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Hyposmia also affects the majority of patients with Parkinson\u2019s disease (PD) where it is caused by \u03b1-synuclein (aSyn) pathology in the olfactory system, and aSyn-seeding-activity can be detected in the OM using aSyn-seeding-amplification-assays (aSyn-SAA). The present pilot study aimed to investigate whether SARS-CoV-2-infection induces local aSyn-misfolding and -aggregation in OM samples using aSyn-SAA. We conducted an observational study including PD patients (n\u2009=\u200951), individuals with a history of documented symptomatic SARS-CoV-2-infection (post-COVID; n\u2009=\u200995), and healthy controls (HC; n\u2009=\u200942). Post-COVID-participants were stratified based on persistent OD (COVID+OD; n\u2009=\u200942) or normal olfaction (COVID\u2013OD; n\u2009=\u200953) using Sniffin\u2019-Sticks-Identification (SSI) and -Discrimination (SSD) tests. OM samples were obtained by ENT specialists and analyzed by aSyn-SAA at the University of Verona. Clinical phenotyping included MDS-UPDRS, MoCA, and the Innsbruck-RBD-Inventory. OM-SAA positivity rates were significantly different between PD and both post-COVID-participants and HCs (80.4% vs 24.2% vs 11.9%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Within the post-COVID-group, positivity rates were higher in COVID+OD vs COVID\u2013OD (35.7% vs 15.1%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.030), and COVID+OD differed from HC (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.030), while COVID\u2013OD did not (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.65). Among post-COVID-participants, aSyn-SAA positivity was associated with lower SSI (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007) and SSD (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) scores, but not with MDS-UPDRS, MoCA, or RBD measures. OM-SAA-positivity was enriched among individuals with persistent post-COVID-OD and correlated with olfactory impairment. These findings support the hypothesis that neuroinflammation following SARS-COV-2-infection might promote local aSyn-aggregation. The biological and prognostic relevance of OM-SAA positivity is unknown and needs further prospective investigation.\n                  <\/jats:p>","DOI":"10.1007\/s00401-026-03104-4","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:20:10Z","timestamp":1792668010000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prevalence of alpha-synuclein seeding activity in the Olfactory Mucosa following SARS-CoV-2 infection: results from a pilot study"],"prefix":"10.1007","volume":"152","author":[{"given":"Beatrice","family":"Heim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Seppi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"De Cleene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Bongianni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Bronzato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clancy","family":"Cerejo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Jagusch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Kindl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"L\u00f6ffler-Ragg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Gottfried","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Schmutzhard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Zanusso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Poewe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"3104_CR1","doi-asserted-by":"publisher","first-page":"4443","DOI":"10.1007\/s00405-022-07381-z","volume":"279","author":"AS Alqahtani","year":"2022","unstructured":"Alqahtani AS, Aldhahi MI, Alqahtani F, Altamimi M, Alshehri MM (2022) Impact of the loss of smell on the sleep quality and fatigue level in COVID\u201119 survivors. 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