Comparison of sixteen serological SARS-CoV-2 immunoassays in sixteen clinical laboratories

Lene H Harritshøj; Mikkel Gybel-Brask; Shoaib Afzal; Pia R Kamstrup; Charlotte S Jørgensen; Marianne Kragh Thomsen; Linda Hilsted; Lennart Friis-Hansen; Pal B Szecsi; Lise Pedersen; Lene Nielsen; Cecilie B Hansen; Peter Garred; Trine-Line Korsholm; Susan Mikkelsen; Kirstine O Nielsen; Bjarne K Møller; Anne T Hansen; Kasper K Iversen; Pernille B Nielsen; Rasmus B Hasselbalch; Kamille Fogh; Jakob B Norsk; Jonas Henrik Kristensen; Kristian Schønning; Nikolai S Kirkby; Alex C Y Nielsen; Lone H Landsy; Mette Loftager; Dorte K Holm; Anna C Nilsson; Susanne G Sækmose; Birgitte Grum-Schwensen; Bitten Aagaard; Thøger G Jensen; Dorte M Nielsen; Henrik Ullum; Ram B C Dessau

doi:10.1128/JCM.02596-20

Comparison of sixteen serological SARS-CoV-2 immunoassays in sixteen clinical laboratories

Lene H Harritshøj, Mikkel Gybel-Brask, Shoaib Afzal, Pia R Kamstrup, Charlotte S Jørgensen, Marianne Kragh Thomsen, Linda Hilsted, Lennart Friis-Hansen, Pal B Szecsi, Lise Pedersen, Lene Nielsen, Cecilie B Hansen, Peter Garred, Trine-Line Korsholm, Susan Mikkelsen, Kirstine O Nielsen, Bjarne K Møller, Anne T Hansen, Kasper K Iversen, Pernille B NielsenRasmus B Hasselbalch, Kamille Fogh, Jakob B Norsk, Jonas Henrik Kristensen, Kristian Schønning, Nikolai S Kirkby, Alex C Y Nielsen, Lone H Landsy, Mette Loftager, Dorte K Holm, Anna C Nilsson, Susanne G Sækmose, Birgitte Grum-Schwensen, Bitten Aagaard, Thøger G Jensen, Dorte M Nielsen, Henrik Ullum, Ram B C Dessau

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Abstract

Serological SARS-CoV-2 assays are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (total-Ab) and immunoglobulin (Ig) G and M against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated fifteen commercial and one in-house anti-SARS-CoV-2 assays in sixteen laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild or moderate COVID-19; nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT), collected 13-73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, Diasorin/LiaisonXL-IgG (97.2%). Sensitivities in descending order were: Wantai/ELISA total-Ab (96.7%), CUH-NOVO/in-house ELISA total-Ab (96.0%), Ortho/Vitros total-Ab (95.3%), YHLO/iFlash-IgG (94.0%), Ortho/Vitros-IgG (93.3%), Siemens/Atellica total-Ab (93.2%), Roche/Elecsys total-Ab (92.7%), Abbott/Architect-IgG (90.0%), Abbott/Alinity-IgG (median 88.0%), Diasorin/LiaisonXL-IgG (median 84.6%), Siemens/Vista total-Ab (81.0%), Euroimmun/ELISA-IgG (78.0%), and Snibe/Maglumi-IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai/ELISA-IgM showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.

Original language	English
Article number	e02596-20
Journal	Journal of Clinical Microbiology
Volume	59
Issue number	5
ISSN	0095-1137
DOIs	https://doi.org/10.1128/JCM.02596-20
Publication status	Published - 11 Feb 2021

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10.1128/JCM.02596-20

Comparison of sixteen serological SARS -CoV -2 immunoassays in sixteen clinical 2 laboratoriesAccepted author manuscript, 1.56 MBLicence: Unspecified

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Harritshøj, L. H., Gybel-Brask, M., Afzal, S., Kamstrup, P. R., Jørgensen, C. S., Thomsen, M. K., Hilsted, L., Friis-Hansen, L., Szecsi, P. B., Pedersen, L., Nielsen, L., Hansen, C. B., Garred, P., Korsholm, T-L., Mikkelsen, S., Nielsen, K. O., Møller, B. K., Hansen, A. T., Iversen, K. K., ... Dessau, R. B. C. (2021). Comparison of sixteen serological SARS-CoV-2 immunoassays in sixteen clinical laboratories. Journal of Clinical Microbiology, 59(5), [e02596-20]. https://doi.org/10.1128/JCM.02596-20

