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SARS Antibody Testing in Children: Development of Oral Fluid Assays for IgG Measurements
Seroepidemiological studies to monitor antibody kinetics are important for assessing the extent and spread of SARS-CoV-2 in a population. Noninvasive sampling methods are advantageous for reducing the need for venipuncture, which may be a barrier to investigations, particularly in pediatric populati...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8729769/ https://www.ncbi.nlm.nih.gov/pubmed/34985331 http://dx.doi.org/10.1128/spectrum.00786-21 |
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author | Hoschler, Katja Ijaz, Samreen Andrews, Nick Ho, Sammy Dicks, Steve Jegatheesan, Keerthana Poh, John Warrener, Lenesha Kankeyan, Thivya Baawuah, Frances Beckmann, Joanne Okike, Ifeanichukwu O. Ahmad, Shazaad Garstang, Joanna Brent, Andrew J. Brent, Bernadette Aiano, Felicity Brown, Kevin E. Ramsay, Mary E. Brown, David Parry, John V. Ladhani, Shamez N. Zambon, Maria |
author_facet | Hoschler, Katja Ijaz, Samreen Andrews, Nick Ho, Sammy Dicks, Steve Jegatheesan, Keerthana Poh, John Warrener, Lenesha Kankeyan, Thivya Baawuah, Frances Beckmann, Joanne Okike, Ifeanichukwu O. Ahmad, Shazaad Garstang, Joanna Brent, Andrew J. Brent, Bernadette Aiano, Felicity Brown, Kevin E. Ramsay, Mary E. Brown, David Parry, John V. Ladhani, Shamez N. Zambon, Maria |
author_sort | Hoschler, Katja |
collection | PubMed |
description | Seroepidemiological studies to monitor antibody kinetics are important for assessing the extent and spread of SARS-CoV-2 in a population. Noninvasive sampling methods are advantageous for reducing the need for venipuncture, which may be a barrier to investigations, particularly in pediatric populations. Oral fluids are obtained by gingiva-crevicular sampling from children and adults and are very well accepted. Enzyme immunoassays (EIAs) based on these samples have acceptable sensitivity and specificity compared to conventional serum-based antibody EIAs and are suitable for population-based surveillance. We describe the development and evaluation of SARS-CoV-2 IgG EIAs using SARS-CoV-2 viral nucleoprotein (NP) and spike (S) proteins in IgG isotype capture format and an indirect receptor-binding-domain (RBD) IgG EIA, intended for use in children as a primary endpoint. All three assays were assessed using a panel of 1,999 paired serum and oral fluids from children and adults participating in school SARS-CoV-2 surveillance studies during and after the first and second pandemic wave in the United Kingdom. The anti-NP IgG capture assay was the best candidate, with an overall sensitivity of 75% (95% confidence interval [CI]: 71 to 79%) and specificity of 99% (95% CI: 78 to 99%) compared with paired serum antibodies. Sensitivity observed in children (80%, 95% CI: 71 to 88%) was higher than that in adults (67%, CI: 60% to 74%). Oral fluid assays (OF) using spike protein and RBD antigens were also 99% specific and achieved reasonable but lower sensitivity in the target population (78%, 95% CI [68% to 86%] and 53%, 95% CI [43% to 64%], respectively). IMPORTANCE We report on the first large-scale assessment of the suitability of oral fluids for detection of SARS-CoV-2 antibody obtained from healthy children attending school. The sample type (gingiva-crevicular fluid, which is a transudate of blood but is not saliva) can be self collected. Although detection of antibodies in oral fluids is less sensitive than that in blood, our study suggests an optimal format for operational use. The laboratory methods we have developed can reliably measure antibodies in children, who are able to take their own samples. Our findings are of immediate practical relevance for use in large-scale seroprevalence studies designed to measure exposure to infection, as they typically require venipuncture. Overall, our data indicate that OF assays based on the detection of SARS-CoV-2 antibodies are a tool suitable for population-based seroepidemiology studies in children and highly acceptable in children and adults, as venipuncture is no longer necessary. |
format | Online Article Text |
