive result for MERS-CoV; green circles indicate negative results. The open circle indicates that patient H did not undergo testing because he was a probable MERS-CoV case patient. ICU = intensive care unit; MERS-CoV = Middle East respiratory syndrome coronavirus.
Table 3. Main Interventions and Outcomes
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Carlos Polanco, PhD, Jorge Alberto Castanon-Gonzales, MD, Jose Lino Samaniego, PhD
Universidad Anahuac, Mexico
February 11, 2014
We read with great interest Arabi and colleagues’ article (1) where they describe
the clinical course and outcome of 12 critically ill patients infected with the
recently isolated (2) “Middle East Respiratory Syndrome Coronavirus” (MERS-
CoV). They pointed out that the presenting symptoms were those of lower
respiratory tract infection with a rapid progression to severe respiratory failure
with extrapulmonary organ dysfunction which required invasive mechanical
ventilation and intensive care. The median interval from onset of symptoms to
intubation was 4.5 days. Seven patients died.
Although most confirmed cases of MERS-CoV infection have been sporadic with
a yet unknown source of infection, human-to-human transmission has been
reported in health care and household settings (3,4). In spite of these facts, a
recent estimation of MERS-CoV pandemic risk by the basic reproduction number
(R0), suggest a low pandemic potential (5).
Research in molecular methods to trace emerging severe acute respiratory
infections via molecular genome analysis as well as automated computational
models that detect new cases and track in real time the viral evolution and speed
of propagation of this infections are of paramount importance. At this time, in
absence of observable data, our group developed a Cumulative sum (CUSUM)
based overcrowd severe respiratory disease index model (6) that reports alerts
only after it detects a statistically significant number of patients as cumulative
sums (CUSUM) or “clusters” disseminated in the hospital network geographical
areas. The model was thoroughly verified in a virtual scenario, generating
multiple epidemic outbreaks in a six-year span for a 13-hospital network. When it
was superimposed over the AH1N1 Influenza outbreak census (2008-2010)
taken by the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
in México City, it showed that it is an effective algorithm to notify early warnings
of severe respiratory disease epidemic outbreaks with a minimum rate of false
alarms. Only after we gather more robust epidemiological data, hybrid models
with a predictive component like hidden Markov models (HMM) will be developed
as a CUSUM-HMM type.
Carlos Polanco, PhD,
Jorge Alberto Castañón-González MD,
José Lino Samaniego PhD
Faculty of Health Sciences,
Huixquilucan estado de México,
1.-Arabi YM, Arifi AA, Balkhy HH, Najm H, Aldawod A, Ghabashi A, Hawa H,
Alothman A, Khaldi A, Al Raly B. Clinical Couse and Outcome of Critically ill
Patients with Middle East Respiratory Syndrome Coronavirus Infection. Ann
Intern Med 2014; To be published.
2.-Zaki AM, Van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA.
Isolation of a novel coronavirus from a man with pneumonia in South Arabia. N
Engl J Med 2012;367:1814-20.
3.-Assiri A, McGeer A, Perl TM, et al. Hospital Outbreak of Middle East
respiratory syndrome coronavirus. N Engl J Med 2013;369:407-16.
4.-Memish ZA, Zumla AI, Al-Hakeem RF, AL-Rabeeah AA, Stephens GM.
Family clusters of Middle East respiratory syndrome coronavirus infections. N
Engl J Med 2013;368:2487-94.
5.-Breban R, Riou J, Fontanet A. Interhuman transmissibility of Middle East
respiratory síndrome coronavirus: estimation of pandemic risk. Lancet
6.-Polanco C, Castañón-González JA, Macías AE, Samaniego JL, Bushe T,
Villanueva-Martínez S. Detection of Severe Respiratory Disease Epidemic
Outbreaks by CUSUM-Based Overcrowd-Severe-Respiratory-Disease-Index
Model. Computational and Mathematical Methods in Medicine 2013;article ID
Arabi YM, Arifi AA, Balkhy HH, Najm H, Aldawood AS, Ghabashi A, et al. Clinical Course and Outcomes of Critically Ill Patients With Middle East Respiratory Syndrome Coronavirus Infection. Ann Intern Med. 2014;160:389-397. doi: 10.7326/M13-2486
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Published: Ann Intern Med. 2014;160(6):389-397.
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