α-synuclein Seeding Activity in the Olfactory Mucosa in COVID-19

Study Overview
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Brief Summary
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Loss of the sense of smell is a characteristic feature of COVID-19 and likely related to viral invasion of the olfactory mucosa but is also a prodromal feature of PD. This constellation has kindled concerns that COVID-19 - similar to the Spanish Flu Pandemic in 1918 - might trigger a second wave of post-infectious parkinsonism. The main objective of the study is to probe for the presence of pathological α-synuclein assemblies in the olfactory mucosa of patients with COVID-19.

Detailed Description
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Deposits of misfolded proteins are the cause of frequent neurological diseases such as Alzheimer's or Parkinson's disease. In Parkinson's disease, the misfolded protein alpha-synuclein is found in the olfactory mucosa of the nose, which contains nerve cells responsible for smell perception, from which the misfolded alpha-synuclein spreads further into the brain. The mechanisms that lead to this misfolding and the resulting damage to the nervous system are still unclear. One hypothesis is that inflammatory processes such as viral infections trigger the misfolding of alpha-synuclein in Parkinson's disease and can lead to its deposition. Based on this assumption and the striking involvement of the sense of smell in SARS-CoV-2 infection (COVID-19), the aim of this study is to investigate the olfactory epithelium of the nasal mucosa of COVID-19 patients for possible alpha-synuclein deposits by using nasal swabs. We hypothesize that the invasion of olfactory neurons and subsequent inflammatory responses could trigger α-synuclein misfolding and aggregation. Therefore, we aim to investigate for the presence of α-synuclein seeding activity in the olfactory mucosa of subjects who have recovered from COVID-19 by using Real-time Quaking-Induced Conversion (RT-QuIC).

Official Title
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α-synuclein Seeding Activity in the Olfactory Mucosa in COVID-19 - A Pilot Study

Conditions
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COVID-19

Intervention / Treatment
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* Other: Real-time Quaking-Induced Conversion (RT-QuIC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be 18 years or older; Participants are able to understand the aim of the study and the planned procedures; Written informed consent form; Participants fulfilling the criteria for one of the following groups: COVID-19 patients with OD: Prior history of COVID-19 (clinical documentation plus corresponding positive PCR test) at least 3 months ago; OD (Sniffin' sticks discrimination and identification both <13/16 items correct) persisting for at least 3 months after SARS-CoV-2 infection; Negative antigen test on day of study inclusion; No evidence of structural nasal pathologies possibly responsible for OD. COVID-19 patients without OD: Prior history of COVID-19 (clinical documentation plus corresponding positive PCR test) at least 3 months ago; No history of/current OD (Sniffin' sticks discrimination and identification both >12/16 items correct); Negative antigen test on day of study inclusion. Healthy Controls: No history of COVID-19 and negative SARS-CoV-2 antibody test unless subject is vaccinated; Negative antigen test on day of study inclusion; No history of OD; Subjective and objective normal olfactory function (Sniffin' sticks discrimination and identification both >12/16 items correct). 10 Application for Clinical Research Patients with Parkinson's disease (n = 50): Confirmed diagnosis of PD according to diagnostic criteria. No history of COVID-19 and negative SARS-CoV-2 antibody test unless subject is vaccinated; Negative antigen test on day of study inclusion; Exclusion Criteria: Patients: History of OD prior to SARS-CoV-2 infection; Pre-existent relevant neurological disorder; Positive SARS-CoV-2 antigen test on day of study inclusion; Patients with OD only: structural pathology possibly responsible for OD. Healthy controls: Pre-existent relevant neurological disorder; History of/presence of olfactory dysfunction (Sniffin' sticks discrimination and identification both <13/16 items correct); Positive SARS-CoV-2 antigen test on day of study inclusion; Positive SARS-CoV-2 antibody test unless subject is vaccinated. Patients with Parkinson's disease: History of COVID-19; Positive SARS-CoV-2 antigen test on day of study inclusion; Positive SARS-CoV-2 antibody test unless subject is vaccinated.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COVID-19 patients with olfactory dysfunction<br> | Other: Real-time Quaking-Induced Conversion (RT-QuIC)<br>* RT-QuIC is increasingly used as diagnostic tools in synucleinopathies and has shown high sensitivity and specificity for the detection of α-synuclein seeds in CSF and tissue samples, including the olfactory mucosa in different patients' cohorts including Parkinson's patientients, patients with REM sleep behavior disorder (RBD), and patients with dementia with Lewy bodies.<br>|
| Experimental: COVID-19 patients without olfactory dysfunction<br> | Other: Real-time Quaking-Induced Conversion (RT-QuIC)<br>* RT-QuIC is increasingly used as diagnostic tools in synucleinopathies and has shown high sensitivity and specificity for the detection of α-synuclein seeds in CSF and tissue samples, including the olfactory mucosa in different patients' cohorts including Parkinson's patientients, patients with REM sleep behavior disorder (RBD), and patients with dementia with Lewy bodies.<br>|
| Experimental: Healthy controls<br> | Other: Real-time Quaking-Induced Conversion (RT-QuIC)<br>* RT-QuIC is increasingly used as diagnostic tools in synucleinopathies and has shown high sensitivity and specificity for the detection of α-synuclein seeds in CSF and tissue samples, including the olfactory mucosa in different patients' cohorts including Parkinson's patientients, patients with REM sleep behavior disorder (RBD), and patients with dementia with Lewy bodies.<br>|
| Experimental: Patients with Parkinson's disease<br> | Other: Real-time Quaking-Induced Conversion (RT-QuIC)<br>* RT-QuIC is increasingly used as diagnostic tools in synucleinopathies and has shown high sensitivity and specificity for the detection of α-synuclein seeds in CSF and tissue samples, including the olfactory mucosa in different patients' cohorts including Parkinson's patientients, patients with REM sleep behavior disorder (RBD), and patients with dementia with Lewy bodies.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstration of ⍺-synuclein seeding activity in the OM (assessed by RT-QuIC) in subjects who recovered from COVID-19 compared to healthy controls. |  | 1 year |