REACOVIM: Study of Clinical and Immune Severity Profiles of Patients Infected With SARS-Cov2 (COVID-19)

Sponsor

Direction Centrale du Service de Santé des Armées (Other)

Overall Status

Recruiting

CT.gov ID

NCT04365166

Collaborator

(none)

100

Enrollment

Locations

Anticipated Duration (Months)

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Tract Infections Respiratory Tract Disease

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

Study of Clinical and Immune Severity Profiles of Patients Infected With SARS-Cov2

Actual Study Start Date :

Apr 21, 2020

Anticipated Primary Completion Date :

Apr 21, 2022

Anticipated Study Completion Date :

Apr 21, 2022

Outcome Measures

Primary Outcome Measures

Mortality [90 days following the enrollment]
Mortality
Immune response - Plasma cytokine profile [Through study completion (90 days following the enrollment)]
Th1/Th2/Th17/Treg balance, Type I Interferons and inflammation
Immune response - Phenotype of circulating cells [Through study completion (90 days following the enrollment)]
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)

Secondary Outcome Measures

Severity criteria - Duration of stay in intensive care unit [90 days following the enrollment]
Number of days in intensive care unit
Severity criteria - Duration of hospitalization stay [90 days following the enrollment]
Number of days of hospitalization
Severity criteria - Duration of period out of hospital [90 days following the enrollment]
Number of days out of hospital
Severity criteria - Duration without mechanical ventilation [90 days following the enrollment]
Number of days without mechanical ventilation (invasive/non-invasive)
Severity criteria - Duration without ventilation [90 days following the enrollment]
Number of days not being ventilated
Severity criteria - Duration without intubation [90 days following the enrollment]
Number of days not being intubated
Severity criteria - Number of transfusions [90 days following the enrollment]
Number of transfusions
Severity criteria - Duration of the period without cathecholamines [90 days following the enrollment]
Number of days without cathecholamines
Severity criteria - Duration of the period without dialysis [90 days following the enrollment]
Number of days without dialysis
Severity criteria - SOFA [Through study completion (90 days following the enrollment)]
Sepsis-related Organ Failure Assessment (SOFA) Score
Severity criteria - LIS [Through study completion (90 days following the enrollment)]
Lung Injury Score (LIS)
SARS-Cov2 viral load [Through study completion (90 days following the enrollment)]
SARS-Cov2 viral load will be measured in blood and in broncho-tracheal secretions
Emergence of concomitant infections [90 days following the enrollment]
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
Emergence of concomitant infections - Phenotype of circulating cells [Through study completion (90 days following the enrollment)]
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)
Stress physiological profile - Sympathetic tone [Through study completion (90 days following the enrollment)]
Heart rate variability
Stress physiological profile - Temperature [Through study completion (90 days following the enrollment)]
Core temperature
Stress physiological profile - Glucocorticoids [Through study completion (90 days following the enrollment)]
Quantity of glucocorticoids in the urine during 24 hours and at night
Angiotensin converting enzyme type II (ACE2) polymorphism - ACE [At enrollment]
ACE Polymorphism
Angiotensin converting enzyme type II (ACE2) polymorphism - ACE2/ACE1 [At enrollment]
Protein expression of ACE2 vs. ACE1 and angiotensin II chain proteins
Comorbidities - diabetes [At enrollment]
Diabete diagnosis
Comorbidities - Heart disease [At enrollment]
Heart disease diagnosis
Comorbidities - organ failure [At enrollment]
Organ failure diagnosis
Plasma concentrations of several metabolic pathways - GABA [Through study completion (90 days following the enrollment)]
GABA level in blood and urine
Plasma concentrations of several metabolic pathways - Glucocorticoid [Through study completion (90 days following the enrollment)]
Glucocorticoid level in blood and urine
Plasma concentrations of several metabolic pathways - Tryptophan [Through study completion (90 days following the enrollment)]
Tryptophan in blood and urine
Plasma concentrations of several metabolic pathways - Serotonin [Through study completion (90 days following the enrollment)]
Serotonin level in blood and urine
Plasma concentrations of several metabolic pathways - Dopamin [Through study completion (90 days following the enrollment)]
Dopamin level in blood and urine
Plasma concentrations of several metabolic pathways - Cathecholamines [Through study completion (90 days following the enrollment)]
Catecholamines level in blood and urine
Plasma concentrations of several metabolic pathways - Arachidonic acid derivatives [Through study completion (90 days following the enrollment)]
Arachidonic acid derivatives level in blood and urine
Plasma concentrations of several metabolic pathways - Endocannabinoids [Through study completion (90 days following the enrollment)]
Endocannabinoids level in blood and urine

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Percy Military Teaching Hospital	Clamart		France	92140
2	Bégin Military Teaching Hospital	Saint-Mandé		France	94163

Sponsors and Collaborators

Direction Centrale du Service de Santé des Armées

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Direction Centrale du Service de Santé des Armées

ClinicalTrials.gov Identifier:

NCT04365166

Other Study ID Numbers:

2020-COVID19-05
2020-A00898-31

First Posted:

Apr 28, 2020

Last Update Posted:

Mar 9, 2021

Last Verified:

Mar 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Respiratory Tract Infections

Respiratory Tract Diseases

Study Results

No Results Posted as of Mar 9, 2021