{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T17:34:35Z","timestamp":1793468075861,"version":"4.5.0"},"reference-count":68,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Federal Ministry of Research, Technology and Space","award":["01EP2108A"],"award-info":[{"award-number":["01EP2108A"]}]},{"name":"German Federal Ministry of Research, Technology and Space","award":["01EO2105"],"award-info":[{"award-number":["01EO2105"]}]},{"name":"German Federal Ministry of Research, Technology and Space","award":["2490-PC-2021-V14"],"award-info":[{"award-number":["2490-PC-2021-V14"]}]},{"name":"Bavarian Health and Food Safety Authority","award":["01EP2108A"],"award-info":[{"award-number":["01EP2108A"]}]},{"name":"Bavarian Health and Food Safety Authority","award":["01EO2105"],"award-info":[{"award-number":["01EO2105"]}]},{"name":"Bavarian Health and Food Safety Authority","award":["2490-PC-2021-V14"],"award-info":[{"award-number":["2490-PC-2021-V14"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03b22 adrenergic receptor (\u03b22-fAAb, 92.8%), the muscarinergic M2 receptor (M2-fAAb, 87.1%), the Angiotensin II type 1 receptor (AT1-fAAb, 85.6%), and angiotensin (1\u20137) Mas receptor (MAS-fAAb, 85.6%). \u03b22-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 \u03b22-fAAb; as in addition, an association of \u03b22-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 \u03b22-fAAb seemed to be essential for the LC-phenotype with a combination of fatigue\/PEM and lack of concentration as major clinical symptoms.<\/jats:p>","DOI":"10.3390\/ijms26146746","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:45:52Z","timestamp":1752572752000},"page":"6746","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Functional Autoantibodies Targeting G-Protein-Coupled Receptors and Their Clinical Phenotype in Patients with Long-COVID"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0846-278X","authenticated-orcid":false,"given":"Sophia","family":"Hofmann","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Lucio","sequence":"additional","affiliation":[{"name":"Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum M\u00fcnchen-German Research Center for Environmental Health, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Wallukat","sequence":"additional","affiliation":[{"name":"Berlin Cures GmbH, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Hoffmanns","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thora","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Raith","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Szewczykowski","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Skornia","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2569-2029","authenticated-orcid":false,"given":"Juergen","family":"Rech","sequence":"additional","affiliation":[{"name":"Rheumatology and Immunology Section, Department of Internal Medicine 3, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Universit\u00e4t of Erlangen-N\u00fcrnberg, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Schottenhamml","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6945-3241","authenticated-orcid":false,"given":"Thomas","family":"Harrer","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Universit\u00e4t of Erlangen-N\u00fcrnberg, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Infectious Disease and Immunodeficiency Section, Department of Internal Medicine 3, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Ganslmayer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 1, Universit\u00e4t of Erlangen-N\u00fcrnberg, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Mardin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merle","family":"Flecks","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Lakatos","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2546-5504","authenticated-orcid":false,"given":"Bettina","family":"Hohberger","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/s41591-021-01283-z","article-title":"Post-acute COVID-19 syndrome","volume":"27","author":"Nalbandian","year":"2021","journal-title":"Nat. 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