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

Selva, Kevin J.;Van De Sandt, Carolien E.;Lemke, Melissa M.;Lee, Christina Y.;Shoffner, Suzanne K.;Chua, Brendon Y.;Davis, Samantha K.;Nguyen, Thi;Rowntree, Louise;Hensen, Luca;Koutsakos, Marios;Wong, Chinn Yi;Mordant, Francesca;Jackson, David C.;Flanagan, Katie L.;Crowe, Jane;Tosif, Shidan;Neeland, Melanie R.;Sutton, Philip;Licciardi, Paul V.;Crawford, Nigel W.;Cheng, Allen C.;Doolan, Denise L.;Amanat, Fatima;Krammer, Florian;Chappell, Keith;Modhiran, Naphak;Watterson, Daniel;Young, Paul;Lee, Wen Shi;Wines, Bruce D.;Hogarth, P. Mark;Esterbauer, Robyn;Kelly, Hannah G.;Tan, Hyon-Xhi;Juno, Jennifer A.;Wheatley, Adam K.;Kent, Stephen J.;Arnold, Kelly B.;Kedzierska, Katherine;Chung, Amy W.

Denise Doolan

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.

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Nature Communications

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2041-1723

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Nature Publishing Group

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DOI

10.1038/s41467-021-22236-7