Clinical trial NCT04365166: Study of Clinical and Immune Severity Profiles of Patients Infected With SARS-Cov2 (COVID-19)
Official title: Study of Clinical and Immune Severity Profiles of Patients Infected With SARS-Cov2
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Respiratory Tract Infections
Respiratory Tract Disease
Lead sponsor: Direction Centrale du Service de Santé des Armées
Sponsor class: OTHER
First posted: 2020-04-28
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The target population is a population infected with SARS-CoV2 and justifying hospitalisation in an intensive care unit, i.e. presenting at least one immediate vital failure that would lead in short term to the death of the patient without the implementation of an adapted active therapeutic intervention. As the variable of interest is immuno-inflammatory activation, patients with an immune deficiency of any origin will be excluded. Patients will be recruited from patients admitted to the intensive care unit with biological confirmation of SARS-Cov2 infection.

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Patient admitted to intensive care unit with confirmed SARS-CoV2 infection
* Patient older than 18 years old

Exclusion Criteria:

* Patient coming from another intensive care unit after more than 5 days in the intensive care unit
* Known immunosuppression:

  * Known or suspected HIV
  * Known or suspected immunosuppression :
  * Organ transplantation
  * Marrow transplant
  * Congenital deficit
  * Received immunosuppressive therapy within 30 days (azathioprine, methotrexate, tacrolimus, cyclosporine, sirolimus, cyclophosphamide, rituximab, anti-TNF, JAK inhibitors, corticosteroids \>10mg/day over the last 30 days, recent covid-19 corticosteroid therapy \>1mg/kg prednisolone or equivalent \>5 days)
  * Administration of chemotherapy within the last 3 months
* Current pregnancy or breastfeeding
* Patient under 18 years of age
* Incapacitated adults and persons deprived of their liberty
* Refusal by the patient or his/her support person

Primary outcomes:
measure: Mortality
timeFrame: 90 days following the enrollment
measure: Immune response - Plasma cytokine profile
timeFrame: Through study completion (90 days following the enrollment)
measure: Immune response - Phenotype of circulating cells
timeFrame: Through study completion (90 days following the enrollment)
Secondary outcomes:
measure: Severity criteria - Duration of stay in intensive care unit
timeFrame: 90 days following the enrollment
measure: Severity criteria - Duration of hospitalization stay
timeFrame: 90 days following the enrollment
measure: Severity criteria - Duration of period out of hospital
timeFrame: 90 days following the enrollment
measure: Severity criteria - Duration without mechanical ventilation
timeFrame: 90 days following the enrollment
measure: Severity criteria - Duration without ventilation
timeFrame: 90 days following the enrollment
measure: Severity criteria - Duration without intubation
timeFrame: 90 days following the enrollment
measure: Severity criteria - Number of transfusions
timeFrame: 90 days following the enrollment
measure: Severity criteria - Duration of the period without cathecholamines
timeFrame: 90 days following the enrollment
measure: Severity criteria - Duration of the period without dialysis
timeFrame: 90 days following the enrollment
measure: Severity criteria - SOFA
timeFrame: Through study completion (90 days following the enrollment)
measure: Severity criteria - LIS
timeFrame: Through study completion (90 days following the enrollment)
measure: SARS-Cov2 viral load
timeFrame: Through study completion (90 days following the enrollment)
measure: Emergence of concomitant infections
timeFrame: 90 days following the enrollment
measure: Emergence of concomitant infections - Phenotype of circulating cells
timeFrame: Through study completion (90 days following the enrollment)
measure: Stress physiological profile - Sympathetic tone
timeFrame: Through study completion (90 days following the enrollment)
measure: Stress physiological profile - Temperature
timeFrame: Through study completion (90 days following the enrollment)
measure: Stress physiological profile - Glucocorticoids
timeFrame: Through study completion (90 days following the enrollment)
measure: Angiotensin converting enzyme type II (ACE2) polymorphism - ACE
timeFrame: At enrollment
measure: Angiotensin converting enzyme type II (ACE2) polymorphism - ACE2/ACE1
timeFrame: At enrollment
measure: Comorbidities - diabetes
timeFrame: At enrollment
measure: Comorbidities - Heart disease
timeFrame: At enrollment
measure: Comorbidities - organ failure
timeFrame: At enrollment
measure: Plasma concentrations of several metabolic pathways - GABA
timeFrame: Through study completion (90 days following the enrollment)
measure: Plasma concentrations of several metabolic pathways - Glucocorticoid
timeFrame: Through study completion (90 days following the enrollment)
measure: Plasma concentrations of several metabolic pathways - Tryptophan
timeFrame: Through study completion (90 days following the enrollment)
measure: Plasma concentrations of several metabolic pathways - Serotonin
timeFrame: Through study completion (90 days following the enrollment)
measure: Plasma concentrations of several metabolic pathways - Dopamin
timeFrame: Through study completion (90 days following the enrollment)
measure: Plasma concentrations of several metabolic pathways - Cathecholamines
timeFrame: Through study completion (90 days following the enrollment)
measure: Plasma concentrations of several metabolic pathways - Arachidonic acid derivatives
timeFrame: Through study completion (90 days following the enrollment)
measure: Plasma concentrations of several metabolic pathways - Endocannabinoids
timeFrame: Through study completion (90 days following the enrollment)
Other outcomes:
Locations:
city: Clamart
country: France
facility: Percy Military Teaching Hospital
city: Saint-Mandé
country: France
facility: Bégin Military Teaching Hospital
Study officials:
References: