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

Gabriela C. Baiocchi, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Aristo Vojdani, Immunosciences Laboratory, Inc., Department of Immunology, Los Angeles, California, USA.
Avi Z. Rosenberg, Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
Elroy Vojdani, Regenera Medical, Los Angeles, California, USA.
Gilad Halpert, Ariel University, Ariel, Israel.
Yuri Ostrinski, Ariel University, Ariel, Israel.
Israel Zyskind, Department of Pediatrics, NYU Langone Medical Center, New York, New York, USA.
Igor S. Filgueiras, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Lena F. Schimke, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Alexandre H. Marques, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Lasse M. Giil, Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.
Yael B. Lavi, Department of Chemistry Ben Gurion University Beer-Sheva, Beer-Sheva, Israel.
Jonathan I. Silverberg, Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, USA.
Jason Zimmerman, Maimonides Medical Center, Brooklyn, New York, USA.
Dana A. Hill, ResourcePath, Sterling, Virginia, USA.
Amanda Thornton, ResourcePath, Sterling, Virginia, USA.
Myungjin Kim, Data Science Initiative at Brown University, Providence, Rhode Island, USA.
Roberta De Vito, Department of Biostatistics and the Data Science Initiative at Brown University, Providence, Rhode Island, USA.
Dennyson L. Fonseca, Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo (USP), Sao Paulo, Brazil.
Desireé R. Plaça, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, São Paulo, Brazil.
Paula P. Freire, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Niels O. Camara, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Vera L. Calich, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Carmen Scheibenbogen, Institute for Medical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
Harald Heidecke, CellTrend Gesellschaft mit beschränkter Haftung (GmbH), Luckenwalde, Germany.
Miriam T. Lattin, Department of Biology, Yeshiva University, Manhatten, New York, USA.
Hans D. Ochs, Department of Pediatrics, University of Washington School of Medicine, and Seattle Children's Research Institute, Seattle, Washington, USA.
Gabriela Riemekasten, Department of Rheumatology, University Medical Center Schleswig-Holstein Campus Lübeck, Lübeck, Germany.
Howard Amital, Ariel University, Ariel, Israel.
Yehuda Shoenfeld, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.
Otavio Cabral-Marques, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

Document Type

Journal Article

Publication Date

2-1-2023

Journal

Journal of medical virology

Volume

95

Issue

2

DOI

10.1002/jmv.28538

Keywords

COVID-19 severity; SARS-CoV-2 infection; autoantibodies; autoimmune diseases

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.

Department

Dermatology

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