Middle East respiratory syndrome coronavirus infection laboratory findings: Difference between revisions

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==Overview==
==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]].<ref name=CDC>{{cite web | title = MERS Clinical Features| url = http://www.cdc.gov/coronavirus/mers/clinical-features.html }}</ref>
Laboratory findings of MERS-CoV may include [[leukopenia]], [[lymphopenia]], [[thrombocytopenia]], elevated inflammatory markers, and elevated [[lactate dehydrogenase]] ([[LDH]]) levels.<ref name=CDC>{{cite web | title = MERS Clinical Features| url = http://www.cdc.gov/coronavirus/mers/clinical-features.html }}</ref> Lab findings are not diagnostic of MERS-CoV but are useful to monitor for the development of MERS-CoV infection.


==Laboratory Findings==
==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:<ref name="AjlanAhyad2014">{{cite journal|last1=Ajlan|first1=Amr M.|last2=Ahyad|first2=Rayan A.|last3=Jamjoom|first3=Lamia Ghazi|last4=Alharthy|first4=Ahmed|last5=Madani|first5=Tariq A.|title=Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Chest CT Findings|journal=American Journal of Roentgenology|year=2014|pages=1–6|issn=0361-803X|doi=10.2214/AJR.14.13021}}</ref><ref name="pmid23891402">{{cite journal| author=Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A et al.| title=Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. | journal=Lancet Infect Dis | year= 2013 | volume= 13 | issue= 9 | pages= 752-61 | pmid=23891402 | doi=10.1016/S1473-3099(13)70204-4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23891402  }} </ref><ref name="MemishZumla2013">{{cite journal|last1=Memish|first1=Ziad A.|last2=Zumla|first2=Alimuddin I.|last3=Al-Hakeem|first3=Rafat F.|last4=Al-Rabeeah|first4=Abdullah A.|last5=Stephens|first5=Gwen M.|title=Family Cluster of Middle East Respiratory Syndrome Coronavirus Infections|journal=New England Journal of Medicine|volume=368|issue=26|year=2013|pages=2487–2494|issn=0028-4793|doi=10.1056/NEJMoa1303729}}</ref><ref name="AssiriMcGeer2013">{{cite journal|last1=Assiri|first1=Abdullah|last2=McGeer|first2=Allison|last3=Perl|first3=Trish M.|last4=Price|first4=Connie S.|last5=Al Rabeeah|first5=Abdullah A.|last6=Cummings|first6=Derek A.T.|last7=Alabdullatif|first7=Zaki N.|last8=Assad|first8=Maher|last9=Almulhim|first9=Abdulmohsen|last10=Makhdoom|first10=Hatem|last11=Madani|first11=Hossam|last12=Alhakeem|first12=Rafat|last13=Al-Tawfiq|first13=Jaffar A.|last14=Cotten|first14=Matthew|last15=Watson|first15=Simon J.|last16=Kellam|first16=Paul|last17=Zumla|first17=Alimuddin I.|last18=Memish|first18=Ziad A.|title=Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus|journal=New England Journal of Medicine|volume=369|issue=5|year=2013|pages=407–416|issn=0028-4793|doi=10.1056/NEJMoa1306742}}</ref><ref name="Abdel-Moneim2014">{{cite journal|last1=Abdel-Moneim|first1=Ahmed S.|title=Middle East respiratory syndrome coronavirus (MERS-CoV): evidence and speculations|journal=Archives of Virology|year=2014|issn=0304-8608|doi=10.1007/s00705-014-1995-5}}</ref>
*Laboratory confirmation of [[MERS-CoV]] infection requires a positive [[PCR]] test of ≥2 specific genomic targets or, a single positive target followed by successful sequencing of a second.
*Blood testing among hospitalized patients is useful. Lab findings may include non-specific findings of viral infections. In addition, lab findings may be useful to monitor for the development of MERS-CoV infection. Laboratory abnormalities may include:<ref name="AjlanAhyad2014">{{cite journal|last1=Ajlan|first1=Amr M.|last2=Ahyad|first2=Rayan A.|last3=Jamjoom|first3=Lamia Ghazi|last4=Alharthy|first4=Ahmed|last5=Madani|first5=Tariq A.|title=Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Chest CT Findings|journal=American Journal of Roentgenology|year=2014|pages=1–6|issn=0361-803X|doi=10.2214/AJR.14.13021}}</ref><ref name="pmid23891402">{{cite journal| author=Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A et al.| title=Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. | journal=Lancet Infect Dis | year= 2013 | volume= 13 | issue= 9 | pages= 752-61 | pmid=23891402 | doi=10.1016/S1473-3099(13)70204-4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23891402  }} </ref><ref name="MemishZumla2013">{{cite journal|last1=Memish|first1=Ziad A.|last2=Zumla|first2=Alimuddin I.|last3=Al-Hakeem|first3=Rafat F.|last4=Al-Rabeeah|first4=Abdullah A.|last5=Stephens|first5=Gwen M.|title=Family Cluster of Middle East Respiratory Syndrome Coronavirus Infections|journal=New England Journal of Medicine|volume=368|issue=26|year=2013|pages=2487–2494|issn=0028-4793|doi=10.1056/NEJMoa1303729}}</ref><ref name="AssiriMcGeer2013">{{cite journal|last1=Assiri|first1=Abdullah|last2=McGeer|first2=Allison|last3=Perl|first3=Trish M.|last4=Price|first4=Connie S.|last5=Al Rabeeah|first5=Abdullah A.|last6=Cummings|first6=Derek A.T.|last7=Alabdullatif|first7=Zaki N.|last8=Assad|first8=Maher|last9=Almulhim|first9=Abdulmohsen|last10=Makhdoom|first10=Hatem|last11=Madani|first11=Hossam|last12=Alhakeem|first12=Rafat|last13=Al-Tawfiq|first13=Jaffar A.|last14=Cotten|first14=Matthew|last15=Watson|first15=Simon J.|last16=Kellam|first16=Paul|last17=Zumla|first17=Alimuddin I.|last18=Memish|first18=Ziad A.|title=Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus|journal=New England Journal of Medicine|volume=369|issue=5|year=2013|pages=407–416|issn=0028-4793|doi=10.1056/NEJMoa1306742}}</ref><ref name="Abdel-Moneim2014">{{cite journal|last1=Abdel-Moneim|first1=Ahmed S.|title=Middle East respiratory syndrome coronavirus (MERS-CoV): evidence and speculations|journal=Archives of Virology|year=2014|issn=0304-8608|doi=10.1007/s00705-014-1995-5}}</ref>
*[[Lymphopenia]]
*[[Lymphopenia]]
*[[Thrombocytopenia]]
*[[Thrombocytopenia]]
*[[Leukopenia]]
*[[Leukopenia]]
*Elevated [[serum]] [[LDH]] levels
*Elevated [[CRP]] and [[ESR]] concentrations
*Elevated [[AST]] and [[ALT]] levels
*Elevated [[serum]] [[LDH]] concentration
*[[Renal function]] abnormalities
*Elevated [[AST]] and [[ALT]] concentration
*Elevated [[serum creatinine]] concentration


