Clinical trial NCT04880720: Deciphering a Specific Signature of the Immunosenescence Induced in COVID-19+ Patients Versus Rheumatoid Arthritis Patients
Official title: Deciphering a Specific Signature of the Immunosenescence Induced in COVID-19+ Patients Versus Rheumatoid Arthritis Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: SARS-Cov-2 Infection
Rheumatoid Arthritis
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2021-05-11
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * COVID-19 patients are recruited through the Covidothèque project and the UANDES center (Chile)
* RA patients and healthy subjects are recruited through 3 rheumatology reference centers (Montpellier, Paris Saint-Antoine and Saint-Etienne)

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Results of phenotypic immunosenescence analyses of COVID-19 patients targeting 5 different immune populations (neutrophils, T lymphocytes, NK lymphocytes, B lymphocytes and monocytes).
timeFrame: At inclusion visit
Secondary outcomes:
measure: Comparison of previous results with the results of senescence immunophenotyping in peripheral blood of a reference population with an inflammatory disease (active RA)
timeFrame: At inclusion visit
measure: Comparison of previous results with the results of senescence immunophenotyping in peripheral blood of a reference population of healthy controls.
timeFrame: At inclusion visit
measure: 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.
timeFrame: At inclusion visit
Other outcomes:
Locations:
city: Montpellier
country: France
facility: CHU Montpellier
Study officials:
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