COVID-19 Infection: Exploration of Respiratory Control Center Abnormalities

Study Overview
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Brief Summary
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The purpose of the present study is to determine whether there is a decrease in the emotional response to experimental induction of dyspnea by hypoxic stimulation in subjects with a neurological form of COVID-19, compared to healthy controls.

Detailed Description
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SARS CoV-2 infection causes lung damage that can be severe enough to require artificial ventilation. Clinicians taking care of these patients are surprised by the scant respiratory sensations and emotional responses described by patients. This attenuation of respiratory interoception deprives clinicians of the usual warning signs during respiratory decompensation of dyspnea and its aggravation. It may be the result of central nerve damage. This hypothesis is bolstered by the observation that within the multiple clinical forms of COVID-19 infection there are some neurological forms (headache, anosmia, agueusia, dizziness, without respiratory signs and with little or no fever), that are most likely the consequence of olfactory penetration of the virus into the central nervous system (mechanism described for SARS CoV-1).

Official Title
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Do Respiratory Control Center Anomalies Explain the Lack of Respiratory Sensations Perceptions Observed in Patients Affected by COVID-19 ?

Conditions
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Covid19, Neurological Complication

Intervention / Treatment
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* Other: hypoxia : 14.3 and 12.7% FIO2, hypercapnia 7% CO2, inspiratory mechanical constraint


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - adult (≥ 18 years old, unprotected); for COVID-19 + patients: COVID-19 + diagnosis; with quantitative or qualitative anomalies in taste and smell; first symptoms appeared in less than 21 days for healthy subjects: have never presented any sign of COVID ; confirmed by recent negative serology understanding French; affiliated to social security; having a BMI between 20 and 30; preferably non-smokers and in the event of recruitment difficulties, smokers but with smoking <5 packs - year signature of the informed consent form Exclusion Criteria: respiratory signs or symptoms (rhinitis, cough, shortness of breath at rest); temperature above 37.5 ° C; existence of a chronic respiratory pathology (including asthma and COPD in the first row); pregnant women ; protected minors and adults, persons deprived of their liberty; not affiliated to a social security (including AME); contraindication to MRI (pace maker, intracranial implants, etc.).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 15 COVID positive patients<br>dyspnea rating to various dyspneic stimulus | Other: hypoxia : 14.3 and 12.7% FIO2, hypercapnia 7% CO2, inspiratory mechanical constraint<br>* the fraction of inspired oxygen is reduced from  21% (room air) to 14.3 and 12.7% allowing the SpO2 to decrease to  75%, rebreathing test allowing the PCO2 to rise to 65 mmHg, inspiratory mechanical constraint with 50 to 75% of maximum inspiratory pressure<br>|
| Active Comparator: 15 healthy controls<br>dyspnea rating to various dyspneic stimulus | Other: hypoxia : 14.3 and 12.7% FIO2, hypercapnia 7% CO2, inspiratory mechanical constraint<br>* the fraction of inspired oxygen is reduced from  21% (room air) to 14.3 and 12.7% allowing the SpO2 to decrease to  75%, rebreathing test allowing the PCO2 to rise to 65 mmHg, inspiratory mechanical constraint with 50 to 75% of maximum inspiratory pressure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of the emotional response to hypoxic exposure (14.3 et 12.7% FIO2) | Slope of the relation between the intensity of a hypoxic stimulus to the intensity of the emotional response (visual analog scale, VAS : 0 is no pain and 10 is the worst pain) | 10 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perception of a hypoxic stimulus induced dyspnea (14.3 et 12.7% FIO2) | ratings of dyspnea immediately after a hypoxic stimulus: Multidisciplinary Dyspnea Profile, MDP : 0 is no change and 10 is unbearable | 5 minutes | 
| Perception of a hypercapnic stimulus induced dyspnea (7% CO2) | ratings of dyspnea intensity and unpleasantness during a hypercapnic stimulus (visual analog scale, VAS : 0 is no pain and 10 is the worst pain) | 10 minutes | 
| Perception of a hypercapnic stimulus induced dyspnea (7% CO2) | ratings of dyspnea immediately after a hypercapnic stimulus: Multidisciplinary Dyspnea Profile, MDP : 0 is no change and 10 is unbearable | 5 minutes | 
| Perception of a inspiratory mechanical constraint induced dyspnea | ratings of dyspnea intensity and unpleasantness during an inspiratory mechanical constraint (visual analog scale, VAS: 0 is no pain and 10 is the worst pain) | 10 min | 
| Perception of a inspiratory mechanical constraint induced dyspnea | ratings of dyspnea immediately after an inspiratory mechanical constraint induced dyspnea(Multidisciplinary Dyspnea Profile, MDP: 0 is no change and 10 is unbearable) | 5 minutes | 
| brain MRI | Multimodal MRI (including anatomical MRI, resting-state functional MRI) | 1,5 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, COVID-19, dyspnea, hypoxic stimulus