Prevalence of alpha-synuclein seeding activity in the Olfactory Mucosa following SARS-CoV-2 infection: results from a pilot study.
6 affiliations
- 1Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
- 2Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. [email protected].
- 3Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
- 4Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria.
- 5Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.
- 6Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. [email protected].
Abstract
Olfactory dysfunction (OD) is a hallmark of SARS-CoV-2-infection where it is believed to result from neuroinflammation induced by viral invasion via the olfactory mucosa (OM). Hyposmia also affects the majority of patients with Parkinson's disease (PD) where it is caused by α-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 = 51), individuals with a history of documented symptomatic SARS-CoV-2-infection (post-COVID; n = 95), and healthy controls (HC; n = 42). Post-COVID-participants were stratified based on persistent OD (COVID+OD; n = 42) or normal olfaction (COVID-OD; n = 53) using Sniffin'-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%; p < 0.001). Within the post-COVID-group, positivity rates were higher in COVID+OD vs COVID-OD (35.7% vs 15.1%; p = 0.030), and COVID+OD differed from HC (p = 0.030), while COVID-OD did not (p = 0.65). Among post-COVID-participants, aSyn-SAA positivity was associated with lower SSI (p = 0.007) and SSD (p < 0.001) 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.
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BibTeX
@article{heim2026prevalence,
title = {{Prevalence of alpha-synuclein seeding activity in the Olfactory Mucosa following SARS-CoV-2 infection: results from a pilot study.}},
author = {Beatrice Heim and Klaus Seppi and Nicolas De Cleene and Matilde Bongianni and Erika Bronzato and Clancy Cerejo and Frank Jagusch and Philipp Kindl and Judith Löffler-Ragg and Günter Weiss and Timo Gottfried and Joachim Schmutzhard and Gianluigi Zanusso and Werner Poewe},
journal = {Acta neuropathologica},
year = {2026},
month = oct,
doi = {10.1007/s00401-026-03104-4},
url = {https://europepmc.org/article/MED/42911254},
note = {CC BY},
}
RIS
TY - JOUR
TI - Prevalence of alpha-synuclein seeding activity in the Olfactory Mucosa following SARS-CoV-2 infection: results from a pilot study.
AU - Beatrice Heim
AU - Klaus Seppi
AU - Nicolas De Cleene
AU - Matilde Bongianni
AU - Erika Bronzato
AU - Clancy Cerejo
AU - Frank Jagusch
AU - Philipp Kindl
AU - Judith Löffler-Ragg
AU - Günter Weiss
AU - Timo Gottfried
AU - Joachim Schmutzhard
AU - Gianluigi Zanusso
AU - Werner Poewe
PY - 2026
DA - 2026/10/22
JO - Acta neuropathologica
DO - 10.1007/s00401-026-03104-4
UR - https://europepmc.org/article/MED/42911254
AB - Olfactory dysfunction (OD) is a hallmark of SARS-CoV-2-infection where it is believed to result from neuroinflammation induced by viral invasion via the olfactory mucosa (OM). Hyposmia also affects the majority of patients with Parkinson's disease (PD) where it is caused by α-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 = 51), individuals with a history of documented symptomatic SARS-CoV-2-infection (post-COVID; n = 95), and healthy controls (HC; n = 42). Post-COVID-participants were stratified based on persistent OD (COVID+OD; n = 42) or normal olfaction (COVID-OD; n = 53) using Sniffin'-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%; p < 0.001). Within the post-COVID-group, positivity rates were higher in COVID+OD vs COVID-OD (35.7% vs 15.1%; p = 0.030), and COVID+OD differed from HC (p = 0.030), while COVID-OD did not (p = 0.65). Among post-COVID-participants, aSyn-SAA positivity was associated with lower SSI (p = 0.007) and SSD (p < 0.001) 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.
SN - 0001-6322
SN - 1432-0533
ER -