Bulk IgG glycosylation predicts COVID-19 severity and vaccine antibody response

Michelle K. Ash; Pavan P. Bhimalli; Byoung Kyu Cho; Basil Baby Mattamana; Stéphanie Gambut; Imad Tarhoni; Cristina L. Fhied; Anjelica F. Reyes; Samantha J. Welninski; Jaison Arivalagan; Fernanda Negrão; Renu Goel; Todd L. Beck; Thomas J. Hope; Beverly E. Sha; Young Ah Goo; Lena Al-Harthi; João I. Mamede; Jeffrey A. Borgia; Neil L. Kelleher; Jeffrey R. Schneider

doi:10.1016/j.celrep.2022.111799

Bulk IgG glycosylation predicts COVID-19 severity and vaccine antibody response

Michelle K. Ash, Pavan P. Bhimalli, Byoung Kyu Cho, Basil Baby Mattamana, Stéphanie Gambut, Imad Tarhoni, Cristina L. Fhied, Anjelica F. Reyes, Samantha J. Welninski, Jaison Arivalagan, Fernanda Negrão, Renu Goel, Todd L. Beck, Thomas J. Hope, Beverly E. Sha, Young Ah Goo, Lena Al-Harthi, João I. Mamede, Jeffrey A. Borgia, Neil L. KelleherJeffrey R. Schneider^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Although vaccination efforts have expanded, there are still gaps in our understanding surrounding the immune response to SARS-CoV-2. Measuring IgG Fc glycosylation provides insight into an infected individual's inflammatory state, among other functions. We set out to interrogate bulk IgG glycosylation changes from SARS-CoV-2 infection and vaccination, using plasma from mild or hospitalized COVID-19 patients, and from vaccinated individuals. Inflammatory glycans are elevated in hospitalized COVID-19 patients and increase over time, while mild patients have anti-inflammatory glycans that increase over time, including increased sialic acid correlating with RBD antibody levels. Vaccinated individuals with low RBD antibody levels and low neutralization have the same IgG glycan traits as hospitalized COVID-19 patients. In addition, a small vaccinated cohort reveals a decrease in inflammatory glycans associated with peak IgG concentrations and neutralization. This report characterizes the bulk IgG glycome associated with COVID-19 severity and vaccine responsiveness and can help guide future studies into SARS-CoV-2 protective immunity.

Original language	English (US)
Article number	111799
Journal	Cell reports
Volume	41
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2022.111799
State	Published - Dec 13 2022

Funding

This work was supported by the Walder Foundation’s Chicago Coronavirus Assessment Network (Chicago CAN) Initiative grants SCI16 and 21-00147 (J.R.S. and J.A.B.). IgG antibody glycan analysis was performed by the Northwestern Proteomics Core Facility, supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center , instrumentation award ( S10OD025194 ) from NIH Office of Director, and the National Resource for Translational and Developmental Proteomics supported by P41 GM108569 , an internal RUSH grant to João Mamede. We thank the Rush COVID-19 Biorepository Core (Dr. Alan Landay, Dr. James Moy, and Cheryl Jennings) and Rush Biomarker Development Core (J.A.B.) for specimen sourcing and antibody titer determinations. Longitudinal COVID-19 patient biospecimens were provided by Advocate Aurora Research Institute’s Biorepository and Specimen Resource Core. We also thank the University of Illinois - Chicago Statistics Core for their independent statistical analysis. This work was supported by the Walder Foundation's Chicago Coronavirus Assessment Network (Chicago CAN) Initiative grants SCI16 and 21-00147 (J.R.S. and J.A.B.). IgG antibody glycan analysis was performed by the Northwestern Proteomics Core Facility, supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center, instrumentation award (S10OD025194) from NIH Office of Director, and the National Resource for Translational and Developmental Proteomics supported by P41 GM108569, an internal RUSH grant to João Mamede. We thank the Rush COVID-19 Biorepository Core (Dr. Alan Landay, Dr. James Moy, and Cheryl Jennings) and Rush Biomarker Development Core (J.A.B.) for specimen sourcing and antibody titer determinations. Longitudinal COVID-19 patient biospecimens were provided by Advocate Aurora Research Institute's Biorepository and Specimen Resource Core. We also thank the University of Illinois - Chicago Statistics Core for their independent statistical analysis. Experiments were carried out by M.K.A. P.P.B. B.B.M. S.G. S.J.W. I.T. and C.L.F. Data were analyzed by J.R.S. P.P.B. M.K.A. S.J.W. B.C. J.F. and F.N. B.E.S. I.T. C.L.F. and A.F.R. helped with sample acquisition. R.G. T.J.H. Y.A.G. L.A. J.I.M. J.A.B. and N.L.K. assisted with overseeing the experiments and data analysis. T.L.B. assisted with statistical analysis. M.K.A. and J.R.S. wrote the manuscript. All authors helped give critique to the manuscript. Dr. Jeffrey Borgia is the inventor of the dual target Luminex assay for SARS-CoV-2 antigen detection.

