Difference between revisions of "Journal:Laboratory testing for coronavirus disease (COVID-19) in suspected human cases"

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==Background==
 
==Background==
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This document provides interim guidance to [[Laboratory|laboratories]] and stakeholders involved in [[COVID-19]] virus laboratory testing of patients. It is based in part on the interim guidance on laboratory testing for Middle East Respiratory Syndrome (MERS) coronavirus.<ref name="WHOLab18">{{cite web |url=https://www.who.int/csr/disease/coronavirus_infections/mers-laboratory-testing/en/ |title=Laboratory testing for Middle East Respiratory Syndrome coronavirus, interim guidance (revised), January 2018 |work=WHO/MERS/LAB/15.1/Rev1/2018 |author=World Health Organization |publisher=World Health Organization |date=January 2018}}</ref><ref name="WHOManaging18">{{cite book |url=https://apps.who.int/iris/handle/10665/272442 |title=Managing epidemics: Key facts about major deadly diseases |author=World Health Organization |publisher=World Health Organization |pages=257 |year=2018 |isbn=9789241565530}}</ref><ref name="WHOManualFor11">{{cite book |url=https://apps.who.int/iris/handle/10665/44518 |title=WHO Global Influenza Surveillance Network: Manual for the laboratory diagnosis and virological surveillance of influenza |author=World Health Organization |publisher=World Health Organization |pages=140 |year=2011 |isbn=9789241548090}}</ref><ref name="WHOProtocol18">{{cite web |url=https://www.who.int/influenza/resources/publications/outbreak_investigation_protocol/en/ |title=Protocol to investigate non-seasonal influenza and other emerging acute respiratory diseases |work=WHO/WHE/IHM/GIP/2018.2 |author=World Health Organization |publisher=World Health Organization |date=October 2018}}</ref><ref name="WHORecomm99">{{cite web |url=https://apps.who.int/iris/handle/10665/65517 |title=WHO Recommended Surveillance Standards, Second Edition |work=WHO/CDS/CSR/ISR/99.2 |author=World Health Organization |publisher=World Health Organization |date=October 1999}}</ref><ref name="WHOGuidelines00">{{cite web |url=https://apps.who.int/iris/handle/10665/66348 |title=Guidelines for the Collection of Clinical Specimens During Field Investigation of Outbreaks |work=WHO/CDS/CSR/EDC/2000.4 |author=World Health Organization |publisher=World Health Organization |date=2000}}</ref> [[Information]] on human [[infection]] with the COVID-19 virus is evolving and WHO continues to monitor developments and revise recommendations as necessary. This document will be revised as new information becomes available. Feedback is welcome and can be sent to WHElab@who.int.
 +
 +
The virus has now been named SARS-CoV-2 by the International Committee of Taxonomy of Viruses (ICTV)(2).<ref name="GorbalenyaSevere20">{{cite journal |title=Severe acute respiratory syndrome-related coronavirus: The species and its viruses – A statement of the Coronavirus Study Group |journal=bioRxiv |author=Gorbalenya, A.E.; Baker, S.C.; Baric, R.S. et al. |at=937862 |year=2020 |doi=10.1101/2020.02.07.937862}}</ref> This virus can cause the disease named coronavirus disease 2019 (COVID-19). WHO refers to the virus as COVID-19 virus in its current documentation.
 +
 +
==Laboratory testing guiding pricinciples for patients who meet the suspect case definition==
 +
The decision to test should be based on [[Clinical pathology|clinical]] and [[Epidemiology|epidemiological]] factors and linked to an assessment of the likelihood of infection. [[Polymerase chain reaction]] (PCR) testing of asymptomatic or mildly symptomatic contacts can be considered in the assessment of individuals who have had contact with a COVID-19 case. Screening protocols should be adapted to the local situation. The case definitions are being regularly reviewed and updated as new information becomes available. For the WHO suspected case definition see ''Global surveillance for COVID-19 caused by human infection with COVID-19 virus''.<ref name="WHOGlobalSurv20">{{cite web |url=https://apps.who.int/iris/handle/10665/331506 |title=Global surveillance for COVID-19 caused by human infection with COVID-19 virus: interim guidance, 20 March 2020 |work=WHO/2019-nCoV/SurveillanceGuidance/2020.6 |author=World Health Organization |publisher=World Health Organization |date=20 March 2020}}</ref>
 +
 +
Rapid collection and testing of appropriate [[Sample (material)|specimens]] from patients meeting the suspected case definition for COVID-19 is a priority for clinical management and outbreak control and should be guided by a laboratory expert. Suspected cases should be screened for the virus with [[Nucleic acid test|nucleic acid amplification tests]] (NAAT), such as [[Reverse transcription polymerase chain reaction]] (RT-PCR).
 +
 +
If testing for COVID-19 is not yet available nationally, specimens should be referred. A list of WHO reference laboratories providing confirmatory testing for COVID-19 and shipment instructions can be found at the bottom of the WHO's national laboratories [https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/laboratory-guidance technical guidance page].
 +
 +
