{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:04:50Z","timestamp":1792789490682,"version":"4.5.0"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ricerca Corrente of the Italian Ministry of Health, Linea 1, Progetto 1, INMI L. Spallanzani I.R.C.C.S.","award":["5x1000 2020"],"award-info":[{"award-number":["5x1000 2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This prospective, single-center, case-control study investigated circulating autoantibodies (AAbs) targeting G protein-coupled receptors (GPCRs) in Long COVID (LC) patients to identify potential diagnostic biomarkers and therapeutic targets. Fifteen participants were enrolled at the LC clinic in Rome: eleven with severe LC\u2014defined as &gt;4 persistent symptoms (fatigue, cognitive impairment, poor exercise tolerance, dyspnea, arthralgia, or dysautonomic manifestations) &gt;3 months post-infection\u2014and four asymptomatic post-COVID (APC) individuals. Fatigue was assessed using the Fatigue Assessment Scale (FAS \u2265 22; severe \u2265 35). Auto-Abs against AT1R, endothelin receptor A, adrenergic (\u03b11, \u03b12, \u03b21, \u03b22), and muscarinic (M1\u2013M5) receptors were quantified, along with blood cortisol and ACTH levels. SARS-CoV-2-specific T-cell responses to Spike and Nucleocapsid proteins were evaluated by ELISpot assay. In our small cohort, LC patients were younger, had fewer comorbidities (p = 0.03), fewer vaccine doses (p = 0.03), and higher FAS scores (33 vs. 12; p = 0.001). Mean GPCR AAbs levels were higher in LC than in APC (8.88 vs. 5.45 Units\/mL; p = 0.17), indicating a coherent autoimmune signature in LC that correlates with symptom development. Morning cortisol was lower in LC (12.7 vs. 17 mg\/dL; p = 0.01), and T-cell responses tended to be weaker. These findings suggest GPCR AAbs may serve as biomarkers and therapeutic targets for a subset of patients, guiding diagnosis and treatments with IV immunoglobulin or immunoadsorption.<\/jats:p>","DOI":"10.3390\/ijms27041787","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T09:09:19Z","timestamp":1770973759000},"page":"1787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Prevalence of Circulating Autoantibodies Against G-Protein-Coupled Receptors as Potential Biomarkers for Long COVID: Preliminary Investigations"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6624-7917","authenticated-orcid":false,"given":"Marta","family":"Camici","sequence":"first","affiliation":[{"name":"Clinical and Research Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Franco","sequence":"additional","affiliation":[{"name":"Endocrinology Clinical Unit, San Camillo Forlanini Hospital, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0846-7946","authenticated-orcid":false,"given":"Lorenzo","family":"Talamanca","sequence":"additional","affiliation":[{"name":"Institute of Molecular Systems Biology, Department of Biology, ETH Z\u00fcrich, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8361-9605","authenticated-orcid":false,"given":"Jessica","family":"Paulicelli","sequence":"additional","affiliation":[{"name":"Clinical and Research Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Scarnecchia","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, San Camillo Forlanini Hospital, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Petino","sequence":"additional","affiliation":[{"name":"Azienda Sanitaria Locale ASL Roma 1, 00193 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0240-7504","authenticated-orcid":false,"given":"Valentina","family":"Mazzotta","sequence":"additional","affiliation":[{"name":"Clinical and Research Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1944-662X","authenticated-orcid":false,"given":"Ilaria","family":"Mastrorosa","sequence":"additional","affiliation":[{"name":"Clinical and Research Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2659-0868","authenticated-orcid":false,"given":"Eleonora","family":"Cimini","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Immunology and Pharmacology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7692-6606","authenticated-orcid":false,"given":"Stefania","family":"Notari","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Immunology and Pharmacology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5314-7010","authenticated-orcid":false,"given":"Paolo","family":"Zuppi","sequence":"additional","affiliation":[{"name":"Ordine di Malta Italia, San Giovanni Battista Hospital, Endocrinology Project, 00148 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Baldelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, San Camillo Forlanini Hospital, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6100-8442","authenticated-orcid":false,"given":"Maria Grazia","family":"Bocci","sequence":"additional","affiliation":[{"name":"Intensive Care and Anestesiology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7489-5271","authenticated-orcid":false,"given":"Fabrizio","family":"Maggi","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8182-5896","authenticated-orcid":false,"given":"Enrico","family":"Girardi","sequence":"additional","affiliation":[{"name":"Scientific Direction, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2121-4684","authenticated-orcid":false,"given":"Andrea","family":"Antinori","sequence":"additional","affiliation":[{"name":"Clinical and Research Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hou, Y., Gu, T., Ni, Z., Shi, X., Ranney, M.L., and Mukherjee, B. 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