Distinct systems serology features in children, elderly and COVID patients

Selva, K. J.; van de Sandt, C. E.; Lemke, M. M.; Lee, C. Y.; Shoffner, S. K.; Chua, B. Y.; Nguyen, T. H. O.; Rowntree, L. C.; Hensen, L.; Koutsakos, M.; Wong, C. Y.; Jackson, D. C.; Flanagan, K. L.; Crowe, J.; Cheng, A. C.; Doolan, D. L.; Amanat, F.; Krammer, F.; Chappell, K.; Modhiran, N.; Watterson, D.; Young, P.; Wines, B.; Hogarth, P. M.; Esterbauer, R.; Kelly, H. G.; Tan, H.-X.; Juno, J. A.; Wheatley, A. K.; Kent, S. J.; Arnold, K. B.; Kedzierska, K.; Chung, A. W.

SARS-CoV-2, the pandemic coronavirus that causes COVID-19, has infected millions worldwide, causing unparalleled social and economic disruptions. COVID-19 results in higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive coronavirus immunological responses, induced by circulating human coronaviruses, is critical to understand such divergent clinical outcomes. The cross-reactivity of coronavirus antibody responses of healthy children (n=89), adults (n=98), elderly (n=57), and COVID-19 patients (n=19) were analysed by systems serology. While moderate levels of cross-reactive SARS-CoV-2 IgG, IgM, and IgA were detected in healthy individuals, we identified serological signatures associated with SARS-CoV-2 antigen-specific Fc{gamma} receptor binding, which accurately distinguished COVID-19 patients from healthy individuals and suggested that SARS-CoV-2 induces qualitative changes to antibody Fc upon infection, enhancing Fc{gamma} receptor engagement. Vastly different serological signatures were observed between healthy children and elderly, with markedly higher cross-reactive SARS-CoV-2 IgA and IgG observed in elderly, whereas children displayed elevated SARS-CoV-2 IgM, including receptor binding domain-specific IgM with higher avidity. These results suggest that less-experienced humoral immunity associated with higher IgM, as observed in children, may have the potential to induce more potent antibodies upon SARS-CoV-2 infection. These key insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.