tetano
Editor, Senior Moderator
Cell Rep
. 2022 May 16;110904.
doi: 10.1016/j.celrep.2022.110904. Online ahead of print.
IgG targeting distinct seasonal coronavirus- conserved SARS-CoV-2 spike subdomains correlates with differential COVID-19 disease outcomes
Jose L Garrido[SUP] 1 [/SUP], Matías A Medina[SUP] 2 [/SUP], Felipe Bravo[SUP] 3 [/SUP], Sarah McGee[SUP] 4 [/SUP], Francisco Fuentes-Villalobos[SUP] 2 [/SUP], Mario Calvo[SUP] 5 [/SUP], Yazmin Pinos[SUP] 6 [/SUP], James W Bowman[SUP] 7 [/SUP], Christopher D Bahl[SUP] 7 [/SUP], Maria Ines Barria[SUP] 8 [/SUP], Rebecca A Brachman[SUP] 9 [/SUP], Raymond A Alvarez[SUP] 10 [/SUP]
Affiliations
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.
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.
. 2022 May 16;110904.
doi: 10.1016/j.celrep.2022.110904. Online ahead of print.
IgG targeting distinct seasonal coronavirus- conserved SARS-CoV-2 spike subdomains correlates with differential COVID-19 disease outcomes
Jose L Garrido[SUP] 1 [/SUP], Matías A Medina[SUP] 2 [/SUP], Felipe Bravo[SUP] 3 [/SUP], Sarah McGee[SUP] 4 [/SUP], Francisco Fuentes-Villalobos[SUP] 2 [/SUP], Mario Calvo[SUP] 5 [/SUP], Yazmin Pinos[SUP] 6 [/SUP], James W Bowman[SUP] 7 [/SUP], Christopher D Bahl[SUP] 7 [/SUP], Maria Ines Barria[SUP] 8 [/SUP], Rebecca A Brachman[SUP] 9 [/SUP], Raymond A Alvarez[SUP] 10 [/SUP]
Affiliations
- PMID: 35617962
- DOI: 10.1016/j.celrep.2022.110904
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.
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.