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Immune Cells Phenotypes During COVID-19 (IMMUNO-COVID)

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ClinicalTrials.gov Identifier: NCT04816760
Recruitment Status : Recruiting
First Posted : March 25, 2021
Last Update Posted : March 25, 2021
Sponsor:
Collaborators:
Hôpital Européen Marseille
Assistance Publique Hopitaux De Marseille
Institut Paoli-Calmettes
Beckman Coulter, Inc.
Information provided by (Responsible Party):
Institut Hospitalo-Universitaire Méditerranée Infection

Brief Summary:

The ongoing pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) has infected more than one hundred twenty million peoples worldwide one year after its onset with a case-fatality rate of almost 2%. The disease due to the coronavirus 2019 (i.e., COVID-19) is associated with a wide range of clinical symptoms. As the primary site of viral invasion is the upper respiratory airways, lung infection is the most common complication. Most infected patients are asymptomatic or experience mild or moderate form of the disease (80 %). A lower proportion (15%) develop severe pneumonia with variable level of hypoxia that may required hospitalization for oxygen therapy. In the most severe cases (5%), patients evolve towards critical illness with organ failure such as the acute respiratory distress syndrome (ARDS). At this stage, invasive mechanical ventilation is required in almost 70 % and the hospital mortality rises to 37 %.

Immune cells are key players during SARS CoV-2 infection and several alterations have been reported including lymphocytes (T, B and NK) and monocytes depletion, and cells exhaustion. Such alterations were much more pronounced in patients with the most severe form of the disease. Beside, a dysregulated proinflammatory response has also been pointed out as a potential mechanism of lung damage. Finally, COVID-19 is associated with an unexpectedly high incidence of thrombosis which probably results from the viral invasion of endothelial cells.

The investigators aim to explore prospectively the alterations of innate and adaptive immune cells during both the acute and the recovery phase of SARS CoV-2 pneumonia. Flow and Spectral cytometry will be used to perform deep subset profiling focusing on T, B, NK, NKT, gamma-gelta T, monocytes and dendritic cells. Each specific cell type will be further characterized using markers of activation/inhibition, maturation/differenciation and senescence as well as chemokines receptors.

T-cell memory specificity will be explore using specific SARS CoV-2 pentamer. Platelet activation and circulating microparticles will be explore using flow cytometry. Serum SARS CoV-2 antibodies (IgA, IgM, IgG), serum cytokines, and serum biomarkers of alveolar epithelial and endothelial cells will be analyze using ELISA and correlate with the severity of the disease.


Condition or disease Intervention/treatment
Sars-CoV2 Innate Immunity Immunization; Infection Alveolar Lung Disease Endothelial Dysfunction Biological: Peripheral blood samples

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Alterations of Innate and Adaptive Immune Cells During the Course of SARS CoV-2 Pneumonia
Actual Study Start Date : March 25, 2020
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : December 2021

Intervention Details:
  • Biological: Peripheral blood samples
    Peripheral blood samples at Day 0, Day 7, Day 14, Day 28, Day 90 and Day 180.


Primary Outcome Measures :
  1. Profiling of innate and adaptive immune cells during SARS CoV-2 infection. [ Time Frame: Day 0 ]
    Determination of cells population using spectral cytometry of PBMCs.

  2. Profiling of innate and adaptive immune cells during SARS CoV-2 infection. [ Time Frame: Day 7 ]
    Determination of cells population using spectral cytometry of PBMCs.

  3. Profiling of innate and adaptive immune cells during SARS CoV-2 infection. [ Time Frame: Day 14 ]
    Determination of cells population using spectral cytometry of PBMCs.

  4. Profiling of innate and adaptive immune cells during SARS CoV-2 infection. [ Time Frame: Day 28 ]
    Determination of cells population using spectral cytometry of PBMCs.

  5. Profiling of innate and adaptive immune cells during SARS CoV-2 infection. [ Time Frame: Day 90 ]
    Determination of cells population using spectral cytometry of PBMCs.

