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

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

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.

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