Comparison of sixteen serological SARS-CoV-2 immunoassays in sixteen clinical laboratories. / Harritshøj, Lene H; Gybel-Brask, Mikkel; Afzal, Shoaib; Kamstrup, Pia R; Jørgensen, Charlotte S; Thomsen, Marianne Kragh; Hilsted, Linda; Friis-Hansen, Lennart; Szecsi, Pal B; Pedersen, Lise; Nielsen, Lene; Hansen, Cecilie B ; Garred, Peter; Korsholm, Trine-Line; Mikkelsen, Susan; Nielsen, Kirstine O; Møller, Bjarne K; Hansen, Anne T ; Iversen, Kasper K; Nielsen, Pernille B; Hasselbalch, Rasmus B; Fogh, Kamille; Norsk, Jakob B; Kristensen, Jonas Henrik; Schønning, Kristian; Kirkby, Nikolai S; Nielsen, Alex C Y; Landsy, Lone H; Loftager, Mette; Holm, Dorte K; Nilsson, Anna C; Sækmose, Susanne G; Grum-Schwensen, Birgitte; Aagaard, Bitten; Jensen, Thøger G; Nielsen, Dorte M; Ullum, Henrik; Dessau, Ram B C.

In: Journal of Clinical Microbiology, Vol. 59, No. 5, e02596-20, 11.02.2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harritshøj, LH, Gybel-Brask, M, Afzal, S, Kamstrup, PR, Jørgensen, CS, Thomsen, MK, Hilsted, L, Friis-Hansen, L, Szecsi, PB, Pedersen, L, Nielsen, L, Hansen, CB , Garred, P, Korsholm, T-L, Mikkelsen, S, Nielsen, KO, Møller, BK, Hansen, AT , Iversen, KK, Nielsen, PB, Hasselbalch, RB, Fogh, K, Norsk, JB, Kristensen, JH, Schønning, K, Kirkby, NS, Nielsen, ACY, Landsy, LH, Loftager, M, Holm, DK, Nilsson, AC, Sækmose, SG, Grum-Schwensen, B, Aagaard, B, Jensen, TG, Nielsen, DM, Ullum, H & Dessau, RBC 2021, 'Comparison of sixteen serological SARS-CoV-2 immunoassays in sixteen clinical laboratories', Journal of Clinical Microbiology, vol. 59, no. 5, e02596-20. https://doi.org/10.1128/JCM.02596-20

Harritshøj, Lene H ; Gybel-Brask, Mikkel ; Afzal, Shoaib ; Kamstrup, Pia R ; Jørgensen, Charlotte S ; Thomsen, Marianne Kragh ; Hilsted, Linda ; Friis-Hansen, Lennart ; Szecsi, Pal B ; Pedersen, Lise ; Nielsen, Lene ; Hansen, Cecilie B ; Garred, Peter ; Korsholm, Trine-Line ; Mikkelsen, Susan ; Nielsen, Kirstine O ; Møller, Bjarne K ; Hansen, Anne T ; Iversen, Kasper K ; Nielsen, Pernille B ; Hasselbalch, Rasmus B ; Fogh, Kamille ; Norsk, Jakob B ; Kristensen, Jonas Henrik ; Schønning, Kristian ; Kirkby, Nikolai S ; Nielsen, Alex C Y ; Landsy, Lone H ; Loftager, Mette ; Holm, Dorte K ; Nilsson, Anna C ; Sækmose, Susanne G ; Grum-Schwensen, Birgitte ; Aagaard, Bitten ; Jensen, Thøger G ; Nielsen, Dorte M ; Ullum, Henrik ; Dessau, Ram B C. / Comparison of sixteen serological SARS-CoV-2 immunoassays in sixteen clinical laboratories. In: Journal of Clinical Microbiology. 2021 ; Vol. 59, No. 5.

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abstract = "Serological SARS-CoV-2 assays are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (total-Ab) and immunoglobulin (Ig) G and M against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated fifteen commercial and one in-house anti-SARS-CoV-2 assays in sixteen laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild or moderate COVID-19; nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT), collected 13-73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, Diasorin/LiaisonXL-IgG (97.2%). Sensitivities in descending order were: Wantai/ELISA total-Ab (96.7%), CUH-NOVO/in-house ELISA total-Ab (96.0%), Ortho/Vitros total-Ab (95.3%), YHLO/iFlash-IgG (94.0%), Ortho/Vitros-IgG (93.3%), Siemens/Atellica total-Ab (93.2%), Roche/Elecsys total-Ab (92.7%), Abbott/Architect-IgG (90.0%), Abbott/Alinity-IgG (median 88.0%), Diasorin/LiaisonXL-IgG (median 84.6%), Siemens/Vista total-Ab (81.0%), Euroimmun/ELISA-IgG (78.0%), and Snibe/Maglumi-IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai/ELISA-IgM showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.",

