Middle East Respiratory Syndrome (MERS)
Middle East respiratory syndrome (MERS) is a respiratory disease caused by a newly recognized coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and is thus far linked to countries in or near the Arabian Peninsula (United Arab Emirates [UAE], Qatar, Oman, Jordan, Kuwait, Yemen, and Lebanon). As of May 2014, two cases had been reported in the United States, both in men who had recently returned from Saudi Arabia. 
See 11 Travel Diseases to Consider Before and After the Trip, a Critical Images slideshow, to help identify and manage several infectious travel diseases.
Also, see the Ebola: Care, Recommendations, and Protecting Practitioners slideshow to review treatment, recommendations, and safeguards for healthcare personnel working with infectious diseases, as well as the Acute Respiratory Distress Syndrome: A Complex Clinical Condition slideshow for more information on ARDS, a condition characterized by acute respiratory failure, hypoxemia, and pulmonary edema.
MERS is typically characterized by cough, fever, and shortness of breath. Most individuals with confirmed MERS have developed acute respiratory illness, and, among the 536 cases reported through May 12, 2014, the mortality rate has been 30%.  However, the number of cases and fatalities reported in Saudi Arabia has recently been revised following alleged underreporting. The updated total number of cases in that country has been increased to 688 from the previous count of 575, and the total number of deaths has been increased to 282 from 190, representing a mortality rate of more than 40%. 
MERS-CoV has been shown to spread from person to person via close contact but without sustained community transmission.  Potentially at-risk individuals include caregivers and close contacts of people with suspected or confirmed MERS-CoV infection.  Transmission has occurred via close contact with infected persons, including from patients to healthcare personnel. 
Laboratory testing for MERS-CoV is not routinely available, although polymerase chain reaction (PCR) for MERS-CoV is available at state health departments, the Centers for Disease Control and Prevention (CDC), and some international laboratories. Some commercial tests are available, but none has received US Food and Drug Administration (FDA) approval. 
No vaccine currently exists for MERS, and no specific treatment has been recommended. Management is currently supportive.  However, at least one group has recommended consideration of interferon alfa 2b plus ribavirin in the management of MERS-CoV cases because of the combination’s efficacy seen in rhesus macaques with MERS. 
Travelers who have recently visited countries in or near the Arabian Peninsula are advised to contact their healthcare provider if they develop MERS symptoms (ie, fever, cough, shortness of breath) within 14 days of travel.  Individuals who have been in recent contact with a symptomatic person who has recently traveled to the Arabian Peninsula should also be evaluated for MERS-CoV infection. 
Because of an ongoing 2015 outbreak of MERS in South Korean healthcare facilities, the CDC has also recently advised clinicians to ask patients with serious respiratory problems whether they have recently been in a healthcare facility in South Korea to screen for MERS-CoV. A patient presenting with fever and pneumonia or acute respiratory distress syndrome should be evaluated for MERS if he or she had been a patient, worker, or visitor in a South Korean healthcare facility within 14 days of symptom onset. 
In patients who meet these screening criteria, the CDC recommends evaluation for common causes of community-acquired pneumonia based on clinical presentation and epidemiologic and surveillance information. Testing for MERS-CoV and other respiratory pathogens can be performed concurrently. Results that confirm a different respiratory pathogen should not necessarily preclude testing for MERS-CoV. 
If possible, the CDC recommends collection of multiple specimens from different sites at various times following the onset of symptoms. Infection-control measures should be used during collection using approved equipment and methods. Specimens should be handled, stored, and shipped following appropriate protocols. 
Lower respiratory specimens are preferable. Oropharyngeal and nasopharyngeal specimens, in addition to serum and stool, are strongly recommended to increase diagnostic yield. 
Collection of respiratory specimens should begin as soon as possible following symptoms onset; nonetheless, respiratory specimens should still be collected beyond this period if the patient remains symptomatic more than one week following symptom onset (particularly lower-respiratory specimens) since real-time reverse-transcription PCR (rRT-PCR) can still be used for detection. 
