@article{fd11ba8ed7614860a8c1eccf886f021f,
title = "IgG targeting distinct seasonal coronavirus- conserved SARS-CoV-2 spike subdomains correlates with differential COVID-19 disease outcomes",
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",
author = "Garrido, {Jose L.} and Medina, {Mat{\'i}as A.} and Felipe Bravo and Sarah McGee and Francisco Fuentes-Villalobos and Mario Calvo and Yazmin Pinos and Bowman, {James W.} and Bahl, {Christopher D.} and Barria, {Maria Ines} and Brachman, {Rebecca A.} and Alvarez, {Raymond A.}",
note = "Funding Information: J.L.G., F.B., and R.A.A. were partially supported by Ichor Biologics LLC. R.A.A. and R.A.B. are inventors on a provisional patent related to this study. The remaining authors declare no commercial or financial relationships that are potential conflicts of interest. Funding Information: We would like to thank Sheila O{\textquoteright}Donoghue, RN, and Beth Sferrazza, RN, for conducting the blood draws for this study; Drs. Svenja Weiss and Biliana Lozanoska-Ochser for their critical review of this manuscript; Dr. Server Ertem for insights on diagnostic design; and Dean Greg Morrisett, PhD, of Cornell Tech for generous institutional support. This study was supported by NIH SBIR grant no. 1R43AI138740-01A1 , awarded to Ichor Biologics and R.A.A.; Chilean National Research and Development Agency grant no. COVID0422 , awarded to M.I.B.; and a Jacobs Technion-Cornell Institute Runway package, awarded to R.A.B. F.B. was supported by an ANID scholarship/PhD no. 21201764 and F.F. was supported by FONDECYT grant no. 3200913 . The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. Funding Information: We would like to thank Sheila O'Donoghue, RN, and Beth Sferrazza, RN, for conducting the blood draws for this study; Drs. Svenja Weiss and Biliana Lozanoska-Ochser for their critical review of this manuscript; Dr. Server Ertem for insights on diagnostic design; and Dean Greg Morrisett, PhD, of Cornell Tech for generous institutional support. This study was supported by NIH SBIR grant no. 1R43AI138740-01A1, awarded to Ichor Biologics and R.A.A.; Chilean National Research and Development Agency grant no. COVID0422, awarded to M.I.B.; and a Jacobs Technion-Cornell Institute Runway package, awarded to R.A.B. F.B. was supported by an ANID scholarship/PhD no.21201764 and F.F. was supported by FONDECYT grant no. 3200913. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. Study design, J.L.G. R.A.A. R.A.B. C.D.B. M.C. F.F. and M.I.B. Experimental work, J.L.G. F.B. S.M. J.W.B. M.I.B. and R.A.A. Data analysis, J.L.G. M.M. S.M. C.D.B. R.A.B. and R.A.A. Reagent development, J.L.G. R.A.A. J.W.B. and C.D.B. Donor plasma acquisition, S.M. J.L.G. Y.P. and R.A.A. Writing, J.L.G. R.A.A. and R.A.B. and the final version was approved by all of the authors. J.L.G. F.B. and R.A.A. were partially supported by Ichor Biologics LLC. R.A.A. and R.A.B. are inventors on a provisional patent related to this study. The remaining authors declare no commercial or financial relationships that are potential conflicts of interest. We worked to ensure sex balance in the selection of non-human subjects. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. One or more of the authors of this paper received support from a program designed to increase minority representation in science. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = may,
day = "31",
doi = "10.1016/j.celrep.2022.110904",
language = "English",
volume = "39",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",
}