If case management requires it, patients should be tested for other respiratory pathogens using routine laboratory procedures, as recommended in local management guidelines for community-acquired pneumonia. Additional testing should not delay testing for COVID-19. As co-infections can occur, all patients who meet the suspected case definition should be tested for COVID-19 virus regardless of whether another respiratory pathogen is found.
 +
 +
In an early study in Wuhan, the mean incubation period for COVID-19 was 5.2 days among 425 cases, though it varies widely among individuals.<ref name="LiEarly20">{{cite journal |title=Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia |journal=The New England Journal of Medicine |author=Li, Q.; Guan, X.; Wu, P. et al. |year=2020 |doi=10.1056/NEJMoa2001316 |pmid=31995857}}</ref><ref name="GuanClinical20">{{cite journal |title=Clinical Characteristics of Coronavirus Disease 2019 in China |journal=The New England Journal of Medicine |author=Guan, W.; Ni, Z.; Hu, Y. et al. |year=2020 |doi=10.1056/NEJMoa2002032 |pmid=32109013}}</ref> [[Viral shedding|Virus shedding]] patterns are not yet well understood, and further investigations are needed to better understand the timing, compartmentalization, and quantity of viral shedding to inform optimal specimen collection. Although respiratory samples have the greatest yield, the virus can be detected in other specimens, including stool and blood.<ref name="LintonIncub20">{{cite journal |title=Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data |journal=Journal of Clinical Medicine |author=Linton, N.M.; Kobayashi, T.; Yang, Y. et al. |volume=9 |issue=2 |at=538 |year=2020 |doi=10.3390/jcm9020538 |pmid=32079150 |pmc=PMC7074197}}</ref><ref name="ZhangMolec20">{{cite journal |title=Molecular and serological investigation of 2019-nCoV infected patients: Implication of multiple shedding routes |journal=Emerging Microbes & Infections |author=Zhang, W.; Du, R.-H.; Li, B. et al. |volume=9 |issue=1 |pages=386–89 |year=2020 |doi=10.1080/22221751.2020.1729071 |pmid=32065057 |pmc=PMC7048229}}</ref> Local guidelines on [[informed consent]] should be followed for specimen collection, testing, and potentially any future research.
 +
 +
==Specimen collection and shipment==
 +
===Safety procedures during specimen collection===
 +
Ensure that adequate [[standard operating procedure]]s (SOPs) are in use and that staff are trained for appropriate specimen collection, storage, packaging, and transport. All specimens collected for laboratory investigations should be regarded as potentially infectious.
 +
 +
Ensure that health care workers who collect specimens adhere rigorously to infection prevention and control guidelines. Specific WHO interim guidance has been published.<ref name="WHOLabBio20">{{cite web |url=https://apps.who.int/iris/handle/10665/331500 |title=Laboratory biosafety guidance related to coronavirus disease (COVID-19): Interim guidance, 19 March 2020 |work=WHO/WPE/GIH/2020.2 |author=World Health Organization |publisher=World Health Organization |date=19 March 2020}}</ref> Also see Box 1, below.
 +
 +
{|
 +
| STYLE="vertical-align:top;"|
 +
{| class="wikitable" border="1" cellpadding="5" cellspacing="0" width="60%"
 +
|-
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;" colspan="1"|'''Box 1.''' Biosafety practices in the laboratory
 +
|-
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|
 +
Testing on clinical specimens from patients meeting the suspected case definition should be performed in appropriately equipped laboratories by staff trained in the relevant technical and safety procedures. National guidelines on laboratory [[biosafety]] should be followed in all circumstances. There is still limited information on the risk posed by COVID-19, but all procedures should be undertaken based on a risk assessment. Specimen handling for [[Molecular diagnostics|molecular testing]] would require [[biosafety level two]] (BSL-2) or equivalent facilities. Attempts to culture the virus require BSL-3 facilities at minimum.<br />&nbsp;<br />For more information related to COVID-19 risk assessment, see ''[https://apps.who.int/iris/handle/10665/331500 Laboratory Biosafety Guidance Related to Coronavirus Disease (COVID-19)]''. Samples that are potentially infectious materials (PIM) for polio need to be handled and stored as described in WHO document ''[https://apps.who.int/iris/handle/10665/276199 Guidance to Minimize Risks for Facilities Collecting, Handling or Storing Materials Potentially Infectious for Polioviruses]''. For general laboratory biosafety guidelines, see the WHO's ''[https://www.who.int/csr/resources/publications/biosafety/WHO_CDS_CSR_LYO_2004_11/en/ Laboratory Biosafety Manual, Third Edition]'' (a fourth edition is still in revision<ref name="KojimaWHOLab19">{{cite web |url=https://www.slideshare.net/MicrobiologySection/who-laboratory-biosafety-manual-revision-update |title=WHO Laboratory Biosafety Manial Revision Update |author=Kojima, K. |publisher=World Health Organization |work=SlideShare |date=07 February 2019}}</ref>).
 +
|-
 +
|}
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|}
 +
 +
===Specimens to be collected===
 +
At a minimum, respiratory material should be collected. This includes:
