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Publications

Journal Article Epublish

PubMed: 39805853 DOI: 10.1038/s41540-025-00488-z

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

NPJ Syst Biol Appl 11(1):7

Authors: Dennyson Leandro M Fonseca, Maj Jäpel, Michael Adu Gyamfi, Igor Salerno Filgueiras, Gabriela Crispim Baiochi, Yuri Ostrinski, Gilad Halpert, Yael Bublil Lavi, Elroy Vojdani, Thayna Silva-Sousa, Júlia Nakanishi Usuda, Juan Carlo Santos E Silva, Paula P Freire, Adriel Leal Nóbile, Anny Silva Adri, Pedro Marçal Barcelos, Yohan Lucas Gonçalves Corrêa, Fernando Yuri Nery do Vale, Letícia Oliveira Lopes, Solveig Lea Schmidt, Xiaoqing Wang, Carl Vahldieck, Benedikt Fels, Lena F Schimke, Gustavo Cabral-Miranda, Mario Hiroyuki Hirata, Taj Ali AKhan, Yen-Rei A Yu, Rodrigo Js Dalmolin, Howard Amital, Aristo Vojdani, Haroldo Dutra Dias, Helder Nakaya, Hans D Ochs, Jonathan I Silverberg, Jason Zimmerman, Israel Zyskind, Avi Z Rosenberg, Kai Schulze-Forster, Harald Heidecke, Rusan Catar, Guido Moll, Alexander Hackel, Kristina Kusche-Vihrog, Yehuda Shoenfeld, Gabriela Riemekasten, Reza Akbarzadeh, Alexandre H C Marques, Otavio Cabral-Marques

Affiliations

  • 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.
  • Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo (USP), Sao Paulo, SP, Brazil.
  • Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
  • Departament of Nephrology and Internal Intensive Care Medicine, Charité University Hospital, Berlin, Germany.
  • Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
  • Institute of Microbiology and Virology, Riga Stradins University, Riga, Latvia.
  • The Dina Recanati School of Medicine, Reichman University, Herzliya, Israel.
  • Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.
  • Scakler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Regenera Medical 11860 Wilshire Blvd. Ste. 301, Los Angeles, CA, 90025, USA.
  • Nuclear and Energy Research Institute, IPEN-CNEN/SP, São Paulo, Brazil.
  • Department of Vascular Surgery, Universitätsklinikum Ruppin-Brandenburg, Medizinische Hochschule Branderburg Theodor Fontane, Fehrbelliner Str. 38, 16816, Neuruppin, Germany.
  • Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
  • Priority Area Chronic Lung Diseases, Research Center Borstel, Borstel, Germany.
  • Institute of Physiology, University of Lübeck, Lübeck, Germany.
  • German Research Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Lübeck/Kiel, Lübeck, Germany.
  • Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar, Pakistan.
  • Emerging Pathogens Institute, Department of Medicine, University of Florida, Gainesville, FL, USA.
  • University of Colorado Anschutz Medical Campus, Denver, CO, USA.
  • Bioinformatics Multidisciplinary Environment, Federal University of Rio Grande do Norte, Natal, Brazil.
  • Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Brazil.
  • Immunosciences Laboratory, Inc, Los Angeles, CA, 90035, USA.
  • Department of Neuroscience, Institute of Biomedical Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil.
  • Instituto Israelita de Ensino e Pesquisa Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Department of Pediatrics, University of Washington School of Medicine, and Seattle Children's Research Institute, Seattle, WA, USA.
  • School of Medicine and Health Sciences, George Washington University, Washington, D.C. USA.
  • Maimonides Medical Center, Brooklyn, NY, USA.
  • Department of Pediatrics, NYU Langone Medical Center, New York, NY, USA.
  • Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
  • CellTrend Gesellschaft mit beschränkter Haftung (GmbH), Luckenwalde, Germany.
  • 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.
  • Reichman University, Herzeliya, Israel.
  • Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
  • 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.
  • Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
  • Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.
  • Department of Medicine, Division of Molecular Medicine, Laboratory of Medical Investigation 29, University of São Paulo (USP) School of Medicine, Sao Paulo, Brazil.
  • Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Sao Paulo, Brazil.
  • D'Or Institute for Research and Education (IDOR), São Paulo, Brazil.

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.

MeSH

Autoantibodies, Antibodies, Systems Biology, Signs And Symptoms, Covid-19