Keywords

COVID-19
CP: Immunology
SARS-CoV-2, IgG, RBD, Nucleocapsid, vaccination, infection, neutralization, inflammation
antibodies
glycosylation

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.celrep.2022.111799

Cite this

Ash, M. K., Bhimalli, P. P., Cho, B. K., Mattamana, B. B., Gambut, S., Tarhoni, I., Fhied, C. L., Reyes, A. F., Welninski, S. J., Arivalagan, J., Negrão, F., Goel, R., Beck, T. L., Hope, T. J., Sha, B. E., Goo, Y. A., Al-Harthi, L., Mamede, J. I., Borgia, J. A., ... Schneider, J. R. (2022). Bulk IgG glycosylation predicts COVID-19 severity and vaccine antibody response. Cell reports, 41(11), Article 111799. https://doi.org/10.1016/j.celrep.2022.111799

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title = "Bulk IgG glycosylation predicts COVID-19 severity and vaccine antibody response",

abstract = "Although vaccination efforts have expanded, there are still gaps in our understanding surrounding the immune response to SARS-CoV-2. Measuring IgG Fc glycosylation provides insight into an infected individual's inflammatory state, among other functions. We set out to interrogate bulk IgG glycosylation changes from SARS-CoV-2 infection and vaccination, using plasma from mild or hospitalized COVID-19 patients, and from vaccinated individuals. Inflammatory glycans are elevated in hospitalized COVID-19 patients and increase over time, while mild patients have anti-inflammatory glycans that increase over time, including increased sialic acid correlating with RBD antibody levels. Vaccinated individuals with low RBD antibody levels and low neutralization have the same IgG glycan traits as hospitalized COVID-19 patients. In addition, a small vaccinated cohort reveals a decrease in inflammatory glycans associated with peak IgG concentrations and neutralization. This report characterizes the bulk IgG glycome associated with COVID-19 severity and vaccine responsiveness and can help guide future studies into SARS-CoV-2 protective immunity.",

keywords = "COVID-19, CP: Immunology, SARS-CoV-2, IgG, RBD, Nucleocapsid, vaccination, infection, neutralization, inflammation, antibodies, glycosylation",

author = "Ash, {Michelle K.} and Bhimalli, {Pavan P.} and Cho, {Byoung Kyu} and Mattamana, {Basil Baby} and St{\'e}phanie Gambut and Imad Tarhoni and Fhied, {Cristina L.} and Reyes, {Anjelica F.} and Welninski, {Samantha J.} and Jaison Arivalagan and Fernanda Negr{\~a}o and Renu Goel and Beck, {Todd L.} and Hope, {Thomas J.} and Sha, {Beverly E.} and Goo, {Young Ah} and Lena Al-Harthi and Mamede, {Jo{\~a}o I.} and Borgia, {Jeffrey A.} and Kelleher, {Neil L.} and Schneider, {Jeffrey R.}",