Standard contact and airborne precautions are recommended for management of hospitalized patients with known or suspected MERS-CoV infection. The complete CDC guidance can be found on the CDC website (Interim Infection Prevention and Control Recommendations for Hospitalized Patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV ); a key recommendation includes placing the patient in contact and airborne isolation room as soon as possible. In addition, personal protective equipment for healthcare personnel, including gloves, gowns, eye protection (goggles or face shield), and respiratory protection that is at least as protective as fit-tested NIOSH-certified disposable N-95 filtering face piece respirator must be utilized.
For current CDC recommendations for healthcare professionals, see also Interim Guidance for Health Professionals.
One of the most important cells of the innate immune system is the macrophages; their function is to eliminate pathogens, to present antigens to T cells, and to produce cytokines and chemokines to maintain homeostasis and modulate the immune response in tissues. 
Compared with severe acute respiratory syndrome coronavirus (SARS-Cov), MERS can establish a productive infection in monocyte-derived macrophages (MDMs) and macrophages. This then induces a release of proinflammatory cytokines, leading to severe inflammation and tissue damage, which may manifest clinically as severe pneumonia and respiratory failure.  Vascular endothelial cells located in the pulmonary interstitium may also be infected by MERS-CoV, and, because MERS-CoV receptor DPP4 is expressed in different human cells and tissues, dissemination of the infection may occur.  This may explain the increased severity and higher fatality rate compared with the SARS-CoV infection.
Interestingly, lymphopenia has been noted in most patients infected with MERS-CoV, as was also noted in SARS infections. This is due to cytokine-induced immune cell sequestration and release and induction of monocyte chemotactic protein-1 (MCP-1) and interferon-gamma-inducible protein-10 (IP-10), which suppress proliferation of human myeloid progenitor cells. 
Coronaviruses are the largest of all RNA viruses, with positive single-stranded RNA genomes of 26-32 kb. They are classified into 4 genera: alphacoronavirus, betacoronavirus, gammacoronavirus, and deltacoronavirus.  SARS-CoV belongs to the lineage B betacoronavirus and was responsible for the 2002-2003 SARS outbreaks, which first defined the potentially highly pathogenic properties of human coronaviruses.
MERS-CoV is a newly discovered betacoronavirus lineage C that was first reported in Saudi Arabia in 2012. The exact origin of this novel coronavirus is still unknown. Early studies indicated that MERS-CoV may be related to a zoonotic virus found in bats,  but more recent evidence suggests that the virus may be more strongly linked to camels. [15, 16, 17, 18, 19, 20] An outbreak investigation was performed in dromedary camels from a farm in Qatar linked to two human cases of infection in October 2013. MERS-CoV was virologically confirmed in nose swabs from 3 camels by 3 independent RT-PCR and sequencing assays. 
The specific transmission mechanisms between humans and the possible source animals are unknown,  and, although human-to-human transmission has been demonstrated, the chains of transmission have not been self-sustained, making early identification and isolation a feasible strategy to limit the spread of the virus. 
As of June 20, 2015, 1,334 laboratory-confirmed cases of infection with MERS-CoV have been reported to the World Health Organization (WHO), including at least 471 related deaths. 
Twenty-six countries have reported MERS cases, including the following: Saudi Arabia, Iran, Jordan, Kuwait, Lebanon, Oman, Qatar, the United Arab Emirates, and Yemen (Middle East); Austria, France, Germany, Greece, Italy, Netherlands, Turkey, and the United Kingdom (Europe); Algeria, Tunisia, and Egypt (Africa); China, Malaysia, Republic of Korea, Thailand, and the Philippines (Asia); and the United States. The vast majority of these cases have so far occurred in the Kingdom of Saudi Arabia. 
A WHO statement in April 2014 indicated that 75% of reported MERS cases appeared to be secondary cases (ie, acquired from another infected person). 