 +
 +
* upper respiratory specimens, using a nasopharyngeal and oropharyngeal swab or wash in ambulatory patients; and/or,
 +
* lower respiratory specimens such as sputum (if produced), or use endotracheal [[Suction (medicine)|aspiration]] or [[bronchoalveolar lavage]] procedures in patients with more severe respiratory disease (note the high risk of aerosolization; adhere strictly to infection prevention and control procedures).
 +
 +
Additional clinical specimens may be collected. For example, COVID-19 virus has been detected in blood and stool, as had the coronaviruses responsible for SARS ([[severe acute respiratory syndrome]]) and MERS ([[Middle East respiratory syndrome]]).<ref name="LintonIncub20" /><ref name="ZhangMolec20" /><ref name="ShiSevere05">{{cite journal |title=Severe acute respiratory syndrome associated coronavirus is detected in intestinal tissues of fatal cases |journal=American Journal of Gastroenterology |author=Shi, X.; Gong, E.; Gao, D. et al. |volume=100 |issue=1 |pages=169–76 |year=2005 |doi=10.1111/j.1572-0241.2005.40377.x |pmid=15654797}}</ref><ref name="ZhouHuman17">{{cite journal |title=Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus |journal=Science Advances |author=Zhou, J.; Li, C.; Zhao, G. et al. |volume=3 |issue=11 |at=eaao4966 |year=2017 |doi=10.1126/sciadv.aao4966 |pmid=29152574 |pmc=PMC5687858}}</ref><ref name="DingOrgan04">{{cite journal |title=Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: Implications for pathogenesis and virus transmission pathways |journal=Journal of Pathology |author=Ding, Y.; He, L.; Zhang, Q. et al. |volume=203 |issue=2 |pages=622-30 |year=2004 |doi=10.1002/path.1560 |pmid=15141376}}</ref> The duration and frequency of shedding of COVID-19 virus in stool and potentially in urine is unknown. In case of patients who are deceased, consider autopsy material, including lung tissue. In surviving patients, paired serum (acute and convalescent) can be useful to retrospectively define cases as serological assays become available.
 +
 +
Further recommendations on materials to collect, including the testing of asymptomatic individuals, can be found in Table 1.
 +
 +
{|
 +
| STYLE="vertical-align:top;"|
 +
{| class="wikitable" border="1" cellpadding="5" cellspacing="0" width="70%"
 +
|-
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;" colspan="4"|'''Table 1.''' Specimens to be collected from symptomatic patients and contacts
 +
|-
 +
  ! style="background-color:#e2e2e2; padding-left:10px; padding-right:10px;"|Patient or contact?
 +
  ! style="background-color:#e2e2e2; padding-left:10px; padding-right:10px;"|Test
 +
  ! style="background-color:#e2e2e2; padding-left:10px; padding-right:10px;"|Type of sample
 +
  ! style="background-color:#e2e2e2; padding-left:10px; padding-right:10px;"|Timing
 +
|-
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|Patient
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|NAAT
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|From the upper respiratory tract: nasopharyngeal and oropharyngeal swabs, or nasopharyngeal wash or aspiration.<br />&nbsp;<br />From the lower respiratory tract: direct spetum collection, endotracheal aspiration, or bronchoalveolar lavage.<br />&nbsp;<br />Also consider stools, whole blood, urine, and, if deceased, material from autopsy.
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|Collect on presentation. May possibly require repeated sampling to monitor clearance. Further research needed to determine effectiveness and reliability of repeated sampling.
 +
|-
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|Patient
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|Serology
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|Serum for serological testing once validated and available
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|Paired samples are necessary for confirmation, with the initial sample collected in the first week of illness and the second ideally collected two to four weeks later (optimal timing for convalescent sample needs to be established).
 +
|-
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;" rowspan="2"|Contact (in healthcare-centre-associated outbreaks or other settings where contacts have symptoms, or where asymptomatic contacts have had high-intensity contact with a COVID-19 case)
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|NAAT
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|Nasopharyngeal and oropharyngeal swabs
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|Within incubation period of last documented contact
 +
|-
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|Serology
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|Serum for serological testing once validated and available
 +
  | style="background-color:white; padding-left:10px; padding-right:10px;"|Baseline serum is taken as early as possible within incubation period of contact, and convalescent serum is taken two to four weeks after last contact (optimal timing for convalescent sample needs to be established).
 +
|-
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|}
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|}
  
