Thymic Function in Patients With COVID-19

Covid19 Clinical Trial

— COVITHYM  

Official title:

Thymic Function in Patients With COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04716907
• Other study ID #: 2020/06
• Status: Completed
• Start date: March 19, 2021
• Est. completion date: April 2, 2022

Study information

• Verified date: April 2022
• Source: CMC Ambroise Paré
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: April 2, 2022
• Est. primary completion date: April 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Genetic:
• Single-Nucleotide Polymorphisms (SNP) within the TCRA/D region
DNA extraction from blood samples, PCR and Sequencing

Biological:
• Blood sample
Dosage of sj/ßTREC ratio, lymphocytes, cytokines and chemokines.

Diagnostic Test:
• CT Scan
Thymus and lung imaging

Biological:
• Bronchial fibroscopy
Bronchoalveolar lavage in mechanically ventilated patients for dosage of recent thymic emigrants in lungs

Locations

Country	Name	City	State
France	CMC Ambroise Paré	Neuilly-sur-Seine

Sponsors (1)

Lead Sponsor	Collaborator
CMC Ambroise Paré

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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/ßTREC ratio.	through study completion, average 1 year
Secondary	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
Secondary	Basal thymic function in COVID patients	Analysis of sj/ßTREC ratio during infection and away from infection (> 6 months).	through study completion, average 1 year
Secondary	Thymic function in COVID patients	Analysis of sj/ßTREC ratio in COVID positive patients and in COVID negative patients	through study completion, average 1 year
Secondary	Immune response in COVID patients	Analysis of lymphocytes in COVID positive patients and in COVID negative patients	through study completion, average 1 year
Secondary	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
Secondary	Inflammatory response in COVID patients	Analysis of serum concentrations of cytokines and chemokines in pg/ml (composite : IFNa, IFNß, IL-17A, IL17F, IL21, IL22, IL23, IL27, IL29, TSLP, GM-CSF, IL10, IL12p70, IL1ß, IL4, IL6, TNFa, VEGF, IL15, IL17E, IL33, IL8, MDC, Mip1a, Mip1ß, Mip3a, SDF1), in COVID positive patients and in COVID negative patients	through study completion, average 1 year