Immunological Profiling of Patients With COVID-19 in Respiratory Distress

Centre Hospitalier Universitaire de Nīmes120 enrolled

Overview

The study investigators hypothesize that the pneumonia arising in patients with COVID-19 is largely of immunopathological origin. The investigators will therefore seek to define the immune activation phenotype of patients in respiratory distress and to see if this immune signature is predictive of mortality. Finally, the investigators will look for overproduced inflammatory mediators to identify potential therapeutic targets.

SARS-CoV inhibits the viral detection systems and the signaling pathways of type I interferons (IFN-I). The weakness of the initial interferon response is predictive of the severity of future lung disease. The effectiveness of this escape strategy seems to allow these coronaviruses to replicate in the human body without triggering an effective innate immune response. This could explain the contagiousness of asymptomatic infected people. However, this initial replication causes a cytokine storm involving inflammatory cytokines. The intensity of this cytokine storm is correlated with the severity of COVID-19 cases. Pulmonary involvement, which is the main cause of death in SARS-CoV infections, has been attributed to local inflammation, with infiltration of CD8 + T cells, polymorphonuclear cells, monocytes and macrophages, infiltration proportional to the severity of respiratory failure as well as increased vascular permeability. SARS-CoV also induces T cell apoptosis. This pro-apoptotic effect could contribute to the lymphopenia observed in 37 to 63% of COVID-19 cases, which is predictive of severe forms. Thus the pulmonary involvement could be partly caused by immunopathological mechanisms. Immunological disturbances associated with respiratory failure need to be better defined. Recently, we measured a panel of soluble and membrane markers allowing to characterize T CD4 +, T CD8 +, B, monocytic, NK, endothelial activation as well as inflammation in a sample made up of 150 volunteers from a general population providing a control population. The study investigators aim to use this panel to define the immune activation state of patients infected with SARS-CoV-2 hospitalized for respiratory distress. In addition, the investigators will identify the soluble factors linked to the immune activation overproduced by the peripheral blood mononuclear cells (PBMC) of these patients. Finally, the investigators want to characterize the transcriptome of the main circulating immune sub-populations. These parameters will be compared with those of patients infected with SARS-CoV-2 hospitalized before experiencing respiratory distress.

Study Type

OBSERVATIONAL

Enrollment

120

Conditions

SARS-CoV-2 Covid-19

Interventions

Immunological profilingOTHER

The immune activation phenotype will be assessed using a standardized panel of soluble and membrane immune activation markers

Immunological profilingOTHER

The immune activation phenotype will be assessed using a standardized panel of soluble and membrane immune activation markers

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * The patient must be a member or beneficiary of a health insurance plan * Patient hospitalized in respiratory resuscitation or in the service of Infectious and Tropical Diseases of the CHU de Nîmes with infection by SARS-CoV-2, confirmed by RT-PCR or by an antigen test. Exclusion Criteria: * The subject is in a period of exclusion determined by a previous study * The patient is under safeguard of justice * Patient already under ventilation transferred from another center

Locations (1)

CHU de Nimes

Nîmes, France

Outcomes

Primary Outcomes

Membrane expression of Human Leukocyte Antigen -DR isotype compared to normal values (based on 150 healthy volunteers previously sampled)