  
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==Notes==
 
==Notes==
This presentation is faithful to the original, with only a few minor changes to presentation, grammar, and punctuation. In some cases important information was missing from the references, and that information was added. Per the WHO's [https://www.who.int/about/who-we-are/publishing-policies/copyright licensing agreement], this reproduction acknowledges the World Health Organization as the source, licensed under the CC BY-NC-SA 3.0 IGO license (see the infobox at top for full details).
+
This presentation is faithful to the original, with only a few minor changes to presentation, grammar, and punctuation. In some cases important information was missing from the references, and that information was added. Their citation #8 referencing the Laboratory Biosafety Manual appears misplaced in the original document; it is appended in where it presumably should go in this version. Their citation #9 is placed where #8 was in the original, as it makes the most sense. The original lists a citation #13, but no in-line citation could be found in the text body; as such, citation #13 is omitted from this version. The original lists a citation #15, but it appears that document no longer exists and was likely superceded by citation #16; as such, citation #15 is omitted from this version. In cases where the document names have changed recently, the correct document name was substituted. A citation concerning the fourth edition of WHO's ''Laboratory Biosafety Manual'' was added for this version. Per the WHO's [https://www.who.int/about/who-we-are/publishing-policies/copyright licensing agreement], this reproduction acknowledges the World Health Organization as the source, licensed under the CC BY-NC-SA 3.0 IGO license (see the infobox at top for full details).
  
