The COVID-19 pandemic is a novel medical challenge, particularly because of the systemicnature of this disease. Indeed, COVID-19 affects several organs and systems at once. Thebrain is affected in several ways: direct infection of nerve cells by SARS-CoV-2,inflammation of the central nervous system, severe systemic inflammation damaging nervecells, global cerebral ischaemia related to respiratory failure, thromboembolic eventsrelated to increased intravascular coagulation and severe psychological stress. As aresult, COVID-19 sometimes manifests as neurological and neuropsychiatric symptoms suchas dizziness, sleep disturbances, cognitive deficits, delirium, or severe depression.Sudden loss of smell is a common symptom associated with COVID-19 and SARS-CoV-2infection of neurons in the olfactory system has been reported in both hamsters andhumans. The vast majority of COVID-19 patients recover their olfactory function within afew weeks. However, a significant minority of infected individuals (1 in 5 cases) stillsuffers from olfactory disorders (anosmia, hyposmia and/or parosmia) several months afterthe primary infection. These olfactory disorders are frequently associated withdepressive behaviour and cognitive complaints. In PET scans, it is even possible tocorrelate 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 theolfactory capacities of patients suffering from persistent smell disorder since one year(+/- 4 months) following COVID-19. The issue is to study the link between viralpersistence in the olfactory sensory organ, chronic inflammation, and central damage tothe olfactory system. The follow-up of the evolution of olfactory and neurocognitivecapacities, in an integrative way by means of molecular, physiological and behaviouralapproaches, will inform us on the specificities of "COVID-long" and on the level ofperipheral and/or central damage of the olfactory system.
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.
Other: 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.
Other: Blood collection
12ml-blood sample
Other: Olfactory evoked potentials
Olfactory evoked potentials will be recorded during olfactory tests.
Other: Brushing of olfactory slits
collection of olfactory slits cells.
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.
Other: Nasal endoscopy
Nasal endoscopy
Other: Assessment of olfactory and taste functions
- scales: VAS and TSS
- Sniffin Stick test
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.
Hôpital Lariboisière
Paris, France
Investigator: Charlotte Hautefort, MD
Contact: 33 1 49959197
charlotte.hautefort@aphp.fr
Pierre-Marie Lledo, Prof.
33 1 45688803
pierre-marie.lledo@pasteur.fr
Pierre-Marie Lledo, Prof., Study Director
Institut Pasteur