IFCC Information Guide on COVID-19 - Monday 28 September updates

IFCC Information Guide on COVID-19

Click aquí para descargar el Resumen traducido de la Guía de Información de la IFCC sobre COVID-19Kliknutím zde stáhnete českou verzi IFCC informačního  souhrnu o COVID 19 z 16 . dubna 2020

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.

Table of Contents:

    1. 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:

    Key IFCC Publications:

    Biosafety measures for preventing infection from COVID-19 in clinical laboratories: IFCC Taskforce Recommendations.

    Molecular, serological, and biochemical diagnosis and monitoring of COVID-19: IFCC taskforce evaluation of the latest evidence

    Laboratory Practices to Mitigate Biohazard Risks During the COVID-19 Outbreak: An IFCC Global Survey

    Operational Considerations and Challenges of Biochemistry Laboratories During the COVID-19 Outbreak: An IFCC Global Survey

    Key Resources:

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

    Center for Disease Control: Information for Laboratories

    Royal College of Pathologists Australasia: Useful COVID-19 Resources

    Royal College of Pathologists UK: COVID-19 Recommendations

    Scientific Journal Resources:

    Journal of the American Medical Association (JAMA): Coronavirus Disease 2019 (COVID-19)

    New England Journal of Medicine (NEJM): Coronavirus (Covid-19)

     

    Global Practice Guidelines/Handbooks:

    Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 7th Edition, Chinese Guidelines)

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

    Handbook for COVID-19 Laboratory  Management (Sociedade Brasileira de Analises Clinicas  - Portuguese and English)

    Orientative Guide on Quality Management for Laboratory Diagnosis of COVID-19 (OBBCSSR, Romania)

     

     

    Other Resources:

    Association for Quality Management in Laboratory Medicine: COVID-19 resources

    The Canadian Public Health Laboratory Network: Resources

    FIND Diagnostics: COVID-19 Diagnostics Research Centre

    Joint Commission International: COVID-19 Guidance & Resources

    Oxford Centre for Evidence-Based Medicine: COVID-19 Evidence Service

    The Scientist Magazine: Follow the Coronavirus Outbreak

     

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    2. Patient Screening

    According to the World Health Organization (WHO) guide for Global surveillance for COVID-19 caused by human infection with COVID-19 virus, a suspect case is defined as:

    1. A patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or residence in a location reporting community transmission of COVID-19 disease during the 14 days prior to symptom onset; OR
    2. A patient with any acute respiratory illness AND having been in contact with a confirmed or probable COVID-19 case (see definition of contact) in the last 14 days prior to symptom onset; OR
    1. A patient with severe acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND requiring hospitalization) AND in the absence of an alternative diagnosis that fully explains the clinical presentation.

    A probable case is defined as:

    1. A suspect case for whom testing for the COVID-19 virus is inconclusive; OR
    2. A suspect case for whom testing could not be performed for any reason.

    A confirmed case is defined as:

    A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms.  See laboratory guidance for details.

     _____________________________________________________________________

     

     

     

    3. 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 (updated April 8th) 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 a 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).

     

    Antigen Testing

    Antigen assays belong to an additional class of pathogen detecting assays. They detect SATS-CoV-2 antigen in virtually the same sample types as molecular test. These types of assays have already used in the past for other respiratory diseases like influenza and are usually POC tests. There are known to have a good specificity, but a limited sensitivity compared to NAAT. Advantages are an almost instant result and lower cost compared to NAAT. They allow an early rule-in of patients. Negative results, however, still require follow-up NAAT testing. One antigen assay recently got an FDA EUA authorization the Quidel Sofia® 2 SARS Antigen FIA. 

     

    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 here via the World Health Organization. Countries who have no testing capacity or national COVID-19 laboratories with limited experience on COVID-19 testing are encouraged to send the first five positives and the first ten negative COVID-19 samples to WHO reference laboratories providing confirmatory testing for COVID-19. Additionally, the WHO also released a Laboratory Assessment Tool (LAT) which is designed to assess the capacity of existing laboratories which aim to implement COVID-19 testing: Access the tool!

    Pre-analytical and Analytical Testing Issues

    There are various 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 (PMID: 31992387).

