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

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

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94 Citations (Scopus)


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.

Original languageEnglish
Article number2037
Number of pages14
JournalNature Communications
Issue number1
Publication statusPublished - Dec 2021

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