close Icon

Systems serology detects functionally distinct coronavirus antibody features in children and elderly.

Selva KJ, van de Sandt CE, Lemke MM, Lee CY, Shoffner SK, Chua BY, Davis SK, Nguyen THO, Rowntree LC, Hensen L, Koutsakos M, Wong CY, Mordant F, Jackson DC, Flanagan KL, Crowe J, Tosif S, Neeland MR, Sutton P, Licciardi PV, Crawford NW, Cheng AC, Doolan DL, Amanat F, Krammer F, Chappell K, Modhiran N, Watterson D, Young P, Lee WS, Wines BD, Mark Hogarth P, Esterbauer R, Kelly HG, Tan HX, Juno JA, Wheatley AK, Kent SJ, Arnold KB, Kedzierska K, Chung AW

VIEW FULL ARTICLE
  • Journal Nature communications

  • Published 01 Apr 2021

  • Volume 12

  • ISSUE 1

  • Pagination 2037

  • DOI 10.1038/s41467-021-22236-7

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.