    In order to increase testing capacity and provide more flexible options for SARS-CoV-2 RNA screening, the prospect of patient self-collection of samples has been recently discussed. Indeed, the FDA recently authorized the first home test kit for COVID-19 (April 20 2020). While expanding consumer access to COVID-19 is important, various preanalytical considerations need to be considered, affecting sample quality and impacting result accuracy.  These concerns are summarized in a recent letter from the AACC and supported by a recent publication by Sullivan and colleagues (PMID: 32310815).

    Serological Testing:

    There has been much debate regarding the current value of serological testing in COVID-19 diagnosis and monitoring. There is general concern regarding their use in the acute phase of infection as they detect infection too late in the course of illness (usually more than 7-10 days), they also may cross-react with serologic responses to seasonal coronaviruses and the rate and kinetics of serological response has not been clearly defined so far. However, there is anticipated value in using improved serological testing in the future for public and occupational health monitoring and assessment. Key publications are listed below.

     

    Key Publications on Diagnostic and Serology Testing: 

    Molecular Testing:

    1. Wang X, Yao H, Xu X, Zhang P, Zhang M, Shao J, Xiao Y, Wang H. Limits of Detection of Six Approved RT–PCR Kits for the Novel SARS-coronavirus-2 (SARS-CoV-2). Clinical Chemistry. 2020 Apr 13. PMID: 32282874
    2. Lippi G, Simundic AM, Plebani M. Potential preanalytical and analytical vulnerabilities in the laboratory diagnosis of coronavirus disease 2019 (COVID-19). Clinical Chemistry and Laboratory Medicine (CCLM). 2020 Mar 16;1(ahead-of-print). PMID: 32172228
    3. Sung H, Yoo CK, Han MG, Lee SW, Lee H, Chun S, Lee WG, Min WK. Preparedness and Rapid Implementation of External Quality Assessment Helped Quickly Increase COVID-19 Testing Capacity in the Republic of Korea. Clinical Chemistry. PMID: 32321159
    4. Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, Tao Q, Sun Z, Xia L. Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology. 2020 Feb 26:200642. PMID: 32101510
    5. Lassaunière R, Frische A, Harboe ZB, Nielsen AC, Fomsgaard A, Krogfelt KA, Jørgensen CS. Evaluation of nine commercial SARS-CoV-2 immunoassays. 2020 Jan 1
    6. Hanley B, Lucas SB, Youd E, Swift B, Osborn M. Autopsy in suspected COVID-19 cases. Journal of Clinical Pathology. 2020 May 1;73(5):239-42. PMID: 32198191
    7. Zhen W, Manji R, Smith E, Berry GJ. Comparison of Four Molecular In Vitro Diagnostic Assays for the Detection of SARS-CoV-2 in Nasopharyngeal Specimens. Journal of Clinical Microbiology. 2020 Apr 27. PMID: 32341143
    8. Lin C, Xiang J, Yan M, Li H, Huang S, Shen C. Comparison of throat swabs and sputum specimens for viral nucleic acid detection in 52 cases of novel coronavirus (SARS-Cov-2)-infected pneumonia (COVID-19). Clinical Chemistry and Laboratory Medicine (CCLM). 2020 Apr 16;1(ahead-of-print). PMID: 32301745
    9. Pan Y, Long L, Zhang D, Yan T, Cui S, Yang P, Wang Q, Ren S. Potential false-negative nucleic acid testing results for Severe Acute Respiratory Syndrome Coronavirus 2 from thermal inactivation of samples with low viral loads. Clinical Chemistry. 2020 Apr 4. PMID: 32246822
