Thymic Function in Patients With COVID-19 (COVITHYM)

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Genetic: Single-Nucleotide Polymorphisms (SNP) within the TCRA/D region; Biological: Blood sample; Diagnostic test: CT Scan; Biological: Bronchial fibroscopy

• Study Type: Observational
• Enrollment (Actual): 85

Contacts and Locations

Study Locations

• France
  • Neuilly-sur-Seine, France, 92200
    • CMC Ambroise Paré

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

A total of 50 cases and 50 control subjects

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case : COVID-19 positive patients; patients hospitalized for COVID-19 infection	Genetic: Single-Nucleotide Polymorphisms (SNP) within the TCRA/D region; DNA extraction from blood samples, PCR and Sequencing; Biological: Blood sample; Dosage of sj/βTREC 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
Control : COVID-19 negative patients; patients hospitalized for other reasons	Biological: Blood sample; Dosage of sj/βTREC ratio, lymphocytes, cytokines and chemokines.; Diagnostic test: CT Scan; Thymus and lung imaging

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CMC Ambroise Paré

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2021
• Primary Completion (Actual): April 2, 2022
• Study Completion (Actual): April 2, 2022

Study Registration Dates

• First Submitted: January 16, 2021
• First Submitted That Met QC Criteria: January 16, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Covid19; Genetic polymorphism; Thymic function
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 2020/06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No