Coronavirus disease 2019, abbreviated to COVID-19, is an emerging global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the number of individuals infected with COVID-19 continues to rise globally and healthcare systems become increasingly stressed, it is clear that the clinical laboratory will play an essential role in this crisis, contributing to patient screening, diagnosis, monitoring/treatment, as well as epidemiologic recovery/surveillance. This guide aims to organize relevant available information on laboratory screening, testing protocols, diagnosis, and other general information on COVID-19 for laboratory professionals, including links to helpful resources and interim guidelines. It will be continually updated as new guidelines and literature become available.

General Information:

Please find below links to helpful websites and guidelines that have been put together by laboratory and clinical specialists from all over the world:

American Association for Clinical Chemistry: COVID-19 Resources for Labs

British Medical Journal: COVID-19 Best Practice Guideline

Center for Disease Control: Information for Laboratories

European Centre for Disease Prevention and Control: COVID-19 Resources

World Health Organization: COVID-19 Technical Guidance for National Laboratories

Zhejiang University School of Medicine: Handbook of COVID-19 Prevention and Treatment

Patient Screening

According to the World Health Organization (WHO) guide for Global surveillance for COVID-19 caused by human infection with COVID-19 virus, there are two main factors to consider when screening patients for COVID-19: epidemiological history and clinical manifestation.

1. Epidemiological History: within the last 14 days of symptom onset, the patient has a travel history or residence in a location with community transmission or contact with a probable or confirmed case.
2. Clinical Manifestation: acute respiratory illness, which is characterized by fever and at least one respiratory sign/symptom, such as cough or shortness of breath.

Suspect cases are defined as:

• A patient with acute respiratory illness AND epidemiological history

OR

• A patient with severe acute respiratory illness (characterized as described above AND requires hospitalization) AND no alternative diagnosis that fully explains the clinical signs/symptoms

Diagnostic Testing: Analytical and Clinical Aspects

Upon confirmation of a suspected case, specimens should be rapidly collected and tested. The Centers for Disease Control and Prevention (CDC) Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons for Coronavirus Disease 2019 recommends collecting an upper respiratory specimen for initial diagnostic testing. The following specimens can be collected for swab-based testing: Nasopharyngeal specimen (preferred), Oropharyngeal specimen, Nasal mid-turbinate specimen and Anterior nares specimen. Lower respiratory tract specimen testing is also recommended by the CDC, if the specimens are available.

Nucleic Acid Amplification Tests (NAAT)

Real-time reverse transcription polymerase chain reaction (rRT-PCR) is the current gold standard for diagnosing suspected cases of COVID-19. rRT-PCR is a nucleic acid amplification test (NAAT) that detects unique sequences of the virus that causes COVID-19 (SARS-CoV-2) in respiratory tract specimens. The N, E, S, and RdRP are the viral genes currently targeted (WHO,  Laboratory testing for coronavirus disease (COVID-19) in suspected human cases). A validated diagnostic workflow for detecting SARS-CoV-2 has been recently published by Corman and colleagues (PMID: 31992387), as follows: (a) First line screening: E gene, (b) Confirmatory screening: RdRP gene, and (c) Additional confirmatory screening: N gene.

The following table presents criteria for a case to be considered as laboratory-confirmed by validated NAAT assays according to the WHO:

In some cases, a negative result may be returned for a suspected case with high likelihood of COVID-19 infection. If the negative result was concluded based on only an upper respiratory tract specimen, a lower respiratory tract specimen should be subsequently tested. Additional specimens eligible for testing include blood and stool (WHO, Laboratory testing for coronavirus disease (COVID-19) in suspected human cases).

