Covid19
Conditions
Keywords
Covid19, Thymic function, Genetic polymorphism
Brief summary
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.
Interventions
GENETICSingle-Nucleotide Polymorphisms (SNP) within the TCRA/D region
DNA extraction from blood samples, PCR and Sequencing
BIOLOGICALBlood sample
Dosage of sj/βTREC ratio, lymphocytes, cytokines and chemokines.
DIAGNOSTIC_TESTCT Scan
Thymus and lung imaging
BIOLOGICALBronchial fibroscopy
Bronchoalveolar lavage in mechanically ventilated patients for dosage of recent thymic emigrants in lungs
Sponsors
CMC Ambroise Paré
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Genetic Predisposition to severe forms of COVID-19 | through study completion, average 1 year | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Genetic Predisposition to thymic enlargement observed during COVID-19 infection | through study completion, average 1 year | 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). |
| Genetic Predisposition to enhanced thymic function during COVID-19 infection | through study completion, average 1 year | 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. |
| Genetic Predisposition to severity of COVID-19 pathology | through study completion, average 1 year | 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. |
| Basal thymic function in COVID patients | through study completion, average 1 year | Analysis of sj/βTREC ratio during infection and away from infection (\> 6 months). |
| Thymic function in COVID patients | through study completion, average 1 year | Analysis of sj/βTREC ratio in COVID positive patients and in COVID negative patients |
| Immune response in COVID patients | through study completion, average 1 year | Analysis of lymphocytes in COVID positive patients and in COVID negative patients |
| Immune response in lungs of COVID patients | through study completion, average 1 year | Analysis of recent thymic emigrants in the bronchoalveolar fluid of COVID positive patients |
| Inflammatory response in COVID patients | through study completion, average 1 year | 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 |
Countries
France
Outcome results
None listed