Author: 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 H. O.; Rowntree, Louise C.; 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.; Mark Hogarth, P.; 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.
Title: Systems serology detects functionally distinct coronavirus antibody features in children and elderly Cord-id: oizj3aws Document date: 2021_4_1
ID: oizj3aws
Snippet: 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-reactiv
Document: 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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