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.
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
Percy Military Teaching Hospital
Clamart, France
Bégin Military Teaching Hospital
Saint-Mandé, France
Nicolas LIBERT, MD, PhD
141466772 - +33
nicolas.libert@intradef.gouv.fr