SARS-CoV-2 Acute Respiratory DiseaseETOCNCT05133596
Study of the Evolution of Olfactory Disorders in Patients With Persistent Loss of Smell Following COVID-19
A study testing Clinical examination, Blood collection and Olfactory evoked potentials in people with SARS-CoV-2 Acute Respiratory Disease, run by Institut Pasteur at 1 site in France.
Trial summary
The COVID-19 pandemic is a novel medical challenge, particularly because of the systemic nature of this disease. Indeed, COVID-19 affects several organs and systems at once. The brain is affected in several ways: direct infection of nerve cells by SARS-CoV-2, inflammation of the central nervous system, severe systemic… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- SARS-CoV-2 Acute Respiratory Disease
- What is being tested?
- Clinical examination, Blood collection and Olfactory evoked potentials
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 20 Jun 2022to 15 Oct 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Adults < 55 years
- History of symptomatic COVID over 1 year +/- 4 months with a positive PCR diagnosis of SARS-CoV-2
- Olfactory complaint
- Able to understand simple questionnaires in French.
- Subject covered by French Social Security (except for Aide Médicale d'Etat).
Who cannot join
- Contraindication to nasal swabbing (for morphological reasons, haemostasis disorders, taking aspirin in the 15 days prior to swabbing or anticoagulants, contraindications to the use of a local anaesthetic such as a history of allergy to local anaesthetics or any other reasons judged by the clinical investigator)
- To have been placed in the intensive care unit following COVID-19.
- Known previous nasal-sinus pathology.
- History of psychiatric pathology according to DSM IV criteria, ischaemic, neoplastic, inflammatory, infectious or neurodegenerative (meningitis, encephalopathy, encephalitis, stroke, neurodegenerative disease) known or suspected.
- History of loss of sense of smell prior to COVID infection.
- Patient affiliated to the Aide Médicale d'Etat.
- Person deprived of liberty by judicial or administrative decision, or subject to legal protection.
Trial locations and contacts
1 site in 1 country.
About this study
The COVID-19 pandemic is a novel medical challenge, particularly because of the systemic nature of this disease. Indeed, COVID-19 affects several organs and systems at once. The brain is affected in several ways: direct infection of nerve cells by SARS-CoV-2, inflammation of the central nervous system, severe systemic inflammation damaging nerve cells, global cerebral ischaemia related to respiratory failure, thromboembolic events related to increased intravascular coagulation and severe psychological stress. As a result, COVID-19 sometimes manifests as neurological and neuropsychiatric symptoms such as dizziness, sleep disturbances, cognitive deficits, delirium, or severe depression.
Sudden loss of smell is a common symptom associated with COVID-19 and SARS-CoV-2 infection of neurons in the olfactory system has been reported in both hamsters and humans. The vast majority of COVID-19 patients recover their olfactory function within a few weeks. However, a significant minority of infected individuals (1 in 5 cases) still suffers from olfactory disorders (anosmia, hyposmia and/or parosmia) several months after the primary infection. These olfactory disorders are frequently associated with depressive behaviour and cognitive complaints. In PET scans, it is even possible to correlate this cognitive dysfunction with hypometabolism of certain brain regions, including the olfactory gyrus.
This project proposes, during one year, to evaluate and follow the evolution of the olfactory capacities of patients suffering from persistent smell disorder since one year (+/- 4 months) following COVID-19. The issue is to study the link between viral persistence in the olfactory sensory organ, chronic inflammation, and central damage to the olfactory system. The follow-up of the evolution of olfactory and neurocognitive capacities, in an integrative way by means of molecular, physiological and behavioural approaches, will inform us on the specificities of "COVID-long" and on the level of peripheral and/or central damage of the olfactory system.
Read the detailed description
Prospective monocentric descriptive study. Evaluation of COVID-19 patients with persistent loss of smell during 2 visits at 1 year intervals (V1 and V2).
V1 :The following examinations will be carried out specifically for the research.
