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

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.

Mild SARS-CoV-2 Infections and Neutralizing Antibody Titers

“…In light of this, we hypothesize that an original antigenic sin driven by repeat exposure to endemic human coronaviruses (hCoV) might impair the response to SARS-CoV-2 in adults, while the less experienced immune repertoire of children could favor a prompt selective response. Recent work published by Selva et al 28 supports this hypothesis proving that infection in elderly patients associates with antibodies targeting the cross-reactive S2 and NP proteins, while in children the response is dominated by antibodies with high Fc-effector function targeting the immunodominant S1 protein of SARS-CoV-2. In addition, Westerhuis et al 29 proved that in adult patients, an expansion of B-cell clones against seasonal hCoVs dominates the response, generating antibodies poorly reactive with SARS-CoV-2.…”

SARS-CoV-2 Seroprevalence and Neutralizing Antibody Response after the First and Second COVID-19 Pandemic Wave in Croatia

“…No differences in the in vitro virus neutralization were observed between the different age groups of Australian COVID-19 patients. However, higher cross-reactive SARS-CoV-2 IgA and IgG antibodies were observed in healthy elderly people, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have had fewer human coronavirus exposures, resulting in less experienced but broadly reactive humoral immunity [ 38 ].…”

Decay of Fc-dependent antibody functions after mild to moderate COVID-19

“…Luminex bead-based multiplex assay A custom bead array was designed using SARS-CoV-2 S trimer, S1 subunit (Sino Biological), S2 subunit (ACRO Biosystems) and RBD (BEI Resources), as well as HCoV (OC43, HKU1, 229E, NL63) S and S1 subunit (Sino Biological) (as described in Table S2) 52 . Tetanus toxoid (Sigma-Aldrich), influenza hemagglutinin (H1Cal2009; Sino Biological) and SIV gp120 (Sino Biological) were also included in the array as positive and negative controls respectively.…”

“…Using the respective antigen-coupled beads, a custom CoV multiplex assay was formed to investigate the dimeric recombinant soluble FcgR-binding capacity of pathogen-specific antibodies present in COVID-19 convalescent plasma samples and uninfected controls 52 . Briefly, 20ml of working bead mixture (1000 beads per antigen-coupled bead region) and 20ml of diluted plasma (final dilution 1:200) were added per well and incubated overnight at 4 C on a shaker.…”