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

NCT ID: NCT04668170

Last Updated: 2024-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

304 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-05-05

Study Completion Date

2023-05-02

Brief Summary

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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.

Detailed Description

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The primary objective of IMMUNOMARK-COV is to define an applicable immune signature predicting clinical worsening on COVID-19 patient admission in order to help physicians to take informed therapeutic decisions able to modify early the course of the disease.

Secondary objectives are:

* To assess the early dynamics of SARS-CoV-2-specific cellular immunity in patients followed longitudinally
* To assess the dynamics of gd T cells during COVID-19
* Transcriptomic analysis of discrete and functionally major T cell populations
* To assess SARS-CoV-2-specific humoral immunity in patients upon recovery

Identification of early predictive biomarkers of worsening of COVID-19 patients is of paramount importance. This goal is expected to be achieved through the fine analysis of circulating immune effectors, and their dynamics, in categories of patients with very different clinical outcomes.

To date, management of clinical worsening relies mainly on supportive care in ICU, leading to prolonged stay and saturation of facilities. Earlier therapeutic intervention based on identification of robust predictive biomarkers should:

* Help physicians to take therapeutic decisions
* Improve prognosis of patients that suffered from clinical worsening
* Prevent clinical worsening and transfer to ICU
* Improve the burden relying on ICU facilities in a setting of overflow
* Improve the prevention and management of COVID-19 patients to be able to face in a near future several other waves of COVID-19 Furthermore, identification of immune effectors implicated in tissular damages may also help to identify new therapeutic targets.

Conditions

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COVID-19

Keywords

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SARS-CoV-2 predictive medicine pathophysiology immune responses

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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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.

Blood collection on admission and longitudinally

Intervention Type BIOLOGICAL

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

healthcare workers

mildly symptomatic patients among healthcare workers attending outpatient dedicated clinics will be recruited

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

Intervention Type BIOLOGICAL

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

Interventions

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Blood collection on admission and longitudinally

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

Intervention Type BIOLOGICAL

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

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

110 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Toulouse

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pierre DELOBEL, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

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University Hospital Bordeaux

Bordeau, , France

Site Status

University Hospital Toulouse

Toulouse, , France

Site Status

Countries

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France

Other Identifiers

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RC31/20/0187

Identifier Type: -

Identifier Source: org_study_id