Abstract

A two-step strategy combining assisted benchmark testing (entry controls) and External Quality Assessments (EQAs) with blinded simulated clinical specimens to enhance and maintain the quality of nucleic acid amplification testing was developed. This strategy was successfully applied to 71 diagnostic laboratories in The Netherlands when upscaling the national diagnostic capacity during the SARS-CoV-2 pandemic. The availability of benchmark testing in combination with advice for improvement substantially enhanced the quality of the laboratory testing procedures for SARS-CoV-2 detection. The three subsequent EQA rounds demonstrated high quality testing with regard to specificity (99.6% correctly identified) and sensitivity (93.3% correctly identified). Even with the implementation of novel assays, changing workflows using diverse equipment and a high degree of assay heterogeneity, the overall high quality was maintained using this two-step strategy. We show that in contrast to the limited value of Cq value for absolute proxies of viral load, these Cq values can, in combination with metadata on strategies and techniques, provide valuable information for laboratories to improve their procedures. In conclusion, our two-step strategy (preparation phase followed by a series of EQAs) is a rapid and flexible system capable of scaling, improving, and maintaining high quality diagnostics even in a rapidly evolving (e.g. pandemic) situation.

Details

Title
High quality of SARS-CoV-2 molecular diagnostics in a diverse laboratory landscape through supported benchmark testing and External Quality Assessment
Author
Sluimer, John 1 ; van den Akker, Willem M. R. 1 ; Goderski, Gabriel 1 ; Swart, Arno 1 ; van der Veer, Bas 1 ; Cremer, Jeroen 1 ; Chung, Ngoc Hoa 1 ; Molenkamp, Richard 2 ; Voermans, Jolanda 2 ; Guldemeester, Judith 2 ; van der Eijk, Annemiek 3 ; de Jong, Menno D. 4 ; Mithoe, Glen 5 ; Hermans, Mirjam H. A. 6 ; de Beer, Jessica L. 7 ; Wessels, Els 8 ; von Wintersdorff, Christian 9 ; Pas, Suzan 10 ; Verweij, Jaco J. 11 ; Melchers, Willem J. G. 12 ; van de Bovenkamp, Jeroen H. B. 13 ; Vahidnia, Ali 14 ; Gard, Lilli 15 ; Schuurman, Rob 16 ; Wintermans, Bas 17 ; Leversteijn-van Hall, Maurine 18 ; Smits, Paul 19 ; de Groot, Theun 20 ; Deiman, Birgit A. L. M. 21 ; Bart, Aldert 22 ; van der Reijden, Wil 23 ; Svraka-Latifovic, Sanela 24 ; van der Zanden, Adri G. M. 25 ; Thijsen, Steven 26 ; Schubbert, Rainer 27 ; Dreesens, Lisa L. 28 ; van Duijn, Gert 29 ; Ong, David S. Y. 30 ; Oostra, Monique 31 ; Bruisten, Sylvia 32 ; van Trijp, Marijke 33 ; Pettersson, Annika 34 ; van Burgel, Nathalie D. 35 ; Oudbier, Joke 36 ; van der Linden, Michael 37 ; van Rijn, Michiel 38 ; Bos, Martine P. 39 ; Rossen, John 40 ; Schuurs, Theo A. 41 ; Grosser, Roger 42 ; Smit, Pieter 43 ; Nijhuis, Roel H. T. 44 ; Rozemeijer, Wouter 45 ; van de Laar, Thijs 46 ; Scheepers, Theodoor M. M. 47 ; Smeets, Leonard C. 48 ; Flipse, Jacky 49 ; de Leeuw, Bertie 50 ; Dijkman, Remco 51 ; van Maarseveen, Noortje 52 ; Koppelman, Marco 53 ; Postma, Bent 54 ; van Hannen, Erik J. 55 ; Thai, Khoa 56 ; Braun, Kathrin 57 ; Schepers, Raf J. F. 58 ; Henning, Jana 59 ; van Hees, Eva R. 60 ; Tacken, Mirriam G. J. 61 ; Mol, Jaqueline 62 ; Heddema, Edou R. 63 ; Eggink, Dirk 1 ; Presser, Lance D. 1 ; Meijer, Adam 1 

1  National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control, Bilthoven, The Netherlands (GRID:grid.31147.30) (ISNI:0000 0001 2208 0118) 
2  Erasmus University Medical Center, Department of Viroscience, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X) 
3  Erasmus University Medical Center, Department of Viroscience, Clinical Virology, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:0000 0004 0459 992X) 
4  Amsterdam University Medical Center, Department of Medical Microbiology and Infection Prevention, Amsterdam, The Netherlands (GRID:grid.509540.d) (ISNI:0000 0004 6880 3010) 
5  Certe Laboratory for Infectious Diseases, Medical Microbiology, Groningen, The Netherlands (GRID:grid.491139.7) 
6  Jeroen Bosch Hospital, Department of Medical Microbiology and Infection Control, ’s-Hertogenbosch, The Netherlands (GRID:grid.413508.b) (ISNI:0000 0004 0501 9798) 