    10. Behrmann O, Bachmann I, Spiegel M, et al. Rapid detection of SARS-CoV-2 by low volume real-time single tube reverse transcription recombinase polymerase amplification using an exo probe with an internally linked quencher (exo-IQ). Clinical Chemistry. 2020 May 8. PMID: 32384153
    11. Peddu V, Shean RC, Xie H, et al. Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization. Clinical Chemistry. 2020 May 7. PMID: 32379863
    12. Dietzen DJ. Unleashing the Power of Laboratory Developed Tests: Closing gaps in COVID diagnosis and beyond. The Journal of Applied Laboratory Medicine. 2020 Apr 29.
    13. Basu A, Zinger T, Inglima K, Woo KM, Atie O, Yurasits L, See B, Aguero-Rosenfeld ME. Performance of the rapid Nucleic Acid Amplification by Abbott ID NOW COVID-19 in nasopharyngeal swabs transported in viral media and dry nasal swabs, in a New York City academic institution. bioRxiv. 2020 Jan 1. Preprint non-peer reviewed
    14. Ramdas K, Darzi A, Jain S. ‘Test, re-test, re-test’: using inaccurate tests to greatly increase the accuracy of COVID-19 testing. Nature Medicine. 2020 May 12:1-2. PMID: 32398878
    15. Wacharapluesadee S, Kaewpom T, Ampoot W, et al. Evaluating the efficiency of specimen pooling for PCR-based detection of COVID-19. J Med Virol. 2020 May 13;10.1002/jmv.26005. PMID: 32401343
    16. Basu A, Zinger T, Inglima K, Woo KM, Atie O, Yurasits L, See B, Aguero-Rosenfeld ME. Performance of Abbott ID NOW COVID-19 rapid nucleic acid amplification test in nasopharyngeal swabs transported in viral media and dry nasal swabs, in a New York City academic institution. J Clin Microbiol. 2020 May 29:JCM.01136-20. doi: 10.1128/JCM.01136-20. Epub ahead of print. PMID: 32471894.
    17. Traugott M, Aberle SW, Aberle JH, Griebler H, Karolyi M, Pawelka E, Puchhammer-Stöckl E, Zoufaly A, Weseslindtner L. Performance of SARS-CoV-2 antibody assays in different stages of the infection: Comparison of commercial ELISA and rapid tests. J Infect Dis. 2020 May 30:jiaa305. doi: 10.1093/infdis/jiaa305. Epub ahead of print. PMID: 32473021.
    18. Binnicker MJ. Emergence of a Novel Coronavirus Disease (COVID-19) and the Importance of Diagnostic Testing: Why Partnership between Clinical Laboratories, Public Health Agencies, and Industry Is Essential to Control the Outbreak. Clin Chem. 2020;66(5):664‐ doi:10.1093/clinchem/hvaa071. PMID: 32077933
    19. Shi J, Han D, Zhang R, Li J, Zhang R. Molecular and serological assays for SARS-CoV-2: insights from genome and clinical characteristics. Clin Chem. 2020 May 21:hvaa122. doi: 10.1093/clinchem/hvaa122. Epub ahead of print. PMID: 32437513.
    20. Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure. Annals of Internal Medicine. 2020 May 23. PMID: 32422057
    21. Jehi L, Ji X, Milinovich A, Erzurum S, Rubin B, Gordon S, Young J, Kattan MW. Individualizing risk prediction for positive COVID-19 testing: results from 11,672 patients. Chest. 2020 Jun 10. doi: 10.1016/j.chest.2020.05.580. Epub ahead of print. PMCID: PMC7286244.
    22. Pilcher CD, Westreich D, Hudgens MG. Group Testing for Sars-Cov-2 to Enable Rapid Scale-Up of Testing and Real-Time Surveillance of Incidence [published online ahead of print, 2020 Jun 27]. J Infect Dis. 2020;jiaa378. doi:10.1093/infdis/jiaa378
    23. Vogels CBF, Brito AF, Wyllie AL, et al. Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT-qPCR primer-probe sets [published online ahead of print, 2020 Jul 10]. Nat Microbiol. 2020;10.1038/s41564-020-0761-6. doi:10.1038/s41564-020-0761-6
    24. Fung B, Gopez A, Servellita V, et al. Direct Comparison of SARS-CoV-2 Analytical Limits of Detection across Seven Molecular Assays [published online ahead of print, 2020 Jul 10]. J Clin Microbiol. 2020;JCM.01535-20. doi:10.1128/JCM.01535-20
