Abstract
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 Fcγ 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 Fcγ 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.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This work was supported by Jack Ma Foundation to KK, AWC and AW, the Clifford Craig Foundation to KLF and KK, NHMRC Leadership Investigator Grant to KK (1173871), NHMRC Program Grant to KK (1071916), NHMRC Program Grant to DLD (#1132975), NHMRC program grant to SJK (#1149990), Research Grants Council of the Hong Kong Special Administrative Region, China (#T11-712/19-N) to KK. AWC is supported by a NHMRC Career Development Fellowship (#1140509), KK by NHMRC Senior Research Fellowship (1102792), DLD by a NHMRC Principal Research Fellowship (#1137285). SJK by NHMRC Senior Principal Research Fellowship (#1136322). CES has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 792532. LH is supported by the Melbourne International Research Scholarship (MIRS) and the Melbourne International Fee Remission Scholarship (MIFRS) from The University of Melbourne. JAJ is supported by an NHMRC Early Career Fellowship (ECF) (APP1123673)
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Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv
The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam.
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