Effector and Regulatory T Cell Receptor Repertoire Analyses in Patients Affected by COVID-19 (CovRep)

The specificity of the adaptive immune response (AIR), and its balance between effector T cells (Teffs) and regulatory T cells (Tregs), is most likely a major determinant of the outcome of a Covid-19 infection.

We aim to analyze (i) the cellular components and (ii) the specificity of the AIR to COVID-19 in 60 patients with moderate and severe form of the disease. This should have important implications for (i) understanding the pathophysiology of the disease, (ii) discovering biomarkers of severity and (iii) designing treatments and vaccines.

Study Overview

• Status: Completed
• Conditions: COVID-19

Detailed Description

The quality of the adaptive immune response (AIR) to COVID-19 probably determines the course of the disease. Therefore, a comprehensive knowledge of the immune response to COVID-19 is required to better anticipate its outcome and identify vaccine targets. In particular, the quality of an AIR can be investigated by immunophenotyping (enumerating immune cells and assessing their fitness) and by analyzing the T cell receptor (TCR) repertoire.

The cellular components of the AIR will be analyzed by a deep immunophenotyping generating >800 measures assessing immune cells quantitatively and qualitatively (Pitoiset et al.,2018). Combined with supervised and unsupervised analyses, it has the power to detect subtle/hidden abnormalities.

The specificity will be analyzed by studying the global T cell receptor (TCR) repertoire of separated Tregs and Teffs from peripheral blood, as well as by single cell sequencing of cells from bronchoalveolar lavages.

These combined approaches should uncover parameters/abnormalities of the AIR linked to the infection severity and outcome, and lead to a better understanding of the nature of the Tregs and Teffs repertoires against COVID-19. This will have important implications for (i) understanding the pathophysiology of the disease, (ii) discovering biomarkers of severity and (iii) designing treatments and vaccines.

• Study Type: Observational
• Enrollment (Actual): 58

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Hôpital Pitie Salpétrère

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Men or women, aged 18 to 75, infected with SARS-CoV-2 and admitted to the Pitié-Salpêtrière hospital for treatment

Description

Inclusion criteria :

• Age≥18 and ≤75 years
• Presenting a confirmed diagnosis of COVID-19 disease in accordance with WHO diagnostic criteria;
• Good venous capital ;
• Affiliation to a social security system;
• Having declared his/her non-opposition to participation in research (for patients hospitalized in intensive care units who are not able to communicate, the non-opposition of a trusted person will be sought.)

Exclusion criteria :

• Still under the exclusion period from another biomedical study
• Psychiatric illness or addiction that could interfere with the ability to comply with the requirements of the protocol or to give consent to participate in the study;
• Patient benefiting from a legal protection measure

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
A list of COVID-19 specific TCR sequences	at day1

Secondary Outcome Measures

Outcome Measure	Time Frame
One or more measures from peripheral blood immunophenotyping that is/are associated with COVID-19 outcome	at day1
Group of COVID-19 specific TCR sequences that is associated with COVID-19 outcome	at day1

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: David KLATZMANN, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2020
• Primary Completion (Actual): January 27, 2021
• Study Completion (Actual): January 27, 2021

Study Registration Dates

• First Submitted: May 4, 2020
• First Submitted That Met QC Criteria: May 6, 2020
• First Posted (Actual): May 7, 2020

Study Record Updates

• Last Update Posted (Actual): June 13, 2022
• Last Update Submitted That Met QC Criteria: June 10, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; Biomarkers; Pathophysiology; Regulatory T cells; T cell receptor; Effector T cells; Single cell sequencing; Modelisation
• 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: APHP200544; 2020-A01245-34 (Other Identifier: IDRCB)

Drug and device information, study documents

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