  6. Profiling of innate and adaptive immune cells during SARS CoV-2 infection. [ Time Frame: Day 180 ]
    Determination of cells population using spectral cytometry of PBMCs.

  7. Functional state of innate and adaptive immune cells during SARS CoV-2 infection. [ Time Frame: Day 0 ]
    Determination of the functional state of immune cells using spectral cytometry

  8. Functional state of innate and adaptive immune cells during SARS CoV-2 infection. [ Time Frame: Day 7 ]
    Determination of the functional state of immune cells using spectral cytometry

  9. Functional state of innate and adaptive immune cells during SARS CoV-2 infection. [ Time Frame: Day 14 ]
    Determination of the functional state of immune cells using spectral cytometry

  10. Functional state of innate and adaptive immune cells during SARS CoV-2 infection. [ Time Frame: Day 28 ]
    Determination of the functional state of immune cells using spectral cytometry

  11. Functional state of innate and adaptive immune cells during SARS CoV-2 infection. [ Time Frame: Day 90 ]
    Determination of the functional state of immune cells using spectral cytometry

  12. Functional state of innate and adaptive immune cells during SARS CoV-2 infection. [ Time Frame: Day 180 ]
    Determination of the functional state of immune cells using spectral cytometry

  13. Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection. [ Time Frame: Day 0 ]
    Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa.

  14. Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection. [ Time Frame: Day 7 ]
    Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa.

  15. Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection. [ Time Frame: Day 14 ]
    Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa.

  16. Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection. [ Time Frame: Day 28 ]
    Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa.

  17. Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection. [ Time Frame: Day 90 ]
    Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa.

  18. Serum IgA, IgM and IgG antibodies during SARS CoV-2 infection. [ Time Frame: Day 180 ]
    Measurement of serum SARS CoV-2 IgA, IgM and IgG antibodies using Elisa.

  19. Platelet activation and circulating microparticles assessment during SARS CoV-2 infection. [ Time Frame: Day 0 ]
    Determination of platelet activation and circulating microparticles levels using flow cytometry.

  20. Platelet activation and circulating microparticles assessment during SARS CoV-2 infection. [ Time Frame: Day 7 ]
    Determination of platelet activation and circulating microparticles levels using flow cytometry.

  21. Platelet activation and circulating microparticles assessment during SARS CoV-2 infection. [ Time Frame: Day 14 ]
    Determination of platelet activation and circulating microparticles levels using flow cytometry.

  22. Platelet activation and circulating microparticles assessment during SARS CoV-2 infection. [ Time Frame: Day 28 ]
    Determination of platelet activation and circulating microparticles levels using flow cytometry.


Secondary Outcome Measures :
  1. Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection. [ Time Frame: Day 0 ]
    Measurement of IL1β, IL-6, IL-10, IL-17A, IL-18, TNFα, IFNγ, CRTP-6 using Elisa.

  2. Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection. [ Time Frame: Day 7 ]
    Measurement of IL1β, IL-6, IL-10, IL-17A, IL-18, TNFα, IFNγ, CRTP-6 using Elisa.

  3. Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection. [ Time Frame: Day 14 ]
    Measurement of IL1β, IL-6, IL-10, IL-17A, IL-18, TNFα, IFNγ, CRTP-6 using Elisa.

  4. Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection. [ Time Frame: Day 28 ]
    Measurement of IL1β, IL-6, IL-10, IL-17A, IL-18, TNFα, IFNγ, CRTP-6 using Elisa.

  5. Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection. [ Time Frame: Day 90 ]
    Measurement of IL1β, IL-6, IL-10, IL-17A, IL-18, TNFα, IFNγ, CRTP-6 using Elisa.

  6. Serum concentration of Pro-inflammatory and Anti-inflammatory cytokines in response to SARS CoV-2 infection. [ Time Frame: Day 180 ]
    Measurement of IL1β, IL-6, IL-10, IL-17A, IL-18, TNFα, IFNγ, CRTP-6 using Elisa.

