Deciphering a Specific Signature of the Immunosenescence Induced in COVID-19+ Patients Versus Rheumatoid Arthritis Patients

Study Overview
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Brief Summary
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Immune aging or immunosenescence is characterized by a loss of T cell clonal diversity and a contraction of naïve T cells with proliferative capacity associated with the functional impairment of many others immune cells as well as a chronic low degree of inflammation. A restrictive T cell repertoire is likely more prone to antigen-mediated exhaustion observed during chronic viral infections. Notably, lymphopenia is the most consistent laboratory abnormality in COVID-19 infected patients and both lung-resident and circulating T cells potently up-regulate markers of T cell exhaustion. It is not clear today if the association of COVID-19 disease severity with age is mainly related with the immunosenescence of infected patients. Interestingly, T cell exhaustion and premature immunosenescence have also been observed in chronic inflammatory diseases such as rheumatoid arthritis (RA). To better understand the immunological mechanisms involved in SARS-Cov-2 pathophysiology, the investigators propose to compare the immunosenescence patterns observed during RA, aging and SARS-Cov-2 infected patients in order to design improved therapeutic interventions.

Official Title
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Deciphering a Specific Signature of the Immunosenescence Induced in COVID-19+ Patients Versus Rheumatoid Arthritis Patients

Conditions
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SARS-Cov-2 Infection, Rheumatoid Arthritis

Intervention / Treatment
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* Other: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Active RA Patients: Patients with rheumatoid arthritis (RA) meeting the 2010 ACR/EULAR diagnostic criteria Patients in inflammatory flare of RA (DAS28 > 3.2) Patients who have been off biological disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic antirheumatic drugs (tsDMARDs) for RA for at least 2 weeks (except for rituximab, where a delay of at least 12 months is required) Conventional synthetic DMARDs (Methotrexate, Hydroxychloroquine, Leflunomide, Sulfasalazine) are allowed Beneficiary of a social security system Informed consent Inclusion Criteria for Healthy Controls: Absence of chronic diseases and current infection Beneficiary of a social security system Informed consent Inclusion Criteria for COVID-19+ Patients: Patients with ongoing SARS-Cov-2 infection (PCR+) Patients hospitalized at D7-D14 of symptoms onset Patients with two or more SARS-Cov-2 symptoms (including fever, cough, dyspnea, sore throat, chest pain, anosmia, diarrhea) Membership in or beneficiary of a social security scheme Collection of free and informed consent Exclusion Criteria for All Groups: Subjects under 18 years of age HIV positive patients Diabetic patients Morbidly obese patients (BMI > 40kg/m2) Use of senolytic drugs in the week prior to inclusion (azithromycin, metformin, cyclosporine, JAK inhibitors) Use of steroids in doses greater than 10 mg/day in the week prior to inclusion Subjects unable to give consent Pregnant, breastfeeding, or non-menopausal women not taking effective contraception Vulnerable subjects protected by law Subjects under guardianship or curatorship

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID-19 Patients<br> | Other: Blood sampling<br>* Blood sampling - 10mL<br>|
| Rheumatoid Arthritis Patients<br> | Other: Blood sampling<br>* Blood sampling - 10mL<br>|
| Healthy Comparator<br> | Other: Blood sampling<br>* Blood sampling - 10mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Results of phenotypic immunosenescence analyses of COVID-19 patients targeting 5 different immune populations (neutrophils, T lymphocytes, NK lymphocytes, B lymphocytes and monocytes). |  | At inclusion visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of previous results with the results of senescence immunophenotyping in peripheral blood of a reference population with an inflammatory disease (active RA) |  | At inclusion visit | 
| Comparison of previous results with the results of senescence immunophenotyping in peripheral blood of a reference population of healthy controls. |  | At inclusion visit | 
| Identification of a specific gene expression of immunosenescence induced in COVID-19 patients, using transcriptomic analysis in the different immune subpopulations previously identified and specific to COVID-19 patients. |  | At inclusion visit |