Effector and Regulatory T Cell Receptor Repertoire Analyses in Patients Affected by COVID-19

Study Overview
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Brief Summary
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The specificity of the adaptive immune response (AIR), and its balance between effector T cells (Teffs) and regulatory T cells (Tregs), is most likely a major determinant of the outcome of a Covid-19 infection. We aim to analyze (i) the cellular components and (ii) the specificity of the AIR to COVID-19 in 60 patients with moderate and severe form of the disease. This should have important implications for (i) understanding the pathophysiology of the disease, (ii) discovering biomarkers of severity and (iii) designing treatments and vaccines.

Detailed Description
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The quality of the adaptive immune response (AIR) to COVID-19 probably determines the course of the disease. Therefore, a comprehensive knowledge of the immune response to COVID-19 is required to better anticipate its outcome and identify vaccine targets. In particular, the quality of an AIR can be investigated by immunophenotyping (enumerating immune cells and assessing their fitness) and by analyzing the T cell receptor (TCR) repertoire. The cellular components of the AIR will be analyzed by a deep immunophenotyping generating >800 measures assessing immune cells quantitatively and qualitatively (Pitoiset et al.,2018). Combined with supervised and unsupervised analyses, it has the power to detect subtle/hidden abnormalities. The specificity will be analyzed by studying the global T cell receptor (TCR) repertoire of separated Tregs and Teffs from peripheral blood, as well as by single cell sequencing of cells from bronchoalveolar lavages. These combined approaches should uncover parameters/abnormalities of the AIR linked to the infection severity and outcome, and lead to a better understanding of the nature of the Tregs and Teffs repertoires against COVID-19. This will have important implications for (i) understanding the pathophysiology of the disease, (ii) discovering biomarkers of severity and (iii) designing treatments and vaccines.

Official Title
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Effector and Regulatory T Cell Receptor Repertoire Analyses in Patients Affected by COVID-19

Conditions
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COVID-19

Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Age≥18 and ≤75 years Presenting a confirmed diagnosis of COVID-19 disease in accordance with WHO diagnostic criteria; Good venous capital ; Affiliation to a social security system; Having declared his/her non-opposition to participation in research (for patients hospitalized in intensive care units who are not able to communicate, the non-opposition of a trusted person will be sought.) Exclusion criteria : Still under the exclusion period from another biomedical study Psychiatric illness or addiction that could interfere with the ability to comply with the requirements of the protocol or to give consent to participate in the study; Patient benefiting from a legal protection measure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A list of COVID-19 specific TCR sequences |  | at day1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One or more measures from peripheral blood immunophenotyping that is/are associated with COVID-19 outcome |  | at day1 | 
| Group of COVID-19 specific TCR sequences that is associated with COVID-19 outcome |  | at day1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, T cell receptor, Effector T cells, Regulatory T cells, Single cell sequencing, Modelisation, Pathophysiology, Biomarkers