The SARS-CoV2 virus causes severe or even fatal disease in a fraction of infected people. The clinical severity is based on a complicated pneumopathy with acute respiratory distress syndrome that can lead to multi-visceral failure. The underlying mechanism is a cytokinergic storm, an emerging facet of immunological dysregulation. This clinical trial is aimed to understand the mechanisms of this immunological dysregulation in order to identify therapeutic levers. The main objective is to understand the relationships between clinical severity, death or morbidity of resuscitation management, and immune status (i.e., immune pathways activated or not). Immune status will be investigated at many levels of organization (i.e., circulating leukocytes, cytokines and chemokines, transcripts). The secondary objectives are : * to understand what is responsible for clinical severity, viral load, or immune activation; * to highlight the consequences of immunological dysregulation on associated risks (i.e., immunosuppression leading to the emergence of infectious comorbidities) as well as the functioning of neurotransmission through metabolic pathway diversions. The impact of dysimmunity on these biological pathways will be assessed with a metabolomic analysis; * to understand the mechanisms of vulnerability related to the field. Moreover, while co-morbidities are likely to be a risk factor for severe disease progression, there are many situations in which they do not occur. Stress, with its neurovegetative and endocrinological dimensions, modulates the immune response. It is essential to know whether the stress response plays a role in immunological dysregulation. This analysis is a prerequisite for understanding the conditions of treatment with glucocorticoids. Angiotensin converting enzyme type 2 (ACE2) also plays a likely role in host viral infection. It is also thought to play an important role in the emergence of severe syndromes by affecting the quality of vascular response.
Study Type
OBSERVATIONAL
Enrollment
100
Percy Military Teaching Hospital
Clamart, France
RECRUITINGBégin Military Teaching Hospital
Saint-Mandé, France
NOT_YET_RECRUITINGMortality
Mortality
Time frame: 90 days following the enrollment
Immune response - Plasma cytokine profile
Th1/Th2/Th17/Treg balance, Type I Interferons and inflammation
Time frame: Through study completion (90 days following the enrollment)
Immune response - Phenotype of circulating cells
T cells (CD3, CD4, CD8, PD1, FAS, CD45RO, CTLA4+, CXCR5, CXCR3, CCR6, CD69, CD95, HLA-DR) and B cells (CD3, CD19, CD27, IgD, CD69) with cell subtypes and memory/naive compartments (CD27, CD38, IgD, IgG1, IgG2, IgG3, CD20, CD24), NK cells (CD14, CD16, CD56, HLA-DR), monocytes (CD14, CD45, HLA-DR, PDL-1)
Time frame: Through study completion (90 days following the enrollment)
Severity criteria - Duration of stay in intensive care unit
Number of days in intensive care unit
Time frame: 90 days following the enrollment
Severity criteria - Duration of hospitalization stay
Number of days of hospitalization
Time frame: 90 days following the enrollment
Severity criteria - Duration of period out of hospital
Number of days out of hospital
Time frame: 90 days following the enrollment
Severity criteria - Duration without mechanical ventilation
Number of days without mechanical ventilation (invasive/non-invasive)
Time frame: 90 days following the enrollment
Severity criteria - Duration without ventilation
Number of days not being ventilated
Time frame: 90 days following the enrollment
Severity criteria - Duration without intubation
Number of days not being intubated
Time frame: 90 days following the enrollment
Severity criteria - Number of transfusions
Number of transfusions
Time frame: 90 days following the enrollment
Severity criteria - Duration of the period without cathecholamines
Number of days without cathecholamines
Time frame: 90 days following the enrollment
Severity criteria - Duration of the period without dialysis
Number of days without dialysis
Time frame: 90 days following the enrollment
Severity criteria - SOFA
Sepsis-related Organ Failure Assessment (SOFA) Score
Time frame: Through study completion (90 days following the enrollment)
Severity criteria - LIS
Lung Injury Score (LIS)
Time frame: Through study completion (90 days following the enrollment)
SARS-Cov2 viral load
SARS-Cov2 viral load will be measured in blood and in broncho-tracheal secretions
Time frame: Through study completion (90 days following the enrollment)
Emergence of concomitant infections
Co-infections and acquired infections (bacterial or fungal) in intensive care unit, in particular based on an all-site positive PCR for EBV and/or CMV and/or HSV
Time frame: 90 days following the enrollment
Emergence of concomitant infections - Phenotype of circulating cells
T cells (CD3, CD4, CD8, PD1, FAS, CD45RO, CTLA4+, CXCR5, CXCR3, CCR6, CD69, CD95, HLA-DR) and B cells (CD3, CD19, CD27, IgD, CD69) with cell subtypes and memory/naive compartments (CD27, CD38, IgD, IgG1, IgG2, IgG3, CD20, CD24), NK cells (CD14, CD16, CD56, HLA-DR), monocytes (CD14, CD45, HLA-DR, PDL-1)
Time frame: Through study completion (90 days following the enrollment)
Stress physiological profile - Sympathetic tone
Heart rate variability
Time frame: Through study completion (90 days following the enrollment)
Stress physiological profile - Temperature
Core temperature
Time frame: Through study completion (90 days following the enrollment)
Stress physiological profile - Glucocorticoids
Quantity of glucocorticoids in the urine during 24 hours and at night
Time frame: Through study completion (90 days following the enrollment)
Angiotensin converting enzyme type II (ACE2) polymorphism - ACE
ACE Polymorphism
Time frame: At enrollment
Angiotensin converting enzyme type II (ACE2) polymorphism - ACE2/ACE1
Protein expression of ACE2 vs. ACE1 and angiotensin II chain proteins
Time frame: At enrollment
Comorbidities - diabetes
Diabete diagnosis
Time frame: At enrollment
Comorbidities - Heart disease
Heart disease diagnosis
Time frame: At enrollment
Comorbidities - organ failure
Organ failure diagnosis
Time frame: At enrollment
Plasma concentrations of several metabolic pathways - GABA
GABA level in blood and urine
Time frame: Through study completion (90 days following the enrollment)
Plasma concentrations of several metabolic pathways - Glucocorticoid
Glucocorticoid level in blood and urine
Time frame: Through study completion (90 days following the enrollment)
Plasma concentrations of several metabolic pathways - Tryptophan
Tryptophan in blood and urine
Time frame: Through study completion (90 days following the enrollment)
Plasma concentrations of several metabolic pathways - Serotonin
Serotonin level in blood and urine
Time frame: Through study completion (90 days following the enrollment)
Plasma concentrations of several metabolic pathways - Dopamin
Dopamin level in blood and urine
Time frame: Through study completion (90 days following the enrollment)
Plasma concentrations of several metabolic pathways - Cathecholamines
Catecholamines level in blood and urine
Time frame: Through study completion (90 days following the enrollment)
Plasma concentrations of several metabolic pathways - Arachidonic acid derivatives
Arachidonic acid derivatives level in blood and urine
Time frame: Through study completion (90 days following the enrollment)
Plasma concentrations of several metabolic pathways - Endocannabinoids
Endocannabinoids level in blood and urine
Time frame: Through study completion (90 days following the enrollment)
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