Predictive Immune Biomarkers for COVID-19 Pathogenesis (COVIDBioToul)

Identification of Predictive Immune Biomarkers Based on the Understanding of COVID-19 Pathogenesis to Influence Therapeutic Management

The spectrum of the COVID-19 disease ranges from benign to asymptomatic to viral pneumopathy that can progress to acute respiratory distress syndrome (ARDS). The host-pathogen relationships and the physiopathological mechanisms underlying the clinical aggravation of COVID-19 patients remain misunderstood. The project aim is to create a prospective cohort of biological samples collected from well characterized COVID-19 patients. This project aims first to identify based on these samples an early immune signature predictive of clinical worsening of COVID-19 patients in order to improve their management, and secondarily to better understand pathophysiological mechanisms underlying the different phases of the disease in order to identify innovative therapeutic targets and vaccine perspectives.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Biological: Blood collection on admission and longitudinally; Biological: Blood collection on their first consultation and 10 to 14 days later

Detailed Description

The World Health Organization (WHO) has recently declared pandemic the coronavirus disease 2019 (COVID-19) due to the causative severe acute respiratory syndrome (SARS) coronavirus (CoV) 2 (SARS-CoV-2). People infected with SARS-CoV-2 vary in severity from being asymptomatic to having severe pneumonia and ARDS. Predictive markers of clinical worsening after admission are lacking. Clinical deterioration often coincides with the development of host antiviral immune responses, suggesting that the inflammatory response to SARS-CoV-2 infection may underpin COVID-19 pathogenesis leading to aberrant and excessive immune responses causing lung functional disability. Relevant therapeutic strategies are still under investigation. Based on a better understanding of COVID-19 immunopathogenesis, the identification of predictive biomarkers early in the disease process would be of outstanding interest to tailor prompt therapeutic interventions.

On this basis, the project aims to create a prospective cohort of biological samples collected from COVID-19 patients followed at the Toulouse University Hospital.

This cohort will collect and cryopreserve biological samples (33 mL), including plasma and peripheral blood mononuclear cells (PBMCs), on admission (day 0) and longitudinally (day 4, 8 12 and in discharge) and will allow us to investigate our primary and secondary objectives. This cohort will be bridged with a clinical cohort in order to have a very well-defined population of COVID-19 patients with the following outcomes:

• Patients with severe disease requiring on admission intensive care unit (ICU) management for ARDS,
• Non-severe hospitalized patients with secondary clinical worsening requiring ICU management,
• Non-severe hospitalized patients without clinical worsening requiring ICU management.

In addition, mildly symptomatic patients among healthcare workers attending outpatient dedicated clinics will be recruited and blood samples will be collected on their first consultation and 10 to 14 days later in the frame of a medical surveillance program.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31059
    • Purpan University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

For COVID-19 hospitalized patients

• Polymerase chain reaction (PCR) proven SARS-CoV-2 infection
• Participation to Toulouse clinical cohort
• Having signed consent for inclusion in the Toulouse biobanks

For COVID-19 healthcare workers attending dedicated clinics

• PCR proven SARS-CoV-2 infection
• Having signed consent for inclusion in the Toulouse biobanks

Exclusion Criteria:

• Pregnancy or breastfeeding
• Participation in another interventional clinical study involving exploratory treatment or blood sampling.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hospitalized patients; very well-defined population of COVID-19 patients with the following outcomes: Patients with severe disease requiring on admission ICU management for ARDS,; Non-severe hospitalized patients with secondary clinical worsening requiring ICU management,; Non-severe hospitalized patients without clinical worsening requiring ICU management.	Biological: Blood collection on admission and longitudinally; 33 mL of blood collected on admission (day 0) and longitudinally (day 4, 8 12 and in discharge)
Experimental: healthcare workers; mildly symptomatic patients among healthcare workers attending outpatient dedicated clinics will be recruited	Biological: Blood collection on their first consultation and 10 to 14 days later; 33 mL of blood collected on their first consultation and 10 to 14 days later

