Distinct systems serology features in children, elderly and COVID patients

Abstract

54 55 SARS-CoV-2, the pandemic coronavirus that causes COVID-19, has infected millions worldwide, 56 causing unparalleled social and economic disruptions. COVID-19 results in higher pathogenicity and 57 mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive 58 coronavirus immunological responses, induced by circulating human coronaviruses, is critical to 59 understand such divergent clinical outcomes. The cross-reactivity of coronavirus antibody responses 60 of healthy children (n=89), adults (n=98), elderly (n=57), and COVID-19 patients (n=19) were 61 analysed by systems serology. While moderate levels of cross-reactive SARS-CoV-2 IgG, IgM, and 62 IgA were detected in healthy individuals, we identified serological signatures associated with SARS-63 CoV-2 antigen-specific Fcγ receptor binding, which accurately distinguished COVID-19 patients 64 from healthy individuals and suggested that SARS-CoV-2 induces qualitative changes to antibody Fc 65 upon infection, enhancing Fcγ receptor engagement. Vastly different serological signatures were 66 observed between healthy children and elderly, with markedly higher cross-reactive SARS-CoV-2 67 IgA and IgG observed in elderly, whereas children displayed elevated SARS-CoV-2 IgM, including 68receptor binding domain-specific IgM with higher avidity. These results suggest that less-experienced 69 humoral immunity associated with higher IgM, as observed in children, may have the potential to 70 induce more potent antibodies upon SARS-CoV-2 infection. These key insights will inform COVID-

Immune responses to SARS-CoV-2 in children of parents with symptomatic COVID-19

“…A custom CoV multiplex assay was designed and coupled as previous described 25 , with SARS-CoV-2 Spike 1 (Sino Biological), SARS-CoV-2 Spike 2, SARS-CoV Spike 1 (ACRO Biosystems, USA) and hCoV (229E, NL63, OC43) spikes (Sino Biologicals), as well as SARS-CoV-2 RBD (produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH USA), SARS-CoV RBD (gift from Dale Godfrey) and both SARS-CoV-2 and HKU1 Trimeric Spikes (gift from Adam Wheatley). Tetanus toxoid (Sigma Aldrich) and in uenza hemagglutinin (H1Cal2009; Sino Biological) were also added to the assay as positive controls.…”

“…The isotypes and subclasses of pathogen-speci c antibodies present in collected plasma were assessed using the above multiplex assay as previously described 25 . Brie y, 20 µl of working bead mixture (1000 beads per bead region) and 20 µl of diluted plasma ( nal dilution 1:100) were added per well and incubated overnight at 4 °C on a shaker.…”

A comparison of non-magnetic and magnetic beads for measuring IgG antibodies againstP. vivaxantigens in a multiplexed bead-based assay using Luminex®technology (Bio-Plex®200 or MAGPIX®)

“…A key focus of P. vivax serology efforts should be to develop a standard WHO reference reagent for P. vivax that is available to any research group worldwide. Non-magnetic beads: A$640/ml/1.25x10 7 beads 20% less than magnetic beads Up to 100 beads available Magnetic beads: ~A$800/ml/1.25x10 7 beads Up to 50 beads available Better beads retention Whilst these results were obtained in the context of P. vivax-specific IgG responses in individuals from malaria-endemic areas, the large panel of proteins used and consistent results obtained for all proteins suggest these results can be applied to guide studies in other fields. Luminex xMAP ® technology has been used to measure antibody responses against other infectious pathogens, such as HIV and influenza [17,18], to a variety of vaccine antigens such as tetanus toxoid [19], and more recently to SARS-CoV-2 [6][7][8].…”

“…This study used a panel of 19 different P. vivax proteins and plasma samples from P. vivax-endemic areas to detect P. vivax-specific IgG responses, however the large number of proteins assessed and consistent results obtained, suggest these findings should be generalizable for optimization of the multiplexed bead-based assay for other pathogens. This is important in the context of the ongoing SARS-CoV-2 pandemic, as multiple laboratory assays based on Luminex technology are under development [6][7][8].…”

Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines

“…This may in part account for the greater immunopathology of COVID-19 in older individuals. Indeed, it has been shown recently that COVID-19-naïve children and elderly have quite different cross-reactive SARS-CoV-2-specific antibody signatures, which would play differing roles upon challenge with the wild-type virus ( 161 ).…”