Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that is transmitted from animals (most likely camels) to humans and is associated with severe acute respiratory illness, with potential multiorgan failure and death. This virus has stayed on the radar of public health authorities around the world not only due to recurrent hospital and community outbreaks, but also due to its high mortality rates.

Middle East respiratory syndrome coronavirus - Image Credit: European Centre for Disease Prevention and Control (ECDC)

Disease Pathogenesis

MERS-CoV belongs to a family of enveloped, large, single-stranded RNA viruses known as Coronaviridae. The virus enters the human body through a common receptor, dipeptidyl peptidase 4 (also known as CD26), and subsequently replicates in bronchial, bronchiolar and alveolar epithelial cells. MERS-CoV has been detected primarily in respiratory secretions, with the viral load being highest in the lower parts of the respiratory tract.

Compared with another member of this viral family known as severe acute respiratory syndrome coronavirus (SARS-CoV), MERS-CoV has the propensity to establish a productive infection in macrophages and dendritic cells. This can in turn instigate the release of proinflammatory cytokines, resulting in protracted inflammation and tissue damage that clinically manifests as a severe form of pneumonia and respiratory failure.

Case Definitions

The World Health Organization (WHO) defines a confirmed case as a patient with laboratory-proven MERS-CoV infection, regardless of clinical presentation in the affected individual. Suspected MERS-CoV cases are defined using three types of case descriptions.

First, a suspected MERS-CoV case is an acute illness with respiratory tract involvement being predominant. It presents with fever and accompanying clinical, histopathological or radiological signs of lung congestion, together with a straightforward epidemiological link to a confirmed case of disease. This definition is useful where the MERS-CoV test is unavailable, inconclusive, or negative, with a single sample which is deemed inadequate.

Secondly, a suspected MERS-CoV case is also a respiratory illness of acute onset, with fever and accompanying clinical, histopathological or radiological signs of lung involvement, together with the patient’s location in or travel history from the Middle East region or any other where the virus has been identified to be present in dromedaries, or where there have been human infections in the recent past, with an inconclusive MERS-CoV test.

Finally, a suspected MERS-CoV case is an acute respiratory infection of any degree of severity, together with a straightforward epidemiological link to a known case of MERS-CoV, and where a MERS-CoV test is inconclusive.

Clinical Manifestations

The incubation period of MERS-CoV infection is from 2 to 14 days (median 5 days), and the disease manifestation varies from asymptomatic or mildly symptomatic to severe respiratory disease with multiorgan dysfunction. Severe cases usually occur in adults who have chronic comorbidities – including chronic lung disease, diabetes mellitus, cardiac disease, hypertension, end-stage kidney disease and any kind of immunosuppression.

Compared with SARS-CoV, MERS-CoV is more prone to affecting older patients, people with comorbid illnesses, and males more commonly than females. Moreover, children have rarely been diagnosed with the Middle East respiratory syndrome, albeit there is a possibility that such infections are mild and hence underdiagnosed.

A majority of critically ill patients infected with MERS-CoV present with fever, cough, dyspnea and gastrointestinal symptoms (primarily dysentery, nausea and vomiting, and stomach pain). Other symptoms comprise rigor, migraine, sore throat, cough, muscular rheumatism and dizziness.

The case-fatality rate of MERS-CoV infection ranges from 20% to 36%. Nevertheless, it should be emphasized that mild or asymptomatic infections are often unreported, and thus the true case-fatality rate is likely to be much lower. Nevertheless, the mortality rate of critically ill patients is much higher (from 58 to 84%.