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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2020
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.
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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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