- Clinical examination;
- Blood sampling;
- Recording of olfactory evoked potentials;
- Neurological examination and neuropsychological assessment;
V2 :
All examinations performed at V1 will be repeated at V2.
If the following examinations are not carried out during care within 3 weeks of V2, they will be carried out as part of the research during this V2 visit.
- Nasal endoscopy ;
- Assessment of olfactory and gustatory functions.
The following explorations will be carried out:
- Passing of two olfactory and gustatory scales; Olfactory and gustatory disorders will be quantified using two scales, the visual analogue scale VAS and the modified TSS;
- Sniffin Stick test.
In addition, MRI data from clinical care will be collected.
- Conditions
- SARS-CoV-2 Acute Respiratory Disease
- Being tested
- Clinical examination, Blood collection, Olfactory evoked potentials, Brushing of olfactory slits, Neurological examination and neuropsychological assessment
- Keywords
- Neuroinflammation, coronavirus, olfaction disorder, evoked potentials
- Medical subject headings
- Neuroinflammatory Diseases, Coronavirus Infections, Olfaction Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinical examinationOther
The investigator will conduct a clinical examination to rule out other causes of olfactory impairment independent of COVID-19. The investigator will also collect the following information: socio-demographic data (age, sex, blood type, weight, height, etc.), history of olfaction disorder symptoms, past or current treatments received and tobacco/alcohol consumption.
Blood collectionOther
12ml-blood sample
Olfactory evoked potentialsOther
Olfactory evoked potentials will be recorded during olfactory tests.
Brushing of olfactory slitsOther
collection of olfactory slits cells.
Neurological examination and neuropsychological assessmentOther
- MOCA, BREF
- CVLT
- WAIS IV, MEM III
- Right-side and left-side empan, Trail Making Test A and B (TMT), verbal fluency tests, PASAT, Attention Assessment Test
- Benton's Line Judgement, VOSP
- Assessment of psychological status, fatigue and screening for psychiatric comorbidities: depression \& anxiety scales (HAD scale, mADRS depression scale, STAI anxiety scale), Fatigue Severity Scale.
Nasal endoscopyOther
Nasal endoscopy
Assessment of olfactory and taste functionsOther
- scales: VAS and TSS
- Sniffin Stick test
| Study group | Role | What they receive |
|---|---|---|
| Study population | Experimental | Adult subjects up to 55 years of age with persistent olfaction disorder after a symptomatic episode of COVID-19. Receives: Other: Clinical examination; Other: Blood collection; Other: Olfactory evoked potentials; Other: Brushing of olfactory slits; Other: Neurological examination and neuropsychological assessment; Other: Nasal endoscopy; Other: Assessment of olfactory and taste functions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of olfactory responses by PEO recording and by calculating the TDI score of the Sniffin'stick tests.
To characterise the evolution of the olfactory capacities of patients suffering from persistent odour disorders following SARS-CoV-2 infection over the course of a year.
Measured: 24 months
Secondary outcomes (6)
Measurement of olfactory perception threshold, olfactory discrimination capacity and odour identification.
Describe the olfactory performance
Measured: 24 months
To characterise the persistence of SARS-CoV-2 in the olfactory epithelium.
Characterisation of the presence of SARS-CoV-2 by PCR in the olfactory mucosa.
Measured: 24 months
To characterise any damage to the olfactory nerve
Mapping analysis of the olfactory nerve of COVID-19 patients by MRI tractography technique.
Measured: 24 months
To identify the presence of inflammatory markers in patients.
Measurement of cellular and inflammatory markers in the olfactory mucosa.
Measured: 24 months
Detection and measurement of markers of neurological disorders in the blood.
To identify the neurological damage in patients.
Measured: 24 months
Measurement of patients' cognitive performance by neuropsychological assessment (standardised tests).
To identify possible cognitive abnormalities in these patients with prolonged loss of smell.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2021
- Study start20 Jun 2022
- Primary completion15 Oct 2024
- Study completion15 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SARS-CoV-2 Acute Respiratory DiseaseStudies of the same condition, open and under way.
