{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:32:28Z","timestamp":1791923548764,"version":"4.3.4"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,12]],"date-time":"2023-02-12T00:00:00Z","timestamp":1676160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yaron and Gila Shemie Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: COVID-19 is a heterogenous disease resulting in long-term sequela in predisposed individuals. It is not uncommon that recovering patients endure non-respiratory ill-defined manifestations, including anosmia, and neurological and cognitive deficit persisting beyond recovery\u2014a constellation of conditions that are grouped under the umbrella of long-term COVID-19 syndrome. Association between COVID-19 and autoimmune responses in predisposed individuals was shown in several studies. Aim and methods: To investigate autoimmune responses against neuronal and CNS autoantigens in SARS-CoV-2-infected patients, we performed a cross-sectional study with 246 participants, including 169 COVID-19 patients and 77 controls. Levels of antibodies against the acetylcholine receptor, glutamate receptor, amyloid \u03b2 peptide, alpha-synucleins, dopamine 1 receptor, dopamine 2 receptor, tau protein, GAD-65, N-methyl D-aspartate (NMDA) receptor, BDNF, cerebellar, ganglioside, myelin basic protein, myelin oligodendrocyte glycoprotein, S100-B, glial fibrillary acidic protein, and enteric nerve were measured using an Enzyme-Linked Immunosorbent Assay (ELISA). Circulating levels of autoantibodies were compared between healthy controls and COVID-19 patients and then classified by disease severity (mild [n = 74], severe [n = 65], and requiring supplemental oxygen [n = 32]). Results: COVID-19 patients were found to have dysregulated autoantibody levels correlating with the disease severity, e.g., IgG to dopamine 1 receptor, NMDA receptors, brain-derived neurotrophic factor, and myelin oligodendrocyte glycoprotein. Elevated levels of IgA autoantibodies against amyloid \u03b2 peptide, acetylcholine receptor, dopamine 2 receptor, myelin basic protein, and \u03b1-synuclein were detected in COVID-19 patients compared with healthy controls. Lower IgA autoantibody levels against NMDA receptors, and IgG autoantibodies against glutamic acid decarboxylase 65, amyloid \u03b2 peptide, tau protein, enteric nerve, and S100-B were detected in COVID-19 patients versus healthy controls. Some of these antibodies have known clinical correlations with symptoms commonly reported in the long COVID-19 syndrome. Conclusions: Overall, our study shows a widespread dysregulation in the titer of various autoantibodies against neuronal and CNS-related autoantigens in convalescent COVID-19 patients. Further research is needed to provide insight into the association between these neuronal autoantibodies and the enigmatic neurological and psychological symptoms reported in COVID-19 patients.<\/jats:p>","DOI":"10.3390\/diagnostics13040687","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T05:25:26Z","timestamp":1676265926000},"page":"687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Dysregulated Levels of Circulating Autoantibodies against Neuronal and Nervous System Autoantigens in COVID-19 Patients"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3162-0988","authenticated-orcid":false,"given":"Yael","family":"Lavi","sequence":"first","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2925-9334","authenticated-orcid":false,"given":"Aristo","family":"Vojdani","sequence":"additional","affiliation":[{"name":"Immunosciences Lab, Inc., Los Angeles, CA 90035, USA"},{"name":"Cyrex Laboratories, LLC, Phoenix, AZ 85034, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilad","family":"Halpert","sequence":"additional","affiliation":[{"name":"Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Department of Molecular Biology, Ariel University, Ariel 40700, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kassem","family":"Sharif","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Department of Medicine B, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Ostrinski","sequence":"additional","affiliation":[{"name":"Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3422-9631","authenticated-orcid":false,"given":"Israel","family":"Zyskind","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, NYU Langone Medical Center, New York, NY 10016, USA"},{"name":"Maimonides Medical Center, Brooklyn, NY 11219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Lattin","sequence":"additional","affiliation":[{"name":"Department of Biology, Yeshiva University, New York, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7372-1376","authenticated-orcid":false,"given":"Jason","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Maimonides Medical Center, Brooklyn, NY 11219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3686-7805","authenticated-orcid":false,"given":"Jonathan","family":"Silverberg","sequence":"additional","affiliation":[{"name":"Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avi","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehuda","family":"Shoenfeld","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5406-7716","authenticated-orcid":false,"given":"Howard","family":"Amital","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Department of Medicine B, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102695","DOI":"10.1016\/j.autrev.2020.102695","article-title":"SARS-CoV-2, the autoimmune virus","volume":"19","author":"Halpert","year":"2020","journal-title":"Autoimmun. 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