Study of the Evolution of Olfactory Disorders in Patients With Persistent Loss of Smell Following COVID-19

NCT05133596 | Completed

• 2 other identifiers: 2021-0062021-A02419-32
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

SARS-CoV-2 Acute Respiratory Disease

Keywords

Neuroinflammation; coronavirus; olfaction disorder; evoked potentials

Outcome Measures

Primary Outcomes (1)

• 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.

  24 months

Secondary Outcomes (6)

• Measurement of olfactory perception threshold, olfactory discrimination capacity and odour identification.

  24 months

• To characterise the persistence of SARS-CoV-2 in the olfactory epithelium.

  24 months

• To characterise any damage to the olfactory nerve

  24 months

• To identify the presence of inflammatory markers in patients.

  24 months

• Detection and measurement of markers of neurological disorders in the blood.

  24 months

Study Arms (1)

Study population

EXPERIMENTAL

Adult subjects up to 55 years of age with persistent olfaction disorder after a symptomatic episode of COVID-19.

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

Interventions

Clinical examination OTHER

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.

Study population

Blood collection OTHER

12ml-blood sample

Study population

Olfactory evoked potentials OTHER

Olfactory evoked potentials will be recorded during olfactory tests.

Study population

Brushing of olfactory slits OTHER

collection of olfactory slits cells.

Study population

Neurological examination and neuropsychological assessment OTHER

* 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.

Study population

Nasal endoscopy OTHER

Nasal endoscopy

Study population

Assessment of olfactory and taste functions OTHER

* scales: VAS and TSS * Sniffin Stick test

Study population

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut Pasteur: lead
• Hopital Lariboisière: collaborator

Study Sites (1)

Hôpital Lariboisière

Paris, 75010, France

Location

MeSH Terms

Conditions

Neuroinflammatory Diseases; Coronavirus Infections; Olfaction Disorders

Interventions

Restraint, Physical; Blood Specimen Collection; Neuropsychological Tests

Condition Hierarchy (Ancestors)

Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Sensation Disorders; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Behavior Control; Therapeutics; Immobilization; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Psychological Tests; Behavioral Disciplines and Activities

Study Officials

• Pierre-Marie Lledo, Prof.

  Institut Pasteur

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Adult subjects up to 55 years of age with persistent olfaction disorder after a symptomatic episode of COVID-19.

Study Record Dates

• First Submitted: November 23, 2021
• First Posted: November 24, 2021
• Study Start: June 20, 2022
• Primary Completion: October 15, 2024
• Study Completion: October 15, 2024
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)