note = "Funding Information: This work was supported by the Walder Foundation{\textquoteright}s Chicago Coronavirus Assessment Network (Chicago CAN) Initiative grants SCI16 and 21-00147 (J.R.S. and J.A.B.). IgG antibody glycan analysis was performed by the Northwestern Proteomics Core Facility, supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center , instrumentation award ( S10OD025194 ) from NIH Office of Director, and the National Resource for Translational and Developmental Proteomics supported by P41 GM108569 , an internal RUSH grant to Jo{\~a}o Mamede. We thank the Rush COVID-19 Biorepository Core (Dr. Alan Landay, Dr. James Moy, and Cheryl Jennings) and Rush Biomarker Development Core (J.A.B.) for specimen sourcing and antibody titer determinations. Longitudinal COVID-19 patient biospecimens were provided by Advocate Aurora Research Institute{\textquoteright}s Biorepository and Specimen Resource Core. We also thank the University of Illinois - Chicago Statistics Core for their independent statistical analysis. Funding Information: This work was supported by the Walder Foundation's Chicago Coronavirus Assessment Network (Chicago CAN) Initiative grants SCI16 and 21-00147 (J.R.S. and J.A.B.). IgG antibody glycan analysis was performed by the Northwestern Proteomics Core Facility, supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center, instrumentation award (S10OD025194) from NIH Office of Director, and the National Resource for Translational and Developmental Proteomics supported by P41 GM108569, an internal RUSH grant to Jo{\~a}o Mamede. We thank the Rush COVID-19 Biorepository Core (Dr. Alan Landay, Dr. James Moy, and Cheryl Jennings) and Rush Biomarker Development Core (J.A.B.) for specimen sourcing and antibody titer determinations. Longitudinal COVID-19 patient biospecimens were provided by Advocate Aurora Research Institute's Biorepository and Specimen Resource Core. We also thank the University of Illinois - Chicago Statistics Core for their independent statistical analysis. Experiments were carried out by M.K.A. P.P.B. B.B.M. S.G. S.J.W. I.T. and C.L.F. Data were analyzed by J.R.S. P.P.B. M.K.A. S.J.W. B.C. J.F. and F.N. B.E.S. I.T. C.L.F. and A.F.R. helped with sample acquisition. R.G. T.J.H. Y.A.G. L.A. J.I.M. J.A.B. and N.L.K. assisted with overseeing the experiments and data analysis. T.L.B. assisted with statistical analysis. M.K.A. and J.R.S. wrote the manuscript. All authors helped give critique to the manuscript. Dr. Jeffrey Borgia is the inventor of the dual target Luminex assay for SARS-CoV-2 antigen detection. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = dec,

day = "13",

doi = "10.1016/j.celrep.2022.111799",

language = "English (US)",

volume = "41",

journal = "Cell reports",

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Ash, MK, Bhimalli, PP, Cho, BK, Mattamana, BB, Gambut, S, Tarhoni, I, Fhied, CL, Reyes, AF, Welninski, SJ, Arivalagan, J, Negrão, F, Goel, R, Beck, TL, Hope, TJ, Sha, BE, Goo, YA, Al-Harthi, L, Mamede, JI, Borgia, JA, Kelleher, NL & Schneider, JR 2022, 'Bulk IgG glycosylation predicts COVID-19 severity and vaccine antibody response', Cell reports, vol. 41, no. 11, 111799. https://doi.org/10.1016/j.celrep.2022.111799

TY - JOUR

T1 - Bulk IgG glycosylation predicts COVID-19 severity and vaccine antibody response

AU - Ash, Michelle K.

AU - Bhimalli, Pavan P.

AU - Cho, Byoung Kyu

AU - Mattamana, Basil Baby

AU - Gambut, Stéphanie

AU - Tarhoni, Imad

AU - Fhied, Cristina L.

AU - Reyes, Anjelica F.

AU - Welninski, Samantha J.

AU - Arivalagan, Jaison

AU - Negrão, Fernanda

AU - Goel, Renu

AU - Beck, Todd L.

AU - Hope, Thomas J.

AU - Sha, Beverly E.

AU - Goo, Young Ah

AU - Al-Harthi, Lena

AU - Mamede, João I.

AU - Borgia, Jeffrey A.

AU - Kelleher, Neil L.

AU - Schneider, Jeffrey R.

