Investigations

1st investigations to order

Test
Result
Test

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.

Result

leukopenia; lymphopenia; thrombocytopenia

Test
Result
Test

Recommended in all patients with suspected MERS. May reveal elevated creatinine, AST, ALT, and lactate dehydrogenase.[8][26][81]

Result

elevated creatinine; elevated LFTs; elevated lactate dehydrogenase

Test
Result
Test

Indicated in patients with respiratory distress and cyanosis.

Result

low oxygen saturation (SpO2 <90%)

Test
Result
Test

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.

Result

negative

Test
Result
Test

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]

Result

positive for MERS-CoV RNA

Test
Result
Test

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.

Result

detects MERS-CoV nucleotide sequences

Test
Result
Test

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]

Result

diffuse bilateral infiltrates; possibly lobar infiltrates or absence of infiltrates

Investigations to consider

Test
Result
Test

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 defineĀ 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.

Result

positive for MERS-CoV antibodies

Test
Result
Test

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.

Result

bilateral subpleural and basal airspace opacities, with more extensive ground-glass opacities than consolidation

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