{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:50:41Z","timestamp":1792785041135,"version":"4.5.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":45,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Cabinet Secretariat of Japan"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To understand the pathophysiology and etiology of COVID-19 patients with depressive symptoms, we investigated the presence of autoantibodies associated with neurological sequelae using salivary IgA antibody profiling in COVID-19 patients with depressive symptoms. We used a human protein microarray system to comprehensively measure IgA antibodies against human proteins in the saliva of three groups of participants: those who developed moderate or severe depressive symptoms 2\u201314\u00a0months after SARS-CoV-2 infection (the \u2018COVID-19 group\u2019), those with no infection history who showed no depressive symptoms or only mild depressive symptoms (the \u2018healthy control group\u2019), and those with no infection history who were diagnosed with depression. As a result, 65 types of IgA antibodies recognizing human proteins were identified, all of which were present only in the COVID-19 group and not in the healthy control group. Several antigens recognized by these antibodies are associated with depressive symptoms. These findings suggest that distinctive salivary IgA antibody profiles may be associated with depressive symptoms following SARS-CoV-2 infection and could serve as candidate biomarkers for further investigation.<\/jats:p>","DOI":"10.1038\/s41598-026-45180-2","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T06:32:06Z","timestamp":1774247526000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Protein microarray-based profiling of salivary IgA antibodies against human proteins in COVID-19 patients with depressive symptoms"],"prefix":"10.1038","volume":"16","author":[{"given":"Yuichi","family":"Hikichi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Kunieda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"45180_CR1","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/s41579-022-00846-2","volume":"21","author":"HE Davis","year":"2023","unstructured":"Davis, H. E., McCorkell, L., Moore Vogel, J., Topol, E. J. & Long, C. O. V. I. D. Major findings, mechanisms and recommendations. Nat. Rev. Microbiol. 21, 133\u2013146 (2023).","journal-title":"Nat. Rev. Microbiol."},{"key":"45180_CR2","doi-asserted-by":"publisher","first-page":"102756","DOI":"10.1016\/j.eclinm.2024.102756","volume":"74","author":"P Engelmann","year":"2024","unstructured":"Engelmann, P. et al. Psychological factors associated with Long COVID: A systematic review and meta-analysis. EClinicalMedicine 74, 102756 (2024).","journal-title":"EClinicalMedicine"},{"key":"45180_CR3","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/S2215-0366(21)00084-5","volume":"8","author":"M Taquet","year":"2021","unstructured":"Taquet, M. et al. 6-month neurological and psychiatric outcomes in 236,379 COVID-19 survivors. Lancet Psychiatry. 8, 416\u2013427 (2021).","journal-title":"Lancet Psychiatry"},{"key":"45180_CR4","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/S2215-0366(24)00276-1","volume":"11","author":"AS Milani","year":"2024","unstructured":"Milani, A. S., Kuo, Y. & Raji, M. COVID-19 and mental health consequences: Moving forward. Lancet Psychiatry. 11, 777\u2013778 (2024).","journal-title":"Lancet Psychiatry"},{"key":"45180_CR5","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/S0140-6736(24)01136-X","volume":"404","author":"T Greenhalgh","year":"2024","unstructured":"Greenhalgh, T., Sivan, M., Perlowski, A. & Nikolich, J. \u017d. Long COVID: A clinical update. Lancet 404, 707\u2013724 (2024).","journal-title":"Lancet"},{"key":"45180_CR6","doi-asserted-by":"publisher","first-page":"222","DOI":"10.3389\/fimmu.2013.00222","volume":"4","author":"P Brandtzaeg","year":"2013","unstructured":"Brandtzaeg, P. Secretory IgA: Designed for anti-microbial defense. Front. Immunol. 4, 222 (2013).","journal-title":"Front. Immunol."},{"key":"45180_CR7","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1177\/1535370216681550","volume":"242","author":"KE Kaczor-Urbanowicz","year":"2017","unstructured":"Kaczor-Urbanowicz, K. E. et al. Saliva diagnostics\u2014Current views and directions. Exp. Biol. Med. 242, 459\u2013472 (2017).","journal-title":"Exp. Biol. Med."},{"key":"45180_CR8","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.jad.2014.10.010","volume":"172","author":"EI Fried","year":"2015","unstructured":"Fried, E. I. & Nesse, R. M. Depression is not a consistent syndrome: An investigation of unique symptom patterns in the STAR*D study. J. Affect. Disord. 172, 96\u2013102 (2015).","journal-title":"J. Affect. Disord"},{"key":"45180_CR9","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/S2215-0366(21)00084-5","volume":"8","author":"M Taquet","year":"2021","unstructured":"Taquet, M. et al. 6-month neurological and psychiatric outcomes in 236,379 COVID-19 survivors. Lancet Psychiatry. 