Cross-sectional analysis reveals autoantibody signatures associated with COVID-19 severity

Gabriela C. Baiocchi; Aristo Vojdani; Avi Z. Rosenberg; Elroy Vojdani; Gilad Halpert; Yuri Ostrinski; Israel Zyskind; Igor S. Filgueiras; Lena F. Schimke; Alexandre H.C. Marques; Lasse M. Giil; Yael B. Lavi; Jonathan I. Silverberg; Jason Zimmerman; Dana A. Hill; Amanda Thornton; Myungjin Kim; Roberta De Vito; Dennyson L.M. Fonseca; Desireé R. Plaça; Paula P. Freire; Niels O.S. Camara; Vera L.G. Calich; Carmen Scheibenbogen; Harald Heidecke; Miriam T. Lattin; Hans D. Ochs; Gabriela Riemekasten; Howard Amital; Yehuda Shoenfeld; Otavio Cabral-Marques

doi:10.1002/jmv.28538

Cross-sectional analysis reveals autoantibody signatures associated with COVID-19 severity

Gabriela C. Baiocchi, Aristo Vojdani, Avi Z. Rosenberg, Elroy Vojdani, Gilad Halpert, Yuri Ostrinski, Israel Zyskind, Igor S. Filgueiras, Lena F. Schimke, Alexandre H.C. Marques, Lasse M. Giil, Yael B. Lavi, Jonathan I. Silverberg, Jason Zimmerman, Dana A. Hill, Amanda Thornton, Myungjin Kim, Roberta De Vito, Dennyson L.M. Fonseca, Desireé R. PlaçaPaula P. Freire, Niels O.S. Camara, Vera L.G. Calich, Carmen Scheibenbogen, Harald Heidecke, Miriam T. Lattin, Hans D. Ochs, Gabriela Riemekasten, Howard Amital, Yehuda Shoenfeld, Otavio Cabral-Marques^*

^*Corresponding author for this work

1 Citation (Scopus)

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased levels of autoantibodies targeting immunological proteins such as cytokines and chemokines. Reports further indicate that COVID-19 patients may develop a broad spectrum of autoimmune diseases due to reasons not fully understood. Even so, the landscape of autoantibodies induced by SARS-CoV-2 infection remains uncharted territory. To gain more insight, we carried out a comprehensive assessment of autoantibodies known to be linked to diverse autoimmune diseases observed in COVID-19 patients in a cohort of 231 individuals, of which 161 were COVID-19 patients (72 with mild, 61 moderate, and 28 with severe disease) and 70 were healthy controls. Dysregulated IgG and IgA autoantibody signatures, characterized mainly by elevated concentrations, occurred predominantly in patients with moderate or severe COVID-19 infection. Autoantibody levels often accompanied anti-SARS-CoV-2 antibody concentrations while stratifying COVID-19 severity as indicated by random forest and principal component analyses. Furthermore, while young versus elderly COVID-19 patients showed only slight differences in autoantibody levels, elderly patients with severe disease presented higher IgG autoantibody concentrations than young individuals with severe COVID-19. This work maps the intersection of COVID-19 and autoimmunity by demonstrating the dysregulation of multiple autoantibodies triggered during SARS-CoV-2 infection. Thus, this cross-sectional study suggests that SARS-CoV-2 infection induces autoantibody signatures associated with COVID-19 severity and several autoantibodies that can be used as biomarkers of COVID-19 severity, indicating autoantibodies as potential therapeutical targets for these patients.