7  Laboratory of Microbiology Twente Achterhoek (LabMicTA), Hengelo, The Netherlands (GRID:grid.413508.b) 
8  Leiden University Medical Center, Department of Medical Microbiology, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000 0000 8945 2978) 
9  Maastricht University Medical Center, Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht, The Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099) 
10  Microvida Location Bravis, Roosendaal, The Netherlands (GRID:grid.5012.6) 
11  Microvida Elisabeth-Tweesteden Hospital, Laboratory for Medical Microbiology and Immunology, Tilburg, The Netherlands (GRID:grid.416373.4) (ISNI:0000 0004 0472 8381) 
12  Radboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands (GRID:grid.10417.33) (ISNI:0000 0004 0444 9382) 
13  PAMM, Laboratory of Medical Microbiology, Veldhoven, The Netherlands (GRID:grid.511956.f) (ISNI:0000 0004 0477 488X) 
14  Regional Public Health Laboratory Kennemerland, Haarlem, The Netherlands (GRID:grid.476756.1) (ISNI:0000 0004 0472 3468) 
15  Universitair Medisch Centrum Groningen, Medische Microbiologie and Infectiepreventie, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598) 
16  University Medical Centre Utrecht, Department of Medical Microbiology, Utrecht, The Netherlands (GRID:grid.7692.a) (ISNI:0000 0000 9012 6352) 
17  ADRZ Admiraal de Ruyter Ziekenhuis, Department of Medical Microbiology and Infection Control, Goes, The Netherlands (GRID:grid.440200.2) (ISNI:0000 0004 0474 0639) 
18  Alrijne Ziekenhuis, Department of Medical Microbiology, Leiden, The Netherlands (GRID:grid.476994.1); Eurofins Hoog Volume Laboratorium, Rijswijk, The Netherlands (GRID:grid.476994.1) 
19  Atalmedial, Laboratory of Medical Microbiology Medische Microbiologie, Section Molecular Biology, Amsterdam, The Netherlands (GRID:grid.476994.1) 
20  Canisius Wilhelmina Ziekenhuis, Department Medical Microbiology and Infectious Diseases, Nijmegen, The Netherlands (GRID:grid.413327.0) (ISNI:0000 0004 0444 9008) 
21  Catharina Ziekenhuis Eindhoven, Clinical Laboratory, Eindhoven, The Netherlands (GRID:grid.413532.2) (ISNI:0000 0004 0398 8384) 
22  CBSL, Department of Medical Microbiology, Tergooi MC, Hilversum, The Netherlands (GRID:grid.413202.6) (ISNI:0000 0004 0626 2490) 
23  Comicro BV, Laboratory for Medical Microbiology, Hoorn, The Netherlands (GRID:grid.413202.6) 
24  Deventer Ziekenhuis, Laboratory for Medical Microbiology and Infection Prevention, Deventer, The Netherlands (GRID:grid.413649.d) (ISNI:0000 0004 0396 5908) 
25  Diagnostiek Voor U, Eindhoven, The Netherlands (GRID:grid.413649.d); Laurentius Ziekenhuis, Department of Medical Microbiology, Roermond, The Netherlands (GRID:grid.415842.e) (ISNI:0000 0004 0568 7032); Viecuri Medisch Centrum, Department of Medical Microbiology, Venlo, The Netherlands (GRID:grid.416856.8) (ISNI:0000 0004 0477 5022) 
26  Diakonessenhuis Utrecht, Department Medical Microbiology and Immunology, Utrecht, The Netherlands (GRID:grid.413681.9) (ISNI:0000 0004 0631 9258) 
27  Eurofins Genomics Europe Applied Genomics GmbH, Ebersberg, Germany (GRID:grid.413681.9) 
28  Eurofins Nederlands Moleculair Diagnostisch Laboratorium B.V, Clinical Laboratory, Rijswijk, The Netherlands (GRID:grid.413681.9) 
29  MasterLab B.V. - Nutreco Nederland B.V., Fenelab Consortium, Boxmeer, The Netherlands (GRID:grid.413681.9); Mérieux NutriSciences, Fenelab Consortium, Ede, The Netherlands (GRID:grid.413681.9); NofaLab B.V., Fenelab Consortium, Schiedam, The Netherlands (GRID:grid.413681.9); Normec Biobeheer, Fenelab Consortium, Rotterdam, The Netherlands (GRID:grid.413681.9); NutriControl B.V., Fenelab Consortium, Veghel, The Netherlands (GRID:grid.413681.9); Nutrilab B.V., Fenelab Consortium, Giessen, The Netherlands (GRID:grid.413681.9); SGS Nederland B.V., Fenelab Consortium, Spijkenisse, The Netherlands (GRID:grid.413681.9); Triskelion, Fenelab Consortium, Utrecht, The Netherlands (GRID:grid.413681.9) 
30  Franciscus Gasthuis and Vlietland, Department of Medical Microbiology and Infection Control, Rotterdam, The Netherlands (GRID:grid.461048.f) (ISNI:0000 0004 0459 9858) 
