IgG targeting distinct seasonal coronavirus- conserved SARS-CoV-2 spike subdomains correlates with differential COVID-19 disease outcomes

Jose L. Garrido, Matías A. Medina, Felipe Bravo, Sarah McGee, Francisco Fuentes-Villalobos, Mario Calvo, Yazmin Pinos, James W. Bowman, Christopher D. Bahl, Maria Ines Barria, Rebecca A. Brachman, Raymond A. Alvarez

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Despite SARS-CoV-2 being a “novel” virus, early detection of anti-spike IgG in severe COVID-19 patients may be caused by the amplification of humoral memory responses against seasonal coronaviruses. Here, we examine this phenomenon by characterizing anti-spike IgG responses in non-hospitalized convalescent individuals across a spectrum of COVID-19 severity. We observe that disease severity positively correlates with anti-spike IgG levels, IgG cross-reactivity against other betacoronaviruses (β-CoVs), and FcγR activation. Analysis of IgG targeting β-CoV-conserved and non-conserved immunodominant epitopes within the SARS-CoV-2 spike protein revealed epitope-specific relationships: IgG targeting the conserved heptad repeat (HR) 2 region significantly correlates with milder disease, while targeting the conserved S2′FP region correlates with more severe disease. Furthermore, a lower HR2-to-S2′FP IgG-binding ratio correlates with greater disease severity, with ICU-hospitalized COVID-19 patients showing the lowest HR2/S2′FP ratios. These findings suggest that HR2/S2′FP IgG profiles may predict disease severity and offer insight into protective versus deleterious humoral recall responses.

Original languageEnglish
Article number110904
JournalCell Reports
Volume39
Issue number9
DOIs
StatePublished - 31 May 2022

Keywords

  • ADE
  • COVID-19
  • CP: Immunology
  • CP: Microbiology
  • Fc-gamma receptor activation
  • OC43
  • SARS-CoV-2
  • SARS1
  • antibody-mediated effector responses
  • disease severity
  • fusion protein region
  • heptad repeat region
  • human betacoronavirus

Fingerprint

Dive into the research topics of 'IgG targeting distinct seasonal coronavirus- conserved SARS-CoV-2 spike subdomains correlates with differential COVID-19 disease outcomes'. Together they form a unique fingerprint.

Cite this