Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT)
ABSTRACTTo understand SARS-CoV-2 immunity after natural infection or vaccination, functional assays such as virus neutralising assays are needed. So far, assays to detect SARS-CoV-2 neutralising antibodies rely on cell-culture based infection assays either using wild type SARS-CoV-2 or pseudotyped v...
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Format: | Article |
Language: | English |
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Taylor & Francis Group
2020-01-01
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Series: | Emerging Microbes and Infections |
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Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2020.1835448 |
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author | Benjamin Meyer Johan Reimerink Giulia Torriani Fion Brouwer Gert-Jan Godeke Sabine Yerly Marieke Hoogerwerf Nicolas Vuilleumier Laurent Kaiser Isabella Eckerle Chantal Reusken |
author_facet | Benjamin Meyer Johan Reimerink Giulia Torriani Fion Brouwer Gert-Jan Godeke Sabine Yerly Marieke Hoogerwerf Nicolas Vuilleumier Laurent Kaiser Isabella Eckerle Chantal Reusken |
author_sort | Benjamin Meyer |
collection | DOAJ |
description | ABSTRACTTo understand SARS-CoV-2 immunity after natural infection or vaccination, functional assays such as virus neutralising assays are needed. So far, assays to detect SARS-CoV-2 neutralising antibodies rely on cell-culture based infection assays either using wild type SARS-CoV-2 or pseudotyped viruses. Such assays are labour-intensive, require appropriate biosafety facilities and are difficult to standardize. Recently, a new surrogate virus neutralisation test (sVNT) was described that uses the principle of an ELISA to measure the neutralisation capacity of anti-SARS-CoV-2 antibodies directed against the receptor binding domain. Here, we performed an independent evaluation of the robustness, specificity and sensitivity on an extensive panel of sera from 269 PCR-confirmed COVID-19 cases and 259 unmatched samples collected before 2020 and compared it to cell-based neutralisation assays. We found a high specificity of 99.2 (95%CI: 96.9–99.9) and overall sensitivity of 80.3 (95%CI: 74.9–84.8) for the sVNT. Clinical sensitivity increased between early (<14 days post symptom onset or post diagnosis, dpos/dpd) and late sera (>14 dpos/dpd) from 75.0 (64.7–83.2) to 83.1 (76.5–88.1). Also, higher severity was associated with an increase in clinical sensitivity. Upon comparison with cell-based neutralisation assays we determined an analytical sensitivity of 74.3 (56.4–86.9) and 98.2 (89.4–99.9) for titres ≥10 to <40 and ≥40 to <160, respectively. Only samples with a titre ≥160 were always positive in the sVNT. In conclusion, the sVNT can be used as an additional assay to determine the immune status of COVID-19 infected of vaccinated individuals but its value needs to be assessed for each specific context. |
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institution | Directory Open Access Journal |
issn | 2222-1751 |
language | English |
last_indexed | 2024-04-25T00:51:23Z |
publishDate | 2020-01-01 |
publisher | Taylor & Francis Group |
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series | Emerging Microbes and Infections |
spelling | doaj.art-2445b8d0ad4b496ab542759169cd2e612024-03-11T16:04:24ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-01912394240310.1080/22221751.2020.1835448Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT)Benjamin Meyer0Johan Reimerink1Giulia Torriani2Fion Brouwer3Gert-Jan Godeke4Sabine Yerly5Marieke Hoogerwerf6Nicolas Vuilleumier7Laurent Kaiser8Isabella Eckerle9Chantal Reusken10Centre for Vaccinology, Department of Pathology and Immunology, University of Geneva, Geneva, SwitzerlandCentre for Infectious Disease Control, WHO COVID-19 reference laboratory, RIVM, Bilthoven, NetherlandsDepartment of Microbiology and Molecular Medicine, University of Geneva, Geneva, SwitzerlandCentre for Infectious Disease Control, WHO COVID-19 reference laboratory, RIVM, Bilthoven, NetherlandsCentre for Infectious Disease Control, WHO COVID-19 reference laboratory, RIVM, Bilthoven, NetherlandsLaboratory of Virology, Geneva University Hospitals, Geneva, SwitzerlandCentre for Infectious Disease Control, WHO COVID-19 reference laboratory, RIVM, Bilthoven, NetherlandsDivision of Laboratory Medicine, Department of Diagnostics, Geneva University Hospitals and Geneva University, Geneva, SwitzerlandLaboratory of Virology, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Microbiology and Molecular Medicine, University of Geneva, Geneva, SwitzerlandCentre for Infectious Disease Control, WHO COVID-19 reference laboratory, RIVM, Bilthoven, NetherlandsABSTRACTTo understand SARS-CoV-2 immunity after natural infection or vaccination, functional assays such as virus neutralising assays are needed. So far, assays to detect SARS-CoV-2 neutralising antibodies rely on cell-culture based infection assays either using wild type SARS-CoV-2 or pseudotyped viruses. Such assays are labour-intensive, require appropriate biosafety facilities and are difficult to standardize. Recently, a new surrogate virus neutralisation test (sVNT) was described that uses the principle of an ELISA to measure the neutralisation capacity of anti-SARS-CoV-2 antibodies directed against the receptor binding domain. Here, we performed an independent evaluation of the robustness, specificity and sensitivity on an extensive panel of sera from 269 PCR-confirmed COVID-19 cases and 259 unmatched samples collected before 2020 and compared it to cell-based neutralisation assays. We found a high specificity of 99.2 (95%CI: 96.9–99.9) and overall sensitivity of 80.3 (95%CI: 74.9–84.8) for the sVNT. Clinical sensitivity increased between early (<14 days post symptom onset or post diagnosis, dpos/dpd) and late sera (>14 dpos/dpd) from 75.0 (64.7–83.2) to 83.1 (76.5–88.1). Also, higher severity was associated with an increase in clinical sensitivity. Upon comparison with cell-based neutralisation assays we determined an analytical sensitivity of 74.3 (56.4–86.9) and 98.2 (89.4–99.9) for titres ≥10 to <40 and ≥40 to <160, respectively. Only samples with a titre ≥160 were always positive in the sVNT. In conclusion, the sVNT can be used as an additional assay to determine the immune status of COVID-19 infected of vaccinated individuals but its value needs to be assessed for each specific context.https://www.tandfonline.com/doi/10.1080/22221751.2020.1835448SARS-CoV-2neutralising antibodiessurrogate virus neutralisation assaypseudovirus neutralisation assaycell-based virus neutralisation assay |
spellingShingle | Benjamin Meyer Johan Reimerink Giulia Torriani Fion Brouwer Gert-Jan Godeke Sabine Yerly Marieke Hoogerwerf Nicolas Vuilleumier Laurent Kaiser Isabella Eckerle Chantal Reusken Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT) Emerging Microbes and Infections SARS-CoV-2 neutralising antibodies surrogate virus neutralisation assay pseudovirus neutralisation assay cell-based virus neutralisation assay |
title | Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT) |
title_full | Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT) |
title_fullStr | Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT) |
title_full_unstemmed | Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT) |
title_short | Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT) |
title_sort | validation and clinical evaluation of a sars cov 2 surrogate virus neutralisation test svnt |
topic | SARS-CoV-2 neutralising antibodies surrogate virus neutralisation assay pseudovirus neutralisation assay cell-based virus neutralisation assay |
url | https://www.tandfonline.com/doi/10.1080/22221751.2020.1835448 |
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