Evaluation and deployment of isotype-specific salivary antibody assays for detecting previous SARS-CoV-2 infection in children and adults

Amy Thomas*, Elizabeth H Oliver, Holly E Baum, Kapil Gupta, Kathryn L Shelley, Anna E Long, Hayley E Jones, Joyce Smith, Benjamin E Hitchings, Natalie D Di Bartolo, Kate Vasileiou, Fruzsina A Rabi, Hanin I A Alamir, Malak A Eghleilib, Ore Francis, Jennifer L Oliver, Begonia Morales-Aza, Ulrike Obst, Debbie J Shattock, Rachael S BarrLucy Collingwood, Kaltun Duale, Niall Grace, Guillaume Gonnage Livera, Lindsay C Bishop, Harriet E Downing, Fernanda Rodrigues, Nicholas John Timpson, Caroline L Relton, Ash M Toye, Dek N Woolfson, Imre Berger, Anu Goenka, Andrew D Davidson, Kathleen M Gillespie, Alistair J K Williams, Mick Bailey, Ellen Brooks Pollock, Adam H R Finn, Alice Halliday, CoMMinS Study Team

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Background
Saliva is easily obtainable non-invasively and potentially suitable for detecting both current and previous SARS-CoV-2 infection, but there is limited evidence on the utility of salivary antibody testing for community surveillance.

Methods
We established 6 ELISAs detecting IgA and IgG antibodies to whole SARS-CoV-2 spike protein, to its receptor binding domain region and to nucleocapsid protein in saliva. We evaluated diagnostic performance, and using paired saliva and serum samples, correlated mucosal and systemic antibody responses. The best-performing assays were field-tested in 20 household outbreaks.

Results
We demonstrate in test accuracy (N = 320), spike IgG (ROC AUC: 95.0%, 92.8–97.3%) and spike IgA (ROC AUC: 89.9%, 86.5–93.2%) assays to discriminate best between pre-pandemic and post COVID-19 saliva samples. Specificity was 100% in younger age groups (0–19 years) for spike IgA and IgG. However, sensitivity was low for the best-performing assay (spike IgG: 50.6%, 39.8–61.4%). Using machine learning, diagnostic performance was improved when a combination of tests was used. As expected, salivary IgA was poorly correlated with serum, indicating an oral mucosal response whereas salivary IgG responses were predictive of those in serum. When deployed to household outbreaks, antibody responses were heterogeneous but remained a reliable indicator of recent infection. Intriguingly, unvaccinated children without confirmed infection showed evidence of exposure almost exclusively through specific IgA responses.

Conclusions
Through robust standardisation, evaluation and field-testing, this work provides a platform for further studies investigating SARS-CoV-2 transmission and mucosal immunity with the potential for expanding salivo-surveillance to other respiratory infections in hard-to-reach settings.
Original languageEnglish
Article number37
Number of pages14
JournalCommunications Medicine
Volume3
Issue number1
DOIs
Publication statusPublished - 15 Mar 2023

Structured keywords

  • Bristol BioDesign Institute

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