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, and Chung, Amy W. (2021) Systems serology detects functionally distinct coronavirus antibody features in children and elderly. Nature Communications, 12. 2037.

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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 ID: 72679
Item Type: Article (Research - C1)
ISSN: 2041-1723
Copyright Information: © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC Leadership Investigator Grant 1173871, NHMRC Program Grant 1071916, NHMRC Program Grant #1132975, NHMRC Program grant #1149990, NHMRC Career Development Fellowship #1140509, NHMRC Senior Research Fellowship 1102792, NHMRC Principal Research Fellowship #1137285, NHMRC Senior Principal Research Fellowship #1136322, NHMRC Early Career Fellowship (ECF) APP1123673, NHMRC CDF2 Fellowship #1146198
Date Deposited: 11 May 2022 23:35
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320705 Medical virology @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 100%
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