| Literature DB >> 33795692 |
Kevin J Selva1, Carolien E van de Sandt1,2, Melissa M Lemke3, Christina Y Lee3, Suzanne K Shoffner3, Brendon Y Chua1, Samantha K Davis1, Thi H O Nguyen1, Louise C Rowntree1, Luca Hensen1, Marios Koutsakos1, Chinn Yi Wong1, Francesca Mordant1, David C Jackson1, Katie L Flanagan4,5,6,7, Jane Crowe8, Shidan Tosif9,10,11, Melanie R Neeland9,11, Philip Sutton9,11, Paul V Licciardi9,11, Nigel W Crawford9,12, Allen C Cheng13,14, Denise L Doolan15, Fatima Amanat16,17, Florian Krammer16, Keith Chappell18, Naphak Modhiran18, Daniel Watterson18, Paul Young18, Wen Shi Lee1, Bruce D Wines19,20,21, P Mark Hogarth19,20,21, Robyn Esterbauer1,22, Hannah G Kelly1,22, Hyon-Xhi Tan1,22, Jennifer A Juno1, Adam K Wheatley1,22, Stephen J Kent1,22,23, Kelly B Arnold3, Katherine Kedzierska24, Amy W Chung25.
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.Entities:
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Year: 2021 PMID： 33795692 DOI： 10.1038/s41467-021-22236-7
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919