Thymic Function in Patients With COVID-19

Completed

• Conditions: Covid19
• Interventions: Genetic: Single-Nucleotide Polymorphisms (SNP) within the TCRA/D region; Biological: Blood sample; Diagnostic Test: CT Scan; Biological: Bronchial fibroscopy

• Registration Number: NCT04716907
• Lead Sponsor: CMC Ambroise Paré

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-16
• Study First Submitted QC: 2021-01-16
• Study First Posted: 2021-01-20
• Study Start: 2021-03-19
• Status Verified: 2022-04
• Primary Completion: 2022-04-02
• Study Completion: 2022-04-02
• Last Update Submitted: 2022-04-05
• Last Update Posted: 2022-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 85

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control : COVID-19 negative patients	CT Scan	patients hospitalized for other reasons
Case : COVID-19 positive patients	Single-Nucleotide Polymorphisms (SNP) within the TCRA/D region	patients hospitalized for COVID-19 infection
Control : COVID-19 negative patients	Blood sample	patients hospitalized for other reasons
Case : COVID-19 positive patients	Blood sample	patients hospitalized for COVID-19 infection
Case : COVID-19 positive patients	CT Scan	patients hospitalized for COVID-19 infection
Case : COVID-19 positive patients	Bronchial fibroscopy	patients hospitalized for COVID-19 infection

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

CMC Ambroise Paré; 🇫🇷 Neuilly-sur-Seine, France