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2. Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison

Author

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

Published
2020
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4. T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses

Author

Ogbe, Ane, Kronsteiner, Barbara, Skelly, Donal T, Pace, Matthew, Brown, Anthony, Adland, Emily, Adair, Kareena, Akhter, Hossain Delowar, Ali, Mohammad, Ali, Serat-E, Angyal, Adrienn, Ansari, M Azim, Arancibia-Carcamo, Carolina V, Brown, Helen, Chinnakannan, Senthil, Conlon, Christopher, de Lara, Catherine, de Silva, Thushan, Dold, Christina, Dong, Tao, Donnison, Timothy, Eyre, David, Flaxman, Amy, Fletcher, Helen, Gardner, Joshua, Grist, James T, Hackstein, Carl-Philipp, Jaruthamsophon, Kanoot, Jeffery, Katie, Lambe, Teresa, Lee, Lian, Li, Wenqin, Lim, Nicholas, Matthews, Philippa C, Mentzer, Alexander J, Moore, Shona C, Naisbitt, Dean J, Ogese, Monday, Ogg, Graham, Openshaw, Peter, Pirmohamed, Munir, Pollard, Andrew J, Ramamurthy, Narayan, Rongkard, Patpong, Rowland-Jones, Sarah, Sampson, Oliver, Screaton, Gavin, Sette, Alessandro, Stafford, Lizzie, Thompson, Craig, Thomson, Paul J, Thwaites, Ryan, Vieira, Vinicius, Weiskopf, Daniela, Zacharopoulou, Panagiota, Chalk, Jeremy, Kerr, Georgina, Phalora, Prabhjeet, Csala, Anna, Jones, Mathew, Robinson, Nicola, Brown, Rachael, Hutchings, Claire, Provine, Nicholas, Ratcliff, Jeremy, Amini, Ali, Borak, Martyna, Dimitriadis, Stavros, Fordwoh, Thomas, Horsington, Bryn, Johnson, Sile, Morrow, Jordan, Warren, Yolanda, Wells, Charlie, Turtle, Lance, Klenerman, Paul, Goulder, Philip, Frater, John, Barnes, Eleanor, Dunachie, Susanna, Immunology, Oxford, and Oxford, Protective TC

Subjects
0301 basic medicine, CD4-Positive T-Lymphocytes, animal diseases, T-Lymphocytes, General Physics and Astronomy, CD8-Positive T-Lymphocytes, Immunological memory, 0302 clinical medicine, 030212 general & internal medicine, Subclinical infection, Immunoassay, Multidisciplinary, ELISPOT, 3. Good health, Multidisciplinary Sciences, medicine.anatomical_structure, Science & Technology - Other Topics, VIRUS, Cytokines, Science, T cell, Health Personnel, Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical Team, chemical and pharmacologic phenomena, Biology, Cross Reactions, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Interferon-gamma, Immune system, Antigen, Immunity, medicine, Humans, Pandemics, Cell Proliferation, Science & Technology, Cell growth, SARS-CoV-2, Oxford Immunology Network Covid-19 Response T Cell Consortium, COVID-19, General Chemistry, biochemical phenomena, metabolism, and nutrition, 030104 developmental biology, HEK293 Cells, Viral infection, Immunoglobulin G, Immunology, bacteria, Peptides, Immunologic Memory, Ex vivo
Abstract

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations., Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.

Published
2020

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