==CDC Guidelines==
==Specimen Collection==
According to [[CDC]] guidelines:<ref name=MMWR>{{cite web | title = 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 | url = http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6238a4.htm }}</ref>
*The [[CDC]] recommends that priority for collection and real-time [[RT-PCR]] testing should be given to [[lower respiratory tract]] [[Laboratory specimen|specimens]]. [[Lower respiratory]] [[Laboratory specimen|specimen]] testing appears to be more [[sensitivity|sensitive]] in the detection of [[MERS-CoV]], when compared to [[Laboratory specimen|specimens]] from the [[upper respiratory tract]].<ref name=WHO>{{cite web | title =  
*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]].<ref name=MMWR>{{cite web | title = 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 | url = http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6238a4.htm }}</ref>
 
===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]].<ref name=MMWR>{{cite web | title = 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 | url = http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6238a4.htm }}</ref>
 
==Specimen Types and Collection==
The [[CDC]] recommends that priority for collection and real-time [[RT-PCR]] testing should be given to [[lower respiratory tract]] [[Laboratory specimen|specimens]]. This preference is due to the fact that [[lower respiratory]] [[Laboratory specimen|specimen]] testing appears to be more [[sensitivity|sensitive]] in the detection of [[MERS-CoV]], when compared to [[Laboratory specimen|specimens]] from the [[upper respiratory tract]].<ref name=WHO>{{cite web | title =  
Interim surveillance recommendations for human infection with Middle East respiratory syndrome coronavirus | url = http://www.who.int/csr/disease/coronavirus_infections/InterimRevisedSurveillanceRecommendations_nCoVinfection_27Jun13.pdf }}</ref><ref name=CDC3>{{cite web | title =  
Interim surveillance recommendations for human infection with Middle East respiratory syndrome coronavirus | url = http://www.who.int/csr/disease/coronavirus_infections/InterimRevisedSurveillanceRecommendations_nCoVinfection_27Jun13.pdf }}</ref><ref name=CDC3>{{cite web | title =  
Laboratory Testing for Middle East Respiratory Syndrome Coronavirus | url = http://www.who.int/csr/disease/coronavirus_infections/MERS_Lab_recos_16_Sept_2013.pdf }}</ref><ref name="pmid23760190">{{cite journal| author=Centers for Disease Control and Prevention (CDC)| title=Update: Severe respiratory illness associated with Middle East Respiratory Syndrome Coronavirus (MERS-CoV)--worldwide, 2012-2013. | journal=MMWR Morb Mortal Wkly Rep | year= 2013 | volume= 62 | issue= 23 | pages= 480-3 | pmid=23760190 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23760190  }} </ref><ref name=CDC4>{{cite web | title =  
Laboratory Testing for Middle East Respiratory Syndrome Coronavirus | url = http://www.who.int/csr/disease/coronavirus_infections/MERS_Lab_recos_16_Sept_2013.pdf }}</ref><ref name="pmid23760190">{{cite journal| author=Centers for Disease Control and Prevention (CDC)| title=Update: Severe respiratory illness associated with Middle East Respiratory Syndrome Coronavirus (MERS-CoV)--worldwide, 2012-2013. | journal=MMWR Morb Mortal Wkly Rep | year= 2013 | volume= 62 | issue= 23 | pages= 480-3 | pmid=23760190 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23760190  }} </ref><ref name=CDC4>{{cite web | title =  
Interim Guidelines for Collection, Processing and Transport of Clinical Specimens from Patients Under Investigation for Middle East Respiratory Syndrome (MERS) | url = http://www.cdc.gov/coronavirus/mers/downloads/Interim-Guidelines-MERS-Collection-Processing-Transport.pdf }}</ref><ref name="pmid24837403">{{cite journal| author=Memish ZA, Al-Tawfiq JA, Makhdoom HQ, Assiri A, Alhakeem RF, Albarrak A et al.| title=Respiratory Tract Samples, Viral Load and Genome Fraction Yield in patients with Middle East Respiratory Syndrome. | journal=J Infect Dis | year= 2014 | volume=  | issue=  | pages=  | pmid=24837403 | doi=10.1093/infdis/jiu292 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24837403  }} </ref>
