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Serum IgG anti-SARS-CoV-2 Binding Antibody Level Is Strongly Associated With IgA and Functional Antibody Levels in Adults Infected With SARS-CoV-2
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 in Wuhan, China, and then rapidly spread causing an unprecedented pandemic. A robust serological assay is needed to evaluate vaccine candidates and better understand the epidemiology of coron...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531527/ https://www.ncbi.nlm.nih.gov/pubmed/34691016 http://dx.doi.org/10.3389/fimmu.2021.693462 |
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author | Ye, Xunyan Angelo, Laura S. Nicholson, Erin G. Iwuchukwu, Obinna P. Cabral de Rezende, Wanderson Rajan, Anubama Aideyan, Letisha O. McBride, Trevor J. Bond, Nanette Santarcangelo, Patricia Rayford, Yolanda J. Ferlic-Stark, Laura Fragoso, Sonia Momin, Zoha Liu, Hongbing Truong, Khanghy Lopez, Brianna Conner, Margaret E. Rice, Andrew P. Kimata, Jason T. Avadhanula, Vasanthi Piedra, Pedro A. |
author_facet | Ye, Xunyan Angelo, Laura S. Nicholson, Erin G. Iwuchukwu, Obinna P. Cabral de Rezende, Wanderson Rajan, Anubama Aideyan, Letisha O. McBride, Trevor J. Bond, Nanette Santarcangelo, Patricia Rayford, Yolanda J. Ferlic-Stark, Laura Fragoso, Sonia Momin, Zoha Liu, Hongbing Truong, Khanghy Lopez, Brianna Conner, Margaret E. Rice, Andrew P. Kimata, Jason T. Avadhanula, Vasanthi Piedra, Pedro A. |
author_sort | Ye, Xunyan |
collection | PubMed |
description | BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 in Wuhan, China, and then rapidly spread causing an unprecedented pandemic. A robust serological assay is needed to evaluate vaccine candidates and better understand the epidemiology of coronavirus disease (COVID-19). METHODS: We used the full-length spike (S) protein of SARS-CoV-2 for the development of qualitative and quantitative IgG and IgA anti-S enzyme linked immunosorbent assays (ELISA). A total of 320 sera used for assay development were comprised of pandemic sera from SARS-CoV-2 infected adults (n=51) and pre-pandemic sera (n=269) including sera from endemic human coronavirus infected adults. Reverse cumulative curves and diagnostic test statistics were evaluated to define the optimal serum dilution and OD cutoff value for IgG anti-S and IgA anti-S ELISAs. The IgG and IgA anti-S, and three functional antibodies (ACE-2 receptor blocking antibody, lentipseudovirus-S neutralizing antibody, and SARS-CoV-2 neutralizing antibody) were measured using additional SARS-CoV-2 PCR positive sera (n=76) and surveillance sera (n=25). Lastly, the IgG and IgA anti-S levels were compared in different demographic groups. RESULTS: The optimal serum dilution for the qualitative IgG anti-S ELISA was at 1:1024 yielding a 99.6% specificity, 92.2% sensitivity, 92.9% positive predictive value (PPV), and 99.6% negative predictive value (NPV) at a SARS-CoV-2 seroprevalence of 5%. The optimal serum dilution for the qualitative IgA anti-S ELISA was at 1:128 yielding a 98.9% specificity, 76.5% sensitivity, 78.3% PPV, and 98.8% NPV at the same seroprevalence. Significant correlations were demonstrated between the IgG and IgA (r=0.833 for concentrations, r=0.840 for titers) as well as between IgG and three functional antibodies (r=0.811-0.924 for concentrations, r=0.795-0.917 for titers). The IgG and IgA anti-S levels were significantly higher in males than females (p<0.05), and in adults with moderate/severe symptoms than in adults with mild/moderate symptoms (p<0.001). CONCLUSION: We developed a highly specific and sensitive IgG anti-S ELISA assay to SARS-CoV-2 using full length S protein. The IgG anti-S antibody level was strongly associated with IgA and functional antibody levels in adults with SARS-CoV-2 infection. Gender and disease severity, rather than age, play an important role in antibody levels. |
format | Online Article Text |
