Predictive Immune Biomarkers of COVID-19 Pathogenesis to Influence Therapeutic Management
Condition: COVID-19
MeSH terms: COVID-19
Study type: Observational

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.
    

Detailed description: 
      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.
    

Intervention name(s): Blood collection on admission and longitudinally; Blood collection on their first consultation and 10 to 14 days later
Intervention type(s): Biological; Biological
Intervention description(s): Samples already collected on admission (day 0) and longitudinally (day 4, 8 12 and in discharge); Samples already collected on consultation (D0) and 14 days later
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Patients hospitalized or healthy workers for COVID-19
      
Keywords: SARS-CoV-2; predictive medicine; pathophysiology; immune responses