Immunological Profiling of Patients With COVID-19 in Respiratory Distress (ACTICOV-2)

Centre Hospitalier Universitaire de Nīmes

Status: Completed

Conditions: Covid-19; SARS-CoV-2

Treatments: Other: Immunological profiling

Study type: Observational

Funder types: Other

Identifiers

NCT04351711

2020-A00875-34 (Other Identifier)

NIMAO/2020-01/PC-01

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 120 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

120 participants in 6 patient groups

Patients SARS-CoV-2 with respiratory failure

Description:

Patients in intensive care

Treatment:

Other: Immunological profiling

Other: Immunological profiling

Patients SARS-CoV-2 without respiratory failure

Description:

Patients hospitalized in normal hospital wards

Treatment:

Other: Immunological profiling

Other: Immunological profiling

HEALTHY VOLUNTEERS

Description:

HEALTHY VOLUNTEERS

Treatment:

Other: Immunological profiling

Other: Immunological profiling

NON-COVID-19 PATIENTS

Description:

Patient hospitalized at the CHU of Nîmes for an infection by a virus other than SARS-CoV-2

Treatment:

Other: Immunological profiling

Other: Immunological profiling

PAUCISYMPTOMATIC SARS-COV-2+ PATIENTS

Description:

Patient positive for SARS-CoV-2 by RT-PCR at the CHU of Nîmes and presenting at most moderate clinical signs without respiratory insufficiency (O2 saturation greater than or equal to 96%) during the confinement period

Treatment:

Other: Immunological profiling

Other: Immunological profiling

convalescent patients

Description:

Additional 1-year follow-up visit

Treatment:

Other: Immunological profiling

Other: Immunological profiling