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146647 - systems serology detects functionally distinct coronavirus.pdf (3.58 MB)

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

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posted on 2023-05-21, 02:32 authored by Selva, KJ, van de Sandt, CE, Lemke, MM, Lee, CY, Shoffner, SK, Chua, BY, Davis, SK, Nguyen, THO, Rowntree, LC, Hensen, L, Koutsakos, M, Wong, CY, Mordant, F, Jackson, DC, Katie FlanaganKatie Flanagan, Crowe, J, Tosif, S, Neeland, MR, Sutton, P, Licciardi, PV, Crawford, NW, Cheng, AC, Doolan, DL, Amanat, F, Krammer, F, Chappell, K, Modhiran, N, Watterson, D, Young, P, Lee, WS, Wines, BD, Hogarth, PM, Esterbauer, R, Kelly, HG, Tan, HX, Juno, JA, Wheatley, AK, Kent, SJ, Arnold, KB, Kedzierska, K, Chung, AW
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

ISSN

2041-1723

Department/School

Tasmanian School of Medicine

Publisher

Nature Pub. Group

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/

Repository Status

  • Open

Socio-economic Objectives

Treatment of human diseases and conditions

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