Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms

Dennyson Leandro Fonseca, BIH Center for Regenerative Therapies (BCRT), Julius Wolff Institute (JWI), and Berlin Institute of Health (BIH); all Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), 10117, Berlin, Germany. dennyson@usp.br.
Maj Jäpel, Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
Michael Adu Gyamfi, Departament of Nephrology and Internal Intensive Care Medicine, Charité University Hospital, Berlin, Germany.
Igor Salerno Filgueiras, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Gabriela Crispim Baiochi, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Yuri Ostrinski, Institute of Microbiology and Virology, Riga Stradins University, Riga, Latvia.
Gilad Halpert, The Dina Recanati School of Medicine, Reichman University, Herzliya, Israel.
Yael Bublil Lavi, Scakler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Elroy Vojdani, Regenera Medical 11860 Wilshire Blvd., Ste. 301, Los Angeles, CA, 90025, USA.
Thayna Silva-Sousa, Nuclear and Energy Research Institute, IPEN-CNEN/SP, São Paulo, Brazil.
Júlia Nakanishi Usuda, Department of Vascular Surgery, Universitätsklinikum Ruppin-Brandenburg, Medizinische Hochschule Branderburg Theodor Fontane, Fehrbelliner Str. 38, 16816, Neuruppin, Germany.
Juan Carlo E Silva, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Paula P. Freire, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Adriel Leal Nóbile, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Anny Silva Adri, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Pedro Marçal Barcelos, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Yohan Lucas Corrêa, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Fernando Yuri do Vale, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Letícia Oliveira Lopes, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Solveig Lea Schmidt, Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
Xiaoqing Wang, Priority Area Chronic Lung Diseases, Research Center Borstel, Borstel, Germany.
Carl Vahldieck, Institute of Physiology, University of Lübeck, Lübeck, Germany.
Benedikt Fels, Institute of Physiology, University of Lübeck, Lübeck, Germany.
Lena F. Schimke, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Gustavo Cabral-Miranda, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Mario Hiroyuki Hirata, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
Taj Ali AKhan, Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar, Pakistan.
Yen-Rei A. Yu, University of Colorado Anschutz Medical Campus, Denver, CO, USA.
Rodrigo Js Dalmolin, Bioinformatics Multidisciplinary Environment, Federal University of Rio Grande do Norte, Natal, Brazil.
Howard Amital, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.
Aristo Vojdani, Immunosciences Laboratory, Inc, Los Angeles, CA, 90035, USA.
Haroldo Dutra Dias, Department of Neuroscience, Institute of Biomedical Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil.

Document Type

Journal Article

Publication Date

1-13-2025

Journal

NPJ systems biology and applications

Volume

11

Issue

1

DOI

10.1038/s41540-025-00488-z

Abstract

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms. Significant correlations were identified between specific AABs and symptoms such as fever, muscle aches, anosmia, and dysgeusia. Notably, anti-AGTR1 antibodies, which contribute to endothelial glycocalyx (eGC) degradation, a process reversed by losartan, have emerged as strong predictors of core symptoms. AAB levels increased with symptom accumulation, peaking in patients exhibiting all four key symptoms. These findings highlight the role of AABs, particularly anti-AGTR1 antibodies, in determining symptom severity and suggest their involvement in the pathophysiology of COVID-19, including vascular complications.

Department

Dermatology

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