Interim Guidelines for Collection, Processing and Transport of Clinical Specimens from Patients Under Investigation for Middle East Respiratory Syndrome (MERS) | url = http://www.cdc.gov/coronavirus/mers/downloads/Interim-Guidelines-MERS-Collection-Processing-Transport.pdf }}</ref><ref name="pmid24837403">{{cite journal| author=Memish ZA, Al-Tawfiq JA, Makhdoom HQ, Assiri A, Alhakeem RF, Albarrak A et al.| title=Respiratory Tract Samples, Viral Load and Genome Fraction Yield in patients with Middle East Respiratory Syndrome. | journal=J Infect Dis | year= 2014 | volume=  | issue=  | pages=  | pmid=24837403 | doi=10.1093/infdis/jiu292 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24837403  }} </ref>
It is recommended the collection of multiple [[Laboratory specimen|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 test]]s for this [[virus]].<ref name=CDC3>{{cite web | title = Laboratory Testing for Middle East Respiratory Syndrome Coronavirus | url = http://www.who.int/csr/disease/coronavirus_infections/MERS_Lab_recos_16_Sept_2013.pdf }}</ref><ref name=CDC6.>{{cite web | title = Morbidity and Mortality Weekly Report (MMWR) | url = http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6319a4.htm?s_cid=mm6319a4_w }}</ref> It is also recommended that, in all cases of severe disease, priority is given to [[respiratory]] samples, particularly [[lower respiratory tract]] [[Laboratory specimen|specimens]]; in the case of mild disease, [[upper respiratory tract|upper tract]] [[Laboratory specimen|specimen]] should be collected, if [[lower respiratory tract|lower tract]] [[Laboratory specimen|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]].<ref name=CDC7>{{cite web | title = Morbidity and Mortality Weekly Report (MMWR) | url = http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6319a4.htm?s_cid=mm6319a4_w }}</ref>
*It is recommended the collection of '''''multiple''''' [[Laboratory specimen|specimens]] from '''''different locations''''' and in '''''different times''''', 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 test]]s for this [[virus]].<ref name=CDC3>{{cite web | title = Laboratory Testing for Middle East Respiratory Syndrome Coronavirus | url = http://www.who.int/csr/disease/coronavirus_infections/MERS_Lab_recos_16_Sept_2013.pdf }}</ref><ref name=CDC6.>{{cite web | title = Morbidity and Mortality Weekly Report (MMWR) | url = http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6319a4.htm?s_cid=mm6319a4_w }}</ref>  
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:<ref name=CDC3>{{cite web | title = Laboratory Testing for Middle East Respiratory Syndrome Coronavirus | url = http://www.who.int/csr/disease/coronavirus_infections/MERS_Lab_recos_16_Sept_2013.pdf }}</ref>
*It is recommended that, in all cases of severe disease, priority is given to [[respiratory]] samples, particularly [[lower respiratory tract]] [[Laboratory specimen|specimens]]
*Poor [[Laboratory specimen|specimen]] quality
**In the case of mild disease, [[upper respiratory tract|upper tract]] [[Laboratory specimen|specimen]] should be collected
*Wrong timing of collection
**In the case of [[lower respiratory tract|lower tract]] [[Laboratory specimen|specimens]] cannot be obtained.
*Mishandled/shipped sample
*[[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]].<ref name=CDC7>{{cite web | title = Morbidity and Mortality Weekly Report (MMWR) | url = http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6319a4.htm?s_cid=mm6319a4_w }}</ref>
*Technical problem during testing
*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 is commonly due to any of the following:<ref name=CDC3>{{cite web | title = Laboratory Testing for Middle East Respiratory Syndrome Coronavirus | url = http://www.who.int/csr/disease/coronavirus_infections/MERS_Lab_recos_16_Sept_2013.pdf }}</ref>
In patients suspected of being [[infected]] with the [[MERS-CoV]], the following [[Laboratory specimen|specimens]] should be collected, by health-care providers, for submission to a [[public health laboratory]] or to the [[CDC]]:
**Poor [[Laboratory specimen|specimen]] quality
*[[Nasopharyngeal]] swab
**Wrong timing of collection
*[[Oropharyngeal]] swab (might be placed in the same container, in [[viral]] transport medium, as the [[nasopharyngeal]] swabs)
**Mishandled/shipped sample
*[[Sputum]]
**Technical problem during testing
*[[Serum]]
*Stool/rectal swab.
During the collection of the [[Laboratory specimen|specimens]], it is recommended the use of [[infection]] control precautions and the health-care practitioners, involved the collection of these [[Laboratory specimen|specimens]], should wear recommended personal protective equipment, such as:
*Gloves
*Gowns
*[[Eye]] protection
*[[Respiratory]] protection


