SARS-CoV-2ACTICOV-2NCT04351711
Immunological Profiling of Patients With COVID-19 in Respiratory Distress
An observational study of SARS-CoV-2 and Covid-19, run by Centre Hospitalier Universitaire de Nīmes at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- SARS-CoV-2, Covid-19
- What is being tested?
- Immunological profiling
- How many people
- 120 participants
- Where
- 1 siteFrance
- Study dates
- 9 Apr 2020to 12 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients in intensive care or normal hospitalization at the CHU de Nîmes for SARS-CoV-2 infection, confirmed by PT-PCR or by an antigen test Healthy Volunteers
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed 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.
- Conditions
- SARS-CoV-2, Covid-19
- Being tested
- Immunological profiling
- Keywords
- respiratory failure
- Medical subject headings
- COVID-19, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immunological profilingOther
The immune activation phenotype will be assessed using a standardized panel of soluble and membrane immune activation markers
Immunological profilingOther
Also called Additional 1-year follow-up visit for 30 convalescent patients
The immune activation phenotype will be assessed using a standardized panel of soluble and membrane immune activation markers
| Study group | Role | What they receive |
|---|---|---|
| Patients SARS-CoV-2 with respiratory failure | Patients in intensive care Receives: Other: Immunological profiling | |
| Patients SARS-CoV-2 without respiratory failure | Patients hospitalized in normal hospital wards Receives: Other: Immunological profiling | |
| HEALTHY VOLUNTEERS | HEALTHY VOLUNTEERS Receives: Other: Immunological profiling | |
| NON-COVID-19 PATIENTS | Patient hospitalized at the CHU of Nîmes for an infection by a virus other than SARS-CoV-2 Receives: Other: Immunological profiling | |
| PAUCISYMPTOMATIC SARS-COV-2+ PATIENTS | 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 Receives: Other: Immunological profiling | |
| convalescent patients | Additional 1-year follow-up visit Receives: Other: Immunological profiling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Membrane expression of Human Leukocyte Antigen -DR isotype compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Membrane expression of cluster of differentiation 38 compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Membrane expression of Programmed cell death 1 protein compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Membrane expression of cluster of differentiation 45RA compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry
Measured: Day 0
Membrane expression of cluster of differentiation 27 (naïve/central memory/effector memory) compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Membrane expression of CD57 on T CD4+ and T CD8+ cells compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Membrane expression of cluster of differentiation 27 on T CD4+ and T CD8+ cells compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Membrane expression of cluster of differentiation 28 on T CD4+ and T CD8+ cells compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Membrane expression of Human Leukocyte Antigen -DR isotype on Naturel Killer cells compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Membrane expression of cluster of differentiation 69 on Naturel Killer cells compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Membrane expression of cluster of differentiation 56 on Naturel Killer cells compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Membrane expression of cluster of differentiation 57 on Naturel Killer cells compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Membrane expression of cluster of differentiation 14 on Naturel Killer cells compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Membrane expression of cluster of differentiation 16 on Naturel Killer cells compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Number of regulatory T cells (CD4+CD25hiCD127loFoxP3+).
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Percentage of regulatory T cells (CD4+CD25hiCD127loFoxP3+).
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Immunoglobulin A compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Immunoglobulin G compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Immunoglobulin M compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Soluble cluster of differentiation 14 compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Soluble cluster of differentiation 163 compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Ultrasensitive C-Reactive Protein compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Soluble tumor necrosis factor alpha receptor type I compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating E-selectin (cluster of differentiation 62E) compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Granulocyte Macrophage Colony-Stimulating Factor compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry
Measured: Day 0
Rate of circulating InterCellular Adhesion Molecule-1 compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Interferon alpha compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Interferon beta compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Interferon gamma compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Interleukin-1 alpha compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Interleukin-1 beta compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Interleukin-4 compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Interleukin-6 compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Interleukin-8 compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Interleukin-10 compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Interleukin-12p70 compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry
Measured: Day 0
Rate of circulating Interleukin-13 compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Interleukin-17A compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Induced Protein 10 (C-X-C motif chemokine 10) compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Monocyte Chemoattractant Protein-1 (C-C Motif Chemokine Ligand 2) compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Macrophage inflammatory protein-1 alpha (C-C Motif Chemokine Ligand 3) compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating Macrophage inflammatory protein-1 beta (C-C Motif Chemokine Ligand 4) compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of circulating P-selectin compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of tumor necrosis factor alpha compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of tissue plasminogen activator compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of soluble form of endothelial protein C receptor compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Rate of D-Dimers compared to normal values (based on 150 healthy volunteers previously sampled)
Quantified by flow cytometry; % variation / normal values
Measured: Day 0
Secondary outcomes (31)
Compare the immune activation phenotype (defined in primary outcome) of patients affected by COVID-19 before any respiratory distress against that of 150 volunteers from the general population (data already existing).
