Chronic Fatigue Etiology and Recovery in Covid-19 Patients: the Role of Fatigability

Study Overview
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Brief Summary
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Chronic fatigue is the most common and debilitating symptom in intensive care unit (ICU) survivors. Indeed, it has been widely reported that patients who stayed in ICU for prolonged periods report a feeling of tiredness for months to years after ICU discharge. This symptom seems particularly pronounced in Covid-19 patients and may affect their quality of life by decreasing their capacity to perform simple tasks of daily life. The aim of the present project is to determine whether deteriorated neuromuscular function (i.e. increased fatigability) is involved in the feeling of fatigue of Covid-19 patients. Because the causes of this feeling are multi-dimensional, a large battery of tests will allow us to better understand the origin of chronic fatigue. A better knowledge of chronic fatigue etiology and its recovery will allow to optimize rehabilitation treatments to shorten the persistence of chronic fatigue and in fine improve life quality.

Official Title
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Chronic Fatigue Etiology and Recovery in Covid-19 Patients : the Role of Fatigability and Stay in Intensive Care

Conditions
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Chronic Fatigue Syndrome, Intensive Care Unit, Muscle

Intervention / Treatment
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* Other: Questionnaires
* Biological: blood test
* Other: Maximal effort test
* Device: actigraphy
* Device: Neuromuscular evaluation
* Other: stool analysis
* Other: food diary


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for patients who have been in intensive care : Diagnosed with Covid-19 Ventilated in ICU for at least 3 consecutive days ICU discharge between 4 and 8 weeks Approval received from a physician Command of the French language Inclusion Criteria for patients who have NOT been in intensive care : Diagnosed with Covid-19 : positive serological test or positive PCR test following nasopharyngeal swabbing Approval received from a physician Command of the French language Exclusion Criteria: Taking neuroactive substances that can alter corticospinal excitability Patients with co-morbidities leading to significant fatigue: e.g. cancerous pathologies, sleep apnea Patients with neurodegenerative or neuromuscular disease Contraindication to the application of a magnetic field Contraindication to the practice of Magnetic Resonance Imaging Participant is pregnant Patients with psychiatric disorders Paraplegic and hemiplegic patients Addictive disorders

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-fatigued patients who have been in intensive care units<br> | Other: Questionnaires<br>* Quality of life Depression Physical pain Social provisions Quality of sleep<br>Biological: blood test<br>* complete blood count and cytokine concentration, TNF-alpha, LDL oxidized, AOPP, SOD, GPX, catalase, albumin, transthyretin, RBP, transferin, α-1 glycoprotein acide, ferritine, selenium, zinc, magnesium<br>Other: Maximal effort test<br>* The maximal effort test with VO2max recordings will be assessed during the first visit to the laboratory.<br>Device: actigraphy<br>* assessment of sleep quality<br>Device: Neuromuscular evaluation<br>* The maximum isometric force produced by the knee extensors will be measured on the ergometer the intensity of muscular electrical activity recorded by surface electromyography Peripheral nerve stimulation Transcranial magnetic stimulation Magnetic resonance imaging<br>Other: stool analysis<br>* analyze the composition of the intestinal microbiote. concerns only the patients of Saint Etienne<br>Other: food diary<br>* 3 days of information to determine nutrient intakes. concerns only the patients of Saint Etienne<br>|
| Experimental: Fatigued patients who have been in intensive care units<br> | Other: Questionnaires<br>* Quality of life Depression Physical pain Social provisions Quality of sleep<br>Biological: blood test<br>* complete blood count and cytokine concentration, TNF-alpha, LDL oxidized, AOPP, SOD, GPX, catalase, albumin, transthyretin, RBP, transferin, α-1 glycoprotein acide, ferritine, selenium, zinc, magnesium<br>Other: Maximal effort test<br>* The maximal effort test with VO2max recordings will be assessed during the first visit to the laboratory.<br>Device: actigraphy<br>* assessment of sleep quality<br>Device: Neuromuscular evaluation<br>* The maximum isometric force produced by the knee extensors will be measured on the ergometer the intensity of muscular electrical activity recorded by surface electromyography Peripheral nerve stimulation Transcranial magnetic stimulation Magnetic resonance imaging<br>Other: stool analysis<br>* analyze the composition of the intestinal microbiote. concerns only the patients of Saint Etienne<br>Other: food diary<br>* 3 days of information to determine nutrient intakes. concerns only the patients of Saint Etienne<br>|
| Experimental: patients who have not been in intensive care units<br> | Other: Questionnaires<br>* Quality of life Depression Physical pain Social provisions Quality of sleep<br>Biological: blood test<br>* complete blood count and cytokine concentration, TNF-alpha, LDL oxidized, AOPP, SOD, GPX, catalase, albumin, transthyretin, RBP, transferin, α-1 glycoprotein acide, ferritine, selenium, zinc, magnesium<br>Other: Maximal effort test<br>* The maximal effort test with VO2max recordings will be assessed during the first visit to the laboratory.<br>Device: actigraphy<br>* assessment of sleep quality<br>Device: Neuromuscular evaluation<br>* The maximum isometric force produced by the knee extensors will be measured on the ergometer the intensity of muscular electrical activity recorded by surface electromyography Peripheral nerve stimulation Transcranial magnetic stimulation Magnetic resonance imaging<br>Other: stool analysis<br>* analyze the composition of the intestinal microbiote. concerns only the patients of Saint Etienne<br>Other: food diary<br>* 3 days of information to determine nutrient intakes. concerns only the patients of Saint Etienne<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| voluntary maximum force reduction |  | 6 weeks post-discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuromuscular function : cortical activity | Level of cortical activation and cortico-spinal excitability measured by transcranial magnetic stimulation | 6 weeks post-discharge | 
| Neuromuscular function : Peripheral function | Peripheral function by electrical nerve stimulation | 6 weeks post-discharge | 
| Maximal oxygen uptake (VO2max) | measured by effort test | 6 weeks post-discharge | 
| quality of sleep | measured by actigraphy | 6 weeks post-discharge | 
| muscle volume | with Magnetic resonance imaging | 6 weeks post-discharge | 
| metabolic fatigue | measured by a Phosphorus 31 Nuclear magnetic resonance test | 6 weeks post-discharge | 
| microbiote intestinal | stool analysis (concerns only the patients of Saint Etienne) | baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuromuscular function, Fatigability