In an ongoing 2015 MERS outbreak in South Korea (and to a lesser extent, China), 172 confirmed cases and 27 related deaths have been reported as of June 22, 2015, 
The first case of MERS in the United States was reported to the CDC by the Indiana State Department of Health on May 1, 2014, and confirmed by the CDC on May 2. The patient was a male who lived and worked in Saudi Arabia as a healthcare provider in a facility that had patients infected with MERS. He began feeling sick around April 18 and traveled by commercial airline from Saudi Arabia to Chicago and then traveled by bus to Indiana. His initial symptoms included low-grade fever, myalgias, and rhinorrhea that later progressed to dyspnea and nonproductive cough. Chest radiography and CT scanning revealed bilateral infiltrates. The patient has recovered uneventfully, and no secondary cases have been reported among healthcare personnel or household contacts.
A second imported case was reported to the CDC by the Florida Department of Health on May 11, 2014, and confirmed by the CDC. The patient was a healthcare worker who resided and worked in Saudi Arabia and had contact with a patient infected with MERS-CoV prior to presentation. He traveled by commercial airlines from Saudi Arabia to the United Kingdom, the United Kingdom to Boston, Boston to Atlanta, and finally from Atlanta to Orlando, where he was visiting family.
His initial symptoms included myalgias, chills, and fever without cough.  Because of persistent symptoms, he sought medical attention, and, soon after admission, he developed cough; chest CT scans showed patchy nodular infiltrates bilaterally without mediastinal lymphadenopathy. As of May 16, 2014, the patient is recovering and doing well (personal communication, Antonio Crespo, MD).
Two healthcare workers developed a respiratory illness within the incubation period after they were exposed to the patient, but PCR testing of both showed negative results. The rest of the healthcare workers who were potentially in contact with the patient were furloughed, and none has tested positive for MERS-CoV as of May 16, 2014.
Many individuals with confirmed MERS have developed severe acute respiratory illness, and some have developed multiorgan dysfunction. The case fatality rate had been reported at 30%,  although this number is likely higher following a recent report that Saudi Arabia underreported the total number of cases and fatalies in that country. The revised mortality rate in Saudi Arabia now exceeds 40% (688 cases reported, with 282 deaths).
The high mortality rate may be due to delayed diagnosis and the lack of effective therapies. Associated comorbidities, including end-stage renal disease on hemodialysis, diabetes, and chronic cardiopulmonary disease, have been associated with increased mortality rates.
The two US cases of MERS substantiate the very low risk to the general US population, which is not considered to be at risk in the absence of close contact with individuals infected with MERS-CoV and travel to countries where the infection has occurred.
CDC’s travel notices have been upgraded to a level 2, suggesting enhanced precautions for travelers who plan to work in healthcare settings in involved countries in or near the Arabian Peninsula.  Travelers to the region who develop fever, cough, shortness of breath, or myalgias during their trip or within 14 days after returning to the United States are strongly encouraged to seek medical attention. 
The CDC advises that people observe the following tips to help prevent respiratory illnesses:
Wash hands often with soap and water for 20 seconds; if water and soap are not available, use an alcohol-based hand sanitizer
Cover nose and mouth with a tissue when coughing or sneezing
Avoid touching eyes, nose, and mouth with unwashed hands
Avoid close contact with sick people, such as kissing, sharing cups, or sharing eating utensils
Clean and disinfect frequently touched surfaces, such as toys and doorknobs
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Diana M Salazar, MD Fellow in Infectious Disease, Orlando Regional Medical Center
Disclosure: Nothing to disclose.
Mark R Wallace, MD, FACP, FIDSA Clinical Professor of Medicine, Florida State University College of Medicine; Clinical Professor of Medicine, University of Central Florida College of Medicine
Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, Florida Infectious Diseases Society
Disclosure: Nothing to disclose.
Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.
Middle East Respiratory Syndrome (MERS)
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