Difference in expression of the biomarkers assayed for primary outcome
Measured: Day 0
Compare the immune activation phenotype (defined in primary outcome) of patients affected by COVID-19 with respiratory failure against versus those without respiratory failure
Difference in expression of the biomarkers assayed for primary outcome
Measured: Day 0
Mortality rate
Mortality
Measured: End of study (2021)
Comparison of E-selectin levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Granulocyte Macrophage Colony-Stimulating Factor levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of InterCellular Adhesion Molecule levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Interferon alpha levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Interferon gamma levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Interleukin-1alpha levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Interleukin-1beta levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Interleukin-4 levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Interleukin-6 levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Interleukin-8 (C-X-C motif ligand 8) levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Interleukin-10 levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Interleukin-12p70 levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Interleukin-13 levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Interleukin-17A levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Induced Protein -10 (C-X-C motif chemokine 10) levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Monocyte Chemoattractant Protein-1 levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Macrophage Inflammatory Protein-1alpha levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Macrophage Inflammatory Protein -1beta levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of P-Selectin levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Comparison of Tumor necrosis factor alpha levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
quantified by Luminex (TruCulture tube system (Myriad RBM))
Measured: Day 0
Identify inflammatory mediators over-produced by the PBMC of patients with COVID-19 before respiratory distress
Difference in expression of the 20 inflammatory markers described in outcomes 51-70
Measured: Day 0
Compare the inflammatory mediators over-produced by the peripheral blood mononuclear cells of patients with COVID-19 with versus without respiratory failure
Difference in expression of the 20 inflammatory markers described in outcomes 51-70
Measured: Day 0
Comparison of transcriptome from peripheral blood mononuclear cells from 12 patients with respiratory failure (from intensive care ward) and 10 without (normal hospitalization)
Performed at the Institut de Génétique Humaine (Montpellier)
Measured: Day 0
To evaluate whether lymphocyte apoptosis measured in the acute phase is predictive of residual specific Ac levels and B and T immune memory one year later.
Lymphocyte caspase activity
Measured: 1 year
o evaluate whether lymphocyte apoptosis measured in the acute phase is predictive of residual specific Ac levels and B and T immune memory one year later.
circulating FasL level
Measured: 1 year
o evaluate whether lymphocyte apoptosis measured in the acute phase is predictive of residual specific Ac levels and B and T immune memory one year later.
expression of phosphatidylserine on the surface of lymphocytes in the acute phase
Measured: 1 year
o evaluate whether lymphocyte apoptosis measured in the acute phase is predictive of residual specific Ac levels and B and T immune memory one year later.
levels of Ac
Measured: 1 year
o evaluate whether lymphocyte apoptosis measured in the acute phase is predictive of residual specific Ac levels and B and T immune memory one year later.
plasmablasts and specific T cells
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2020
- Study start9 Apr 2020
- Primary completion12 Dec 2022
- Study completion12 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SARS-CoV-2Studies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NīmesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nīmes
- Sponsor type
- University, hospital or other
- Collaborators
- Institute of Human Genetics, Montpellier
- Responsible party
- Sponsor
- Investigators
- Pierre Corbeau, Principal investigator, CHU Nimes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04351711
- Sponsor's protocol ID
- NIMAO/2020-01/PC-01
- Other IDs
- 2020-A00875-34
- Acronym
- ACTICOV-2
- Status last verified
- Dec 2025
- First submitted
- 10 Apr 2020
- Last updated
- 10 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Andre S, Picard M, Cezar R, Roux-Dalvai F, Alleaume-Butaux A, Soundaramourty C, Cruz AS, Mendes-Frias A, Gotti C, Leclercq M, Nicolas A, Tauzin A, Carvalho A, Capela C, Pedrosa J, Castro AG, Kundura L, Loubet P, Sotto A, Muller L, Lefrant JY, Roger C, Claret PG, Duvnjak S, Tran TA, Racine G, Zghidi-Abouzid O, Nioche P, Silvestre R, Droit A, Mammano F, Corbeau P, Estaquier J. T cell apoptosis characterizes severe Covid-19 disease. Cell Death Differ. 2022 Aug;29(8):1486-1499. doi: 10.1038/s41418-022-00936-x. Epub 2022 Jan 22.
