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Abstract

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.

Item Type:	Article
Authors/Creators:	Selva, KJ and van de Sandt, CE and Lemke, MM and Lee, CY and Shoffner, SK and Chua, BY and Davis, SK and Nguyen, THO and Rowntree, LC and Hensen, L and Koutsakos, M and Wong, CY and Mordant, F and Jackson, DC and Flanagan, KL and Crowe, J and Tosif, S and Neeland, MR and Sutton, P and Licciardi, PV and Crawford, NW and Cheng, AC and Doolan, DL and Amanat, F and Krammer, F and Chappell, K and Modhiran, N and Watterson, D and Young, P and Lee, WS and Wines, BD and Hogarth, PM and Esterbauer, R and Kelly, HG and Tan, HX and Juno, JA and Wheatley, AK and Kent, SJ and Arnold, KB and Kedzierska, K and Chung, AW
Journal or Publication Title:	Nature Communications
Publisher:	Nature Pub. Group
ISSN:	2041-1723
DOI / ID Number:	10.1038/s41467-021-22236-7
Copyright Information:	Copyright 2021 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
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