Thymic Function in Patients With COVID-19

Study Overview
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Brief Summary
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The main clinical manifestation associated with SARS-CoV-2 infection is an influenza-like illness that follows the infection of the respiratory tract. In a few percent of infected people, inflammation of the lungs leads to severe pneumonia that requires hospitalization, in intensive care units for the more severe cases. Despite intensive care, a fatal outcome occurs in 6% and 12% of women and men over 80 years of age hospitalized for severe COVID, respectively. Factors associated with a higher risk of death in patients with SARS-CoV-2 include age and low circulating lymphocyte counts. Significant lymphopenia is indeed frequently observed in patients with severe COVID-19 and both phenotypic and functional changes in antiviral T cells have been correlated with the severity of COVID-19. The thymus, the organ that produces T lymphocytes, undergoes progressive physiological involution with age. However, in the elderly, rare cases of thymic hyperplasia are reported in autoimmune diseases or cancers, or are observed in response to deep lymphopenia, whether or not associated with sepsis. This cohort of patients treated for a SARS-CoV-2 infection could allow to better understand the role of the thymus in this pathology.

Official Title
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Thymic Function in Patients With COVID-19

Conditions
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Covid19

Intervention / Treatment
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* Genetic: Single-Nucleotide Polymorphisms (SNP) within the TCRA/D region
* Biological: Blood sample
* Diagnostic Test: CT Scan
* Biological: Bronchial fibroscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cases : Patients with confirmed COVID-19 infection Hospitalized for COVID-19 infection Having signed a written informed consent form Affiliation to the social security system Controls : Non-COVID-19 patients Hospitalized for other reasons Age and sex-matched controls Having signed a written informed consent form, Affiliation to the social security system Exclusion Criteria: Autoimmune disease HIV, Hepatitis B or Hepatitis C Pregnant or breastfeeding women A mental or linguistic inability to understand the study Patient under protection of the adults (guardianship, curators or safeguard of justice)

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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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case : COVID-19 positive patients<br>patients hospitalized for COVID-19 infection | Genetic: Single-Nucleotide Polymorphisms (SNP) within the TCRA/D region<br>* DNA extraction from blood samples, PCR and Sequencing<br>Biological: Blood sample<br>* Dosage of sj/βTREC ratio, lymphocytes, cytokines and chemokines.<br>Diagnostic Test: CT Scan<br>* Thymus and lung imaging<br>Biological: Bronchial fibroscopy<br>* Bronchoalveolar lavage in mechanically ventilated patients for dosage of recent thymic emigrants in lungs<br>|
| Control : COVID-19 negative patients<br>patients hospitalized for other reasons | Biological: Blood sample<br>* Dosage of sj/βTREC ratio, lymphocytes, cytokines and chemokines.<br>Diagnostic Test: CT Scan<br>* Thymus and lung imaging<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic Predisposition to severe forms of COVID-19 | Test of association between single-nucleotide polymorphisms (SNP) within the TCRA/D region known to influence the level of thymopoiesis (Clave et al., Sci Transl Med., 2018) and CT scan classification of COVID-associated pneumopathy (0=Absent or minor pulmonary parenchymal changes ; 1=Limited ground-glass opacities ; 2=Bilateral ground-glass opacities < 50% of pulmonary parenchyma ; 3=Idem 2, with superimposed inter/intra lobular septal thickening, i.e. 'crazy paving' ; 4=Bilateral ground-glass opacities > 50% of pulmonary parenchyma ; 5=Idem 4, with superimposed 'crazy paving' ; 6=Idem 5, with pulmonary fibrosis). | through study completion, average 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic Predisposition to thymic enlargement observed during COVID-19 infection | Test of association between single-nucleotide polymorphisms (SNP) within the TCRA/D region known to influence the level of thymopoiesis (Clave et al., Sci Transl Med., 2018) and CT scan classification of thymus aspects (0=Fatty thymus atrophy (the most common in middle aged adults) ; A=Homogeneous non-fatty thymus (common in young adults) or Fat in the thymus area associated with micronodules or Moderate infiltration of the thymus area ; B=Hyperplasia, marked infiltration, micronodules or Hyperplasia with well-defined contours or Nodular hyperplasia without a tumour mass or Pseudo-tumoral mass with well-defined contours). | through study completion, average 1 year | 
| Genetic Predisposition to enhanced thymic function during COVID-19 infection | Test of association between single-nucleotide polymorphisms (SNP) within the TCRA/D region known to influence the level of thymopoiesis (Clave et al., Sci Transl Med., 2018) and sj/βTREC ratio. | through study completion, average 1 year | 
| Genetic Predisposition to severity of COVID-19 pathology | Test of association between single-nucleotide polymorphisms (SNP) within the TCRA/D region known to influence the level of thymopoiesis (Clave et al., Sci Transl Med., 2018) and ICU length of stay. | through study completion, average 1 year | 
| Basal thymic function in COVID patients | Analysis of sj/βTREC ratio during infection and away from infection (> 6 months). | through study completion, average 1 year | 
| Thymic function in COVID patients | Analysis of sj/βTREC ratio in COVID positive patients and in COVID negative patients | through study completion, average 1 year | 
| Immune response in COVID patients | Analysis of lymphocytes in COVID positive patients and in COVID negative patients | through study completion, average 1 year | 
| Immune response in lungs of COVID patients | Analysis of recent thymic emigrants in the bronchoalveolar fluid of COVID positive patients | through study completion, average 1 year | 
| Inflammatory response in COVID patients | Analysis of serum concentrations of cytokines and chemokines in pg/ml (composite : IFNα, IFNβ, IL-17A, IL17F, IL21, IL22, IL23, IL27, IL29, TSLP, GM-CSF, IL10, IL12p70, IL1β, IL4, IL6, TNFα, VEGF, IL15, IL17E, IL33, IL8, MDC, Mip1α, Mip1β, Mip3α, SDF1), in COVID positive patients and in COVID negative patients | through study completion, average 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid19, Thymic function, Genetic polymorphism