Middle East Respiratory Syndrome (MERS) Workup

Updated: May 10, 2019
  • Author: Sandra G Gompf, MD, FACP, FIDSA; 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 have been developed. 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 and considered equivalent to upE versus the ORF 1b assay. [3]

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. [34]

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. [3]

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. [3]

The CDC Novel Coronavirus 2012 Real-time RT-PCR Assay (NCV-2012 rRT-PCR) is a qualitative, real-time (TaqMan®) RT-PCR developed in the United States that screens with upE rRT-PCR and confirms with N2 assay. [35]

On June 5, 2013, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for CDC’s 2012 real-time reverse transcription–PCR assay to detect MERS-CoV in clinical respiratory, serum, and stool specimens. CDC has distributed the assay to qualified laboratories in the United States and internationally. Most US state laboratories are thus able to test for suspected MERS-CoV infection with the rRT-PCR assay. [36, 37, 35]

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Serology

Serologic testing for MERS-CoV is available as a research/surveillance test from the CDC; it is not considered a diagnostic test but may offer valuable epidemiologic data. It must be ordered in consultation and with approval of CDC via the EOC.

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 consultation and approval, since it is only for research or surveillance purposes.

The CDC performs a 2-stage procedure. First, serum is screened with enzyme-linked immunosorbent assays (ELISA) for nucleocapsid (N) and spike (S) proteins. If either is positive, confirmatory microneutralization testing is performed for neutralizing antibodies. A positive ELISA result and positive microneutralization test result is considered positive.

Further investigation is needed it to determine the sensitivity and specificity of these assays. [38]

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Laboratory Studies

Laboratory findings at presentation may include leukopenia, lymphopenia, thrombocytopenia, and elevated lactate dehydrogenase levels. These are most likely with increasing severity of illness. Critically ill patients may develop acute renal failure requiring hemodialysis or continuous renal replacement therapy. [32]

Co-infection with other community-acquired viruses and bacteria have been described. [32]

Upon suspicion of MERS, clinicians in the United States should contact the CDC Emergency Operations Center (EOC) (770-488-7100; 24 hours/day, 7 days/week) for consultation.

As long as the patient remains symptomatic, specimens should be collected from nasopharynx, lower respiratory (bronchoalveolar lavage), and blood for CDC MERS rRT-PCR testing, even if more than 14 days from onset of illness. Specimens may be refrigerated at 3-8°C but should be frozen at -70°C if held longer than 72 hours. They are then shipped on dry ice.

Prior to collection of any laboratory specimens in suspected MERS cases, the laboratory should be notified of the possibility so that appropriate laboratory precautions are taken in processing them for shipping.

Specimen requirements for rRT-PCR are as follows: [37]

  • Bronchoalveolar lavage: 2-3 mL in a sterile, leak-proof, screw-cap sputum collection cup
  • Deep sputum specimen: After rinsing the mouth with water, expectorated directly into a sterile, leak-proof, screw-cap sputum collection cup
  • Nasopharyngeal swab and oropharyngeal swab (NP/OP swab) (synthetic fiber swab with plastic shaft only): Both swabs may be placed into the same sterile tube containing viral transport media.
  • Blood: 1 tube (5-10 mL) of whole blood in a serum separator tube

Other types of specimens, such as stool or urine, may harbor the virus for up to 6 weeks. They are not recommended for diagnostic testing but may have epidemiologic value. [39]

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Imaging Studies

The clinical presentation of MERS overlaps with that of other viral and bacterial syndromes; this is also true for radiographic findings.

Chest imaging findings are abnormal in more than 80% of MERS cases. Ground-glass opacity (GGO) is found in over 60% of chest radiographs, with about 20% incidence of consolidation. Some infiltrates may be nodular.

Early findings occur in the peripheral mid-lung and lower-lung zones and are often unilateral. As illness progresses in severity, patchy infiltrates may spread to involve upper lung zones and may reflect noncardiac pulmonary edema due to ARDS.

Cavitation may occur early owing to a concurrent bacterial or other process. It may also appear 2-3 weeks into severe illness, along with other features of ARDS.

Pleural effusion, a notable feature that distinguishes MERS from other respiratory viral infections, occurs within one week of onset in about a third of cases. It may also predict higher mortality risk and poor outcome. [40]

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Procedures

Procedures may include the following:

  • Mechanical intubation
  • Bronchoscopy with bronchoalveolar lavage
  • Renal replacement therapy or hemodialysis
  • Extracorporeal membrane oxygenation
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