Currently Available Diagnostic Assays

Several in-house and commercial assays are currently being developed and optimized. Links to currently available in-house protocols can be accessed below (available via WHO):

China CDC Primers and probes for detection 2019-nCoV (24 January 2020)

Diagnostic detection of Wuhan coronavirus 2019 by real-time RT-PCR – Charité, Berlin Germany (17 January 2020)

Detection of 2019 novel coronavirus (2019-nCoV) in suspected human cases by RT-PCR – Hong Kong University (23 January 2020)

PCR and sequencing protocol for 2019-nCoV - Department of Medical Sciences, Ministry of Public Health, Thailand (Updated 28 January 2020)

PCR and sequencing protocols for 2019-nCoV- National Institute of Infectious Diseases Japan (24 January 2020)

US CDC Real-Time RT-PCR Panel for Detection 2019-Novel Coronavirus  (28 January 2020)

US CDC panel primer and probes– U.S. CDC, USA (28 January 2020)

Real-time RT-PCR assays for the detection of SARS-CoV-2 Institut Pasteur, Paris (2 March 2020)

There are a variety of pre-analytical and analytical issues that can affect diagnostic testing for COVID-19 infection. Some pre-analytical issues include improper collection, handling, transport and usage of swabs, as well as collection of inappropriate or inadequate material, interfering substances, and sample contamination. A common analytical issue is testing outside of the diagnostic window, in addition to active viral recombination and inadequately validated assays (Lippi et al, PMID: 31992387).

Additional Resources/Publications for COVID-19 Serological Testing & Viral Sequencing:

John Hopkin’s Center for Health Security: Serology Testing for COVID-19

WHO: Laboratory testing for coronavirus disease 2019 (COVID-19) in suspected human cases

Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, Sun R, Wang Y, Hu B, Chen W, Zhang Y. Development and Clinical Application of A Rapid IgM‐IgG Combined Antibody Test for SARS‐CoV‐2 Infection Diagnosis. Journal of medical virology. 2020 Feb 27. PMID: 32104917

Meyer B, Drosten C, Müller MA. Serological assays for emerging coronaviruses: challenges and pitfalls. Virus research. 2014 Dec 19;194:175-83. PMID: 24670324

Biosafety Guidelines for the Clinical Laboratory

It is of the utmost importance that proper biosafety guidelines are followed by clinical laboratories when handling samples from suspected COVID-19 patients. Interim guidelines from the World Health Organization on laboratory biosafety guidance related to coronavirus disease were updated on March 19th 2020. Excerpted highlights include:

• All procedures must be performed based on risk assessment and only by personnel with demonstrated capability, in strict observance of any relevant protocols at all times
• Initial processing (before inactivation) of all specimens should take place in a validated biological safety cabinet (BSC) or primary containment device
• Non-propagative diagnostic laboratory work (for example, sequencing, nucleic acid amplification test [NAAT]) should be conducted at a facility using procedures equivalent to Biosafety Level 2 (BSL-2)
• Propagative work (for example, virus culture, isolation or neutralization assays) should be conducted at a containment laboratory with inward directional airflow (BSL-3)
• Appropriate disinfectants with proven activity against enveloped viruses should be used (for example, hypochlorite [bleach], alcohol, hydrogen peroxide, quaternary ammonium compounds, and phenolic compounds)
• Patient specimens from suspected or confirmed cases should be transported as UN3373, “Biological Substance Category B”

Additional biosafety guidelines/resources from other associations include:

Center for Disease Control: Biosafety Frequently Asked Questions

Health Canada: COVID-19 BioSafety Advisory

Public Health England: Safe handling and processing for COVID-19 samples in laboratories

Biochemical Monitoring of COVID-19 Patients:

The essential role of clinical laboratories in this pandemic extends beyond etiological diagnosis of COVID-19. Biochemical monitoring of COVID-19 patients through in vitro diagnostic testing is critical for assessing disease severity and progression as well as monitoring therapeutic intervention. Several common in vitro diagnostic tests have been implicated in unfavourable COVID-19 progression, potentially providing important prognostic information. A recommended test list based on current literature is included below along with the major laboratory abnormalities associated with adult COVID-19 patients and their potential clinical indications (1-10). In addition to more common laboratory tests, new evidence suggests that patients with severe COVID-19 could be at risk for cytokine storm syndrome. Cytokine tests, particularly IL-6, should be used where possible to assess severe patients suspected of hyperinflammation (7,9).

Importantly, unlike adults, the laboratory profile in severe COVID-19 pediatric patients is not clear and does not appear to be consistent with SARS. A recent publication recommends clinicians monitor lymphocyte count, c-reactive protein, and procalcitonin to assess severe infection. IL-6 should also be investigated as a potential pediatric prognostic indicator (2). 

