{"doi":"10.1093/ofid/ofae626","title":"Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children","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.","journal":"Open Forum Infectious Diseases","year":2024,"id":504788,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":384283,"name":"Vinit Karmali","orcid":null,"position":1,"is_corresponding":false},{"id":91960,"name":"Bhoj Kumar","orcid":"0000-0001-8311-7025","position":2,"is_corresponding":false},{"id":794007,"name":"Trevor W. Simon","orcid":"0000-0001-9930-1011","position":3,"is_corresponding":false},{"id":619539,"name":"Sarah Bechnak","orcid":null,"position":4,"is_corresponding":false},{"id":1350626,"name":"Anusha Panjwani","orcid":null,"position":5,"is_corresponding":false},{"id":619538,"name":"Caroline Ciric","orcid":null,"position":6,"is_corresponding":false},{"id":1350371,"name":"Dongli Wang","orcid":"0000-0002-6704-1646","position":7,"is_corresponding":false},{"id":106172,"name":"Christopher Huerta","orcid":null,"position":8,"is_corresponding":false},{"id":616977,"name":"Brandi Johnson","orcid":null,"position":9,"is_corresponding":false},{"id":94484,"name":"Evan J. Anderson","orcid":"0000-0002-1576-4420","position":10,"is_corresponding":false},{"id":104987,"name":"Nadine Rouphael","orcid":"0000-0002-2512-7919","position":11,"is_corresponding":false},{"id":237968,"name":"Matthew H. Collins","orcid":"0000-0001-7974-1933","position":12,"is_corresponding":false},{"id":94488,"name":"Christina A. Rostad","orcid":"0000-0001-8439-0592","position":13,"is_corresponding":false},{"id":91961,"name":"Parastoo Azadi","orcid":"0000-0002-6166-9432","position":14,"is_corresponding":false},{"id":226165,"name":"Erin M. Scherer","orcid":"0000-0002-8794-1932","position":15,"is_corresponding":false},{"id":848590,"name":"Jacob D. Sherman","orcid":"0009-0002-2597-7654","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:10:39.578471Z","pmid":"39494457","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}