author = "Harritsh{\o}j, {Lene H} and Mikkel Gybel-Brask and Shoaib Afzal and Kamstrup, {Pia R} and J{\o}rgensen, {Charlotte S} and Thomsen, {Marianne Kragh} and Linda Hilsted and Lennart Friis-Hansen and Szecsi, {Pal B} and Lise Pedersen and Lene Nielsen and Hansen, {Cecilie B} and Peter Garred and Trine-Line Korsholm and Susan Mikkelsen and Nielsen, {Kirstine O} and M{\o}ller, {Bjarne K} and Hansen, {Anne T} and Iversen, {Kasper K} and Nielsen, {Pernille B} and Hasselbalch, {Rasmus B} and Kamille Fogh and Norsk, {Jakob B} and Kristensen, {Jonas Henrik} and Kristian Sch{\o}nning and Kirkby, {Nikolai S} and Nielsen, {Alex C Y} and Landsy, {Lone H} and Mette Loftager and Holm, {Dorte K} and Nilsson, {Anna C} and S{\ae}kmose, {Susanne G} and Birgitte Grum-Schwensen and Bitten Aagaard and Jensen, {Th{\o}ger G} and Nielsen, {Dorte M} and Henrik Ullum and Dessau, {Ram B C}",

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T1 - Comparison of sixteen serological SARS-CoV-2 immunoassays in sixteen clinical laboratories

AU - Harritshøj, Lene H

AU - Gybel-Brask, Mikkel

AU - Afzal, Shoaib

AU - Kamstrup, Pia R

AU - Jørgensen, Charlotte S

AU - Thomsen, Marianne Kragh

AU - Hilsted, Linda

AU - Friis-Hansen, Lennart

AU - Szecsi, Pal B

AU - Pedersen, Lise

AU - Nielsen, Lene

AU - Hansen, Cecilie B

AU - Garred, Peter

AU - Korsholm, Trine-Line

AU - Mikkelsen, Susan

AU - Nielsen, Kirstine O

AU - Møller, Bjarne K

AU - Hansen, Anne T

AU - Iversen, Kasper K

AU - Nielsen, Pernille B

AU - Hasselbalch, Rasmus B

AU - Fogh, Kamille

AU - Norsk, Jakob B

AU - Kristensen, Jonas Henrik

AU - Schønning, Kristian

AU - Kirkby, Nikolai S

AU - Nielsen, Alex C Y

AU - Landsy, Lone H

AU - Loftager, Mette

AU - Holm, Dorte K

AU - Nilsson, Anna C

AU - Sækmose, Susanne G

AU - Grum-Schwensen, Birgitte

AU - Aagaard, Bitten

AU - Jensen, Thøger G

AU - Nielsen, Dorte M

AU - Ullum, Henrik

AU - Dessau, Ram B C

PY - 2021/2/11

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N2 - Serological SARS-CoV-2 assays are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (total-Ab) and immunoglobulin (Ig) G and M against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated fifteen commercial and one in-house anti-SARS-CoV-2 assays in sixteen laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild or moderate COVID-19; nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT), collected 13-73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, Diasorin/LiaisonXL-IgG (97.2%). Sensitivities in descending order were: Wantai/ELISA total-Ab (96.7%), CUH-NOVO/in-house ELISA total-Ab (96.0%), Ortho/Vitros total-Ab (95.3%), YHLO/iFlash-IgG (94.0%), Ortho/Vitros-IgG (93.3%), Siemens/Atellica total-Ab (93.2%), Roche/Elecsys total-Ab (92.7%), Abbott/Architect-IgG (90.0%), Abbott/Alinity-IgG (median 88.0%), Diasorin/LiaisonXL-IgG (median 84.6%), Siemens/Vista total-Ab (81.0%), Euroimmun/ELISA-IgG (78.0%), and Snibe/Maglumi-IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai/ELISA-IgM showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.

AB - Serological SARS-CoV-2 assays are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (total-Ab) and immunoglobulin (Ig) G and M against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated fifteen commercial and one in-house anti-SARS-CoV-2 assays in sixteen laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild or moderate COVID-19; nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT), collected 13-73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, Diasorin/LiaisonXL-IgG (97.2%). Sensitivities in descending order were: Wantai/ELISA total-Ab (96.7%), CUH-NOVO/in-house ELISA total-Ab (96.0%), Ortho/Vitros total-Ab (95.3%), YHLO/iFlash-IgG (94.0%), Ortho/Vitros-IgG (93.3%), Siemens/Atellica total-Ab (93.2%), Roche/Elecsys total-Ab (92.7%), Abbott/Architect-IgG (90.0%), Abbott/Alinity-IgG (median 88.0%), Diasorin/LiaisonXL-IgG (median 84.6%), Siemens/Vista total-Ab (81.0%), Euroimmun/ELISA-IgG (78.0%), and Snibe/Maglumi-IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai/ELISA-IgM showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.

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DO - 10.1128/JCM.02596-20

M3 - Journal article

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VL - 59

JO - Journal of Clinical Microbiology

JF - Journal of Clinical Microbiology

SN - 0095-1137

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M1 - e02596-20

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