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune signature	Analysis of the phenotypic profiling of blood T-cells by multicolor fluorescence-activated cell sorter (FACS) analysis assessing T cell subsets through the expression of a wide range of surface and intracellular markers	Day 0
Dosage of cytokines and chemokines in plasma samples	Analysis on plasma samples of a wide range of cytokines and chemokines using multiplex	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune signature	Analysis of the phenotypic profiling of blood T-cells by multicolor FACS analysis assessing T cell subsets through the expression of a wide range of surface and intracellular markers	Day 2
Immune signature	Analysis of the phenotypic profiling of blood T-cells by multicolor FACS analysis assessing T cell subsets through the expression of a wide range of surface and intracellular markers	Day 4
Immune signature	Analysis of the phenotypic profiling of blood T-cells by multicolor FACS analysis assessing T cell subsets through the expression of a wide range of surface and intracellular markers	Day 8
Immune signature	Analysis of the phenotypic profiling of blood T-cells by multicolor FACS analysis assessing T cell subsets through the expression of a wide range of surface and intracellular markers	Day 12
Immune signature	Analysis of the phenotypic profiling of blood T-cells by multicolor FACS analysis assessing T cell subsets through the expression of a wide range of surface and intracellular markers	Day 30 (or in discharge)
Analysis of the early dynamics of SARS-CoV-2-specific humoral immunity	Measurement of SARS-CoV-2 specific Immunoglobulin M, Immunoglobulin G and Immunoglobulin	Day 0
Analysis of the early dynamics of SARS-CoV-2-specific humoral immunity	Measurement of SARS-CoV-2 specific Immunoglobulin M, Immunoglobulin G and Immunoglobulin	Day 2
Analysis of the early dynamics of SARS-CoV-2-specific humoral immunity	Measurement of SARS-CoV-2 specific Immunoglobulin M, Immunoglobulin G and Immunoglobulin	Day 4
Analysis of the early dynamics of SARS-CoV-2-specific humoral immunity	Measurement of SARS-CoV-2 specific Immunoglobulin M, Immunoglobulin G and Immunoglobulin	Day 8
Analysis of the early dynamics of SARS-CoV-2-specific humoral immunity	Measurement of SARS-CoV-2 specific Immunoglobulin M, Immunoglobulin G and Immunoglobulin	Day 12
Analysis of the early dynamics of SARS-CoV-2-specific humoral immunity	Measurement of SARS-CoV-2 specific Immunoglobulin M, Immunoglobulin G and Immunoglobulin	Day 30 (or in discharge)

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Guillaume MARTIN-BLONDEL, MD PhD, University Hospital, Toulouse

Publications and helpful links

General Publications

• Dimeglio C, Herin F, Da-Silva I, Gernigon C, Porcheron M, Chapuy-Regaud S, Izopet J. Decreased Efficiency of Neutralizing Antibodies from Previously Infected or Vaccinated Individuals against the B.1.617.2 (Delta) SARS-CoV-2 Variant. Microbiol Spectr. 2022 Aug 31;10(4):e0270621. doi: 10.1128/spectrum.02706-21. Epub 2022 Jul 5.
• Kreutmair S, Unger S, Nunez NG, Ingelfinger F, Alberti C, De Feo D, Krishnarajah S, Kauffmann M, Friebel E, Babaei S, Gaborit B, Lutz M, Jurado NP, Malek NP, Goepel S, Rosenberger P, Haberle HA, Ayoub I, Al-Hajj S, Nilsson J, Claassen M, Liblau R, Martin-Blondel G, Bitzer M, Roquilly A, Becher B. Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia. Immunity. 2021 Jul 13;54(7):1578-1593.e5. doi: 10.1016/j.immuni.2021.05.002. Epub 2021 May 9. Erratum In: Immunity. 2022 Feb 8;55(2):366-375.
• Dimeglio C, Herin F, Da-Silva I, Jougla I, Pradere C, Porcheron M, Martin-Blondel G, Chapuy-Regaud S, Izopet J. Heterologous ChAdOx1-S/BNT162b2 Vaccination: Neutralizing Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2022 Apr 9;74(7):1315-1316. doi: 10.1093/cid/ciab705. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2020
• Primary Completion (Actual): December 31, 2020
• Study Completion (Estimated): January 7, 2025

Study Registration Dates

• First Submitted: May 5, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (Actual): May 12, 2020

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 26, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; pathophysiology; predictive medicine; immune responses
• 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: RC31/20/0162

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