id | pubmed-8531527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85315272021-10-23 Serum IgG anti-SARS-CoV-2 Binding Antibody Level Is Strongly Associated With IgA and Functional Antibody Levels in Adults Infected With SARS-CoV-2 Ye, Xunyan Angelo, Laura S. Nicholson, Erin G. Iwuchukwu, Obinna P. Cabral de Rezende, Wanderson Rajan, Anubama Aideyan, Letisha O. McBride, Trevor J. Bond, Nanette Santarcangelo, Patricia Rayford, Yolanda J. Ferlic-Stark, Laura Fragoso, Sonia Momin, Zoha Liu, Hongbing Truong, Khanghy Lopez, Brianna Conner, Margaret E. Rice, Andrew P. Kimata, Jason T. Avadhanula, Vasanthi Piedra, Pedro A. Front Immunol Immunology BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 in Wuhan, China, and then rapidly spread causing an unprecedented pandemic. A robust serological assay is needed to evaluate vaccine candidates and better understand the epidemiology of coronavirus disease (COVID-19). METHODS: We used the full-length spike (S) protein of SARS-CoV-2 for the development of qualitative and quantitative IgG and IgA anti-S enzyme linked immunosorbent assays (ELISA). A total of 320 sera used for assay development were comprised of pandemic sera from SARS-CoV-2 infected adults (n=51) and pre-pandemic sera (n=269) including sera from endemic human coronavirus infected adults. Reverse cumulative curves and diagnostic test statistics were evaluated to define the optimal serum dilution and OD cutoff value for IgG anti-S and IgA anti-S ELISAs. The IgG and IgA anti-S, and three functional antibodies (ACE-2 receptor blocking antibody, lentipseudovirus-S neutralizing antibody, and SARS-CoV-2 neutralizing antibody) were measured using additional SARS-CoV-2 PCR positive sera (n=76) and surveillance sera (n=25). Lastly, the IgG and IgA anti-S levels were compared in different demographic groups. RESULTS: The optimal serum dilution for the qualitative IgG anti-S ELISA was at 1:1024 yielding a 99.6% specificity, 92.2% sensitivity, 92.9% positive predictive value (PPV), and 99.6% negative predictive value (NPV) at a SARS-CoV-2 seroprevalence of 5%. The optimal serum dilution for the qualitative IgA anti-S ELISA was at 1:128 yielding a 98.9% specificity, 76.5% sensitivity, 78.3% PPV, and 98.8% NPV at the same seroprevalence. Significant correlations were demonstrated between the IgG and IgA (r=0.833 for concentrations, r=0.840 for titers) as well as between IgG and three functional antibodies (r=0.811-0.924 for concentrations, r=0.795-0.917 for titers). The IgG and IgA anti-S levels were significantly higher in males than females (p<0.05), and in adults with moderate/severe symptoms than in adults with mild/moderate symptoms (p<0.001). CONCLUSION: We developed a highly specific and sensitive IgG anti-S ELISA assay to SARS-CoV-2 using full length S protein. The IgG anti-S antibody level was strongly associated with IgA and functional antibody levels in adults with SARS-CoV-2 infection. Gender and disease severity, rather than age, play an important role in antibody levels. Frontiers Media S.A. 2021-10-08 /pmc/articles/PMC8531527/ /pubmed/34691016 http://dx.doi.org/10.3389/fimmu.2021.693462 Text en Copyright © 2021 Ye, Angelo, Nicholson, Iwuchukwu, Cabral de Rezende, Rajan, Aideyan, McBride, Bond, Santarcangelo, Rayford, Ferlic-Stark, Fragoso, Momin, Liu, Truong, Lopez, Conner, Rice, Kimata, Avadhanula and Piedra https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Ye, Xunyan Angelo, Laura S. Nicholson, Erin G. Iwuchukwu, Obinna P. Cabral de Rezende, Wanderson Rajan, Anubama Aideyan, Letisha O. McBride, Trevor J. Bond, Nanette Santarcangelo, Patricia Rayford, Yolanda J. Ferlic-Stark, Laura Fragoso, Sonia Momin, Zoha Liu, Hongbing Truong, Khanghy Lopez, Brianna Conner, Margaret E. Rice, Andrew P. Kimata, Jason T. Avadhanula, Vasanthi Piedra, Pedro A. Serum IgG anti-SARS-CoV-2 Binding Antibody Level Is Strongly Associated With IgA and Functional Antibody Levels in Adults Infected With SARS-CoV-2 |
title | Serum IgG anti-SARS-CoV-2 Binding Antibody Level Is Strongly Associated With IgA and Functional Antibody Levels in Adults Infected With SARS-CoV-2 |
title_full | Serum IgG anti-SARS-CoV-2 Binding Antibody Level Is Strongly Associated With IgA and Functional Antibody Levels in Adults Infected With SARS-CoV-2 |
title_fullStr | Serum IgG anti-SARS-CoV-2 Binding Antibody Level Is Strongly Associated With IgA and Functional Antibody Levels in Adults Infected With SARS-CoV-2 |
title_full_unstemmed | Serum IgG anti-SARS-CoV-2 Binding Antibody Level Is Strongly Associated With IgA and Functional Antibody Levels in Adults Infected With SARS-CoV-2 |
title_short | Serum IgG anti-SARS-CoV-2 Binding Antibody Level Is Strongly Associated With IgA and Functional Antibody Levels in Adults Infected With SARS-CoV-2 |
title_sort | serum igg anti-sars-cov-2 binding antibody level is strongly associated with iga and functional antibody levels in adults infected with sars-cov-2 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531527/ https://www.ncbi.nlm.nih.gov/pubmed/34691016 http://dx.doi.org/10.3389/fimmu.2021.693462 |
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