Middle East respiratory syndrome coronavirus infection laboratory findings
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]
Overview
Laboratory findings for MERS at admission may include leukopenia, lymphopenia, thrombocytopenia, and elevated lactate dehydrogenase (LDH) levels. MERS-CoV virus can be detected with higher viral load and longer duration in the lower respiratory tract compared to the upper respiratory tract, and has been detected in feces, serum, and urine.[1]
Laboratory Findings
Despite the insufficiency of laboratory data regarding MERS and its changes throughout the course of the disease, the laboratory abnormalities documented until now include:[2][3][4][5][6]
- Lymphopenia
- Thrombocytopenia
- Leukopenia
- Elevated serum LDH levels
- Elevated AST and ALT levels
- Renal function abnormalities
CDC Guidelines
According to CDC guidelines:[7]
- Investigations of MERS-CoV and other respiratory pathogens may now be conducted simultaneously and additionally, positive results for another respiratory pathogen should not hinder testing for MERS-CoV.
- Health-care providers in the United States should continue to evaluate patients for MERS-CoV infection if they develop fever and pneumonia or acute respiratory distress syndrome within 14 days after traveling from countries in or near the Arabian Peninsula.
- Providers should also evaluate patients for MERS-CoV infection, in the presence of ARDS, fever or pneumonia and if they have been in close contact with recent travelers from the Arabian Peninsula who have fever and acute respiratory illness.
- Clusters of patients with severe acute respiratory illness, such as fever and pneumonia that requires hospitalization, must be evaluated for common respiratory pathogens and reported to local and state public health departments. In case a diagnosis isn't reached, particularly if the cluster includes health-care providers, testing for MERS-CoV should be considered, in consultation with state and local health departments. In this situation, all patients should be tested, even if they haven't had travel-related exposure.
- If symptoms have started more than 14 days prior, CDC guidelines recommend additional testing of a serum specimen via the CDC MERS-CoV serologic assay
- Laboratory confirmation of infection by MERS-CoV now requires a positive PCR test of ≥2 specific genomic targets or, a single positive target followed by successful sequencing of a second.
- Laboratory tests, such as the PCR for MERS-CoV are available at state health departments, CDC and some international laboratories. Otherwise, MERS-CoV tests are not routinely available, despite the existence of a limited number of non-FDA-approved commercial tests.
Confirmed Case
According to the CDC, a confirmed case of MERS-CoV infection is considered an individual who shows laboratory confirmation of infection by MERS-CoV.[7]
Probable Case
According to the CDC, it is considered a probable case of MERS-CoV infection, an individual under investigation who has missing or inconclusive laboratory test results for the infection and that has been in close contact with another individual who is a "laboratory-confirmed case" of MERS-CoV infection.[7]
Specimen Types and Collection
The CDC recommends that priority for collection and real-time RT-PCR testing should be given to lower respiratory tract specimens. This preference is due to the fact that lower respiratory specimen testing appears to be more sensitive in the detection of MERS-CoV, when compared to specimens from the upper respiratory tract.[8][9][10][11][12] It is recommended the collection of multiple specimens from different locations and in different time periods, in order to increase the probability of collecting and detecting the pathogen, by virtue of the potential impact of the infection by MERS-CoV, the risk of transmission and how little is known about the sensitivity of the diagnostic tests for this virus.[9][13] It is also recommended that, in all cases of severe disease, priority is given to respiratory samples, particularly lower respiratory tract specimens; in the case of mild disease, upper tract specimen should be collected, if lower tract specimens cannot be obtained. Also, serum samples should be collected for serologic testing, as well as a stool sample or a rectal swab. However, contrariwise to SARS-CoV, stool samples have a very low concentration of MERS-CoV.[14] In the presence of a negative test result in an highly suspicious patient, for infection by MERS-CoV, further samples should be collected for testing. A false-negative result might be due to:[9]
- Poor specimen quality
- Wrong timing of collection
- Mishandled/shipped sample
- Technical problem during testing
In patients suspected of being infected with the MERS-CoV, the following specimens should be collected, by health-care providers, for submission to a public health laboratory or to the CDC:
- Nasopharyngeal swab
- Oropharyngeal swab (might be placed in the same container, in viral transport medium, as the nasopharyngeal swabs)
- Sputum
- Serum
- Stool/rectal swab.
