Objective: To determine whether symptomatic SARS-CoV-2 infection is associated with local α-synuclein (aSyn) aggregation in the olfactory mucosa (OM) as measured by an aSyn seeding amplification assay (SAA), and to assess whether OM-SAA status relates to olfactory performance and Parkinson’s disease (PD)-related clinical features.

Background: Olfactory dysfunction (OD) is a common feature of SARS-CoV-2 infection and is thought to arise from inflammatory processes related to viral entry at the level of the OM. Impaired smell is also highly prevalent in PD, where it is linked to aSyn pathology within the olfactory system. Importantly, aSyn seeding activity can be identified in OM specimens using SAA. In this pilot study, we explored whether prior SARS-CoV-2 infection is associated with local aSyn misfolding and aggregation in the OM detectable by SAA.

Method: We enrolled PD patients (n=51), individuals with documented symptomatic SARS-CoV-2 infection (post-COVID group; n=98), and healthy controls (HC, n=42). Post-COVID participants were categorized according to persistent OD (COVID+OD; n=44) versus preserved olfaction (COVID–OD; n=54) based on Sniffin’ Sticks Identification (SSI) and Discrimination (SSD) testing. OM samples were collected by ENT specialists and processed for SAA at the University of Verona. Clinical characterization comprised MDS-UPDRS, MoCA, and the Innsbruck RBD Inventory.

Results: OM-SAA positivity differed markedly across groups, with higher rates in PD (80.4%) compared with post-COVID participants (23.4%) and HCs (11.9%) (p<0.001). Within the post-COVID cohort, positivity was more frequent in COVID+OD than in COVID–OD (34.1% vs 14.8%; p=0.038). COVID+OD also differed from HCs (p=0.038), whereas COVID–OD did not (p=0.679). Among post-COVID individuals, SAA positivity was linked to poorer olfactory performance, reflected by lower SSI (p=0.005) and SSD (p=0.003) scores, but showed no association with MDS-UPDRS, MoCA, or RBD-related measures.

Conclusion: OM-SAA positivity was more common in individuals with persistent post-COVID OD and was associated with greater olfactory impairment. These pilot data are consistent with the concept that post-infectious neuroinflammatory mechanisms following SARS-CoV-2 may facilitate local aSyn aggregation in the olfactory region. The biological meaning and prognostic implications of OM-SAA positivity remain unclear and warrant longitudinal, prospective studies.

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/assessment-of-%ce%b1-synuclein-seeding-activity-in-the-olfactory-mucosa-after-sars-cov-2-a-pilot-study/