Original language	English
Article number	e28538
Journal	Journal of Medical Virology
Volume	95
Issue number	2
Pages (from-to)	e28538
ISSN	0146-6615
DOIs	https://doi.org/10.1002/jmv.28538
Publication status	Published - 02.2023

Funding

We acknowledge the patients for participating in this study. We would like to recognize the contributions of Lev Rochel Bikur Cholim of Lakewood (led by Rabbi Yehuda Kasirer and Mrs. Leeba Prager) and the hundreds of volunteers who collected samples for this research through the MITZVA Cohort. We thank Immunosciences and Cyrex Laboratories for financial support and INOVA Diagnostics for providing their diagnostic ELISA kits for autoimmunity at a significantly discounted rate. Furthermore, we would like to thank Vilma Samayoa, David Cisneros, Roberto Melgar, Dana A. Hill, and Amanda Thornton for their technical assistance. We also thank the São Paulo Research Foundation (FAPESP grants: 2020/07972‐1 to GCB; 2020/09146‐1 to PPF; 2020/11710‐2 to DRP, 2020/16246‐2 to DLMF, 2018/18886‐9, 2020/01688‐0, and 2020/07069‐0 to OCM), and the Coordination for the Improvement of Higher Education Personnel (CAPES) Financial Code 001 (grant to ISF) for financial support. We acknowledge the patients for participating in this study. We would like to recognize the contributions of Lev Rochel Bikur Cholim of Lakewood (led by Rabbi Yehuda Kasirer and Mrs. Leeba Prager) and the hundreds of volunteers who collected samples for this research through the MITZVA Cohort. We thank Immunosciences and Cyrex Laboratories for financial support and INOVA Diagnostics for providing their diagnostic ELISA kits for autoimmunity at a significantly discounted rate. Furthermore, we would like to thank Vilma Samayoa, David Cisneros, Roberto Melgar, Dana A. Hill, and Amanda Thornton for their technical assistance. We also thank the São Paulo Research Foundation (FAPESP grants: 2020/07972-1 to GCB; 2020/09146-1 to PPF; 2020/11710-2 to DRP, 2020/16246-2 to DLMF, 2018/18886-9, 2020/01688-0, and 2020/07069-0 to OCM), and the Coordination for the Improvement of Higher Education Personnel (CAPES) Financial Code 001 (grant to ISF) for financial support.

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

2.21-05 Immunology

Coronavirus related work

Research on SARS-CoV-2 / COVID-19

UN SDGs

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

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10.1002/jmv.28538

Cite this

Baiocchi, G. C., Vojdani, A., Rosenberg, A. Z., Vojdani, E., Halpert, G., Ostrinski, Y., Zyskind, I., Filgueiras, I. S., Schimke, L. F., Marques, A. H. C., Giil, L. M., Lavi, Y. B., Silverberg, J. I., Zimmerman, J., Hill, D. A., Thornton, A., Kim, M., De Vito, R., Fonseca, D. L. M., ... Cabral-Marques, O. (2023). Cross-sectional analysis reveals autoantibody signatures associated with COVID-19 severity. Journal of Medical Virology, 95(2), e28538. Article e28538. https://doi.org/10.1002/jmv.28538

@article{f97abd73c56e4f66acc5e5edfa2f72b2,

title = "Cross-sectional analysis reveals autoantibody signatures associated with COVID-19 severity",

abstract = "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased levels of autoantibodies targeting immunological proteins such as cytokines and chemokines. Reports further indicate that COVID-19 patients may develop a broad spectrum of autoimmune diseases due to reasons not fully understood. Even so, the landscape of autoantibodies induced by SARS-CoV-2 infection remains uncharted territory. To gain more insight, we carried out a comprehensive assessment of autoantibodies known to be linked to diverse autoimmune diseases observed in COVID-19 patients in a cohort of 231 individuals, of which 161 were COVID-19 patients (72 with mild, 61 moderate, and 28 with severe disease) and 70 were healthy controls. Dysregulated IgG and IgA autoantibody signatures, characterized mainly by elevated concentrations, occurred predominantly in patients with moderate or severe COVID-19 infection. Autoantibody levels often accompanied anti-SARS-CoV-2 antibody concentrations while stratifying COVID-19 severity as indicated by random forest and principal component analyses. Furthermore, while young versus elderly COVID-19 patients showed only slight differences in autoantibody levels, elderly patients with severe disease presented higher IgG autoantibody concentrations than young individuals with severe COVID-19. This work maps the intersection of COVID-19 and autoimmunity by demonstrating the dysregulation of multiple autoantibodies triggered during SARS-CoV-2 infection. Thus, this cross-sectional study suggests that SARS-CoV-2 infection induces autoantibody signatures associated with COVID-19 severity and several autoantibodies that can be used as biomarkers of COVID-19 severity, indicating autoantibodies as potential therapeutical targets for these patients.",

