Predictive Immune Biomarkers of COVID-19 Pathogenesis to Influence Therapeutic Management

NCT04668170 | Completed DMC

• 1 other identifier: RC31/20/0187
• Study Type: observational
• Target: 304
• Locations: 1 country
• Sites: 2

Brief Summary

Persons infected with Severe Acute Respiratory Syndrome (SARS) SARS-CoV-2 vary in severity from being asymptomatic to having fever, cough, sore throat, general weakness and fatigue and muscular pain and in the most severe cases, severe pneumonia, acute respiratory distress syndrome and sepsis potentially leading to death. Predictive markers of clinical worsening after admission are lacking. COVID-19 immunopathogenesis and relevant therapeutic strategies are still under investigation. Although viral shedding peaks during the first week of symptoms, reports show that clinical deterioration often coincides with the development of host antiviral immune responses. The inflammatory response to SARS-CoV-2 infection may underpin COVID-19 pathogenesis leading to aberrant and excessive immune responses that may enter the pulmonary circulation in large numbers and play an immune damaging role causing lung functional disability resulting in clinical worsening. Therapeutic strategies using corticosteroids or biotherapies targeting IL-6 may be valuable in some patients. 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 these bases, the present project aims to unravel, using innovative integrated multimodal immunological approaches, immunologic predictive markers by finely characterizing from their admission innate and adaptive immune responses in two well described cohorts of COVID-19 patients that are being collected in Toulouse (COVID-BioToul) and Bordeaux (COLCOV-19 BX).Those two biological cohorts are connected with two clinical cohorts in Toulouse and Bordeaux in order to have a very well defined population of COVID-19 patients and their clinical outcome. In both cohorts, investigators harvest and cryopreserve biological samples, including plasma and peripheral blood mononuclear cells (PBMCs), on admission and longitudinally from patients evolving or not toward severe forms of the disease in Bordeaux and Toulouse University Hospitals and will allow to investigate primary and secondary objectives. Moreover in the two centers, there are also two clinical outpatients cohorts of healthcare workers attending dedicated clinics in the frame of their surveillance medical program, which constitute groups of patients with benign forms of COVID-19.

Conditions

COVID-19

Keywords

SARS-CoV-2; predictive medicine; pathophysiology; immune responses

Outcome Measures

Primary Outcomes (2)

• Immune signature on admission : phenotypic profile of blood T-cells

  Immune signature will be compared between COVID-19 patients according to their clinical characteristics and outcome, together with SARS-CoV2 viral shedding (known for every patient in the cohort) on samples harvested on admission: a phenotypic profiling of blood T-cells by multicolor FACS analysis (using 30+ color panels analyzed by multiparametric flow cytometry) assessing T cell subsets (classical CD4 or CD8 T-cells as well as unconventional gdT-cells and regulatory T cells) through the expression of a wide range of surface and intracellular markers.

  Day 0

• Immune signature on admission : inflammatory cytokines

  Immune signature will be compared between COVID-19 patients according to their clinical characteristics and outcome, together with SARS-CoV2 viral shedding (known for every patient in the cohort) on samples harvested on admission: An analysis on plasma samples of concentration of a wide range of inflammatory cytokines such as IFNa, IFNb and IL-6.

  Day 0

Secondary Outcomes (4)

• Dynamics of cellular immunity: CD4 and CD8 T cells

  Day 0, Day 4, Day 8, Day 12, Day 30 (or in discharge)

• Dynamics of cellular immunity: gd T cells

  Day 0, Day 4, Day 8, Day 12, Day 30 (or in discharge)

• Dynamics of cellular immunity: T cell transcriptomic analysis

  Day 0, Day 4, Day 8, Day 12, Day 30 (or in discharge)

• Dynamics of cellular immunity: humoral immunity

  Day 0, Day 4, Day 8, Day 12, Day 30 (or in discharge)

Study Arms (2)

hospitalized patients

very well-defined population of COVID-19 patients with the following outcomes: Patients with severe disease requiring on admission ICU management for SARS, 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

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

Interventions

Blood collection on admission and longitudinally BIOLOGICAL

Samples already collected on admission (day 0) and longitudinally (day 4, 8 12 and in discharge)

hospitalized patients

Blood collection on their first consultation and 10 to 14 days later BIOLOGICAL

Samples already collected on consultation (D0) and 14 days later

healthcare workers

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients hospitalized or healthy workers for COVID-19

You may qualify if:

• For COVID-19 hospitalized patients
• Polymerase chain reaction (PCR) proven SARS-CoV-2 infection
• Participation to Toulouse clinical cohort
• PCR proven SARS-CoV-2 infection

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (2)

University Hospital Bordeaux

Bordeau, 33000, France

Location

University Hospital Toulouse

Toulouse, 31059, France

Location

Related Publications (1)

• 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.

  PMID: 34051147 RESULT

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Pierre DELOBEL, MD PhD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: December 16, 2020
• Study Start: May 5, 2020
• Primary Completion: December 31, 2021
• Study Completion: May 2, 2023
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)