 
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Revision as of 23:50, 22 March 2020

Full article title Laboratory testing for coronavirus disease (COVID-19) in suspected human cases
Author(s) World Health Organization; Leitmeyer, Katrin; Zambon, Maria; Drosten, Christian; Koopmans, Marion; Poon, Leo; Gao, George;
Nahapetyan, Karen; Inbanathan, Francis; Pereyaslov, Dmitriy; Uhlenhaut, Christine; Grabovac, Varja; Vandemaele, Katelijn;
Samaan, Magdi; Fuster, Christian; Zhang, Wenqing; Stevens, Lisa; Oxenford, Chris; Cognat, Sebastian; Kojima, Kazunobu;
Dolea, Carmen; Brown, Caroline; Barnadas, Céline; Van Kerkhove, Maria; Carter, Lisa; Perkins, Mark D.; von Eije, Karin
Author affiliation(s) European Center for Disease Control, Public Health England, Charité - Universitätsmedizin Berlin,
Erasmus University Medical Center, Hong Kong University, Chinese Center for Disease Control and Prevention,
World Health Organization
Primary contact Email: WHElab at who dot int
Year published 2020
Volume and issue 2020.5
Page(s) 1–7
Distribution license Attribution-NonCommercial-ShareAlike 3.0 IGO
Website https://apps.who.int/iris/handle/10665/331501
Download https://apps.who.int/iris/bitstream/handle/10665/331501/WHO-COVID-19-laboratory-2020.5-eng.pdf (PDF)

Background

This document provides interim guidance to laboratories and stakeholders involved in COVID-19 virus laboratory testing of patients. It is based in part on the interim guidance on laboratory testing for Middle East Respiratory Syndrome (MERS) coronavirus.[1][2][3][4][5][6] Information on human infection with the COVID-19 virus is evolving and WHO continues to monitor developments and revise recommendations as necessary. This document will be revised as new information becomes available. Feedback is welcome and can be sent to WHElab@who.int.

The virus has now been named SARS-CoV-2 by the International Committee of Taxonomy of Viruses (ICTV)(2).[7] This virus can cause the disease named coronavirus disease 2019 (COVID-19). WHO refers to the virus as COVID-19 virus in its current documentation.

Laboratory testing guiding pricinciples for patients who meet the suspect case definition

The decision to test should be based on clinical and epidemiological factors and linked to an assessment of the likelihood of infection. Polymerase chain reaction (PCR) testing of asymptomatic or mildly symptomatic contacts can be considered in the assessment of individuals who have had contact with a COVID-19 case. Screening protocols should be adapted to the local situation. The case definitions are being regularly reviewed and updated as new information becomes available. For the WHO suspected case definition see Global surveillance for COVID-19 caused by human infection with COVID-19 virus.[8]

Rapid collection and testing of appropriate specimens from patients meeting the suspected case definition for COVID-19 is a priority for clinical management and outbreak control and should be guided by a laboratory expert. Suspected cases should be screened for the virus with nucleic acid amplification tests (NAAT), such as Reverse transcription polymerase chain reaction (RT-PCR).

If testing for COVID-19 is not yet available nationally, specimens should be referred. A list of WHO reference laboratories providing confirmatory testing for COVID-19 and shipment instructions can be found at the bottom of the WHO's national laboratories technical guidance page.

If case management requires it, patients should be tested for other respiratory pathogens using routine laboratory procedures, as recommended in local management guidelines for community-acquired pneumonia. Additional testing should not delay testing for COVID-19. As co-infections can occur, all patients who meet the suspected case definition should be tested for COVID-19 virus regardless of whether another respiratory pathogen is found.

In an early study in Wuhan, the mean incubation period for COVID-19 was 5.2 days among 425 cases, though it varies widely among individuals.[9][10] Virus shedding patterns are not yet well understood, and further investigations are needed to better understand the timing, compartmentalization, and quantity of viral shedding to inform optimal specimen collection. Although respiratory samples have the greatest yield, the virus can be detected in other specimens, including stool and blood.[11][12] Local guidelines on informed consent should be followed for specimen collection, testing, and potentially any future research.

Specimen collection and shipment

Safety procedures during specimen collection

Ensure that adequate standard operating procedures (SOPs) are in use and that staff are trained for appropriate specimen collection, storage, packaging, and transport. All specimens collected for laboratory investigations should be regarded as potentially infectious.

Ensure that health care workers who collect specimens adhere rigorously to infection prevention and control guidelines. Specific WHO interim guidance has been published.[13] Also see Box 1, below.