PubMed 35066575
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunological Profiling of Patients With COVID-19 in Respiratory Distress
- ClinicalTrials.gov ID
- NCT04351711
- Acronym / sponsor ID
- ACTICOV-2 / NIMAO/2020-01/PC-01
- Conditions
- SARS-CoV-2, Covid-19
- Keywords
- respiratory failure
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NīmesUniversity, hospital or other
- Collaborators
- Institute of Human Genetics, Montpellier
- Study start
- 9 Apr 2020 (actual)
- Primary completion
- 12 Dec 2022 (actual)
- Study completion
- 12 Dec 2022 (actual)
- First posted
- 17 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Patients SARS-CoV-2 with respiratory failure | – | Other: Immunological profilingPatients in intensive care |
| Patients SARS-CoV-2 without respiratory failure | – | Other: Immunological profilingPatients hospitalized in normal hospital wards |
| HEALTHY VOLUNTEERS | – | Other: Immunological profilingHEALTHY VOLUNTEERS |
| NON-COVID-19 PATIENTS | – | Other: Immunological profilingPatient hospitalized at the CHU of Nîmes for an infection by a virus other than SARS-CoV-2 |
| PAUCISYMPTOMATIC SARS-COV-2+ PATIENTS | – | Other: Immunological profilingPatient 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 |
| convalescent patients | – | Other: Immunological profilingAdditional 1-year follow-up visit |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients in intensive care or normal hospitalization at the CHU de Nîmes for SARS-CoV-2 infection, confirmed by PT-PCR or by an antigen test Healthy Volunteers
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Immunological profilingThe immune activation phenotype will be assessed using a standardized panel of soluble and membrane immune activation markers | Other | HEALTHY VOLUNTEERS, NON-COVID-19 PATIENTS, PAUCISYMPTOMATIC SARS-COV-2+ PATIENTS, Patients SARS-CoV-2 with respiratory failure, Patients SARS-CoV-2 without respiratory failure, convalescent patients |
| Immunological profilingAlso: Additional 1-year follow-up visit for 30 convalescent patientsThe immune activation phenotype will be assessed using a standardized panel of soluble and membrane immune activation markers | Other | convalescent patients |
Primary outcome
Membrane expression of Human Leukocyte Antigen -DR isotype compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Membrane expression of cluster of differentiation 38 compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Membrane expression of Programmed cell death 1 protein compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Membrane expression of cluster of differentiation 45RA compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry
Membrane expression of cluster of differentiation 27 (naïve/central memory/effector memory) compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Membrane expression of CD57 on T CD4+ and T CD8+ cells compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Membrane expression of cluster of differentiation 27 on T CD4+ and T CD8+ cells compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Membrane expression of cluster of differentiation 28 on T CD4+ and T CD8+ cells compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Membrane expression of Human Leukocyte Antigen -DR isotype on Naturel Killer cells compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Membrane expression of cluster of differentiation 69 on Naturel Killer cells compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Membrane expression of cluster of differentiation 56 on Naturel Killer cells compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Membrane expression of cluster of differentiation 57 on Naturel Killer cells compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Membrane expression of cluster of differentiation 14 on Naturel Killer cells compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Membrane expression of cluster of differentiation 16 on Naturel Killer cells compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Number of regulatory T cells (CD4+CD25hiCD127loFoxP3+).
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Percentage of regulatory T cells (CD4+CD25hiCD127loFoxP3+).