id | pubmed-8729769 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-87297692022-01-06 SARS Antibody Testing in Children: Development of Oral Fluid Assays for IgG Measurements Hoschler, Katja Ijaz, Samreen Andrews, Nick Ho, Sammy Dicks, Steve Jegatheesan, Keerthana Poh, John Warrener, Lenesha Kankeyan, Thivya Baawuah, Frances Beckmann, Joanne Okike, Ifeanichukwu O. Ahmad, Shazaad Garstang, Joanna Brent, Andrew J. Brent, Bernadette Aiano, Felicity Brown, Kevin E. Ramsay, Mary E. Brown, David Parry, John V. Ladhani, Shamez N. Zambon, Maria Microbiol Spectr Research Article Seroepidemiological studies to monitor antibody kinetics are important for assessing the extent and spread of SARS-CoV-2 in a population. Noninvasive sampling methods are advantageous for reducing the need for venipuncture, which may be a barrier to investigations, particularly in pediatric populations. Oral fluids are obtained by gingiva-crevicular sampling from children and adults and are very well accepted. Enzyme immunoassays (EIAs) based on these samples have acceptable sensitivity and specificity compared to conventional serum-based antibody EIAs and are suitable for population-based surveillance. We describe the development and evaluation of SARS-CoV-2 IgG EIAs using SARS-CoV-2 viral nucleoprotein (NP) and spike (S) proteins in IgG isotype capture format and an indirect receptor-binding-domain (RBD) IgG EIA, intended for use in children as a primary endpoint. All three assays were assessed using a panel of 1,999 paired serum and oral fluids from children and adults participating in school SARS-CoV-2 surveillance studies during and after the first and second pandemic wave in the United Kingdom. The anti-NP IgG capture assay was the best candidate, with an overall sensitivity of 75% (95% confidence interval [CI]: 71 to 79%) and specificity of 99% (95% CI: 78 to 99%) compared with paired serum antibodies. Sensitivity observed in children (80%, 95% CI: 71 to 88%) was higher than that in adults (67%, CI: 60% to 74%). Oral fluid assays (OF) using spike protein and RBD antigens were also 99% specific and achieved reasonable but lower sensitivity in the target population (78%, 95% CI [68% to 86%] and 53%, 95% CI [43% to 64%], respectively). IMPORTANCE We report on the first large-scale assessment of the suitability of oral fluids for detection of SARS-CoV-2 antibody obtained from healthy children attending school. The sample type (gingiva-crevicular fluid, which is a transudate of blood but is not saliva) can be self collected. Although detection of antibodies in oral fluids is less sensitive than that in blood, our study suggests an optimal format for operational use. The laboratory methods we have developed can reliably measure antibodies in children, who are able to take their own samples. Our findings are of immediate practical relevance for use in large-scale seroprevalence studies designed to measure exposure to infection, as they typically require venipuncture. Overall, our data indicate that OF assays based on the detection of SARS-CoV-2 antibodies are a tool suitable for population-based seroepidemiology studies in children and highly acceptable in children and adults, as venipuncture is no longer necessary. American Society for Microbiology 2022-01-05 /pmc/articles/PMC8729769/ /pubmed/34985331 http://dx.doi.org/10.1128/spectrum.00786-21 Text en © Crown copyright 2022. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Hoschler, Katja Ijaz, Samreen Andrews, Nick Ho, Sammy Dicks, Steve Jegatheesan, Keerthana Poh, John Warrener, Lenesha Kankeyan, Thivya Baawuah, Frances Beckmann, Joanne Okike, Ifeanichukwu O. Ahmad, Shazaad Garstang, Joanna Brent, Andrew J. Brent, Bernadette Aiano, Felicity Brown, Kevin E. Ramsay, Mary E. Brown, David Parry, John V. Ladhani, Shamez N. Zambon, Maria SARS Antibody Testing in Children: Development of Oral Fluid Assays for IgG Measurements |
title | SARS Antibody Testing in Children: Development of Oral Fluid Assays for IgG Measurements |
title_full | SARS Antibody Testing in Children: Development of Oral Fluid Assays for IgG Measurements |
title_fullStr | SARS Antibody Testing in Children: Development of Oral Fluid Assays for IgG Measurements |
title_full_unstemmed | SARS Antibody Testing in Children: Development of Oral Fluid Assays for IgG Measurements |
title_short | SARS Antibody Testing in Children: Development of Oral Fluid Assays for IgG Measurements |
title_sort | sars antibody testing in children: development of oral fluid assays for igg measurements |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8729769/ https://www.ncbi.nlm.nih.gov/pubmed/34985331 http://dx.doi.org/10.1128/spectrum.00786-21 |
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