    25. Mallett S, Allen J, Graziadio S, Taylor SA, Sakai NS, Green K, Suklan J, Hyde C, Shinkins B, Zhelev Z, Peters J. At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR based tests?: A systematic review of individual participant data. 2020 Jan 1.
    26. Mattiuzzi C, Henry BM, Sanchis-Gomar F, Lippi G. SARS-CoV-2 recurrent RNA positivity after recovering from coronavirus disease 2019 (COVID-19): a meta-analysis. Acta BioMed. 2020;91(3): Epub ahead of print. Doi: 10.23750/abm.v91i3.10303
    27. Artesi M, Bontems S, Göbbels P, Franckh M, Maes P, Boreux R, Meex C, Melin P, Hayette MP, Bours V, Durkin K. A recurrent mutation at position 26,340 of SARS-CoV-2 is associated with failure of the E-gene qRT-PCR utilized in a commercial dual-target diagnostic assay. Journal of Clinical Microbiology. 2020 Jul 20.
    28. Matheeussen V, Corman VM, Mantke OD, McCulloch E, Lammens C, Goossens H, Niemeyer D, Wallace PS, Klapper P, Niesters HG, Drosten C. International external quality assessment for SARS-CoV-2 molecular detection and survey on clinical laboratory preparedness during the COVID-19 pandemic, April/May 2020. Eurosurveillance. 2020 Jul 9;25(27):2001223.
    29. Bossuyt PM. Testing COVID-19 tests faces methodological challenges. Journal of Clinical Epidemiology. 2020 Jul 3.
    30. Zhang Y, Wang C, Han M, et al. Discrimination of False Negative Results in RT-PCR Detection of SARS-CoV-2 RNAs in Clinical Specimens by Using an Internal Reference [published online ahead of print, 2020 Aug 4]. Virol Sin. 2020;1-10. doi:10.1007/s12250-020-00273-8
    31. Sriwijitalai W, Wiwanitkit V. Cost-Utility Analysis for Chest CT versus RT-PCR for COVID-19 Detection. Int J Prev Med. 2020;11:67. Published 2020 Jun 5. doi:10.4103/ijpvm.IJPVM_83_20
    32. Koyama T, Platt D, Parida L. Variant analysis of SARS-CoV-2 genomes. Bull World Health Organ. 2020;98(7):495-504. doi:10.2471/BLT.20.253591
    33. Pourbagheri-Sigaroodi A, Bashash D, Fateh F, Abolghasemi H. Laboratory Findings in COVID-19 Diagnosis and Prognosis [published online ahead of print, 2020 Aug 13]. Clin Chim Acta. 2020;S0009-8981(20)30412-5. doi:10.1016/j.cca.2020.08.019
    34. Kumari P, Singh A, Rinchui Ngasainao M, et al. Potential diagnostics and therapeutic approaches in COVID-19 [published online ahead of print, 2020 Aug 11]. Clin Chim Acta. 2020;S0009-8981(20)30395-8. doi:10.1016/j.cca.2020.08.013
    35. Wang B, Hu M, Ren Y, et al. Evaluation of seven commercial SARS-CoV-2 RNA detection kits based on real-time polymerase chain reaction (PCR) in China [published online ahead of print, 2020 Jul 13]. Clin Chem Lab Med. 2020;/j/cclm.ahead-of-print/cclm-2020-0271/cclm-2020-0271.xml. doi:10.1515/cclm-2020-0271
    36. Rödel J, Egerer R, Suleyman A, et al. Use of the variplex™ SARS-CoV-2 RT-LAMP as a rapid molecular assay to complement RT-PCR for COVID-19 diagnosis [published online ahead of print, 2020 Aug 31]. J Clin Virol. 2020;132:104616. doi:10.1016/j.jcv.2020.104616
    37. Michel D, Danzer KM, Groß R, et al. Rapid, convenient and efficient kit-independent detection of SARS-CoV-2 RNA [published online ahead of print, 2020 Sep 3]. J Virol Methods. 2020;113965. doi:10.1016/j.jviromet.2020.113965
    38. Mascuch SJ, Fakhretaha-Aval S, Bowman JC, et al. A blueprint for academic labs to produce SARS-CoV-2 RT-qPCR test kits [published online ahead of print, 2020 Sep 3]. J Biol Chem. 2020;jbc.RA120.015434. doi:10.1074/jbc.RA120.015434
