Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Diagnosis

Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus that was discovered in 2012. Since then, sporadic cases, as well as cases caused by transmission in the families, and major outbreaks within healthcare settings, have been described or epidemiologically linked to the Arabian Peninsula.

Definite factors that contribute to the spread of MERS-CoV still have to be systematically studied, but the acquired data suggest that viral, host and environmental factors all play a significant role. As this virus is responsible for acute respiratory syndrome in humans and shows a high case fatality rate, adequate diagnosis is of the utmost importance.

The Centers for Disease Control and Prevention (CDC) recommends taking multiple specimens from various sites at different times when MERS-CoV infection is suspected. Lower respiratory tract specimens that have a higher viral load should be preferably used. They provide improved sensitivity when compared to upper respiratory tract specimens.

Immediate notifications should be sent to the local health departments if there is a patient suspected of harboring MERS-CoV. Furthermore, appropriate protective precautions are recommended for all personnel involved in the collection of specimens (such as gowns, gloves, respiratory and eye protection). Specimen type and condition, as well as the avoidance of contamination, may affect the test result.

Non-sSpecific Diagnostic Mmethods

The diagnosis of MERS-CoV infection is based on exposure history, clinical criteria and diagnostic findings. Although these steps can establish a suspected case, it is quite hard to differentiate MERS-CoV infection from other causes of severe respiratory infections based merely on the clinical and radiological manifestations.

The most frequently observed CT finding in hospitalized patients infected with MERS-CoV is bilateral basilar and subpleural airspace changes, with ground-glass opacities that are more pronounced than consolidation. In fatal cases, the mean number of involved lung segments is 12.3, compared to 3.4 of affected segments in those who survived the infection.

Nonspecific laboratory abnormalities that are seen in patients with MERS-CoV include leucopenia, lymphopenia, thrombocytopenia, as well as increased levels of lactate dehydrogenase (LDH) and increased hepatic transaminases (alanine transaminase and aspartate transaminase).

Serologic testing is also available to confirm past infection, and the diagnosis of MERS-CoV infection can be established by seroconversion in two samples taken at the acute stage and during the convalescence phase (i.e. three weeks after the first sample) respectively. Several serologic assays specific for MERS-CoV have been developed, but they all need additional validation.

Molecular Testing

Rapid and reliable laboratory diagnosis of suspected cases is pivotal for timely implementation of infection control practices and disease management. At the moment, the diagnosis of MERS-CoV can be confirmed by molecular testing using the real‐time reverse-transcription polymerase chain reaction (r-RT-PCR).

Two different regions of the viral genome are targeted by this type of PCR: the detection of upstream E protein (upE) is more sensitive and used for screening, whereas the ORF1a or ORF1b genes (ORF stands for open reading frame) are used for confirmation.

Recently it was demonstrated that reverse-transcriptase loop-mediated isothermal amplification has a sensitivity similar to that of Q-RT‐PCR. Amplification can be completed in less than one hour, and the process necessitates only a single temperature. Gene sequencing that targets RdRp (encountered in all coronaviruses) and N (which is specific to MERS-CoV) gene fragments may be used for confirmation.