Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison
Authors: Mark Ainsworth, Monique Andersson, Kathryn Auckland, J Kenneth Baillie, Eleanor Barnes, Sally Beer, Amy Beveridge, Sagida Bibi, Luke Blackwell, Martyna Borak, Abbie Bown, Tim Brooks, Nicola A Burgess-Brown, Susana Camara, Matthew Catton, Kevin K. Chau, Thomas Christott, Elizabeth Clutterbuck, Jesse Coker, Richard J Cornall, Stuart Cox, David Crawford-Jones, Derrick W Crook, Silvia D'Arcangelo, Wanwisa Dejnirattsai, Julie M M Dequaire, Stavros Dimitriadis, Kate E Dingle, George Doherty, Christina Dold, Tao Dong, Susanna J Dunachie, Daniel Ebner, Marc Emmenegger, Alexis Espinosa, David W Eyre, Rory Fairhead, Shayan Fassih, Conor Feehily, Sally Felle, Alejandra Fernandez-Cid, Maria Fernandez Mendoza, Thomas H Foord, Thomas Fordwoh, Deborah Fox McKee, John Frater, Veronica Gallardo Sanchez, Nick Gent, Dominique Georgiou, Christopher J Groves, Bassam Hallis, Peter M Hammond, Stephanie B. Hatch, Heli J Harvala, Jennifer Hill, Sarah J Hoosdally, Bryn Horsington, Alison Howarth, Tim James, Katie Jeffery, Elizabeth Jones, Anita Justice, Fredrik Karpe, James Kavanagh, David S Kim, Richard Kirton, Paul Klenerman, Julian C Knight, Leonidas Koukouflis, Andrew Kwok, Ullrich Leuschner, Robert Levin, Aline Linder, Teresa Lockett, Sheila F Lumley, Spyridoula Marinou, Brian D Marsden, Jose Martinez, Lucas Martins Ferreira, Lara Mason, Philippa C Matthews, Alexander J Mentzer, Alexander Mobbs, Juthathip Mongkolsapaya, Jordan Morrow, Shubhashish M M Mukhopadhyay, Matthew J Neville, Sarah Oakley, Marta Oliveira, Ashley Otter, Kevin Paddon, Jordan Pascoe, Yanchun Peng, Elena Perez, Prem K Perumal, Timothy E A Peto, Hayleah Pickford, Rutger J Ploeg, Andrew J Pollard, Anastasia Richardson, Thomas G Ritter, David J Roberts, Gillian Rodger, Christine S Rollier, Cathy Rowe, Justine K Rudkin, Gavin Screaton, Malcolm G Semple, Alex Sienkiewicz, Laura Silva-Reyes, Donal T Skelly, Alberto Sobrino Diaz, Lizzie Stafford, Lisa Stockdale, Nicole Stoesser, Teresa Street, David I Stuart, Angela Sweed, Adan Taylor, Hannah Thraves, Hoi P Tsang, Marije K Verheul, Richard Vipond, Timothy M Walker, Susan Wareing, Yolanda Warren, Charlie Wells, Clare Wilson, Kate Withycombe, Rebecca K Young
Journal: The Lancet Infectious Diseases (2020)

<h2>Summary</h2><h3>Background</h3> 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. <h3>Methods</h3> 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. <h3>Findings</h3> 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. <h3>Interpretation</h3> 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. <h3>Funding</h3> Public Health England and UK National Institute for Health Research.