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.

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.

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.

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

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

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

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

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

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

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

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.

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