Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach

Authors

• Dennyson Leandro Fonseca, Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo (USP), Sao Paulo, SP, Brazil. dennyson@usp.br.
• Igor Salerno Filgueiras, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
• Alexandre H. Marques, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
• Elroy Vojdani, Regenera Medical 11860 Wilshire Blvd., Ste. 301, Los Angeles, CA, 90025, USA.
• Gilad Halpert, Ariel University, Ari'el, Israel.
• Yuri Ostrinski, Ariel University, Ari'el, Israel.
• Gabriela Crispim Baiocchi, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
• Desirée Rodrigues Plaça, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
• Paula P. Freire, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
• Shahab Zaki Pour, Laboratory of Molecular Evolution and Bioinformatics, Department of Microbiology, Biomedical Sciences Institute, University of São Paulo, São Paulo, 05508-000, Brazil.
• Guido Moll, Departament of Nephrology and Internal Intensive Care Medicine, Charité University Hospital, Berlin, Germany.
• Rusan Catar, Departament of Nephrology and Internal Intensive Care Medicine, Charité University Hospital, Berlin, Germany.
• Yael Bublil Lavi, Scakler faculty of medicine, Tel Aviv University, Tel Aviv, Israel.
• Jonathan I. Silverberg, Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
• Jason Zimmerman, Maimonides Medical Center, Brooklyn, NY, USA.
• Gustavo Cabral-Miranda, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
• Robson F. Carvalho, Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
• Taj Ali Khan, Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar, Pakistan.
• Harald Heidecke, CellTrend Gesellschaft mit beschränkter Haftung (GmbH), Luckenwalde, Germany.
• Rodrigo J. Dalmolin, Bioinformatics Multidisciplinary Environment, Federal University of Rio Grande do Norte, Natal, Brazil.
• Andre Ducati Luchessi, Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, R.N., Natal, Brazil.
• Hans D. Ochs, Department of Pediatrics, University of Washington School of Medicine, and Seattle Children's Research Institute, Seattle, WA, USA.
• Lena F. Schimke, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
• Howard Amital, Ariel University, Ari'el, Israel.
• Gabriela Riemekasten, Department of Rheumatology, University Medical Center Schleswig-Holstein Campus Lübeck, Lübeck, Germany.
• Israel Zyskind, Maimonides Medical Center, Brooklyn, NY, USA.
• Avi Z. Rosenberg, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
• Aristo Vojdani, Department of Immunology, Immunosciences Laboratory, Inc., Los Angeles, CA, USA.
• Yehuda Shoenfeld, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.
• Otavio Cabral-Marques, Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo (USP), Sao Paulo, SP, Brazil. otavio.cmarques@usp.br.

Document Type

Journal Article

Publication Date

8-24-2023

Journal

npj aging

Volume

9

Issue

1

DOI

10.1038/s41514-023-00118-0

Abstract

Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) severity due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, and chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health and disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 severity (71 mild, 61 moderate, and 27 with severe symptoms) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multiple linear regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid β peptide, β catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition and hierarchical clustering analysis based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe COVID-19 patients ≥50 years of age. Follow-up analysis using binomial logistic regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies significantly increased the likelihood of developing a severe COVID-19 phenotype with aging. These findings provide key insights to explain why aging increases the chance of developing more severe COVID-19 phenotypes.

APA Citation

Fonseca, Dennyson Leandro; Filgueiras, Igor Salerno; Marques, Alexandre H.; Vojdani, Elroy; Halpert, Gilad; Ostrinski, Yuri; Baiocchi, Gabriela Crispim; Plaça, Desirée Rodrigues; Freire, Paula P.; Pour, Shahab Zaki; Moll, Guido; Catar, Rusan; Lavi, Yael Bublil; Silverberg, Jonathan I.; Zimmerman, Jason; Cabral-Miranda, Gustavo; Carvalho, Robson F.; Khan, Taj Ali; Heidecke, Harald; Dalmolin, Rodrigo J.; Luchessi, Andre Ducati; Ochs, Hans D.; Schimke, Lena F.; Amital, Howard; Riemekasten, Gabriela; Zyskind, Israel; Rosenberg, Avi Z.; Vojdani, Aristo; Shoenfeld, Yehuda; and Cabral-Marques, Otavio, "Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach" (2023). GW Authored Works. Paper 3210.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3210

Department

Dermatology