==Collecting, Handling, and Testing Clinical Specimens==
===Collection of Respiratory Specimens===
According to the [[CDC]], each [[Laboratory specimen|specimen]] container should be labeled with the patient’s ID number, [[Laboratory specimen|specimen]] type and the date when the sample was collected. The guidelines to collect and store [[biological]] [[Laboratory specimen|specimens]] include:<ref name=CDC2>{{cite web | title = Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Patients Under Investigation (PUIs) for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – Version 2
| url = http://www.cdc.gov/coronavirus/mers/guidelines-clinical-specimens.html }}</ref>
===Respiratory Specimens===
====Lower respiratory tract broncheoalveolar lavage, tracheal aspirate and pleural fluid====
====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 [[Laboratory specimen|specimen]] at 2-8°C up to 72 hours; if exceeding 72 hours, freeze at -70°C and ship on dry ice.<ref name=CDC2>{{cite web | title = Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Patients Under Investigation (PUIs) for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – Version 2
Collect 2-3 mL into a [[sterile]], leak-proof, screw-cap [[sputum]] collection cup or [[sterile]] dry container. Refrigerate [[Laboratory specimen|specimen]] at 2-8°C up to 72 hours; if exceeding 72 hours, freeze at -70°C and ship on dry ice.<ref name=CDC2>{{cite web | title = Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Patients Under Investigation (PUIs) for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – Version 2
Line 85: Line 61:
====Serum (for serologic testing)====
====Serum (for serologic testing)====
For [[serum]] [[antibody]] testing: [[serum]] [[Laboratory specimen|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.<ref name=CDC2>{{cite web | title = Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Patients Under Investigation (PUIs) for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – Version 2
For [[serum]] [[antibody]] testing: [[serum]] [[Laboratory specimen|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.<ref name=CDC2>{{cite web | title = Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Patients Under Investigation (PUIs) for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – Version 2
| url = http://www.cdc.gov/coronavirus/mers/guidelines-clinical-specimens.html }}</ref>
====Serum (for rRT-PCR testing)====
* For [[Real-time polymerase chain reaction|rRT-PCR]] testing (i.e., detection of the [[virus]] and not [[antibodies]]), a single [[serum]] [[Laboratory specimen|specimen]] collected optimally during the first week after [[symptom]] onset, preferably within 3-4 days, after [[symptom]] onset, may be also be beneficial.<ref name=CDC2>{{cite web | title = Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Patients Under Investigation (PUIs) for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – Version 2
| url = http://www.cdc.gov/coronavirus/mers/guidelines-clinical-specimens.html }}</ref>
* Children and adults: Collect 1 tube (5-10 mL) of [[blood]] in a [[serum]] separator tube. Allow the [[blood]] to [[clot]], [[centrifuge]] briefly, and separate [[serum|sera]] into [[sterile]] tube container. The minimum amount of [[serum]] required for testing is 200 µL. Refrigerate the [[Laboratory specimen|specimen]] at 2-8°C and ship on ice-pack; freezing and shipment on dry ice is permissible.<ref name=CDC2>{{cite web | title = Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Patients Under Investigation (PUIs) for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – Version 2
| url = http://www.cdc.gov/coronavirus/mers/guidelines-clinical-specimens.html }}</ref>
* Infants: A minimum of 1 mL of [[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.<ref name=CDC2>{{cite web | title = Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Patients Under Investigation (PUIs) for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – Version 2
  | url = http://www.cdc.gov/coronavirus/mers/guidelines-clinical-specimens.html }}</ref>
  | url = http://www.cdc.gov/coronavirus/mers/guidelines-clinical-specimens.html }}</ref>


