Middle East Respiratory Syndrome (MERS) Workup

Updated: Jun 22, 2015
  • Author: Diana M Salazar, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Workup

Approach Considerations

The CDC recommends collecting multiple specimens from different sites and times in suspected cases of Middle East respiratory syndrome (MERS), including nasopharyngeal and oropharyngeal swabs, sputum, serum, and stool/rectal swabs after symptom onset.

Evidence shows that lower respiratory tract specimens such as bronchoalveolar lavage (BAL), sputum, and tracheal aspirates contain the highest viral loads, and these are recommended. Some cases, including the second US case, have been confirmed only in sputum after negative or equivocal results on PCR for MERS-CoV in nasopharyngeal and oropharyngeal specimens.

The local health department should be notified immediately if a patient is suspected of having MERS-CoV infection. Proper personal protective precautions should be used by personnel collecting specimens (ie, gloves, eye protection, gowns, and respiratory protection with N-95 masks).

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Real-Time Reverse-Transcriptase Polymerase Chain Reaction

The recommended algorithm for detection of MERS-CoV includes testing using rRT-PCR. Three assays are currently available for diagnosis. One assay targeting upstream of the E protein gene (upE) is recommended for screening. The other two assays target the open reading frame 1b (ORF 1b) and the open reading frame 1a (ORF 1a). The ORF 1a is more sensitive than the ORF 1b assay. [25]

There are two target sites on the novel coronavirus genome identified that can be sequenced; these are located in the RNA-dependent RNA polymerase (RdRp) and N genes. [30]

To consider a case as laboratory confirmed, one of the following criteria must be met: (1) a positive PCR result for at least 2 different specific targets on the MERS-CoV genome or (2) one positive PCR result for a specific target on the MERS-CoV genome and an additional different PCR product sequenced confirming known sequences of MERS-CoV. [25]

The diagnostic algorithm for a case under investigation is as follows:

  • upE-specific rRT-PCR: if positive, confirm with ORF 1a rRT-PCR assay, and, if positive, case is confirmed
  • upE-specific rRT-PCR: if positive, confirm with one sequenced of the 2 target sites (RdRp or N assay), and, if positive, case is confirmed

A case with a positive PCR result for only one specific target in a patient with a history of possible exposure and compatible clinical presentation is considered probable.

False-negative results can occur if a poor-quality specimen is used, if the specimen was collected either late or very early in the illness, or if the specimen was not handled and shipped properly. [25]

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Serology

Serologic testing is available for the evaluation of MERS-CoV infection or exposure. The serum specimens should be collected during the acute stage of the disease and repeated during the convalescence phase (>3 weeks after the initial sample was collected). This serologic test is available from the CDC and requires approval, since it is only for research or surveillance purposes.

The test uses indirect fluorescent antibody (IFA) and detection of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies based on protein microarray technology. [31] IFA assay may generate false-positive results owing to cross-reactivity with other coronaviruses; confirmation with neutralization assays is required, but they are not widely available.

Further investigation is needed it to determine the sensitivity and specificity of these assays.

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