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

Nat Commun. 2021 Apr 1;12(1):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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood*
  • Antibodies, Viral / immunology*
  • Antibody Formation / immunology*
  • COVID-19 / immunology
  • COVID-19 Vaccines / immunology
  • Child
  • Child, Preschool
  • Cross Reactions / immunology
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin M / blood
  • Immunoglobulin M / immunology
  • Middle Aged
  • Receptors, IgG / immunology
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology
  • Young Adult

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • Receptors, IgG
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2