Proinflammatory IgG Fc structures in patients with severe COVID-19

Nat Immunol. 2021 Jan;22(1):67-73. doi: 10.1038/s41590-020-00828-7. Epub 2020 Nov 9.

Abstract

Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on severe acute respiratory syndrome coronavirus 2 IgGs enhanced interactions with the activating Fcγ receptor FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. These results show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated IgG1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • COVID-19 / immunology*
  • COVID-19 / metabolism
  • COVID-19 / virology
  • Child
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Female
  • Glycosylation
  • Humans
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / metabolism
  • Interleukin-6
  • Male
  • Middle Aged
  • Receptors, IgG / immunology*
  • Receptors, IgG / metabolism
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / metabolism
  • SARS-CoV-2 / physiology
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • FCGR3A protein, human
  • Immunoglobulin G
  • Interleukin-6
  • Receptors, IgG
  • Tumor Necrosis Factor-alpha