During the collection of the specimens, it is recommended the use of infection control precautions and the health-care practitioners, involved the collection of these specimens, should wear recommended personal protective equipment, such as:
- Gloves
- Gowns
- Eye protection
- Respiratory protection
Collecting, Handling, and Testing Clinical Specimens
According to the CDC, each specimen container should be labeled with the patient’s ID number, specimen type and the date when the sample was collected. The guidelines to collect and store biological specimens include:[15]
Respiratory Specimens
Lower respiratory tract broncheoalveolar lavage, tracheal aspirate and pleural fluid
Collect 2-3 mL into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container. Refrigerate specimen at 2-8°C up to 72 hours; if exceeding 72 hours, freeze at -70°C and ship on dry ice.[15]
Sputum
Have the patient rinse the mouth with water and then expectorate deep cough sputum directly into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container. Refrigerate specimen at 2-8°C up to 72 hours; if exceeding 72 hours, freeze at -70°C and ship on dry ice.[15]
Upper respiratory tract
Nasopharyngeal AND oropharyngeal swabs (NP/OP swabs)
Use only synthetic fiber swabs with plastic shafts. Do not use calcium alginate swabs or swabs with wooden shafts, as they may contain substances that inactivate some viruses and inhibit PCR testing. Place swabs immediately into sterile tubes containing 2-3 ml of viral transport media. NP/OP specimens can be combined, placing both swabs in the same vial. Refrigerate specimen at 2-8°C up to 72 hours; if exceeding 72 hours, freeze at -70°C and ship on dry ice.[15]
Nasopharyngeal swabs
Insert a swab into the nostril parallel to the palate. Leave the swab in place for a few seconds to absorb secretions. Swab both nasopharyngeal areas.[15]
Oropharyngeal swabs
Swab the posterior pharynx, avoiding the tongue.[15]
Nasopharyngeal wash/aspirate or nasal aspirates
Collect 2-3 mL into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container. Refrigerate specimen at 2-8°C up to 72 hours; if exceeding 72 hours, freeze at -70°C and ship on dry ice.[15]
Blood Components
Serum (for serologic testing)
For serum antibody testing: Serum specimens should be collected during the acute stage of the disease, preferably during the first week after onset of illness, and again during convalescence, ≥ 3 weeks after the acute sample was collected. However, since we do not want to delay detection at this time, a single serum sample collected 14 or more days after symptom onset may be beneficial. Serologic testing is currently available at CDC upon request and approval. Please be aware that the MERS-CoV serologic test is for research/surveillance purposes and not for diagnostic purposes - it is a tool developed in response to the MERS-CoV outbreak. Contact CDC’s Emergency Operations Center (EOC) (770-488-7100) for consultation and approval if serologic testing is being considered.[15]
Serum (for rRT-PCR testing)
- For rRT-PCR testing (i.e., detection of the virus and not antibodies), a single serum specimen collected optimally during the first week after symptom onset, preferably within 3-4 days, after symptom onset, may be also be beneficial.[15]
- Children and adults: Collect 1 tube (5-10 mL) of whole blood in a serum separator tube. Allow the blood to clot, centrifuge briefly, and separate sera into sterile tube container. The minimum amount of serum required for testing is 200 µL. Refrigerate the specimen at 2-8°C and ship on ice- pack; freezing and shipment on dry ice is permissible.[15]
- Infants: A minimum of 1 mL of whole blood is needed for testing of pediatric patients. If possible, collect 1 mL in an EDTA tube and in a serum separator tube. If only 1 mL can be obtained, use a serum separator tube.[15]
EDTA blood (plasma)
Collect 1 tube (10 mL) of heparinized (green-top) or EDTA (purple-top) blood. Refrigerate specimen at 2-8°C and ship on ice-pack; do not freeze.[15]
Stool
Collect 2-5 grams of stool specimen (formed or liquid) in sterile, leak-proof, screw-cap sputum collection cup or sterile dry container. Refrigerate specimen at 2-8°C up to 72 hours; if exceeding 72 hours, freeze at -70°C and ship on dry ice.[15]
References
- ↑ "MERS Clinical Features".