Box 1. Biosafety practices in the laboratory

Testing on clinical specimens from patients meeting the suspected case definition should be performed in appropriately equipped laboratories by staff trained in the relevant technical and safety procedures. National guidelines on laboratory biosafety should be followed in all circumstances. There is still limited information on the risk posed by COVID-19, but all procedures should be undertaken based on a risk assessment. Specimen handling for molecular testing would require biosafety level two (BSL-2) or equivalent facilities. Attempts to culture the virus require BSL-3 facilities at minimum.
 
For more information related to COVID-19 risk assessment, see Laboratory Biosafety Guidance Related to Coronavirus Disease (COVID-19). Samples that are potentially infectious materials (PIM) for polio need to be handled and stored as described in WHO document Guidance to Minimize Risks for Facilities Collecting, Handling or Storing Materials Potentially Infectious for Polioviruses. For general laboratory biosafety guidelines, see the WHO's Laboratory Biosafety Manual, Third Edition (a fourth edition is still in revision[14]).

Specimens to be collected

At a minimum, respiratory material should be collected. This includes:

  • upper respiratory specimens, using a nasopharyngeal and oropharyngeal swab or wash in ambulatory patients; and/or,
  • lower respiratory specimens such as sputum (if produced), or use endotracheal aspiration or bronchoalveolar lavage procedures in patients with more severe respiratory disease (note the high risk of aerosolization; adhere strictly to infection prevention and control procedures).

Additional clinical specimens may be collected. For example, COVID-19 virus has been detected in blood and stool, as had the coronaviruses responsible for SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome).[11][12][15][16][17] The duration and frequency of shedding of COVID-19 virus in stool and potentially in urine is unknown. In case of patients who are deceased, consider autopsy material, including lung tissue. In surviving patients, paired serum (acute and convalescent) can be useful to retrospectively define cases as serological assays become available.

Further recommendations on materials to collect, including the testing of asymptomatic individuals, can be found in Table 1.

Table 1. Specimens to be collected from symptomatic patients and contacts
Patient or contact? Test Type of sample Timing
Patient NAAT From the upper respiratory tract: nasopharyngeal and oropharyngeal swabs, or nasopharyngeal wash or aspiration.
 
From the lower respiratory tract: direct spetum collection, endotracheal aspiration, or bronchoalveolar lavage.
 
Also consider stools, whole blood, urine, and, if deceased, material from autopsy.
Collect on presentation. May possibly require repeated sampling to monitor clearance. Further research needed to determine effectiveness and reliability of repeated sampling.
Patient Serology Serum for serological testing once validated and available Paired samples are necessary for confirmation, with the initial sample collected in the first week of illness and the second ideally collected two to four weeks later (optimal timing for convalescent sample needs to be established).
Contact (in healthcare-centre-associated outbreaks or other settings where contacts have symptoms, or where asymptomatic contacts have had high-intensity contact with a COVID-19 case) NAAT Nasopharyngeal and oropharyngeal swabs Within incubation period of last documented contact
Serology Serum for serological testing once validated and available Baseline serum is taken as early as possible within incubation period of contact, and convalescent serum is taken two to four weeks after last contact (optimal timing for convalescent sample needs to be established).


