Investigations
Recommended in all patients with suspected MERS. Commonly reveals leukopenia, lymphopenia, and thrombocytopenia.[8][26][81] Patients may have leukocytosis, particularly in the setting of a secondary bacterial infection.
Other diagnostic testing for MERS should be pursued even in the absence of a typical FBC result.
leukopenia; lymphopenia; thrombocytopenia
Indicated in patients with respiratory distress and cyanosis.
low oxygen saturation (SpO2 <90%)
Blood cultures should be collected to test for potential bacterial pathogens that can also cause pneumonia or sepsis.[92]Should be collected before empirical antimicrobial therapy is started, if possible.
negative
Confirms Middle East respiratory syndrome coronavirus (MERS-CoV) infection.
Lower respiratory tract specimens (e.g., sputum, tracheal aspirates, bronchoalveolar lavage fluid) are the preferred specimen for RT-PCR as sputum and tracheal aspirates contain the highest viral loads, and hence have the highest yield.[5][93] However, bronchoscopy may generate aerosols and is generally not recommended. Upper respiratory tract specimens (e.g., nasopharyngeal and oropharyngeal swabs, nasopharyngeal aspirate/wash) and serum collection for virus detection are recommended, especially if lower respiratory specimens are not available and it is 7 days or less since symptom onset.[89][94][95] Urine and stool specimens may also be used; however, these specimens contain lower levels of the virus compared with respiratory tract specimens.
Healthcare workers should wear appropriate personal protective equipment (e.g., mask, eye protection, gloves, gown) when collecting specimens.[94]
MERS-CoV RT-PCR (upE): highly sensitive screening assay targeting regions upstream of the E protein gene (upE).[112]
MERS-CoV RT-PCR (ORF 1b): confirmatory assay targeting open reading frame 1b (ORF 1b). Less sensitive than the upE assay, but more specific.[112]
MERS-CoV RT-PCR (ORF 1a): confirmatory assay targeting ORF 1a. Highly specific and more sensitive than ORF 1b assay, but similar sensitivity to upE assay.[96]
The World Health Organization (WHO) recommends a screening assay first and, if positive, a confirmatory assay performed. If confirmatory assay is positive, infection is confirmed. If the confirmatory assay is negative, consider repeating the tests if epidemiological evidence is suggestive, or perform sequencing assays.[94]
Diagnosis requires a positive PCR on at least 2 specific genomic targets or a single positive target with sequencing on a second target.[90][91]
positive for MERS-CoV RNA
An assay targeting the RdRp gene (RdRpSeq) broadly detects betacoronavirus clade C sequences; however, it is not specific and will detect other coronavirus strains including human coronaviruses HKU1 and OC43.[96]
N gene sequencing (NSeq) can also be used. This region was chosen as it comprised a 2 amino acid deletion in the corresponding sequence published from a patient treated in the UK. Highly sensitive and specific for detection of human coronavirus Erasmus Medical Center/2012 (hCoV-EMC), the strain isolated from the first person infected with MERS.[96]
Both assays are sensitive enough to detect virus at very low concentrations, but if used should be coupled with a subsequent confirmatory assay.
detects MERS-CoV nucleotide sequences
Recommended in all patients with suspected pneumonia. Diffuse bilateral infiltrates have been reported in 22% to 67% of cases. Lobar infiltrates or the absence of infiltrates have also been reported, particularly in healthy, young patients.[5][8]
diffuse bilateral infiltrates; possibly lobar infiltrates or absence of infiltrates
Generally used for epidemiological surveillance or investigational purposes (e.g., retrospective diagnosis). May also be used to confirm diagnosis; however, a single specimen would only identify a probable case. Paired sampling taken at least 14 to 21 days apart is required to confirm diagnosis.
Includes indirect fluorescent antibody (IFA), enzyme-linked immunosorbent assay (ELISA), and serum neutralisation.
The WHO defines a confirmed case as a patient with evidence of seroconversion in at least one screening assay (e.g., IFA, ELISA) and confirmation by a neutralisation assay in samples taken at least 14 days apart. They define a probable case as a symptomatic patient without a positive RT-PCR test who has a positive result for at least one screening assay (e.g., IFA, ELISA) plus a positive result for a neutralisation assay in a single specimen.[94]
The CDC has developed a two-stage approach to serological testing which uses an ELISA test for screening, followed by a microneutralisation test to confirm diagnosis.[91]
False-positive results can occur due to cross-reactivity with other betacoronaviruses.
positive for MERS-CoV antibodies
May be helpful in patients with suspected pneumonia who have a normal chest x-ray. May reveal bilateral subpleural and basal airspace opacities, with more extensive ground-glass opacities than consolidation.[97]Recognition of these patterns can aid early diagnosis of MERS; however, routine use of this test is not recommended.
bilateral subpleural and basal airspace opacities, with more extensive ground-glass opacities than consolidation
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