Heli Harvala1, Matthew L Robb2, Nick Watkins3, Samreen Ijaz4, Steven Dicks4, Monika Patel5, Piyada Supasa6, Dejnirattisai Wanwisa6, Chang Liu6, Juthathip Mongkolsapaya6,7, Abbie Bown8, Daniel Bailey8, Richard Vipond8, Nicholas Grayson9, Nigel Temperton10, Sunetra Gupta11, Rutger J Ploeg12,13, Jai Bolton11, Alex Fyfe11, Robin Gopal4, Peter Simmonds14, Gavin Screaton6, Craig Thompson11, Tim Brooks8, Maria Zambon4, Gail Miflin15, David J Roberts16,17. 1. National Microbiology Services, NHS Blood and Transplant, London, UK. 2. Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, UK. 3. Department of Research and Development, NHS Blood and Transplant Cambridge, Cambridge, UK. 4. Virology Reference Department, National Infection Service, Public Health England, London, UK. 5. High Containment Microbiology, National Infection Service, Public Health England, London, UK. 6. Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. 7. Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 8. Rare and Imported Pathogens Laboratory, Public Health England, Porton Down, Wiltshire, UK. 9. Department of Paediatric Medicine, University of Oxford, University of Oxford, Oxford, UK. 10. Medway School of Pharmacy, University of Kent, Chatham, UK. 11. Department of Zoology, University of Oxford, Oxford, UK. 12. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. 13. Department of Transplant Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. 14. Nuffield Department of Medicine, University of Oxford, Oxford, UK. 15. Department of Chief Medical Officer, NHS Blood and Transplant, Bristol, UK. 16. NHS Blood and Transplant, Oxford, John Radcliffe Hospital, Oxford, UK. 17. Radcliffe Department of Medicine and BRC Haematology Theme, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Abstract
INTRODUCTION: The lack of approved specific therapeutic agents to treat coronavirus disease (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to the rapid implementation of convalescent plasma therapy (CPT) trials in many countries, including the United Kingdom. Effective CPT is likely to require high titres of neutralising antibody (nAb) in convalescent donations. Understanding the relationship between functional neutralising antibodies and antibody levels to specific SARS-CoV-2 proteins in scalable assays will be crucial for the success of a large-scale collection. We assessed whether neutralising antibody titres correlated with reactivity in a range of enzyme-linked immunosorbent assays (ELISA) targeting the spike (S) protein, the main target for human immune response. METHODS: Blood samples were collected from 52 individuals with a previous laboratory-confirmed SARS-CoV-2 infection. These were assayed for SARS-CoV-2 nAbs by microneutralisation and pseudo-type assays and for antibodies by four different ELISAs. Receiver operating characteristic (ROC) analysis was used to further identify sensitivity and specificity of selected assays to identify samples containing high nAb levels. RESULTS: All samples contained SARS-CoV-2 antibodies, whereas neutralising antibody titres of greater than 1:20 were detected in 43 samples (83% of those tested) and >1:100 in 22 samples (42%). The best correlations were observed with EUROimmun immunoglobulin G (IgG) reactivity (Spearman Rho correlation coefficient 0.88; p < 0.001). Based on ROC analysis, EUROimmun would detect 60% of samples with titres of >1:100 with 100% specificity using a reactivity index of 9.1 (13/22). DISCUSSION: Robust associations between nAb titres and reactivity in several ELISA-based antibody tests demonstrate their possible utility for scaled-up production of convalescent plasma containing potentially therapeutic levels of anti-SARS-CoV-2 nAbs.
INTRODUCTION: The lack of approved specific therapeutic agents to treat coronavirus disease (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to the rapid implementation of convalescent plasma therapy (CPT) trials in many countries, including the United Kingdom. Effective CPT is likely to require high titres of neutralising antibody (nAb) in convalescent donations. Understanding the relationship between functional neutralising antibodies and antibody levels to specific SARS-CoV-2 proteins in scalable assays will be crucial for the success of a large-scale collection. We assessed whether neutralising antibody titres correlated with reactivity in a range of enzyme-linked immunosorbent assays (ELISA) targeting the spike (S) protein, the main target for human immune response. METHODS: Blood samples were collected from 52 individuals with a previous laboratory-confirmed SARS-CoV-2 infection. These were assayed for SARS-CoV-2nAbs by microneutralisation and pseudo-type assays and for antibodies by four different ELISAs. Receiver operating characteristic (ROC) analysis was used to further identify sensitivity and specificity of selected assays to identify samples containing high nAb levels. RESULTS: All samples contained SARS-CoV-2 antibodies, whereas neutralising antibody titres of greater than 1:20 were detected in 43 samples (83% of those tested) and >1:100 in 22 samples (42%). The best correlations were observed with EUROimmun immunoglobulin G (IgG) reactivity (Spearman Rho correlation coefficient 0.88; p < 0.001). Based on ROC analysis, EUROimmun would detect 60% of samples with titres of >1:100 with 100% specificity using a reactivity index of 9.1 (13/22). DISCUSSION: Robust associations between nAb titres and reactivity in several ELISA-based antibody tests demonstrate their possible utility for scaled-up production of convalescent plasma containing potentially therapeutic levels of anti-SARS-CoV-2nAbs.
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