    39. Sapkota D, Søland TM, Galtung HK, et al. COVID-19 salivary signature: diagnostic and research opportunities [published online ahead of print, 2020 Aug 7]. J Clin Pathol. 2020;jclinpath-2020-206834. doi:10.1136/jclinpath-2020-206834
    40. Campbell JR, Uppal A, Oxlade O, et al. Active testing of groups at increased risk of acquiring SARS-CoV-2 in Canada: costs and human resource needs [published online ahead of print, 2020 Sep 9]. CMAJ. 2020;cmaj.201128. doi:10.1503/cmaj.201128
    41. Yokota I, Shane PY, Okada K, Unoki Y, Yang Y, Inao T, Sakamaki K, Iwasaki S, Hayasaka K, Sugita J, Nishida M, Fujisawa S, Teshima T. Mass screening of asymptomatic persons for SARS-CoV-2 using saliva. Clin Infect Dis. 2020 Sep 25:ciaa1388. doi: 10.1093/cid/ciaa1388. Epub ahead of print. PMID: 32976596.
    42. Li L, Lowe CF, Ritchie G, Stefanovic A, Champagne S, Romney MG, Leung V, Matic N. SARS-CoV-2 molecular testing for the diagnosis of COVID-19: One test does not fit all. J Med Virol. 2020 Sep 19. doi: 10.1002/jmv.26532. Epub ahead of print. PMID: 32949164.
    43. Fernandes LL, Pacheco VB, Borges L, Athwal HK, de Paula Eduardo F, Bezinelli L, Correa L, Jimenez M, Dame-Teixeira N, Lombaert IMA, Heller D. Saliva in the Diagnosis of COVID-19: A Review and New Research Directions. J Dent Res. 2020 Sep 16:22034520960070. doi: 10.1177/0022034520960070. Epub ahead of print. PMID: 32936047.
    44. Fogarty A, Joseph A, Shaw D. Pooled saliva samples for COVID-19 surveillance programme. Lancet Respir Med. 2020 Sep 22:S2213-2600(20)30444-6. doi: 10.1016/S2213-2600(20)30444-6. Epub ahead of print. PMID: 32976755.
    45. Wyllie AL, Fournier J, Casanovas-Massana A, Campbell M, Tokuyama M, Vijayakumar P, Warren JL, Geng B, Muenker MC, Moore AJ, Vogels CBF, Petrone ME, Ott IM, Lu P, Venkataraman A, Lu-Culligan A, Klein J, Earnest R, Simonov M, Datta R, Handoko R, Naushad N, Sewanan LR, Valdez J, White EB, Lapidus S, Kalinich CC, Jiang X, Kim DJ, Kudo E, Linehan M, Mao T, Moriyama M, Oh JE, Park A, Silva J, Song E, Takahashi T, Taura M, Weizman OE, Wong P, Yang Y, Bermejo S, Odio CD, Omer SB, Dela Cruz CS, Farhadian S, Martinello RA, Iwasaki A, Grubaugh ND, Ko AI. Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2. N Engl J Med. 2020 Sep 24;383(13):1283-1286. doi: 10.1056/NEJMc2016359. Epub 2020 Aug 28. PMID: 32857487.
    46. Liu M, Li Q, Zhou J, Ai W, Zheng X, Zeng J, Liu Y, Xiang X, Guo R, Li X, Wu X, Xu H, Jiang L, Zhang H, Chen J, Tian L, Luo J, Luo C. Value of swab types and collection time on SARS-COV-2 detection using RT-PCR assay. J Virol Methods. 2020 Sep 16;286:113974. doi: 10.1016/j.jviromet.2020.113974. Epub ahead of print. PMID: 32949663.
    47. Larson D, Brodniak SL, Voegtly LJ, Cer RZ, Glang LA, Malagon FJ, Long KA, Potocki R, Smith DR, Lanteri C, Burgess T, Bishop-Lilly KA. A Case of Early Re-infection with SARS-CoV-2. Clin Infect Dis. 2020 Sep 19:ciaa1436. doi: 10.1093/cid/ciaa1436. Epub ahead of print. PMID: 32949240.
    48. Yang Z, Wu J, Ye F, Zhu B, Guan W, Huang J, Songyang Z, Liu Y, Chen Y, Du Q, Chen J, Zhang Y, Ke C, Lin Y, Sun B, Zeng J, Chen L, Ren J, Jiang X, Yu M, Di B, Zhong N, Zheng L. Expert consensus-based laboratory testing of SARS-CoV-2. J Thorac Dis. 2020 Aug;12(8):4378-4390. doi: 10.21037/jtd-20-1928. PMID: 32944351; PMCID: PMC7475603.
    49. Lee A, Thornley S, Morris AJ, Sundborn G. Should countries aim for elimination in the covid-19 pandemic? BMJ. 2020 Sep 9;370:m3410. doi: 10.1136/bmj.m3410. PMID: 32909958.