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[[category:disease]]
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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 of MERS-CoV may include leukopenia, lymphopenia, thrombocytopenia, elevated inflammatory markers, and elevated lactate dehydrogenase (LDH) levels.[1] Lab findings are not diagnostic of MERS-CoV but are useful to monitor for the development of MERS-CoV infection.

Laboratory Findings

  • Laboratory confirmation of MERS-CoV infection requires a positive PCR test of ≥2 specific genomic targets or, a single positive target followed by successful sequencing of a second.
  • Blood testing among hospitalized patients is useful. Lab findings may include non-specific findings of viral infections. In addition, lab findings may be useful to monitor for the development of MERS-CoV infection. Laboratory abnormalities may include:[2][3][4][5][6]
  • Lymphopenia
  • Thrombocytopenia
  • Leukopenia
  • Elevated CRP and ESR concentrations
  • Elevated serum LDH concentration
  • Elevated AST and ALT concentration
  • Elevated serum creatinine concentration

Specimen Collection

Collection of 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.[14]

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.[14]

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.[14]

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.[14]

Oropharyngeal swabs

Swab the posterior pharynx, avoiding the tongue.[14]

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.[14]

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.[14]

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.[14]

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.[14]

References

  1. ↑ "MERS Clinical Features".
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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. ↑ "Interim surveillance recommendations for human infection with Middle East respiratory syndrome coronavirus" (PDF).
  8. ↑ 8.0 8.1 8.2 "Laboratory Testing for Middle East Respiratory Syndrome Coronavirus" (PDF).
  9. ↑ 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.
  10. ↑ "Interim Guidelines for Collection, Processing and Transport of Clinical Specimens from Patients Under Investigation for Middle East Respiratory Syndrome (MERS)" (PDF).
  11. ↑ 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.
  12. ↑ "Morbidity and Mortality Weekly Report (MMWR)".
  13. ↑ "Morbidity and Mortality Weekly Report (MMWR)".
  14. ↑ 14.0 14.1 14.2 14.3 14.4 14.5 14.6 14.7 14.8 "Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Patients Under Investigation (PUIs) for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – Version 2".

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