- More trials run by Institut PasteurThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Adult subjects up to 55 years of age with persistent olfaction disorder after a symptomatic episode of COVID-19.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Pasteur
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hopital Lariboisière
- Responsible party
- Sponsor
- Investigators
- Pierre-Marie Lledo, Prof., Study director, Institut Pasteur
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05133596
- Sponsor's protocol ID
- 2021-006
- Other IDs
- 2021-A02419-32
- Acronym
- ETOC
- Status last verified
- May 2025
- First submitted
- 23 Nov 2021
- Last updated
- 14 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Evolution of Olfactory Disorders in Patients With Persistent Loss of Smell Following COVID-19
- ClinicalTrials.gov ID
- NCT05133596
- Acronym / sponsor ID
- ETOC / 2021-006
- Conditions
- SARS-CoV-2 Acute Respiratory Disease
- Keywords
- Neuroinflammation, coronavirus, olfaction disorder, evoked potentials
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Institut PasteurIndustry (pharma, biotech, devices)
- Collaborators
- Hopital Lariboisière
- Study start
- 20 Jun 2022 (actual)
- Primary completion
- 15 Oct 2024 (actual)
- Study completion
- 15 Oct 2024 (actual)
- First posted
- 24 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The COVID-19 pandemic is a novel medical challenge, particularly because of the systemic nature of this disease. Indeed, COVID-19 affects several organs and systems at once. The brain is affected in several ways: direct infection of nerve cells by SARS-CoV-2, inflammation of the central nervous system, severe systemic inflammation damaging nerve cells, global cerebral ischaemia related to respiratory failure, thromboembolic events related to increased intravascular coagulation and severe psychological stress. As a result, COVID-19 sometimes manifests as neurological and neuropsychiatric symptoms such as dizziness, sleep disturbances, cognitive deficits, delirium, or severe depression.
Sudden loss of smell is a common symptom associated with COVID-19 and SARS-CoV-2 infection of neurons in the olfactory system has been reported in both hamsters and humans. The vast majority of COVID-19 patients recover their olfactory function within a few weeks. However, a significant minority of infected individuals (1 in 5 cases) still suffers from olfactory disorders (anosmia, hyposmia and/or parosmia) several months after the primary infection. These olfactory disorders are frequently associated with depressive behaviour and cognitive complaints. In PET scans, it is even possible to correlate this cognitive dysfunction with hypometabolism of certain brain regions, including the olfactory gyrus.
This project proposes, during one year, to evaluate and follow the evolution of the olfactory capacities of patients suffering from persistent smell disorder since one year (+/- 4 months) following COVID-19. The issue is to study the link between viral persistence in the olfactory sensory organ, chronic inflammation, and central damage to the olfactory system. The follow-up of the evolution of olfactory and neurocognitive capacities, in an integrative way by means of molecular, physiological and behavioural approaches, will inform us on the specificities of "COVID-long" and on the level of peripheral and/or central damage of the olfactory system.
Detailed description
Prospective monocentric descriptive study. Evaluation of COVID-19 patients with persistent loss of smell during 2 visits at 1 year intervals (V1 and V2).
V1 :The following examinations will be carried out specifically for the research.
- Clinical examination;
- Blood sampling;
- Recording of olfactory evoked potentials;
- Neurological examination and neuropsychological assessment;
V2 :
All examinations performed at V1 will be repeated at V2.
If the following examinations are not carried out during care within 3 weeks of V2, they will be carried out as part of the research during this V2 visit.
- Nasal endoscopy ;
- Assessment of olfactory and gustatory functions.
The following explorations will be carried out:
- Passing of two olfactory and gustatory scales; Olfactory and gustatory disorders will be quantified using two scales, the visual analogue scale VAS and the modified TSS;
- Sniffin Stick test.
