Middle East respiratory syndrome coronavirus infection overview

# Overview
MERS-CoV is a viral respiratory illness caused by a lineage C betacoronavirus, an enveloped, spherical (120 nm in diameter), single-stranded, positive-strand RNA virus that belongs to the family Coronaviridae. Its clinical significance was initially described following an outbreak in 2012 in Jeddah, Saudi Arabia. To date, little is known about MERS-CoV virus. The natural reservoir of MERS-CoV is unknown, but either bats or camels are thought to be the most likely natural reservoir with unconfirmed potential for sustained human-to-human transmission. MERS-CoV has been associated with residence in 9 countries in the Middle East and in South Korea. Approximately, 1,300 cases have been reported with a case-fatality rate reaching 30-40%. Following exposure, patients with MERS-CoV often remain asymptomatic during the viral incubation period for 5 to 14 days. Patients typically develop non-specific flu-like symptoms, such as high-grade fever, myalgia, sore throat, and cough. Many patients experience spontaneous self-resolution of symptoms a few days following the onset of symptoms. Individuals with systemic chronic comorbidities and immunosuppression are at high risk of developing worsening clinical features, such as acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), pericarditis, disseminated intravascular coagulopathy (DIC), septic shock, and death. According to the Centers of Disease Control and Prevention (CDC), laboratory confirmation of MERS-CoV infection requires either a positive PCR test of  2 specific genomic targets or a single positive target followed by successful sequencing of a second. Serologic testing is recommended in patients when PCR is not available. Additional lab testing is not diagnostic buy may be useful to monitor for the development of complications. Antiviral therapy against MERS-CoV is not yet recommended. Supportive care is the mainstay of management of MERS-CoV, but monitoring for and early management of MERS-CoV-associated complications are equally important. While there is no vaccine available for MERS-CoV, at-risk individuals are advised to implement infection control measures to prevent the spread of the infection in hospitals and in the communities.

# Historical Perspective
The index case of MERS-CoV infection was reported in Saudi Arabia in September, 2012. Dr. Ali Mohamed Zaki, an Egyptian virologist, was the first to attribute MERS-CoV to coronavirus.

# Pathophysiology
MERS-CoV has a strong tropism for the non-ciliated bronchial epithelium. The virus has the capacity to evade the innate immune system and inhibit interferon production. It uses the DPP4 (or CD26) receptor to bind to the host cell and to release viral nucleocapsid into the cellular cytoplasm. Once inside the cell, viral replication follows and proteins are expressed. The viral genes encode 4 structural proteins and 5 accessory proteins.

# Causes
MERS-CoV is caused by a lineage C betacoronavirus, an enveloped, spherical (120 nm in diameter), single-stranded, positive-strand RNA virus that belongs to the family Coronaviridae of the order Nidovirales. The natural reservoir of MERS-CoV is unknown, but bats are thought to be the most likely natural reservoir. MERS-CoV is thought to have a zoonotic activity, whereby transmission occurs from animals to humans. Limited data is available to confirm or rule out human-to-human transmission.

# Differentiating Middle East Respiratory Syndrome Coronavirus Infection from Other Diseases
MERS-CoV must be differentiated from other respiratory tract infections that cause flu-like symptoms, such as influenza virus, respiratory syncytial virus (RSV), and other coronaravirus infections.

# Epidemiology and Demographics
MERS-CoV has been associated with residence in 9 countries in the Middle East and in South Korea. However, cases with a history of recent travel had been reported in several countries worldwide. As of June 2015, 1289 laboratory-confirmed cases of MERS-CoV infection have been reported. The case fatality rate of MERS-CoV ranges between 30% to 40%. The median age at infection is 47 years with no age preponderance to MERS-CoV infection (range: 9 months to 94 years). Approximately 2/3 of infected patients are males.

# Risk Factors
Risk factors in the development of either MERS-CoV infection or MERS-CoV-associated complications include recent travel to the Arabian Peninsula, exposure to patients with suspected or confirmed MERS-CoV infection, immunocompromised status, and history of prior systemic comorbidities, such as diabetes mellitus, hypertension, active malignancy, chronic kidney disease, respiratory disease, liver disease, and chronic cardiac disease.

# Natural History, Complications and Prognosis
Following exposure, patients with MERS-CoV remain asymptomatic during the incubation period for 5 to 14 days. If left untreated, patients typically develop non-specific flu-like symptoms, such as high-grade fever, myalgia, sore throat, and cough. Many patients experience spontaneous self-resolution of symptoms a few days following the onset of symptoms. Patients with systemic chronic comorbidities and immunosuppression are at high risk of developing worsening clinical features, such as acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), pericarditis, disseminated intravascular coagulopathy (DIC), and septic shock. Approximately 30-40% of patients die following MERS-CoV infection.

# Diagnosis

## History and Symptoms
Symptoms of MERS-CoV typically include high-grade fever, cough, headache, dyspnea, and myalgia. Gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain may also be present.

## Physical Examination
Patients with MERS-CoV infection typically present with vital signs derangement, such as high-grade fever, tachycardia, tachypnea, and decreased oxygen saturation. Signs on physical examination may include decreased breath sounds, crackles, dullness on percussion, and increased tactile fremitus on pulmonary auscultation. Signs of complications may also be present, such as profound hypotension (suggestive of shock) or pericardial rub (suggestive of pericarditis).

## Laboratory Findings
Laboratory findings of MERS-CoV may include leukopenia, lymphopenia, thrombocytopenia, elevated inflammatory markers, and elevated lactate dehydrogenase (LDH) levels. Lab findings are not diagnostic of MERS-CoV but are useful to monitor for the development of MERS-CoV infection.

## Chest x ray
Radiographic findings MERS-CoV infection include unilateral or bilateral patchy densities or opacities, interstitial infiltrates, consolidation] and pleural effusions on chest x-ray.

## CT
On chest CT-scan, patients with MERS-CoV may demonstrate changes similar to patients with ARDS. CT scan may demonstrate bilateral airspace abnormalities with ground glass opacities, predominantly located at the bases of the lungs, suggestive of organizing pneumonia.

## Other Diagnostic Studies
Laboratory confirmation of MERS-CoV infection requires either a positive PCR test of 2 specific genomic targets or a single positive target followed by successful sequencing of a second. If a patient has a positive serologic test, but no PCR or sequencing test, the individual is considered a probable case.

# Treatment

## Medical Therapy
Antiviral therapy against MERS-CoV is not yet recommended. Supportive care is the mainstay of management of MERS-CoV. Monitoring for and early management of MERS-CoV-associated complications is also important.

## Contact and Airborne Precautions
Implementation of infection prevention and control measures is critical to prevent the possible spread of MERS-CoV in hospitals and communities. Hospitalized patients should be admitted to airborne infection isolation rooms. All healthcare personall should also wear personal protective equipment, including gloves, gowns, and eye and respiratory protection, when exposed to patients with MERS-CoV. Patients evaluated for MERS-CoV infection who do not require hospitalization may be treated and isolated at home to prevent the nosocomial spread of infection. Isolation at home is defined as the separation or restriction of activities of an ill person with a contagious disease from those who are well.

## Primary Prevention
There is no vaccine available for the prevention of MERS infection. All individuals should implement precaution measures including washing hands with soap, avoiding personal physical contact or sharing utensils with sick individuals, and avoiding drinking raw food that may be contaminated with animal products.