Effect of Plasmapheresis on Clinical Improvement and Biological Parameters of Patients With Long-haul COVID

Study Overview
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Brief Summary
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Many patients infected with SARS-Cov-2 present in the months following infection with non-specific symptoms such as non-resolving fatigue, cognitive disorders, dyspnea, headaches, myalgias, sleep disorders, anosmia/ ageusia and post exertion malaise. The persistence of these symptoms is called post covid syndrome or long Covid. According to the literature, the pathophysiological mechanisms involved in post-covid syndromes would include an inadequate immune response, activation of autoimmunity, persistence of pro-inflammatory biomarkers, endothelial dysfunction and alterations in the intestinal microbiota. In view of the involved pathophysiological mechanisms, linked to the circulation of pro-inflammatory molecules, autoimmunity or endothelial activation, the role of immuno-modulation in the treatment of long Covid need to be evaluated. Plasma exchange (PE) by decreasing blood levels of pro-inflammatory cytokines and/or autoimmune markers results in moderate to marked clinical improvement in various types of autoantibody-associated inflammatory, autoimmune and neurological diseases. The goal of our study is to evaluate the effects of plasmapheresis in patients with moderate to severe long-term COVID compared to patients receiving no treatment.

Official Title
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Effect of Plasmapheresis on Clinical Improvement and Biological Parameters of Patients With Long-haul COVID: PLEXCOVIL Study, a Randomized Controlled Study.

Conditions
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Long-Haul COVID-19

Intervention / Treatment
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* Drug: Plasmapheresis
* Other: Blood collection
* Other: Stool samples
* Other: PET scan
* Other: Cycle ergometer stress test
* Other: Questionnaires at baseline
* Other: Medical consultations


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years Who have had confirmed SARS-COV2 infection (RT PCR) for at least 6 months Having for more than 6 months at least 3 symptoms among the following: fatigue, post effort malaise, dyspnea, headache, diffuse myalgia/arthromyalgia, neuropathic pain, cognitive disorders, anosmia/ageusia Whose above symptoms have an impact on daily activities And/or on sick leave for more than 3 months And/or having to take to bed for more than 2 hours a day Having given free and informed written consent Being affiliated with or benefiting from social security Exclusion Criteria: With suspected Covid-19 but not confirmed by RT-PCR test Having a known history of any other pathology that could be confused with the diagnosis of long COVID: multiple sclerosis, autoimmune disease (lupus and Gougerot syndrome, inflammatory muscle disease, and myasthenia gravis), untreated hypothyroidism, major depression, use of narcotics regular. Unable to perform a cycle ergometer stress test With innate or drug-induced coagulation disorders (oral or parenteral anticoagulation) With contraindications to plasmapheresis such as: lack of peripheral venous access or unstable cardiac pathology Pregnant or breastfeeding woman

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group: receiving plasmapheresis<br> | Drug: Plasmapheresis<br>* 5 sessions of plasma exchanges<br>Other: Blood collection<br>* Blood collection to assess biological markers at baseline, M3 and M12<br>Other: Stool samples<br>* Stool samples will be collected from participants at baseline,M3 and M12<br>Other: PET scan<br>* PET scan at baseline and M6<br>Other: Cycle ergometer stress test<br>* Cycle ergometer stress test at M6<br>Other: Questionnaires at baseline<br>* Questionnaires at baseline, M3 and M6<br>|
| Other: Control group : no treatment<br> | Other: Blood collection<br>* Blood collection to assess biological markers at baseline, M3 and M12<br>Other: Stool samples<br>* Stool samples will be collected from participants at baseline,M3 and M12<br>Other: PET scan<br>* PET scan at baseline and M6<br>Other: Cycle ergometer stress test<br>* Cycle ergometer stress test at M6<br>Other: Questionnaires at baseline<br>* Questionnaires at baseline, M3 and M6<br>Other: Medical consultations<br>* Medical consultations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients whose fatigue has decreased by 30% on the Chalder scale at M3 compared to its initial state measured at baseline |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observation of the evolution of the fatigue (Chalder scale) felt by the patients during the 6 months of the study in the two groups of patients |  | 6 months | 
| Evaluation of the quality of life (SF-36) of patients at month 3 and month 6 |  | 3 months and 6 months | 
| Evaluation of the overall impression of change of patients at month 3 and month 6 (PGIC scale) |  | 3 months and 6 months | 
| Evolution at month 3 and month 6 of the following clinical signs: post-exertional malaise, dyspnea, headache, myalgia, neuropathic pain, cognitive impairment, anosmia/ageusia, anxiety/depression |  | 3 months and 6 months | 
| Assessment of patients' functional status at month 3 and month 6 (Post-COVID-19 functional status scale) |  | 3 months 6 months | 
| Evaluation of the professional or student activity at month 3 and month 6 |  | 3 months and 6 months | 
| Percentage of patients with 25% improvement in neuromuscular activity of M wave abnormalities at month 6 compared to baseline |  | 6 months | 
| Percentage of patients with improved brain and/or spinal cord metabolism at month 6 compared to baseline |  | 6 months | 
| Evolution of cytokine profiles and lymphocyte activation markers at month 3 and month 6 |  | 3 months and 6 months | 
| Rate and evolution of autoimmune markers at month 3 and month 6 |  | 3 months and 6 months | 
| Level and evolution of endothelial activity markers at month 3 and month 6 |  | 3 months and 6 months | 
| Evaluation of the microbiotic signature at month 3 and month 6 |  | 3 months and 6 months |