    Antigen Testing:

    1. Selove W, Rao LV. Performance of rapid SOFIA Influenza A+ B test compared to Luminex x-TAG respiratory viral panel assay in the diagnosis of influenza A, B, and subtype H3. Journal of Investigative Medicine. 2016 Apr 1;64(4):905-7. PMID: 26911275
    2. Blairon L, Wilmet A, Beukinga I, Tré-Hardy M. Implementation of rapid SARS-CoV-2 antigenic testing in a laboratory without access to molecular methods: experiences of a general hospital. Journal of Clinical Virology. 2020 May 30:104472. PMID: 32504944
    3. Mak GC, Cheng PK, Lau SS, et al. Evaluation of rapid antigen test for detection of SARS-CoV-2 virus [published online ahead of print, 2020 Jun 8]. J Clin Virol. 2020;129:104500. doi:10.1016/j.jcv.2020.104500
    4. Dinnes J, Deeks JJ, Adriano A, et al. Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection.Cochrane Database Syst Rev. 2020;8:CD013705. Published 2020 Aug 26. doi:10.1002/14651858.CD013705
    5. Kyosei Y, Namba M, Yamura S, et al. Proposal of De Novo Antigen Test for COVID-19: Ultrasensitive Detection of Spike Proteins of SARS-CoV-2.Diagnostics (Basel). 2020;10(8):E594. Published 2020 Aug 14. doi:10.3390/diagnostics10080594
    6. Nuovo G, Tili E, Suster D, Matys E, Hupp L, Magro C. Strong homology between SARS-CoV-2 envelope protein and a Mycobacterium sp. antigen allows rapid diagnosis of Mycobacterial infections and may provide specific anti-SARS-CoV-2 immunity via the BCG vaccine [published online ahead of print, 2020 Aug 13].Ann Diagn Pathol. 2020;48:151600. doi:10.1016/j.anndiagpath.2020.151600
    7. Scohy A, Anantharajah A, Bodéus M, Kabamba-Mukadi B, Verroken A, Rodriguez-Villalobos H. Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis.J Clin Virol. 2020;129:104455. doi:10.1016/j.jcv.2020.104455
    8. Ogata AF, Maley AM, Wu C, et al. Ultra-sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease [published online ahead of print, 2020 Sep 8]. Clin Chem. 2020;hvaa213. doi:10.1093/clinchem/hvaa213
    9. Ogawa T, Fukumori T, Nishihara Y, et al. Another false-positive problem for a SARS-CoV-2 antigen test in Japan [published online ahead of print, 2020 Aug 25]. J Clin Virol. 2020;131:104612. doi:10.1016/j.jcv.2020.104612