8, 416\u2013427 (2021).","journal-title":"Lancet Psychiatry"},{"key":"45180_CR10","doi-asserted-by":"publisher","first-page":"102756","DOI":"10.1016\/j.eclinm.2024.102756","volume":"74","author":"P Engelmann","year":"2024","unstructured":"Engelmann, P. et al. Psychological factors associated with Long COVID: A systematic review and meta-analysis. EClinicalMedicine 74, 102756 (2024).","journal-title":"EClinicalMedicine"},{"key":"45180_CR11","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/s41586-021-03631-y","volume":"595","author":"EY Wang","year":"2021","unstructured":"Wang, E. Y. et al. Diverse functional autoantibodies in patients with COVID-19. Nature 595, 283\u2013288 (2021).","journal-title":"Nature"},{"key":"45180_CR12","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1016\/j.cell.2022.01.014","volume":"185","author":"Y Su","year":"2022","unstructured":"Su, Y. et al. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell 185, 881\u2013895e20 (2022).","journal-title":"Cell"},{"key":"45180_CR13","doi-asserted-by":"publisher","first-page":"100100","DOI":"10.1016\/j.jtauto.2021.100100","volume":"4","author":"G Wallukat","year":"2021","unstructured":"Wallukat, G. et al. Functional autoantibodies against G-protein coupled receptors in patients with persistent long-COVID-19 symptoms. J. Transl Autoimmun. 4, 100100 (2021).","journal-title":"J. Transl Autoimmun."},{"key":"45180_CR14","doi-asserted-by":"publisher","first-page":"e0257016","DOI":"10.1371\/journal.pone.0257016","volume":"16","author":"JM Arthur","year":"2021","unstructured":"Arthur, J. M. et al. Development of ACE2 autoantibodies after SARS-CoV-2 infection. PLoS ONE. 16, e0257016 (2021).","journal-title":"PLoS ONE"},{"key":"45180_CR15","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.clim.2019.03.011","volume":"203","author":"A Hoshino","year":"2019","unstructured":"Hoshino, A. et al. Identification of autoantibodies using human proteome microarrays in patients with IPEX syndrome. Clin. Immunol. 203, 9\u201313 (2019).","journal-title":"Clin. Immunol."},{"key":"45180_CR16","doi-asserted-by":"publisher","first-page":"e0247045","DOI":"10.1371\/journal.pone.0247045","volume":"16","author":"M Michigami","year":"2021","unstructured":"Michigami, M. et al. A ligand-targeting peptide-drug conjugate: Targeted intracellular drug delivery by VEGF-binding helix-loop-helix peptides via receptor-mediated endocytosis. PLoS ONE. 16, e0247045 (2021).","journal-title":"PLoS ONE"},{"key":"45180_CR17","doi-asserted-by":"publisher","first-page":"3155","DOI":"10.1523\/JNEUROSCI.0586-14.2015","volume":"35","author":"R Chassefeyre","year":"2015","unstructured":"Chassefeyre, R. et al. Regulation of postsynaptic function by the dementia-related ESCRT-III subunit CHMP2B. J. Neurosci. 35, 3155\u20133173 (2015).","journal-title":"J. Neurosci."},{"key":"45180_CR18","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/s40478-024-01916-7","volume":"12","author":"O Keeley","year":"2024","unstructured":"Keeley, O. et al. CHMP2B promotes CHMP7 mediated nuclear pore complex injury in sporadic ALS. Acta Neuropathol. Commun. 12, 199 (2024).","journal-title":"Acta Neuropathol. Commun."},{"key":"45180_CR19","doi-asserted-by":"publisher","first-page":"eabe1923","DOI":"10.1126\/scitranslmed.abe1923","volume":"13","author":"AN Coyne","year":"2021","unstructured":"Coyne, A. N. et al. Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and TDP-43 dysfunction in ALS. Sci. Transl Med. 13, eabe1923 (2021).","journal-title":"Sci. Transl Med."},{"key":"45180_CR20","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/s41582-024-00955-x","volume":"20","author":"M Khalil","year":"2024","unstructured":"Khalil, M. et al. Neurofilaments as biomarkers in neurological disorders \u2014 towards clinical application. Nat. Rev. Neurol. 20, 123\u2013139 (2024).","journal-title":"Nat. Rev. Neurol."},{"key":"45180_CR21","doi-asserted-by":"publisher","first-page":"70","DOI":"10.3390\/ijms26010070","volume":"26","author":"PS Mart\u00ednez Lozada","year":"2025","unstructured":"Mart\u00ednez Lozada, P. S. et al. Roles of CDR2 and CDR2L in anti-Yo paraneoplastic cerebellar degeneration: A literature review. Int. J. Mol. Sci. 26, 70 (2025).","journal-title":"Int. J. Mol. Sci."},{"key":"45180_CR22","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1007\/s10633-022-09901-y","volume":"145","author":"WC Hung","year":"2022","unstructured":"Hung, W. C. et al. Melanoma-associated retinopathy with anti-TRPM1 autoantibodies showing concomitant OFF-bipolar cell dysfunction. Doc. Ophthalmol. 145, 233\u2013240 (2022).","journal-title":"Doc. Ophthalmol."},{"key":"45180_CR23","doi-asserted-by":"publisher","first-page":"2866","DOI":"10.1038\/ncomms3866","volume":"4","author":"M Biel","year":"2013","unstructured":"Biel, M. et al. Hysteresis of ligand binding in CNGA2 ion channels. Nat. Commun. 