author = "Baiocchi, \{Gabriela C.\} and Aristo Vojdani and Rosenberg, \{Avi Z.\} and Elroy Vojdani and Gilad Halpert and Yuri Ostrinski and Israel Zyskind and Filgueiras, \{Igor S.\} and Schimke, \{Lena F.\} and Marques, \{Alexandre H.C.\} and Giil, \{Lasse M.\} and Lavi, \{Yael B.\} and Silverberg, \{Jonathan I.\} and Jason Zimmerman and Hill, \{Dana A.\} and Amanda Thornton and Myungjin Kim and \{De Vito\}, Roberta and Fonseca, \{Dennyson L.M.\} and Pla{\c c}a, \{Desire{\'e} R.\} and Freire, \{Paula P.\} and Camara, \{Niels O.S.\} and Calich, \{Vera L.G.\} and Carmen Scheibenbogen and Harald Heidecke and Lattin, \{Miriam T.\} and Ochs, \{Hans D.\} and Gabriela Riemekasten and Howard Amital and Yehuda Shoenfeld and Otavio Cabral-Marques",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. {\textcopyright} 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.",

year = "2023",

month = feb,

doi = "10.1002/jmv.28538",

language = "English",

volume = "95",

pages = "e28538",

journal = "Journal of Medical Virology",

issn = "0146-6615",

publisher = "John Wiley and Sons Inc",

number = "2",

}

Baiocchi, GC, Vojdani, A, Rosenberg, AZ, Vojdani, E, Halpert, G, Ostrinski, Y, Zyskind, I, Filgueiras, IS, Schimke, LF, Marques, AHC, Giil, LM, Lavi, YB, Silverberg, JI, Zimmerman, J, Hill, DA, Thornton, A, Kim, M, De Vito, R, Fonseca, DLM, Plaça, DR, Freire, PP, Camara, NOS, Calich, VLG, Scheibenbogen, C, Heidecke, H, Lattin, MT, Ochs, HD, Riemekasten, G, Amital, H, Shoenfeld, Y & Cabral-Marques, O 2023, 'Cross-sectional analysis reveals autoantibody signatures associated with COVID-19 severity', Journal of Medical Virology, vol. 95, no. 2, e28538, pp. e28538. https://doi.org/10.1002/jmv.28538

TY - JOUR

T1 - Cross-sectional analysis reveals autoantibody signatures associated with COVID-19 severity

AU - Baiocchi, Gabriela C.

AU - Vojdani, Aristo

AU - Rosenberg, Avi Z.

AU - Vojdani, Elroy

AU - Halpert, Gilad

AU - Ostrinski, Yuri

AU - Zyskind, Israel

AU - Filgueiras, Igor S.

AU - Schimke, Lena F.

AU - Marques, Alexandre H.C.

AU - Giil, Lasse M.

AU - Lavi, Yael B.

AU - Silverberg, Jonathan I.

AU - Zimmerman, Jason

AU - Hill, Dana A.

AU - Thornton, Amanda

AU - Kim, Myungjin

AU - De Vito, Roberta

AU - Fonseca, Dennyson L.M.

AU - Plaça, Desireé R.

AU - Freire, Paula P.

AU - Camara, Niels O.S.

AU - Calich, Vera L.G.

AU - Scheibenbogen, Carmen

AU - Heidecke, Harald

AU - Lattin, Miriam T.

AU - Ochs, Hans D.

