Loss of the sense of smell is a characteristic feature of COVID-19 and likely related toviral invasion of the olfactory mucosa but is also a prodromal feature of PD. Thisconstellation has kindled concerns that COVID-19 - similar to the Spanish Flu Pandemic in1918 - might trigger a second wave of post-infectious parkinsonism. The main objective ofthe study is to probe for the presence of pathological α-synuclein assemblies in theolfactory mucosa of patients with COVID-19.
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).
Other: Real-time Quaking-Induced Conversion (RT-QuIC)
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.
Inclusion Criteria:
1. Participants must be 18 years or older;
2. Participants are able to understand the aim of the study and the planned procedures;
3. Written informed consent form;
4. Participants fulfilling the criteria for one of the following groups:
1. 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.
2. 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.
3. 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
4. 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:
1. 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.
2. 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.
3. 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.
Medical University of Innsbruck
Innsbruck, Austria
Investigator: beatrice Heim, MD PhD
Contact: + 43 512 504 81128
beatrice.heim@tirol-kliniken.at; beatrice.heim@i-med.ac.at
Beatrice Heim, MD PhD
+43 512 504 81128
beatrice.heim@tirol-kliniken.at; beatrice.heim@i-med.ac.at
Not Provided