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

NCT ID: NCT05133596

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-20
• Study Completion Date: 2024-10-15

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Study population

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

Group Type: EXPERIMENTAL

Clinical examination

Intervention Type: 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.

Blood collection

Intervention Type: OTHER

12ml-blood sample

Olfactory evoked potentials

Intervention Type: OTHER

Olfactory evoked potentials will be recorded during olfactory tests.

Brushing of olfactory slits

Intervention Type: OTHER

collection of olfactory slits cells.

Neurological examination and neuropsychological assessment

Intervention Type: 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.

Nasal endoscopy

Intervention Type: OTHER

Nasal endoscopy

Assessment of olfactory and taste functions

Intervention Type: OTHER

• scales: VAS and TSS
• Sniffin Stick test

Interventions

Clinical examination

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.

Intervention Type: OTHER

Blood collection

12ml-blood sample

Intervention Type: OTHER

Olfactory evoked potentials

Olfactory evoked potentials will be recorded during olfactory tests.

Intervention Type: OTHER

Brushing of olfactory slits

collection of olfactory slits cells.

Intervention Type: OTHER

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.

Intervention Type: OTHER

Nasal endoscopy

Nasal endoscopy

Intervention Type: OTHER

Assessment of olfactory and taste functions

• scales: VAS and TSS
• Sniffin Stick test

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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).

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hopital Lariboisière

OTHER

Sponsor Role: collaborator

Institut Pasteur

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre-Marie Lledo, Prof.

Role: STUDY_DIRECTOR

Institut Pasteur

Locations

Hôpital Lariboisière

Paris, , France

Countries

France

Other Identifiers

2021-A02419-32

Identifier Type: OTHER

Identifier Source: secondary_id

2021-006

Identifier Type: -

Identifier Source: org_study_id