AU - Riemekasten, Gabriela

AU - Amital, Howard

AU - Shoenfeld, Yehuda

AU - Cabral-Marques, Otavio

PY - 2023/2

Y1 - 2023/2

N2 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased levels of autoantibodies targeting immunological proteins such as cytokines and chemokines. Reports further indicate that COVID-19 patients may develop a broad spectrum of autoimmune diseases due to reasons not fully understood. Even so, the landscape of autoantibodies induced by SARS-CoV-2 infection remains uncharted territory. To gain more insight, we carried out a comprehensive assessment of autoantibodies known to be linked to diverse autoimmune diseases observed in COVID-19 patients in a cohort of 231 individuals, of which 161 were COVID-19 patients (72 with mild, 61 moderate, and 28 with severe disease) and 70 were healthy controls. Dysregulated IgG and IgA autoantibody signatures, characterized mainly by elevated concentrations, occurred predominantly in patients with moderate or severe COVID-19 infection. Autoantibody levels often accompanied anti-SARS-CoV-2 antibody concentrations while stratifying COVID-19 severity as indicated by random forest and principal component analyses. Furthermore, while young versus elderly COVID-19 patients showed only slight differences in autoantibody levels, elderly patients with severe disease presented higher IgG autoantibody concentrations than young individuals with severe COVID-19. This work maps the intersection of COVID-19 and autoimmunity by demonstrating the dysregulation of multiple autoantibodies triggered during SARS-CoV-2 infection. Thus, this cross-sectional study suggests that SARS-CoV-2 infection induces autoantibody signatures associated with COVID-19 severity and several autoantibodies that can be used as biomarkers of COVID-19 severity, indicating autoantibodies as potential therapeutical targets for these patients.

AB - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased levels of autoantibodies targeting immunological proteins such as cytokines and chemokines. Reports further indicate that COVID-19 patients may develop a broad spectrum of autoimmune diseases due to reasons not fully understood. Even so, the landscape of autoantibodies induced by SARS-CoV-2 infection remains uncharted territory. To gain more insight, we carried out a comprehensive assessment of autoantibodies known to be linked to diverse autoimmune diseases observed in COVID-19 patients in a cohort of 231 individuals, of which 161 were COVID-19 patients (72 with mild, 61 moderate, and 28 with severe disease) and 70 were healthy controls. Dysregulated IgG and IgA autoantibody signatures, characterized mainly by elevated concentrations, occurred predominantly in patients with moderate or severe COVID-19 infection. Autoantibody levels often accompanied anti-SARS-CoV-2 antibody concentrations while stratifying COVID-19 severity as indicated by random forest and principal component analyses. Furthermore, while young versus elderly COVID-19 patients showed only slight differences in autoantibody levels, elderly patients with severe disease presented higher IgG autoantibody concentrations than young individuals with severe COVID-19. This work maps the intersection of COVID-19 and autoimmunity by demonstrating the dysregulation of multiple autoantibodies triggered during SARS-CoV-2 infection. Thus, this cross-sectional study suggests that SARS-CoV-2 infection induces autoantibody signatures associated with COVID-19 severity and several autoantibodies that can be used as biomarkers of COVID-19 severity, indicating autoantibodies as potential therapeutical targets for these patients.

UR - https://www.scopus.com/pages/publications/85148626630

UR - https://www.mendeley.com/catalogue/e2f4b021-1836-3fd1-8447-f5e6a618b483/

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M3 - Journal articles

C2 - 36722456

AN - SCOPUS:85148626630

SN - 0146-6615

VL - 95

SP - e28538

JO - Journal of Medical Virology

JF - Journal of Medical Virology

IS - 2

M1 - e28538

ER -

Cross-sectional analysis reveals autoantibody signatures associated with COVID-19 severity

Abstract

Funding

Research Areas and Centers

DFG Research Classification Scheme

Coronavirus related work

UN SDGs

Access to Document

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