N1 - Funding Information: This work was supported by the Walder Foundation’s Chicago Coronavirus Assessment Network (Chicago CAN) Initiative grants SCI16 and 21-00147 (J.R.S. and J.A.B.). IgG antibody glycan analysis was performed by the Northwestern Proteomics Core Facility, supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center , instrumentation award ( S10OD025194 ) from NIH Office of Director, and the National Resource for Translational and Developmental Proteomics supported by P41 GM108569 , an internal RUSH grant to João Mamede. We thank the Rush COVID-19 Biorepository Core (Dr. Alan Landay, Dr. James Moy, and Cheryl Jennings) and Rush Biomarker Development Core (J.A.B.) for specimen sourcing and antibody titer determinations. Longitudinal COVID-19 patient biospecimens were provided by Advocate Aurora Research Institute’s Biorepository and Specimen Resource Core. We also thank the University of Illinois - Chicago Statistics Core for their independent statistical analysis. Funding Information: This work was supported by the Walder Foundation's Chicago Coronavirus Assessment Network (Chicago CAN) Initiative grants SCI16 and 21-00147 (J.R.S. and J.A.B.). IgG antibody glycan analysis was performed by the Northwestern Proteomics Core Facility, supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center, instrumentation award (S10OD025194) from NIH Office of Director, and the National Resource for Translational and Developmental Proteomics supported by P41 GM108569, an internal RUSH grant to João Mamede. We thank the Rush COVID-19 Biorepository Core (Dr. Alan Landay, Dr. James Moy, and Cheryl Jennings) and Rush Biomarker Development Core (J.A.B.) for specimen sourcing and antibody titer determinations. Longitudinal COVID-19 patient biospecimens were provided by Advocate Aurora Research Institute's Biorepository and Specimen Resource Core. We also thank the University of Illinois - Chicago Statistics Core for their independent statistical analysis. Experiments were carried out by M.K.A. P.P.B. B.B.M. S.G. S.J.W. I.T. and C.L.F. Data were analyzed by J.R.S. P.P.B. M.K.A. S.J.W. B.C. J.F. and F.N. B.E.S. I.T. C.L.F. and A.F.R. helped with sample acquisition. R.G. T.J.H. Y.A.G. L.A. J.I.M. J.A.B. and N.L.K. assisted with overseeing the experiments and data analysis. T.L.B. assisted with statistical analysis. M.K.A. and J.R.S. wrote the manuscript. All authors helped give critique to the manuscript. Dr. Jeffrey Borgia is the inventor of the dual target Luminex assay for SARS-CoV-2 antigen detection. Publisher Copyright: © 2022 The Author(s)

PY - 2022/12/13

Y1 - 2022/12/13

N2 - Although vaccination efforts have expanded, there are still gaps in our understanding surrounding the immune response to SARS-CoV-2. Measuring IgG Fc glycosylation provides insight into an infected individual's inflammatory state, among other functions. We set out to interrogate bulk IgG glycosylation changes from SARS-CoV-2 infection and vaccination, using plasma from mild or hospitalized COVID-19 patients, and from vaccinated individuals. Inflammatory glycans are elevated in hospitalized COVID-19 patients and increase over time, while mild patients have anti-inflammatory glycans that increase over time, including increased sialic acid correlating with RBD antibody levels. Vaccinated individuals with low RBD antibody levels and low neutralization have the same IgG glycan traits as hospitalized COVID-19 patients. In addition, a small vaccinated cohort reveals a decrease in inflammatory glycans associated with peak IgG concentrations and neutralization. This report characterizes the bulk IgG glycome associated with COVID-19 severity and vaccine responsiveness and can help guide future studies into SARS-CoV-2 protective immunity.

AB - Although vaccination efforts have expanded, there are still gaps in our understanding surrounding the immune response to SARS-CoV-2. Measuring IgG Fc glycosylation provides insight into an infected individual's inflammatory state, among other functions. We set out to interrogate bulk IgG glycosylation changes from SARS-CoV-2 infection and vaccination, using plasma from mild or hospitalized COVID-19 patients, and from vaccinated individuals. Inflammatory glycans are elevated in hospitalized COVID-19 patients and increase over time, while mild patients have anti-inflammatory glycans that increase over time, including increased sialic acid correlating with RBD antibody levels. Vaccinated individuals with low RBD antibody levels and low neutralization have the same IgG glycan traits as hospitalized COVID-19 patients. In addition, a small vaccinated cohort reveals a decrease in inflammatory glycans associated with peak IgG concentrations and neutralization. This report characterizes the bulk IgG glycome associated with COVID-19 severity and vaccine responsiveness and can help guide future studies into SARS-CoV-2 protective immunity.

KW - COVID-19

KW - CP: Immunology

KW - SARS-CoV-2, IgG, RBD, Nucleocapsid, vaccination, infection, neutralization, inflammation

KW - antibodies

KW - glycosylation

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UR - http://www.scopus.com/inward/citedby.url?scp=85143853191&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2022.111799

DO - 10.1016/j.celrep.2022.111799

M3 - Article

C2 - 36493786

AN - SCOPUS:85143853191

SN - 2211-1247

VL - 41

JO - Cell reports

JF - Cell reports

IS - 11

M1 - 111799

ER -

Bulk IgG glycosylation predicts COVID-19 severity and vaccine antibody response

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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