    Serology Testing:

      Breath Testing:

        Additional Resources Related to Testing:

        Food & Drug Administration (FDA): FAQs on Diagnostic Testing for COVID-19 (Recently Updated with Guidance for Serology Testing)

        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

        Public Health Laboratory Network:  Statement on Point-of-Care Serology Testing for SARS-CoV-2

        Public Health England: Evaluation of Roche Elecsys AntiSARS-CoV-2 serology assay for the detection of anti-SARS-CoV-2 antibodies

        Royal College of Pathologists: Recommendations for verification and validation methodology and sample sets for evaluation of assays for SARS-CoV-2 (COVID-19)

        4. 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. The IFCC TF on COVID-19 recently published recommendations for biosafety measures for preventing infection from COVID-19 in clinical laboratories accessible at the following link. Key summary recommendations are listed below:

        How can biosafety measures be implemented in clinical chemistry laboratories during the COVID-19 pandemic?

        1a. Laboratories should adopt social distancing measures within the workplace as much as possible and feasible.

        1b. The potential exposure and health status of the laboratory personnel is monitored daily.

        What personal hygiene and personal protective equipment (PPE) should be used in clinical chemistry laboratories during the COVID-19 pandemic?

        2a. Laboratory professionals must adhere rigorously to universally recommended standard precautions (i.e. frequent hand washing for at least 40 s with soap and water, or hand sanitizer when there is no access to handwashing, and to avoid touching the face) to minimize the risk of exposure to the virus.

        2b. Laboratory professionals must wear standard laboratory PPE (i.e. masks and gloves, laboratory coat or gown, and eye protection) at all times.

        2c. Laboratory professionals should wear preferably an N95 mask while engaged in aerosol-generating procedures on all non-centrifuged samples potentially containing vital SARS-CoV-2 particles.

        How should laboratory staff handle routine patient specimens during the COVID-19 pandemic?

        3a. For routine testing of blood, urine and body fluids, laboratories should use automated instruments and analyzers with closed preanalytical robotics, where possible.

        3b. When manually handling non-respiratory specimens, aerosol-generating non-centrifuged sample processing steps should be carried out in a BSL2 cabinet, wearing the recommended PPE.

        3c. The specimens should be sealed immediately after testing. High-risk specimens should be promptly disinfected or autoclaved.

        3d. If there are no accidents, wait for more than 10 min for further processing after centrifugation stops. When the specimen suspected of COVID-19 is centrifuged, the operator must not leave the centrifuge. If an accident is suspected, or in some way the centrifugation is abnormal, stop the centrifugation. After replacing the biosafety level 3 protection equipment, stop centrifugation for more than 30 min, carefully open the lid, and spray and sterilize with 75% ethanol or other disinfectants. Take out the centrifuge rotor with blood collection tubes and then put them in the biosafety cabinet to treat.

        How should staff decontaminate laboratory equipment and surfaces during the COVID-19 pandemic?

        4a. Laboratory staff should decontaminate working surfaces with standard disinfectants approved for SARS-CoV-2 infections. The frequency shall be decided on local basis according to the volume of work, but shall not be basically less frequent than every 3 h.

        4b. If a sample positive for SARS-CoV-2 is suspected of being leaked or contaminates the biosafety cabinet and bench and causes limited pollution: use a disinfectant with an effective chlorine content of 5500 mg/L for disinfection for more than 30 min; the disinfectant must be prepared immediately and used within 24 h. If positive specimens cause laboratory contamination: keep the laboratory space closed to prevent access by unauthorized personnel and to prevent the spread of pollutants. Cover the contaminated area with a towel containing 5500 mg/L of effective chlorine disinfectant and disinfect for more than 30 min. Peracetic acid (2 g/m3) or other disinfectants (3% H2O2, 100 mg/L chlorine dioxide, etc.) can be used to fumigate the laboratory overnight or disinfectant aerosol can be sprayed for 1–2 h.

        In addition, interim guidelines from the World Health Organization on laboratory biosafety guidance related to coronavirus disease were updated on March 19th, 2020.

        Click here for a full list of WHO suggested decontaminants and here for a full list of EPA suggested decontaminants.

        Efficacy of Masking: The efficacy and necessity of surgical grade or N95 masks in the clinical laboratory and the general public has not been well defined. In a recent paper in Nature Medicine by Leung and colleagues, surgical face masks were shown to significantly reduce the detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. In light of increasing evidence towards the efficacy of masking, the WHO has reversed its initial recommendation and now supports government initiatives that require or encourage the public wearing of masks, marking a major shift. The CDC has also encouraged general masking, highlighting the importance of masking for all healthcare workers whether patient-facing or not.

        COVID-19 Detection in Different Clinical Specimens: An important consideration in biosafety is the detectability of COVID-19 in clinical specimens. A recent JAMA article investigated biodistribution among different clinical specimens of inpatients with COVID-19. Study findings are summarized below:

        COVID-19 Detection in Domestic Animals: A recent publication in Science investigated the susceptibility of domestic animals, including dogs, cats, chickens, pigs, and ducks. Their findings demonstrated that cats are susceptible to airborne infection while COVID-19 replicates poorly in dogs, pigs, chickens, and dogs. Healthcare workers should keep this in mind when interacting with domestic pets.