References

  1. World Health Organization (January 2018). "Laboratory testing for Middle East Respiratory Syndrome coronavirus, interim guidance (revised), January 2018". WHO/MERS/LAB/15.1/Rev1/2018. World Health Organization. https://www.who.int/csr/disease/coronavirus_infections/mers-laboratory-testing/en/. 
  2. World Health Organization (2018). Managing epidemics: Key facts about major deadly diseases. World Health Organization. pp. 257. ISBN 9789241565530. https://apps.who.int/iris/handle/10665/272442. 
  3. World Health Organization (2011). WHO Global Influenza Surveillance Network: Manual for the laboratory diagnosis and virological surveillance of influenza. World Health Organization. pp. 140. ISBN 9789241548090. https://apps.who.int/iris/handle/10665/44518. 
  4. World Health Organization (October 2018). "Protocol to investigate non-seasonal influenza and other emerging acute respiratory diseases". WHO/WHE/IHM/GIP/2018.2. World Health Organization. https://www.who.int/influenza/resources/publications/outbreak_investigation_protocol/en/. 
  5. World Health Organization (October 1999). "WHO Recommended Surveillance Standards, Second Edition". WHO/CDS/CSR/ISR/99.2. World Health Organization. https://apps.who.int/iris/handle/10665/65517. 
  6. World Health Organization (2000). "Guidelines for the Collection of Clinical Specimens During Field Investigation of Outbreaks". WHO/CDS/CSR/EDC/2000.4. World Health Organization. https://apps.who.int/iris/handle/10665/66348. 
  7. Gorbalenya, A.E.; Baker, S.C.; Baric, R.S. et al. (2020). "Severe acute respiratory syndrome-related coronavirus: The species and its viruses – A statement of the Coronavirus Study Group". bioRxiv: 937862. doi:10.1101/2020.02.07.937862. 
  8. World Health Organization (20 March 2020). "Global surveillance for COVID-19 caused by human infection with COVID-19 virus: interim guidance, 20 March 2020". WHO/2019-nCoV/SurveillanceGuidance/2020.6. World Health Organization. https://apps.who.int/iris/handle/10665/331506. 
  9. Li, Q.; Guan, X.; Wu, P. et al. (2020). "Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia". The New England Journal of Medicine. doi:10.1056/NEJMoa2001316. PMID 31995857. 
  10. Guan, W.; Ni, Z.; Hu, Y. et al. (2020). "Clinical Characteristics of Coronavirus Disease 2019 in China". The New England Journal of Medicine. doi:10.1056/NEJMoa2002032. PMID 32109013. 
  11. 11.0 11.1 Linton, N.M.; Kobayashi, T.; Yang, Y. et al. (2020). "Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data". Journal of Clinical Medicine 9 (2): 538. doi:10.3390/jcm9020538. PMC PMC7074197. PMID 32079150. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7074197. 
  12. 12.0 12.1 Zhang, W.; Du, R.-H.; Li, B. et al. (2020). "Molecular and serological investigation of 2019-nCoV infected patients: Implication of multiple shedding routes". Emerging Microbes & Infections 9 (1): 386–89. doi:10.1080/22221751.2020.1729071. PMC PMC7048229. PMID 32065057. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC7048229. 
  13. World Health Organization (19 March 2020). "Laboratory biosafety guidance related to coronavirus disease (COVID-19): Interim guidance, 19 March 2020". WHO/WPE/GIH/2020.2. World Health Organization. https://apps.who.int/iris/handle/10665/331500. 
  14. Kojima, K. (07 February 2019). "WHO Laboratory Biosafety Manial Revision Update". SlideShare. World Health Organization. https://www.slideshare.net/MicrobiologySection/who-laboratory-biosafety-manual-revision-update. 
  15. Shi, X.; Gong, E.; Gao, D. et al. (2005). "Severe acute respiratory syndrome associated coronavirus is detected in intestinal tissues of fatal cases". American Journal of Gastroenterology 100 (1): 169–76. doi:10.1111/j.1572-0241.2005.40377.x. PMID 15654797. 
  16. Zhou, J.; Li, C.; Zhao, G. et al. (2017). "Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus". Science Advances 3 (11): eaao4966. doi:10.1126/sciadv.aao4966. PMC PMC5687858. PMID 29152574. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC5687858. 
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Notes

This presentation is faithful to the original, with only a few minor changes to presentation, grammar, and punctuation. In some cases important information was missing from the references, and that information was added. Their citation #8 referencing the Laboratory Biosafety Manual appears misplaced in the original document; it is appended in where it presumably should go in this version. Their citation #9 is placed where #8 was in the original, as it makes the most sense. The original lists a citation #13, but no in-line citation could be found in the text body; as such, citation #13 is omitted from this version. The original lists a citation #15, but it appears that document no longer exists and was likely superceded by citation #16; as such, citation #15 is omitted from this version. In cases where the document names have changed recently, the correct document name was substituted. A citation concerning the fourth edition of WHO's Laboratory Biosafety Manual was added for this version. Per the WHO's licensing agreement, this reproduction acknowledges the World Health Organization as the source, licensed under the CC BY-NC-SA 3.0 IGO license (see the infobox at top for full details).