4, 2866 (2013).","journal-title":"Nat. Commun."},{"key":"45180_CR24","doi-asserted-by":"publisher","first-page":"44235","DOI":"10.1038\/s41598-023-44235-y","volume":"13","author":"E Ott","year":"2023","unstructured":"Ott, E. et al. A novel role for the chloride intracellular channel protein Clic5 in ciliary function. Sci. Rep. 13, 44235 (2023).","journal-title":"Sci. Rep."},{"key":"45180_CR25","doi-asserted-by":"publisher","first-page":"6377","DOI":"10.1523\/JNEUROSCI.0067-14.2014","volume":"34","author":"G Ying","year":"2014","unstructured":"Ying, G. et al. Centrin 2 is required for mouse olfactory ciliary trafficking and development of ependymal cilia planar polarity. J. Neurosci. 34, 6377\u20136388 (2014).","journal-title":"J. Neurosci."},{"key":"45180_CR26","first-page":"283","volume":"29","author":"X He","year":"2020","unstructured":"He, X. et al. CFAP58 is essential for sperm flagellar axoneme assembly and male fertility. Hum. Mol. Genet. 29, 283\u2013293 (2020).","journal-title":"Hum. Mol. Genet."},{"key":"45180_CR27","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ajhg.2019.02.018","volume":"104","author":"R Shaheen","year":"2019","unstructured":"Shaheen, R. et al. Mutations in FAM149B1 cause Joubert syndrome by disrupting ciliary function. Am. J. Hum. Genet. 104, 101\u2013109 (2019).","journal-title":"Am. J. Hum. Genet."},{"key":"45180_CR28","unstructured":"World Health Organization. Post COVID-19 condition (Long COVID). https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/post-covid-19-condition-(long-covid)"},{"key":"45180_CR29","doi-asserted-by":"publisher","first-page":"1275155","DOI":"10.3389\/fcell.2023.1275155","volume":"11","author":"F Kotaich","year":"2023","unstructured":"Kotaich, F., Caillol, D. & Bomont, P. Neurofilaments in health and Charcot-Marie-Tooth disease. Front. Cell. Dev. Biol. 11, 1275155 (2023).","journal-title":"Front. Cell. Dev. Biol."},{"key":"45180_CR30","doi-asserted-by":"publisher","first-page":"3106","DOI":"10.1038\/s41380-024-02554-0","volume":"29","author":"EG Gutman","year":"2024","unstructured":"Gutman, E. G. et al. Long COVID: Plasma levels of neurofilament light chain in mild COVID-19 patients with neurocognitive symptoms. Mol. Psychiatry. 29, 3106\u20133116 (2024).","journal-title":"Mol. Psychiatry"},{"key":"45180_CR31","doi-asserted-by":"publisher","first-page":"e1151","DOI":"10.1212\/NXI.0000000000001151","volume":"9","author":"BA Hanson","year":"2022","unstructured":"Hanson, B. A. et al. Plasma biomarkers of neuropathogenesis in hospitalized patients with COVID-19 and those with postacute sequelae of SARS-CoV-2 infection. Neurol. Neuroimmunol. Neuroinflamm. 9, e1151 (2022).","journal-title":"Neurol. Neuroimmunol. Neuroinflamm"},{"key":"45180_CR32","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/nri.2015.5","volume":"16","author":"AH Miller","year":"2016","unstructured":"Miller, A. H. & Raison, C. L. The role of inflammation in depression: From evolutionary imperative to modern treatment target. Nat. Rev. Immunol. 16, 22\u201334 (2016).","journal-title":"Nat. Rev. Immunol."},{"key":"45180_CR33","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.neuroscience.2013.04.060","volume":"246","author":"JC Felger","year":"2013","unstructured":"Felger, J. C. & Lotrich, F. E. Inflammatory cytokines in depression: Neurobiological mechanisms and therapeutic implications. Neuroscience 246, 199\u2013229 (2013).","journal-title":"Neuroscience"},{"key":"45180_CR34","doi-asserted-by":"publisher","DOI":"10.1101\/2024.06.18.24309100","author":"K Santos Guedes de Sa","year":"2024","unstructured":"Santos Guedes de Sa, K. et al. A causal link between autoantibodies and neurological symptoms in long COVID. medRxiv https:\/\/doi.org\/10.1101\/2024.06.18.24309100 (2024).","journal-title":"medRxiv"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45180-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45180-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45180-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:41:01Z","timestamp":1781642461000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45180-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["45180"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-45180-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]},"assertion":[{"value":"2 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"YH is the founder and shareholder of Tuning Fork Bio, Inc., which may benefit from the results of this study. YH also holds shares in other biotechnology and pharmaceutical companies unrelated to this work. KK is an employee of Tuning Fork Bio, Inc. and declares no stock ownership or other financial interests related to this work. The intellectual contributions and results presented in this manuscript have been granted as intangible assets by Yamaha Motor Co., Ltd. The authors declare no financial or nonfinancial conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14583"}}