  7. Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection. [ Time Frame: Day 0 ]
    Measurement of KL-6, CC-16, S-RAGE, ANG-2 using ELISA.

  8. Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection. [ Time Frame: Day 7 ]
    Measurement of KL-6, CC-16, S-RAGE, ANG-2 using ELISA.

  9. Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection. [ Time Frame: Day 14 ]
    Measurement of KL-6, CC-16, S-RAGE, ANG-2 using ELISA.

  10. Serum alveolar epithelial and endothelial cells biomarkers during SARS CoV-2 infection. [ Time Frame: Day 28 ]
    Measurement of KL-6, CC-16, S-RAGE, ANG-2 using ELISA.

  11. Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. [ Time Frame: Day 0 ]
    Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.

  12. Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. [ Time Frame: Day 1 ]
    Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.

  13. Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. [ Time Frame: Day 2 ]
    Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.

  14. Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. [ Time Frame: Day 3 ]
    Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.

  15. Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. [ Time Frame: Day 5 ]
    Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.

  16. Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. [ Time Frame: Day 7 ]
    Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.

  17. Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. [ Time Frame: Day 9 ]
    Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.

  18. Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. [ Time Frame: Day 11 ]
    Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.

  19. Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. [ Time Frame: Day 14 ]
    Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.

  20. Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. [ Time Frame: Day 17 ]
    Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.

  21. Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. [ Time Frame: Day 21 ]
    Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.

  22. Kinetic of surface biomarkers expression on neutrophils (C64) and monocytes (CD169, HLA-DR) during SARS CoV-2 infection. [ Time Frame: Day 28 ]
    Measurement of nCD64, mCD169 and mHLA-DR using the VersaPOC one-step rapid flow cytometry method.



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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Patients presenting with a first episode of SARS CoV-2 pneumonia and requiring hospitalization either in a ward or an Intensive Care Unit will constitute the COVID-19 group.

Healthy blood donors from the Etablissement Français du Sang (EFS) will constituted the control group

Criteria

Inclusion Criteria:

  • Age > 18 y
  • Laboratory confirmed SARS CoV-2 infection (positive RT-PCR).
  • Ground-glass opacity on chest computed-tomography
  • Time from hospital admission to inclusion < or equal to 72 h

Exclusion Criteria:

  • Pregnant
  • Under legal restriction

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04816760


Contacts
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Contact: Line MEDDEB 0413732347 ext 33 line.meddeb@ap-hm.fr
Contact: Joana VITTE, MD, PhD joana.vitte@ap-hm.fr

Locations
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France
Hopital Europeen Marseille Recruiting
Marseille, France, 13003
Contact: Jérôme ALLARDET-SERVENT, MD    0413427450 ext 33    j.allardetservent@hopital-europeen.fr   
Contact: Philippe HALFON, MD, PhD    0413428120 ext 33    philippe.halfon@alphabio.fr   
Hopital Nord Recruiting
Marseille, France, 13015
Contact: Marc LEONE, MD, PhD       m.leone@aph-hm.fr   
Sub-Investigator: Amélie MENARD, MD         
Sponsors and Collaborators
Institut Hospitalo-Universitaire Méditerranée Infection
Hôpital Européen Marseille
Assistance Publique Hopitaux De Marseille
Institut Paoli-Calmettes
Beckman Coulter, Inc.
Investigators
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Principal Investigator: Jean-Louis MEGE, MD, PhD Institut Hospitalo-Universitaire Méditérranée Infection
Additional Information:
Publications:

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Responsible Party: Institut Hospitalo-Universitaire Méditerranée Infection
ClinicalTrials.gov Identifier: NCT04816760    
Other Study ID Numbers: 2020-A00756-33
First Posted: March 25, 2021    Key Record Dates
Last Update Posted: March 25, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Diseases
Respiratory Tract Diseases