Functional Autoantibodies Targeting G-Protein-Coupled Receptors and Their Clinical Phenotype in Patients with Long-COVID

Hofmann S, Lucio M, Wallukat G, Hoffmanns J, Schröder T, Raith F, Szewczykowski C, Skornia A, Rech J, Schottenhamml J, Harrer T, Ganslmayer M, Mardin C, Flecks M, Lakatos P, Hohberger B (2025)

Publication Language: English

Publication Type: Journal article

Publication year: 2025

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 26

Article Number: 6746

Journal Issue: 14

DOI: 10.3390/ijms26146746

Abstract

Long-COVID (LC) is characterized by diverse and persistent symptoms, potentially mirroring different molecular pathways. Recent data might offer that one of them is mediated by functional autoantibodies (fAAb) targeting G protein-coupled receptors (GPCR). Thus, the aim of this study was to investigate the clinical phenotype of patients with LC in relation to their GPCR-fAAb seropositivity. The present study recruited 194 patients with LC and profiled them based on self-reported symptoms. GPCR-fAAb seropositivity was identified by using a cardiomyocyte bioassay, testing the presence and functionality of the AAbs. Logistic regression, clustering, and decision tree analyses were applied to examine associations between GPCR-fAAb profiles and self-reported symptoms considering age and gender. The most prevalent GPCR-fAAbs in patients with LC were fAAB targeting the β2 adrenergic receptor (β2-fAAb, 92.8%), the muscarinergic M2 receptor (M2-fAAb, 87.1%), the Angiotensin II type 1 receptor (AT1-fAAb, 85.6%), and angiotensin (1–7) Mas receptor (MAS-fAAb, 85.6%). β2-fAAb showed a significant relation with dizziness, lack of concentration, and POTS, while Endothelin Type A receptor functional autoantibody (ET-A-fAAb) was significantly related to deterioration of pre-existing neurological disorders. Statistical analysis indicated a strong positive correlation between M2- and β2-fAAb; as in addition, an association of β2-fAAb and gender was observed to one of the major clinical symptoms (fatigue/PEM), a critical impact of GPCR-fAAb on LC-pathogenesis can be assumed. Summing up, the present data show that specific GPCR-fAAb are associated with distinct clinical phenotypes. Especially, the combination of M2- and β2-fAAb seemed to be essential for the LC-phenotype with a combination of fatigue/PEM and lack of concentration as major clinical symptoms.

Authors with CRIS profile

Charlotte Szewczykowski Department of Ophthalmology Adam Skornia Department of Ophthalmology Jürgen Rech Department of Medicine 3 – Rheumatology and Immunology Julia Schottenhamml Department of Ophthalmology Thomas Harrer Professur für Innere Medizin mit dem Schwerpunkt Immundefizienz Marion Ganslmayer Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Christian Mardin Department of Ophthalmology Merle Flecks Department of Ophthalmology Petra Lakatos Department of Ophthalmology Bettina Hohberger Department of Ophthalmology

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Berlin Cures GmbH DE Germany (DE)

How to cite

APA:

Hofmann, S., Lucio, M., Wallukat, G., Hoffmanns, J., Schröder, T., Raith, F.,... Hohberger, B. (2025). Functional Autoantibodies Targeting G-Protein-Coupled Receptors and Their Clinical Phenotype in Patients with Long-COVID. International Journal of Molecular Sciences, 26(14). https://doi.org/10.3390/ijms26146746

MLA:

Hofmann, Sophia, et al. "Functional Autoantibodies Targeting G-Protein-Coupled Receptors and Their Clinical Phenotype in Patients with Long-COVID." International Journal of Molecular Sciences 26.14 (2025).

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