Clinical Course and Outcomes of Critically Ill Patients With Middle East Respiratory Syndrome Coronavirus Infection

Context Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen with a clinical spectrum that is not yet fully delineated. Contribution 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. Caution A small case series may not be representative of all patients presenting to hospitals with MERS-CoV infection. Implication Additional information on optimal management of MERS-CoV infection is urgently needed. The Editors In September 2012, a new coronavirus was isolated for the first time from a patient in Saudi Arabia, who presented with acute pneumonia and renal failure (1). The virus was identified as a human -coronavirus and was subsequently named Middle East respiratory syndrome coronavirus (MERS-CoV) (2). Since then, 170 laboratory-confirmed cases of infection with MERS-CoV have been reported to the World Health Organization, including 72 deaths (3). The disease has a high fatality rate and has several clinical features that resemble the infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV) (4). As such, there has been concern that the virus has the potential to cause a pandemic. World knowledge about this virus is accumulating, but data on critically ill patients infected with MERS-CoV are limited. We describe the clinical course and outcomes of 12 critically ill patients with MERS-CoV admitted to 3 intensive care units (ICUs) in 2 tertiary hospitals in Saudi Arabia. Methods The study was approved by the Institutional Review Board of the National Guard Health Affairs, Riyadh, Saudi Arabia, and consent was not required. Setting The Saudi Arabian National Guard Health Affairs serves close to 1 million individuals of the Saudi Arabian National Guard soldiers and their dependents through a primary, secondary, and tertiary health care system that includes 4 tertiary care hospitals and more than 90 primary health care clinics. We report on critically ill patients with MERS-CoV infection from 1 ICU (a medicalsurgical ICU referred to as ICU 1) at King Abdulaziz Hospital, Al-Ahsa, and from 2 ICUs (a medicalsurgical ICU and a cardiac ICU, referred to as ICU 2 and ICU 3, respectively) at King Abdulaziz Medical City, Riyadh. Although ICU 2 and ICU 3 are located in the same hospital, they are in geographically separate locations and have limited staff crossover. Both hospitals have board-certified intensivists who treat patients in closed medicalsurgical ICUs and provide consultations to patients in the cardiac ICU as required. The hospitals are accredited by the Joint Commission International and have Infection Prevention and Control programs that work collaboratively with the ICU staff. Hand-hygiene compliance in the ICUs for 2012 was 85% to 98%, and the influenza vaccination rate among health care workers (HCWs) was 83%. Since the first case of MERS-CoV was identified in Saudi Arabia in September 2012, the National Guard hospitals along with all other health care facilities in Saudi Arabia implemented the guidelines for testing of suspected cases and screening (surveillance of potential exposures) for MERS-CoV according to Ministry of Health directives. The multidisciplinary outbreak committee was reactivated to manage the current MERS-CoV outbreak. The infection control precautions for suspected MERS-CoV included placement of patients in a single-bed negative-pressure room and the use of personal protective equipment (N-95 mask, gown, and gloves) by HCWs. This study includes all cases encountered from December 2012, the date of the first suspected case, until August 2013. The first confirmed case of MERS-CoV was in May 2013 in Al-Ahsa and in June 2013 in Riyadh. The time frame overlaps with that of a previously reported case series, and the authors cannot entirely exclude the possibility that 1 or 2 of the patients in the current report have been included in the previous case series. Patients Infection with MERS-CoV was suspected in patients presenting with acute respiratory illness and chest radiographs suggestive of pneumonia and the acute respiratory distress syndrome (ARDS), especially if the patient required ICU admission. Suspected cases were tested for MERS-CoV with real-time polymerase chain reaction (RT-PCR), using the recommended sampling technique (nasopharyngeal swab and tracheal aspirates or bronchoalveolar lavage in intubated patients). In suspected cases with negative RT-PCR results, the test was repeated at