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Convalescent plasma therapy for the treatment of patients with COVID‐19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels
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 t...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246874/ https://www.ncbi.nlm.nih.gov/pubmed/33333627 http://dx.doi.org/10.1111/tme.12746 |
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author | Harvala, Heli Robb, Matthew L. Watkins, Nick Ijaz, Samreen Dicks, Steven Patel, Monika Supasa, Piyada Wanwisa, Dejnirattisai Liu, Chang Mongkolsapaya, Juthathip Bown, Abbie Bailey, Daniel Vipond, Richard Grayson, Nicholas Temperton, Nigel Gupta, Sunetra Ploeg, Rutger J. Bolton, Jai Fyfe, Alex Gopal, Robin Simmonds, Peter Screaton, Gavin Thompson, Craig Brooks, Tim Zambon, Maria Miflin, Gail Roberts, David J. |
author_facet | Harvala, Heli Robb, Matthew L. Watkins, Nick Ijaz, Samreen Dicks, Steven Patel, Monika Supasa, Piyada Wanwisa, Dejnirattisai Liu, Chang Mongkolsapaya, Juthathip Bown, Abbie Bailey, Daniel Vipond, Richard Grayson, Nicholas Temperton, Nigel Gupta, Sunetra Ploeg, Rutger J. Bolton, Jai Fyfe, Alex Gopal, Robin Simmonds, Peter Screaton, Gavin Thompson, Craig Brooks, Tim Zambon, Maria Miflin, Gail Roberts, David J. |
author_sort | Harvala, Heli |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8246874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-82468742021-07-02 Convalescent plasma therapy for the treatment of patients with COVID‐19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels Harvala, Heli Robb, Matthew L. Watkins, Nick Ijaz, Samreen Dicks, Steven Patel, Monika Supasa, Piyada Wanwisa, Dejnirattisai Liu, Chang Mongkolsapaya, Juthathip Bown, Abbie Bailey, Daniel Vipond, Richard Grayson, Nicholas Temperton, Nigel Gupta, Sunetra Ploeg, Rutger J. Bolton, Jai Fyfe, Alex Gopal, Robin Simmonds, Peter Screaton, Gavin Thompson, Craig Brooks, Tim Zambon, Maria Miflin, Gail Roberts, David J. Transfus Med Original Articles 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. Blackwell Publishing Ltd 2020-12-17 2021-06 /pmc/articles/PMC8246874/ /pubmed/33333627 http://dx.doi.org/10.1111/tme.12746 Text en © 2020 The Authors. Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Harvala, Heli Robb, Matthew L. Watkins, Nick Ijaz, Samreen Dicks, Steven Patel, Monika Supasa, Piyada Wanwisa, Dejnirattisai Liu, Chang Mongkolsapaya, Juthathip Bown, Abbie Bailey, Daniel Vipond, Richard Grayson, Nicholas Temperton, Nigel Gupta, Sunetra Ploeg, Rutger J. Bolton, Jai Fyfe, Alex Gopal, Robin Simmonds, Peter Screaton, Gavin Thompson, Craig Brooks, Tim Zambon, Maria Miflin, Gail Roberts, David J. Convalescent plasma therapy for the treatment of patients with COVID‐19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels |
title | Convalescent plasma therapy for the treatment of patients with COVID‐19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels |
title_full | Convalescent plasma therapy for the treatment of patients with COVID‐19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels |
title_fullStr | Convalescent plasma therapy for the treatment of patients with COVID‐19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels |
title_full_unstemmed | Convalescent plasma therapy for the treatment of patients with COVID‐19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels |
title_short | Convalescent plasma therapy for the treatment of patients with COVID‐19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels |
title_sort | convalescent plasma therapy for the treatment of patients with covid‐19: assessment of methods available for antibody detection and their correlation with neutralising antibody levels |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246874/ https://www.ncbi.nlm.nih.gov/pubmed/33333627 http://dx.doi.org/10.1111/tme.12746 |
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