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Immunoglobulin A compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Immunoglobulin G compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Immunoglobulin M compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Soluble cluster of differentiation 14 compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Soluble cluster of differentiation 163 compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Ultrasensitive C-Reactive Protein compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Soluble tumor necrosis factor alpha receptor type I compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating E-selectin (cluster of differentiation 62E) compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Granulocyte Macrophage Colony-Stimulating Factor compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry
Rate of circulating InterCellular Adhesion Molecule-1 compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Interferon alpha compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Interferon beta compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Interferon gamma compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Interleukin-1 alpha compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Interleukin-1 beta compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Interleukin-4 compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Interleukin-6 compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Interleukin-8 compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Interleukin-10 compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Interleukin-12p70 compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry
Rate of circulating Interleukin-13 compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Interleukin-17A compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Induced Protein 10 (C-X-C motif chemokine 10) compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Monocyte Chemoattractant Protein-1 (C-C Motif Chemokine Ligand 2) compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Macrophage inflammatory protein-1 alpha (C-C Motif Chemokine Ligand 3) compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating Macrophage inflammatory protein-1 beta (C-C Motif Chemokine Ligand 4) compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of circulating P-selectin compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of tumor necrosis factor alpha compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of tissue plasminogen activator compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of soluble form of endothelial protein C receptor compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
Rate of D-Dimers compared to normal values (based on 150 healthy volunteers previously sampled)
Time frame: Day 0
Quantified by flow cytometry; % variation / normal values
31 secondary outcomes
Compare the immune activation phenotype (defined in primary outcome) of patients affected by COVID-19 before any respiratory distress against that of 150 volunteers from the general population (data already existing).
Time frame: Day 0
Compare the immune activation phenotype (defined in primary outcome) of patients affected by COVID-19 with respiratory failure against versus those without respiratory failure
Time frame: Day 0
Mortality rate
Time frame: End of study (2021)
Comparison of E-selectin levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Granulocyte Macrophage Colony-Stimulating Factor levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of InterCellular Adhesion Molecule levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Interferon alpha levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Interferon gamma levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Interleukin-1alpha levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Interleukin-1beta levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Interleukin-4 levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Interleukin-6 levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Interleukin-8 (C-X-C motif ligand 8) levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Interleukin-10 levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Interleukin-12p70 levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Interleukin-13 levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Interleukin-17A levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Induced Protein -10 (C-X-C motif chemokine 10) levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Monocyte Chemoattractant Protein-1 levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Macrophage Inflammatory Protein-1alpha levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Macrophage Inflammatory Protein -1beta levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of P-Selectin levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Comparison of Tumor necrosis factor alpha levels from plasma and the supernatant of PBMC activated or not by lipopolysaccharide and Staphylococcal enterotoxin B against norms previously established from 16 healthy subjects
Time frame: Day 0
Identify inflammatory mediators over-produced by the PBMC of patients with COVID-19 before respiratory distress
Time frame: Day 0
Compare the inflammatory mediators over-produced by the peripheral blood mononuclear cells of patients with COVID-19 with versus without respiratory failure
Time frame: Day 0
Comparison of transcriptome from peripheral blood mononuclear cells from 12 patients with respiratory failure (from intensive care ward) and 10 without (normal hospitalization)
Time frame: Day 0
To evaluate whether lymphocyte apoptosis measured in the acute phase is predictive of residual specific Ac levels and B and T immune memory one year later.
Time frame: 1 year
o evaluate whether lymphocyte apoptosis measured in the acute phase is predictive of residual specific Ac levels and B and T immune memory one year later.
Time frame: 1 year
o evaluate whether lymphocyte apoptosis measured in the acute phase is predictive of residual specific Ac levels and B and T immune memory one year later.
Time frame: 1 year
o evaluate whether lymphocyte apoptosis measured in the acute phase is predictive of residual specific Ac levels and B and T immune memory one year later.
Time frame: 1 year
o evaluate whether lymphocyte apoptosis measured in the acute phase is predictive of residual specific Ac levels and B and T immune memory one year later.
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2025.
- Results publication: PubMed 35066575Andre S, Picard M, Cezar R, Roux-Dalvai F, Alleaume-Butaux A, Soundaramourty C, Cruz AS, Mendes-Frias A, Gotti C, Leclercq M, Nicolas A, Tauzin A, Carvalho A, Capela C, Pedrosa J, Castro AG, Kundura L, Loubet P, Sotto A, Muller L, Lefrant JY, Roger C, Claret PG, Duvnjak S, Tran TA, Racine G, Zghidi-Abouzid O, Nioche P, Silvestre R, Droit A, Mammano F, Corbeau P, Estaquier J. T cell apoptosis characterizes severe Covid-19 disease. Cell Death Differ. 2022 Aug;29(8):1486-1499. doi: 10.1038/s41418-022-00936-x. Epub 2022 Jan 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre Corbeau principal investigator
CHU Nimes
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of SARS-CoV-2 and Covid-19, run by Centre Hospitalier Universitaire de Nīmes at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Membrane expression of Human Leukocyte Antigen -DR isotype compared to normal values (based on 150 healthy volunteers previously sampled) (time frame: Day 0). The study lists 47 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04351711, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2025.