Recommended Test List:

Key Publications:

1. Fan BE, Chong VC, Chan SS, Lim GH, Lim KG, Tan GB, Mucheli SS, Kuperan P, Ong KH. Hematologic parameters in patients with COVID-19 infection. American journal of hematology. 2020 Mar 4. PMID: 32129508
2. Henry BM, Lippi G, Plebani M. Laboratory abnormalities in children with novel coronavirus disease 2019. Clinical Chemistry and Laboratory Medicine (CCLM). 2020 Mar 16. PMID: 32172227
3. Lippi G, Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clinical Chemistry and Laboratory Medicine (CCLM). 2020 Mar 19. PMID: 32191623
4. Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clinical Chemistry and Laboratory Medicine (CCLM). 2020 Mar 3. PMID: 32119647
5. Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis. Clinica chimica acta; international journal of clinical chemistry. 2020 Mar 4. PMID: 32145275
6. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clinica Chimica Acta. 2020 Mar 13. PMID: 32178975
7. Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis. Progress in cardiovascular diseases. 2020 Mar 10. PMID: 32169400
8. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. 2020 Mar 16. PMID: 32192578
9. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, Alvarado-Arnez LE, Bonilla-Aldana DK, Franco-Paredes C, Henao-Martinez AF, Paniz-Mondolfi A. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Medicine and Infectious Disease. 2020 Mar 13:101623. PMID: 32179124
10. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Medicine. 2020 Mar 3:1-3. PMID: 32125452

Other Educational Materials & Webinars

Free Course on COVID-19 from AACC Learning Lab: AACC developed this content with leading scientists as part of AACC Learning Lab on NEJM Knowledge+. The free course covers COVID-19 transmission, complications, diagnosis, and more.

Free AACC Laboratory Pearl on COVID-19: The Pearl by Dr. Lippi reveals potential origins for the virus, how it attacks the body, it's symptoms, and associated laboratory abnormalities.

Free AACC Clinical Chemistry Podcast - Why Clinical Labs Are Essential to Containing COVID-19: Dr. Matthew Binnicker gives an update on the coronavirus outbreak and discusses what is needed to bring this global epidemic under control.

Free AACC Clinical Chemistry Podcast - Molecular Diagnosis of a Novel Coronavirus: Dr. Leo Poon of the University of Hong Kong gives expert insight into the 2019 novel coronavirus, and discusses the new molecular diagnostic assays his team has developed to detect and quantify this virus.

We are looking forward to welcoming all our invited speakers, registered delegates, and exhibitors to this rescheduled conference in the beautiful city of Seoul. We also apologize for any inconvenience caused by rescheduling the conference and hope to see all of you at this important international event to celebrate the end of the COVID-19 epidemic! 

The Organizing Secretariat MZ Congressi will be contacting all parties involved (Speakers, Sponsors & Exhibitors, Delegates, Poster Presenters, and others) with further information.

Kind regards,

Professor Maurizio Ferrari, IFCC President

Professor Khosrow Adeli, IFCC President-Elect

To access the Course click on the link: https://area9lyceum.com/covid19_course/

To access the Pearl click on the link: https://www.aacc.org/clinical-chemistry-trainee-council/trainee-council-in-english/pearls-of-laboratory-medicine/2020/coronavirus-disease-2019

The full details of each candidate’s nomination including a personal statement, are available here

Kind regards,

Professor Maurizio Ferrari, IFCC President

Professor Khosrow Adeli, IFCC President-Elect

• Education and Management Division
  • Committee on Proficiency Testing (C-PT): one member and one corporate member positions. Applications close on 26^th February 2020.
  • Committee on Point of Care Testing (C-PoCT): one corporate member position. Applications close on 22^nd March 2020.

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• • Task Force on Ethics (TF-E): one member position. Applications close on 15^th March 2020.

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Applications for these positions should be submitted by IFCC members (National Societies or Corporate members). If you are interested, please refer to your National Representative or Corporate Representative for information on procedures for nominations. Find your representative HERE

For further information on the open Calls for Nominations, please visit the IFCC Call for Nominations page.

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