the discretion of the treating physician. The HCWs and ICU patients who were potentially exposed to MERS-CoV were systematically screened. Samples were tested at the regional reference laboratory of the Saudi Arabian Ministry of Health and the hospital laboratory at King Abdulaziz Medical City, Riyadh, as described elsewhere (5). The RT-PCR amplification targeted both the upstream E protein (upE gene) and ORF1a for confirmation. Definitions We included all patients admitted to ICUs with confirmed or probable MERS-CoV infection as defined by the World Health Organization (6). A confirmed case was defined as a suspected case with a positive result for MERS-CoV on RT-PCR. A probable case was defined as a suspected case if the RT-PCR result for MERS-CoV was unavailable, negative, or inconclusive in a patient with an epidemiologic link to a patient with confirmed MERS-CoV (6). Data on demographic characteristics, contact history with a MERS-CoV confirmed case patient, underlying comorbid conditions, presenting symptoms, and radiographic findings were collected from the medical records. On the day of intubation, we assessed severity of illness by using Acute Physiology and Chronic Health Evaluation II scores and Sequential Organ Failure Assessment (SOFA) scores (7). On days 1, 3, 7, and 14 of intubation, we documented laboratory and ventilator variables and arterial blood gases. Leukopenia was defined as leukocyte count less than 4.0109 cells/L, lymphopenia as a lymphocyte count less than 1.5109 cells/L, and thrombocytopenia as a platelet count less than 140109 cells/L. Aspartate aminotransferase and alanine aminotransferase levels were considered elevated if they were more than twice the upper reference limit (34 U/L and 55 U/L, respectively). We recorded the time course of the patient's illness, microbiological test results, and treatments received. We also recorded the following outcomes: duration of mechanical ventilation, ICU length of stay, and survival to ICU discharge, at day 28 and at day 90. Role of the Funding Source This study did not receive external funding. Results During the 9-month study period in the 2 hospitals, 114 patients were suspected of having and were tested for MERS-CoV infection (Figures 1 and 2). Of these, 10 ICU patients (9%) met the definition of confirmed cases, and 1 (1%) was a probable case. Among these cases, 8 were community-acquired, and 3 occurred in patients in ICU 3 (the cardiac ICU) who were part of a health careassociated cluster that included HCWs. In the latter patients, the initial hospitalization was for aortic valve replacement, coronary artery bypass graft surgery, or pericardiectomy for constrictive pericarditis. All of the hospitalized patients with confirmed MERS-CoV infection required ICU admission. Figure 1. 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. Figure 2. Study flow diagram. HCW = health care worker; ICU = intensive care unit; MERS-CoV = Middle East respiratory syndrome coronavirus. *Cases described in this report. In addition, 23 cardiac ICU patients were screened as part of active surveillance because of possible contact with confirmed HCW cases; all tested negative. The surveillance also included 520 HCWs who were screened for MERS-CoV; only 4 (1%) were positive. Three of the infections in HCWs occurred as a part of the health careassociated MERS-CoV cluster. These HCWs were nurses reported to have had exposure, without the use of personal protective equipment, to patients who were subsequently confirmed to have MERS-CoV infection. Only 1 of the HCWs (patient L), who had asthma, became severely ill and required ICU admission and is fully described in this series along with the other 11 patients. The other HCWs were mildly symptomatic or asymptomatic and were managed at home until the RT-PCR result was negative. Figure 1 shows the distribution of these cases between the 2 hospitals in Al-Ahsa and Riyadh. Clinical Presentation The demographic and clinical characteristics of the 12 critically ill patients with confirmed or probable MERS-CoV infection are shown in Table 1 and Appendix Tables 1, 2, and 3. The median age of the patients was 59 years (range, 36 to 83 years). Eight patients (67%) were male. 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 The presenting symptoms were mainly those of lower respiratory tract infection (dyspnea in 11 patients [92%], cough in 10 [83%], and fever in 8 [67%]); in contrast, symptoms of upper respiratory tract infection were infrequent