- ↑ Ajlan, Amr M.; Ahyad, Rayan A.; Jamjoom, Lamia Ghazi; Alharthy, Ahmed; Madani, Tariq A. (2014). "Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Chest CT Findings". American Journal of Roentgenology: 1–6. doi:10.2214/AJR.14.13021. ISSN 0361-803X.
- ↑ Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A; et al. (2013). "Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study". Lancet Infect Dis. 13 (9): 752–61. doi:10.1016/S1473-3099(13)70204-4. PMID 23891402.
- ↑ Memish, Ziad A.; Zumla, Alimuddin I.; Al-Hakeem, Rafat F.; Al-Rabeeah, Abdullah A.; Stephens, Gwen M. (2013). "Family Cluster of Middle East Respiratory Syndrome Coronavirus Infections". New England Journal of Medicine. 368 (26): 2487–2494. doi:10.1056/NEJMoa1303729. ISSN 0028-4793.
- ↑ Assiri, Abdullah; McGeer, Allison; Perl, Trish M.; Price, Connie S.; Al Rabeeah, Abdullah A.; Cummings, Derek A.T.; Alabdullatif, Zaki N.; Assad, Maher; Almulhim, Abdulmohsen; Makhdoom, Hatem; Madani, Hossam; Alhakeem, Rafat; Al-Tawfiq, Jaffar A.; Cotten, Matthew; Watson, Simon J.; Kellam, Paul; Zumla, Alimuddin I.; Memish, Ziad A. (2013). "Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus". New England Journal of Medicine. 369 (5): 407–416. doi:10.1056/NEJMoa1306742. ISSN 0028-4793.
- ↑ Abdel-Moneim, Ahmed S. (2014). "Middle East respiratory syndrome coronavirus (MERS-CoV): evidence and speculations". Archives of Virology. doi:10.1007/s00705-014-1995-5. ISSN 0304-8608.
- ↑ 7.0 7.1 7.2 "Updated Information on the Epidemiology of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Guidance for the Public, Clinicians, and Public Health Authorities, 2012–2013".
- ↑ "Interim surveillance recommendations for human infection with Middle East respiratory syndrome coronavirus" (PDF).
- ↑ 9.0 9.1 9.2 "Laboratory Testing for Middle East Respiratory Syndrome Coronavirus" (PDF).
- ↑ Centers for Disease Control and Prevention (CDC) (2013). "Update: Severe respiratory illness associated with Middle East Respiratory Syndrome Coronavirus (MERS-CoV)--worldwide, 2012-2013". MMWR Morb Mortal Wkly Rep. 62 (23): 480–3. PMID 23760190.
- ↑ "Interim Guidelines for Collection, Processing and Transport of Clinical Specimens from Patients Under Investigation for Middle East Respiratory Syndrome (MERS)" (PDF).
- ↑ Memish ZA, Al-Tawfiq JA, Makhdoom HQ, Assiri A, Alhakeem RF, Albarrak A; et al. (2014). "Respiratory Tract Samples, Viral Load and Genome Fraction Yield in patients with Middle East Respiratory Syndrome". J Infect Dis. doi:10.1093/infdis/jiu292. PMID 24837403.
- ↑ "Morbidity and Mortality Weekly Report (MMWR)".
- ↑ "Morbidity and Mortality Weekly Report (MMWR)".
- ↑ 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 15.12 "Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Patients Under Investigation (PUIs) for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – Version 2".