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Systems serology detects functionally distinct coronavirus antibody features in children and elderly

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Version 2 2024-11-21, 01:04
Version 1 2023-05-21, 02:32
journal contribution
posted on 2024-11-21, 01:04 authored by KJ Selva, CE van de Sandt, MM Lemke, CY Lee, SK Shoffner, BY Chua, SK Davis, THO Nguyen, LC Rowntree, L Hensen, M Koutsakos, CY Wong, F Mordant, DC Jackson, Katie FlanaganKatie Flanagan, J Crowe, S Tosif, MR Neeland, P Sutton, PV Licciardi, NW Crawford, AC Cheng, DL Doolan, F Amanat, F Krammer, K Chappell, N Modhiran, D Watterson, P Young, WS Lee, BD Wines, PM Hogarth, R Esterbauer, HG Kelly, HX Tan, JA Juno, AK Wheatley, SJ Kent, KB Arnold, K Kedzierska, AW Chung
The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.

History

Publication title

Nature Communications

Volume

12

Issue

1

Pagination

14

ISSN

2041-1723

Department/School

Medicine

Publisher

Nature Pub. Group

Publication status

  • Published

Place of publication

United Kingdom

Rights statement

Copyright 2021 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

Socio-economic Objectives

200105 Treatment of human diseases and conditions

UN Sustainable Development Goals

3 Good Health and Well Being

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