Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic in 2020. Testing is crucial for mitigating public health and economic effects. Serology is considered key to population-level surveillance and potentially individual-level risk assessment. However, immunoassay performance has not been compared on large, identical sample sets. We aimed to investigate the performance of four high-throughput commercial SARS-CoV-2 antibody immunoassays and a novel 384-well ELISA. Methods: We did a head-to-head assessment of SARS-CoV-2 IgG assay (Abbott, Chicago, IL, USA), LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy), Elecsys Anti-SARS-CoV-2 assay (Roche, Basel, Switzerland), SARS-CoV-2 Total assay (Siemens, Munich, Germany), and a novel 384-well ELISA (the Oxford immunoassay). We derived sensitivity and specificity from 976 pre-pandemic blood samples (collected between Sept 4, 2014, and Oct 4, 2016) and 536 blood samples from patients with laboratory-confirmed SARS-CoV-2 infection, collected at least 20 days post symptom onset (collected between Feb 1, 2020, and May 31, 2020). Receiver operating characteristic (ROC) curves were used to assess assay thresholds. Findings: At the manufacturers' thresholds, for the Abbott assay sensitivity was 92·7% (95% CI 90·2–94·8) and specificity was 99·9% (99·4–100%); for the DiaSorin assay sensitivity was 96·2% (94·2–97·7) and specificity was 98·9% (98·0–99·4); for the Oxford immunoassay sensitivity was 99·1% (97·8–99·7) and specificity was 99·0% (98·1–99·5); for the Roche assay sensitivity was 97·2% (95·4–98·4) and specificity was 99·8% (99·3–100); and for the Siemens assay sensitivity was 98·1% (96·6–99·1) and specificity was 99·9% (99·4–100%). All assays achieved a sensitivity of at least 98% with thresholds optimised to achieve a specificity of at least 98% on samples taken 30 days or more post symptom onset. Interpretation: Four commercial, widely available assays and a scalable 384-well ELISA can be used for SARS-CoV-2 serological testing to achieve sensitivity and specificity of at least 98%. The Siemens assay and Oxford immunoassay achieved these metrics without further optimisation. This benchmark study in immunoassay assessment should enable refinements of testing strategies and the best use of serological testing resource to benefit individuals and population health. Funding: Public Health England and UK National Institute for Health Research.
| Original language | English |
|---|---|
| Pages (from-to) | 1390-1400 |
| Number of pages | 11 |
| Journal | The Lancet Infectious Diseases |
| Volume | 20 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 1 Dec 2020 |
Bibliographical note
Funding Information:We thank Neil Almond and Mark Page of the UK's National Institute for Biological Standards and Control (NIBSC) for supplying the NIBSC reagents . We are grateful to Janet Darbyshire (Emeritus Professor of Epidemiology at University College London, London UK) and Sir David Spiegelhalter (Winton Professor of the Public Understanding of Risk, University of Cambridge, Cambridge UK) who made up the external review group for the analyses, for their comments on the analyses and results. This work was supported by the UK National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford, Oxford, UK in partnership with Public Health England, and the NIHR Oxford Biomedical Research Centre. The report presents independent research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, NIHR, or the UK Department of Health. DWC and TEAP are NIHR senior investigators. DWE is a Robertson Foundation Fellow and an NIHR Oxford Biomedical Research Centre senior fellow. BDM is supported by the Kennedy Trust for Rheumatology Research and SGC, a registered charity ( number 1097737 ) that receives funds from AbbVie, Bayer Pharma, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada through Ontario Genomics Institute (OGI-055), Innovative Medicines Initiative (EU and European Federation of Pharmaceutical Industries and Associations; Unrestricted Leveraging of Targets for Research Advancement and Drug Discovery grant 115766), Janssen, Merck, Darmstadt, Germany, MSD, Novartis Pharma, Pfizer, São Paulo Research Foundation, Takeda, and Wellcome. PCM is funded through a Wellcome Trust Fellowship ( 110110/15/Z/15 ) and the NIHR Oxford Biomedical Research Centre. GS is a Wellcome Trust Senior Investigator and is supported by the Schmidt Foundation. DIS is supported by the UK Medical Research Council (MR/N00065X/1) and The Chinese Academy of Medical Sciences Innovation Fund for Medical Science, China (2018-I2M-2-002).
Funding Information:
RC reports personal fees and reports acting as a co-founder and consultant at MIROBIO, a University of Oxford spinout. The company targets immune inhibitory receptors as treatments for inflammation and autoimmune disease. This work is unrelated to the serology work. DWE has received lecture fees from Gilead, outside of the submitted work. MGS reports grants from the UK Department of Health and Social Care, National Institute of Health Research UK, Medical Research Council UK, Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK, during the conduct of the study; and acting as a member of the Infectious Disease Scientific Advisory Board to Integrum Scientific, Greensboro, NC, USA, outside of the submitted work. All other authors declare no competing interests.
Funding Information:
We thank Neil Almond and Mark Page of the UK's National Institute for Biological Standards and Control (NIBSC) for supplying the NIBSC reagents. We are grateful to Janet Darbyshire (Emeritus Professor of Epidemiology at University College London, London UK) and Sir David Spiegelhalter (Winton Professor of the Public Understanding of Risk, University of Cambridge, Cambridge UK) who made up the external review group for the analyses, for their comments on the analyses and results. This work was supported by the UK National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford, Oxford, UK in partnership with Public Health England, and the NIHR Oxford Biomedical Research Centre. The report presents independent research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, NIHR, or the UK Department of Health. DWC and TEAP are NIHR senior investigators. DWE is a Robertson Foundation Fellow and an NIHR Oxford Biomedical Research Centre senior fellow. BDM is supported by the Kennedy Trust for Rheumatology Research and SGC, a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada through Ontario Genomics Institute (OGI-055), Innovative Medicines Initiative (EU and European Federation of Pharmaceutical Industries and Associations; Unrestricted Leveraging of Targets for Research Advancement and Drug Discovery grant 115766), Janssen, Merck, Darmstadt, Germany, MSD, Novartis Pharma, Pfizer, S?o Paulo Research Foundation, Takeda, and Wellcome. PCM is funded through a Wellcome Trust Fellowship (110110/15/Z/15) and the NIHR Oxford Biomedical Research Centre. GS is a Wellcome Trust Senior Investigator and is supported by the Schmidt Foundation. DIS is supported by the UK Medical Research Council (MR/N00065X/1) and The Chinese Academy of Medical Sciences Innovation Fund for Medical Science, China (2018-I2M-2-002).
Publisher Copyright:
© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
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Copyright 2020 Elsevier B.V., All rights reserved.
