Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children

Jacob D Sherman; Vinit Karmali; Bhoj Kumar; Trevor W Simon; Sarah Bechnak; Anusha Panjwani; Caroline R Ciric; Dongli Wang; Christopher Huerta; Brandi Johnson; Evan J Anderson; Nadine Rouphael; Matthew H Collins; Christina A Rostad; Parastoo Azadi; Erin M Scherer

doi:10.1093/ofid/ofae626

Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children

Open Forum Infect Dis. 2024 Oct 16;11(11):ofae626. doi: 10.1093/ofid/ofae626. eCollection 2024 Nov.

Authors

Jacob D Sherman¹, Vinit Karmali¹, Bhoj Kumar², Trevor W Simon¹, Sarah Bechnak¹, Anusha Panjwani¹, Caroline R Ciric³, Dongli Wang¹, Christopher Huerta¹, Brandi Johnson¹, Evan J Anderson^{1

3}, Nadine Rouphael¹, Matthew H Collins¹, Christina A Rostad³, Parastoo Azadi², Erin M Scherer¹

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
² Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA.
³ Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.

Abstract

Background: Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines.

Methods: We analyzed longitudinal (n = 146) and cross-sectional (n = 49) serum/plasma samples from adult and pediatric COVID-19 patients, MIS-C patients, adult vaccinees, and adult and pediatric controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis and measured levels of 10 inflammatory cytokines/chemokines by multiplexed enzyme-linked immunosorbent assay.

Results: Spike IgG was more afucosylated than bulk IgG during acute adult COVID-19 and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG was more galactosylated and sialylated and less bisected than bulk IgG during adult COVID-19, with similar trends observed during pediatric COVID-19/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID-19 or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with proinflammatory cytokines in adult COVID-19 and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups.

Conclusions: We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID-19 and MIS-C immunopathology.

Keywords: COVID-19; Fc; MIS-C; antibody glycosylation; inflammation.

Abstract

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