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NCT Number: NCT04351711

Immunological Profiling of Patients With COVID-19 in Respiratory Distress

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.

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Key information

Conditions

SARS-CoV-2 COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiration Disorders Respiratory Insufficiency Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

CHU de Nimes

Nîmes, France

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Immunological profiling

Other

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

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. Number of regulatory T cells (CD4+CD25hiCD127loFoxP3+).

    Time frame: Day 0

    Quantified by flow cytometry; % variation / normal values

  16. Percentage of regulatory T cells (CD4+CD25hiCD127loFoxP3+).

    Time frame: Day 0

    Quantified by flow cytometry; % variation / normal values

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. Rate of circulating Interleukin-12p70 compared to normal values (based on 150 healthy volunteers previously sampled)

    Time frame: Day 0

    Quantified by flow cytometry

  37. 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

  38. 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

  39. 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

  40. 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

  41. 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

  42. 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

  43. 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

  44. 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

  45. 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

  46. 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

  47. 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

Secondary outcomes

  1. 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

    Difference in expression of the biomarkers assayed for primary outcome

  2. 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

    Difference in expression of the biomarkers assayed for primary outcome

  3. Mortality rate

    Time frame: End of study (2021)

    Mortality

  4. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  5. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  6. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  7. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  8. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  9. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  10. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  11. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  12. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  13. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  14. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  15. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  16. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  17. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  18. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  19. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  20. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  21. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  22. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  23. 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

    quantified by Luminex (TruCulture tube system (Myriad RBM))

  24. Identify inflammatory mediators over-produced by the PBMC of patients with COVID-19 before respiratory distress

    Time frame: Day 0

    Difference in expression of the 20 inflammatory markers described in outcomes 51-70

  25. 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

    Difference in expression of the 20 inflammatory markers described in outcomes 51-70

  26. 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

    Performed at the Institut de Génétique Humaine (Montpellier)

  27. 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

    Lymphocyte caspase activity

  28. 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

    circulating FasL level

  29. 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

    expression of phosphatidylserine on the surface of lymphocytes in the acute phase

  30. 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

    levels of Ac

  31. 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

    plasmablasts and specific T cells

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Nīmes

Other

Collaborators

  • Institute of Human Genetics, Montpellier

Registry information

Acronym: ACTICOV-2

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Apr 17, 2020
Registry last updated
Dec 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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