31  Gelre Ziekenhuizen Apeldoorn, Department of Medical Microbiology, Apeldoorn, The Netherlands (GRID:grid.415355.3) (ISNI:0000 0004 0370 4214) 
32  GGD Amsterdam, Public health laboratory, Department of Infectious Diseases, Amsterdam, The Netherlands (GRID:grid.413928.5) (ISNI:0000 0000 9418 9094) 
33  Groene Hart Ziekenhuis, Department of Medical Microbiology and Infection Prevention, Gouda, The Netherlands (GRID:grid.413370.2) (ISNI:0000 0004 0405 8883) 
34  Haaglanden Medisch Centrum locatie Westeinde, Department of Medical Microbiology, Den Haag, The Netherlands (GRID:grid.413370.2) 
35  Hagaziekenhuis, Department of Medical Microbiology, Den Haag, The Netherlands (GRID:grid.413591.b) (ISNI:0000 0004 0568 6689) 
36  How Are You Diagnostics, Lelystad, The Netherlands (GRID:grid.413591.b) 
37  IJsselland Ziekenhuis, Department of Medical Microbiology, Capelle aan den IJssel, The Netherlands (GRID:grid.414559.8) (ISNI:0000 0004 0501 4532) 
38  Ikazia Ziekenhuis, Department of Medical Microbiology, Rotterdam, The Netherlands (GRID:grid.414565.7) (ISNI:0000 0004 0568 7120) 
39  inBiome, Amsterdam, The Netherlands (GRID:grid.414565.7) 
40  Isala Ziekenhuis, Laboratory of Medical Microbiology and Infectious Diseases, Zwolle, The Netherlands (GRID:grid.452600.5) (ISNI:0000 0001 0547 5927) 
41  Izore – Centrum Infectieziekten Friesland, Leeuwarden, The Netherlands (GRID:grid.452600.5) 
42  Labor Dr. Wisplinghoff, Köln, Germany (GRID:grid.452600.5) 
43  Maasstad Ziekenhuis, Maasstad laboratorium, Molecular Diagnostics Unit, LMM, Rotterdam, The Netherlands (GRID:grid.416213.3) (ISNI:0000 0004 0460 0556) 
44  Meander Medisch Centrum, Laboratory for Medical Microbiology and Medical Immunology, Amersfoort, The Netherlands (GRID:grid.414725.1) (ISNI:0000 0004 0368 8146) 
45  Noordwest Ziekenhuisgroep, Laboratory for Medical Microbiology, Alkmaar, The Netherlands (GRID:grid.491364.d) 
46  OLVG Lab B.V., Laboratory for Medical Microbiology, Amsterdam, The Netherlands (GRID:grid.440209.b) (ISNI:0000 0004 0501 8269) 
47  Pro Health Medical, Nederweert, The Netherlands (GRID:grid.440209.b) 
48  Reinier Haga Medisch Diagnostisch Centrum, Department of Molecular Biology, Delft, The Netherlands (GRID:grid.440209.b) 
49  Rijnstate Ziekenhuis, Laboratory for Medical Microbiology and Immunology, Velp, The Netherlands (GRID:grid.415930.a) 
50  Regionaal Laboratorium medische Microbiologie Dordrecht en Gorinchem, Dordrecht, The Netherlands (GRID:grid.415930.a) 
51  Royal GD (GD Animal Health), Deventer, The Netherlands (GRID:grid.512151.3) 
52  Saltro Diagnostic Center for Primary Care, Utrecht, The Netherlands (GRID:grid.512151.3) 
53  National Screening Laboratory, Research and Lab Services, Sanquin, Amsterdam, The Netherlands (GRID:grid.417732.4) (ISNI:0000 0001 2234 6887) 
54  Slingeland Ziekenhuis Doetinchem, Department Medical Microbiology, Doetinchem, The Netherlands (GRID:grid.416043.4) (ISNI:0000 0004 0396 6978) 
55  St. Antonius Ziekenhuis, Department of Medical Microbiology and Immunology, Utrecht, The Netherlands (GRID:grid.415960.f) (ISNI:0000 0004 0622 1269) 
56  Star-shl Medical Diagnostic Center, Rotterdam, the Netherlands (GRID:grid.415960.f) 
57  SYNLAB MVZ Leverkusen, Leverkusen, Germany (GRID:grid.415960.f) 
58  SYNLAB Heppignies, Heppignies, Belgium (GRID:grid.415960.f) 
59  SYNLAB Jena ONCOSCREEN, Jena, Germany (GRID:grid.415960.f) 
60  TLR International Laboratories, Ridderkerk, The Netherlands (GRID:grid.415960.f) 
61  Wageningen University and Research (WUR), Department of Diagnostics and Crisis Organization (DCO), Wageningen Bioveterinary Research (WBVR), Lelystad, The Netherlands (GRID:grid.4818.5) (ISNI:0000 0001 0791 5666) 
62  Ziekenhuis St. Jansdal, Department of Medical Microbiology, Harderwijk, The Netherlands (GRID:grid.4818.5) 
63  Zuyderland Medisch Centrum, Department of Medical Microbiology, Heerlen/Sittard-Geleen, The Netherlands (GRID:grid.416905.f) 
Pages
1378
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-023-50912-9
ProQuest document ID
2915455324
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.