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. Antibody responses to SARS-CoV-2 are critical in the immune response to infection, but the potential cross-reactivity to other human corona viruses is poorly appreciated. Here the authors apply a systems based approach to characterise the antibody response in pre-pandemic cohorts and assess heterotypic reactivity to SARS-CoV-2.
【저자키워드】 antibodies, SARS-CoV-2, viral infection, Infection, 【초록키워드】 COVID-19, IgG, coronavirus, immune response, Mortality, serology, antibody, SARS-COV-2 infection, children, Antibody Response, virus, diagnostics, clinical outcomes, cross-reactivity, Humoral immunity, Cohort, SARS-CoV-2 antibody, COVID-19 vaccination, IgA, response, HCoV, immunological responses, pathogenicity, serological, change, Critical, COVID-19 patients, SARS-CoV-2 IgM, Analysis, Receptor binding, COVID-19 patient, cross-reactive, healthy individuals, circulating, hallmark, healthy children, HCoVs, receptor engagement, approach, human coronavirus, resulting, healthy, elevated, induce, reactivity, the antibody response, baseline, Examining, 【제목키워드】 coronavirus, serology, antibody, children, System, feature, detect,