COVID-19 Infection: Exploration of Respiratory Control Center Abnormalities (CRC-COVID)

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19; Neurological Complication
• Intervention / Treatment: Other: hypoxia : 14.3 and 12.7% FIO2, hypercapnia 7% CO2, inspiratory mechanical constraint

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Département R3S, hôpital de la pitié-salpêtrière

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 15 COVID positive patients; dyspnea rating to various dyspneic stimulus	Other: hypoxia : 14.3 and 12.7% FIO2, hypercapnia 7% CO2, inspiratory mechanical constraint; 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
Active Comparator: 15 healthy controls; dyspnea rating to various dyspneic stimulus	Other: hypoxia : 14.3 and 12.7% FIO2, hypercapnia 7% CO2, inspiratory mechanical constraint; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2020
• Primary Completion (Actual): January 11, 2021
• Study Completion (Actual): January 11, 2021

Study Registration Dates

• First Submitted: April 20, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): August 30, 2021
• Last Update Submitted That Met QC Criteria: August 27, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; dyspnea; hypoxic stimulus
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: APHP200476

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No