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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.
  • Hoschler K; Virus Reference Department, Public Health Englandgrid.271308.f, London, United Kingdom.
  • Ijaz S; Virus Reference Department, Public Health Englandgrid.271308.f, London, United Kingdom.
  • Andrews N; Immunisation and Countermeasures Division, Public Health Englandgrid.271308.f, London, United Kingdom.
  • Ho S; Virus Reference Department, Public Health Englandgrid.271308.f, London, United Kingdom.
  • Dicks S; Virus Reference Department, Public Health Englandgrid.271308.f, London, United Kingdom.
  • Jegatheesan K; Microbiology Services Laboratory, NHS Blood and Transplant, Bristol, United Kingdom.
  • Poh J; Virus Reference Department, Public Health Englandgrid.271308.f, London, United Kingdom.
  • Warrener L; Microbiology Services Laboratory, NHS Blood and Transplant, Bristol, United Kingdom.
  • Kankeyan T; Virus Reference Department, Public Health Englandgrid.271308.f, London, United Kingdom.
  • Baawuah F; Virus Reference Department, Public Health Englandgrid.271308.f, London, United Kingdom.
  • Beckmann J; Virus Reference Department, Public Health Englandgrid.271308.f, London, United Kingdom.
  • Okike IO; Immunisation and Countermeasures Division, Public Health Englandgrid.271308.f, London, United Kingdom.
  • Ahmad S; East London NHS Foundation Trustgrid.450709.f, London, United Kingdom.
  • Garstang J; Derbyshire Healthcare NHS Foundation Trust, Derby, United Kingdom.
  • Brent AJ; Manchester University NHS Foundation Trust, Manchester, United Kingdom.
  • Brent B; Birmingham Community Healthcare NHS Trustgrid.439530.8, Aston, United Kingdom.
  • Aiano F; Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
  • Brown KE; University of Oxford, Oxford, United Kingdom.
  • Ramsay ME; Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
  • Brown D; University of Oxford, Oxford, United Kingdom.
  • Parry JV; Immunisation and Countermeasures Division, Public Health Englandgrid.271308.f, London, United Kingdom.
  • Ladhani SN; Immunisation and Countermeasures Division, Public Health Englandgrid.271308.f, London, United Kingdom.
  • Zambon M; Immunisation and Countermeasures Division, Public Health Englandgrid.271308.f, London, United Kingdom.
Microbiol Spectr ; 10(1): e0078621, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1605388
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin G / Gingival Crevicular Fluid / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Diagnostic study Limits: Adolescent / Child / Child, preschool / Humans / Infant Language: English Journal: Microbiol Spectr Year: 2022 Document Type: Article Affiliation country: Spectrum.00786-21

Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin G / Gingival Crevicular Fluid / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Diagnostic study Limits: Adolescent / Child / Child, preschool / Humans / Infant Language: English Journal: Microbiol Spectr Year: 2022 Document Type: Article Affiliation country: Spectrum.00786-21