        Additional biosafety resources/publications from other associations include:

        Center for Disease Control: Biosafety Frequently Asked Questions

        Center for Disease Control: Guidance for Use of Pneumatic Tube Systems for Transport of Respiratory Specimens from Suspected or Confirmed COVID-19 Patients

        Health Canada: COVID-19 BioSafety Advisory

        Pan American Health Organization: Requirements and technical specifications of personal protective equipment (PPE) in healthcare

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

        NSW Clinical Excellence Commission: Application of PPE in Response to COVID-19 Pandemic

        Key Publications on Biosafety: 

          5. 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 unfavorable 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 indication. 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.

          Special considerations for pediatrics: 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). A preliminary description of pediatric U.S. COVID-19 cases was published by the CDC on April 10th, 2020. In line with data from China, the CDC reports that pediatric COVID-19 cases might be less severe when compared to adults and that children may experience different symptoms. Specifically, positive pediatric patients were reported to not always be associated with fever or cough as reported signs and symptoms.  Additionally, although most cases reported among children to date have not been severe, the CDC recommends clinicians maintain a high index of suspicion for COVID-19 infection in children and monitor for progression of illness, particularly among infants and children with underlying conditions. Importantly, interpretation of pediatric laboratory tests based on known adult trends is not recommended due to lack of pediatric information and characteristics. Recent data also suggests a new phenomenon affecting previously asymptomatic children with SARS-CoV-2 infection manifesting as a hyperinflammatory syndrome with multiorgan involvement similar to Kawasaki disease shock syndrome. Further research into the pediatric manifestations of COVID-19 is essential.

          Special considerations for pregnant women during COVID-19 pandemic: Researchers have reported potential vertical transmission of COVID-19 in China (19, 20). Thus, minimizing the risk transmission and viral exposure to pregnant women is incredibly important. Many labs have implemented modifications for the required Gestational Diabetes Mellitus screening, including:

            Key Publications on Biochemical Monitoring: 

            General

              Inflammatory Markers:

                Cardiac Markers:

                  Hematology Markers:

                    Hepatic & Renal Markers:

                      Pediatrics:

                        Maternal:

                          6. Other Educational Materials & Webinars

                          Webinar on COVID-19 – Approach to Laboratory Testing and Biosafety - Cosponsored by the Canadian Society of Clinical Chemists (CSCC) and Roche CanadaModerator: Dr. David Kinniburgh (CA)Speakers: Prof Giuseppe Lippi (IT); Prof Khosrow Adeli (CA).

                          TransAsia Webinar on COVID-19 – Challenges in Laboratory Investigations and Clinical Management - Cosponsored by: IFCC EMD and Transasia Erba MannheimSpeakers: Prof. Nader Rifai (US); Professor Mark Berg (US); Professor Leo Poon (HK).

                          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, its 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.

                          Roche-Sponsored COVID-19 Online Education Program: Featuring three presentations and the live roundtable discussion, the upcoming edition is set to provide you with important information on the role of each of the tests to control the pandemic (Streaming June 2 2020).

                          Science Webinar: Coronavirus - A survival guide

                          Science Webinar: Monitoring the immune system to fight COVID-19: CD4 status, lymphopenia, and infectivity

                          Siemens Healthineers COVID-19 Testing Guide: A new COVID-19 Laboratory Testing Guide from Siemens Healthineers provides essential information for clinicians to help manage each stage of COVID-19 patient care: diagnosis, prognosis, therapy and follow-up.

                          CAP Webinar: Navigating Implementation of SARS-CoV-2 Testing in Your Laboratory

                          7. Big Data Tools in COVID-19

                          Datasets:

                            Machine learning tools:

                              Disclaimer: This collection of resources on this webpage reflects a rapidly changing situation and due to the need for quick answers during the COVID-19 pandemic, we acknowledge that most fast-tracked publications are based on observations, often on a small number of cases, which would be considered as preliminary evidence. The IFCC Task Force has not critically appraised all resources cited here for scientific validity but tried to present information that is believed to help laboratory professionals in formulating their local policies in a more informed manner. The interim advice or conclusions presented here may change as more information is gathered.