In addition, MRI data from clinical care will be collected.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Adult subjects up to 55 years of age with persistent olfaction disorder after a symptomatic episode of COVID-19.
| Arm | Type | Receives |
|---|---|---|
| Study population | Experimental | Other: Clinical examination, Other: Blood collection, Other: Olfactory evoked potentials, Other: Brushing of olfactory slits, Other: Neurological examination and neuropsychological assessment, Other: Nasal endoscopy, Other: Assessment of olfactory and taste functionsAdult subjects up to 55 years of age with persistent olfaction disorder after a symptomatic episode of COVID-19. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Adults < 55 years
- History of symptomatic COVID over 1 year +/- 4 months with a positive PCR diagnosis of SARS-CoV-2
- Olfactory complaint
- Able to understand simple questionnaires in French.
- Subject covered by French Social Security (except for Aide Médicale d'Etat).
Key exclusion criteria (7 listed)
- Contraindication to nasal swabbing (for morphological reasons, haemostasis disorders, taking aspirin in the 15 days prior to swabbing or anticoagulants, contraindications to the use of a local anaesthetic such as a history of allergy to local anaesthetics or any other reasons judged by the clinical investigator)
- To have been placed in the intensive care unit following COVID-19.
- Known previous nasal-sinus pathology.
- History of psychiatric pathology according to DSM IV criteria, ischaemic, neoplastic, inflammatory, infectious or neurodegenerative (meningitis, encephalopathy, encephalitis, stroke, neurodegenerative disease) known or suspected.
- History of loss of sense of smell prior to COVID infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clinical examinationThe investigator will conduct a clinical examination to rule out other causes of olfactory impairment independent of COVID-19. The investigator will also collect the following information: socio-demographic data (age, sex, blood type, weight, height, etc.), history of olfaction disorder symptoms, past or current treatments received and tobacco/alcohol consumption. | Other | Study population |
| Blood collection12ml-blood sample | Other | Study population |
| Olfactory evoked potentialsOlfactory evoked potentials will be recorded during olfactory tests. | Other | Study population |
| Brushing of olfactory slitscollection of olfactory slits cells. | Other | Study population |
| Neurological examination and neuropsychological assessment* MOCA, BREF * CVLT * WAIS IV, MEM III * Right-side and left-side empan, Trail Making Test A and B (TMT), verbal fluency tests, PASAT, Attention Assessment Test * Benton's Line Judgement, VOSP * Assessment of psychological status, fatigue and screening for psychiatric comorbidities: depression \& anxiety scales (HAD scale, mADRS depression scale, STAI anxiety scale), Fatigue Severity Scale. | Other | Study population |
| Nasal endoscopyNasal endoscopy | Other | Study population |
| Assessment of olfactory and taste functions* scales: VAS and TSS * Sniffin Stick test | Other | Study population |
Primary outcome
Measurement of olfactory responses by PEO recording and by calculating the TDI score of the Sniffin'stick tests.
Time frame: 24 months
To characterise the evolution of the olfactory capacities of patients suffering from persistent odour disorders following SARS-CoV-2 infection over the course of a year.
6 secondary outcomes
Measurement of olfactory perception threshold, olfactory discrimination capacity and odour identification.
Time frame: 24 months
To characterise the persistence of SARS-CoV-2 in the olfactory epithelium.
Time frame: 24 months
To characterise any damage to the olfactory nerve
Time frame: 24 months
To identify the presence of inflammatory markers in patients.
Time frame: 24 months
Detection and measurement of markers of neurological disorders in the blood.
Time frame: 24 months
Measurement of patients' cognitive performance by neuropsychological assessment (standardised tests).
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre-Marie Lledo, Prof. study director
Institut Pasteur
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Clinical examination, Blood collection and Olfactory evoked potentials in people with SARS-CoV-2 Acute Respiratory Disease, run by Institut Pasteur at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of olfactory responses by PEO recording and by calculating the TDI score of the Sniffin'stick tests. (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.