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Myeloid Cells in Patients With Covid-19 Pneumonia (MyeloidCovid)

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ClinicalTrials.gov Identifier: NCT04590261
Recruitment Status : Not yet recruiting
First Posted : October 19, 2020
Last Update Posted : October 25, 2022
Sponsor:
Collaborator:
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE October 15, 2020
First Posted Date  ICMJE October 19, 2020
Last Update Posted Date October 25, 2022
Estimated Study Start Date  ICMJE December 2022
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 15, 2020)		 Myeloid cell sub-population phenotype [ Time Frame: Month zero-month 36 ]
Cytometric analysis of surface and intracellular molecules to identify myeloid cell sub-populations and define their function in vivo
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2020)
  • Myeloid cell functions [ Time Frame: Month zero-month 36 ]
    Cell culture and cytometric and analyte analysis of their functions, including IFN production
  • Myeloid cell transcriptomic and proteomic study [ Time Frame: Month zero-month 36 ]
    Transcriptomic and proteomic analysis of the functions of myeloid cell subtypes
  • Transcriptomic study of nasal epithelial cells [ Time Frame: Month zero-month 36 ]
    Single cell RNA sequencing of the nasal brush products
  • Plasma analyte concentration measurement [ Time Frame: Month zero-month 36 ]
    High sensitivity detection by state-of-the art ELISA type methods
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Myeloid Cells in Patients With Covid-19 Pneumonia
Official Title  ICMJE Myeloid Cells in Patients With Covid-19 Pneumonia
Brief Summary

The purpose of this study is to analyze in depth the relationship of myeloid cell subpopulations during infection by Severe acute respiratory syndrome coronavirus 2 (SARS-Cov2), the virus mediating Covid-19. Myeloid cells include neutrophils, monocytes and dendritic cells, each divided into subpopulations with different functions in immune defense and immune pathologies.

The study is based on the following hypotheses:

  • Infection and the interferon response to infection may induce hyperactive or immunosuppressive differentiation of myeloid cells, that may be treated by specific inhibitors.
  • Some myeloid cell subpopulations currently identified in our laboratories might be markers for Covid-19 prognosis.
  • Alternative receptors may be present on myeloid cells, inducing the cytokine storm, a target for therapy.
  • The expression of Interferon (IFN) receptor and IFN responding genes on myeloid cells and on respiratory epithelial cells may correlate with prognosis and indicate potential treatment targets.
  • Interferon responses are known to be skewed during Covid-19, but some IFN subtype polymorphisms may correlate with prognosis and these subtypes migt be supplemented or inhibited for therapy.
Detailed Description

Infection by SARS-Cov2 drives to pneumonia in most cases, 30 percent of which require hospitalization in a pneumology ward, among which 30 percent with severe acute respiratory syndrome (SARS) must go to critical care units, with a high mortality rate.

This infection drives a strong cytokine response. In patients developing SARS, a profound, paradoxical defect in IFN alpha and in the expression of genes responding to IFN alpha was discovered. IFNs are strong anti-viral proteins, used for the treatment of viral hepatitis. Type I IFNs, including IFN alpha, have ubiquitous receptors on almost every cell type. Type III IFNs, or IFN lambda, have a more restricted receptor expression, including on neutrophils. Their polymorphisms were already related to the prognosis of another ribonucleic acid (RNA) virus with mucosal entry, hepatitis C virus (HCV), especially in people with African origins.

Coronaviruses responsible for the previous SARS-Cov or Middle East respiratory syndrome coronavirus (MERS-Cov) epidemics induce a defective IFN signal transduction. Many other viral infection lead to desensitization. Moreover, IFN alpha by itself can lead to defective antiviral responses. At the immune cell level, lymphopenia with an increased neutrophil/lymphocyte ratio were noted in severe SARS-Cov2 case. New subpopulations of neutrophils have been characterized by phenotypic and proteomic studies, with inflammatory or suppressive functions.

It will be important to know if

  • hyperactive or immunosuppressive myeloid cell differentiation is caused by SARS-Cov2 and can be inhibited specifically.
  • some myeloid subpopulations
  • correlate with the prognosis of the disease,
  • myeloid cells have alternative receptors for SARS-Cov2,
  • some IFN polymorphisms may correlate with prognosis and might be supplemented or inhibited for therapy.

The answers will be obtained through the primary and secondary outcome measures, as described below.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Condition  ICMJE Covid-19; SARS-Cov2
Intervention  ICMJE
  • Other: Blood sampling
    Peripheral Blood sampling, 25 mL
  • Other: Nasal Brushing
    Nasal Brushing, facultative
Study Arms  ICMJE
  • group 1
    Former mild SARS-Cov2 Pneumonia, 2 to 12 moths before, ≤ 5 L/mn Oxygen treatment
    Interventions:
    • Other: Blood sampling
    • Other: Nasal Brushing
  • Group 2
    Former severe SARS-Cov2 Pneumonia, 2 to 12 moths before, > 5 L/mn Oxygen treatment
    Interventions:
    • Other: Blood sampling
    • Other: Nasal Brushing
  • Group 3
    Physician examination in the Pneumology ward, Cochin Hospital
    Interventions:
    • Other: Blood sampling
    • Other: Nasal Brushing
  • Group 4
    Current hospitalization for Sars-Cov2 Pneumonia at Cochin Hospital
    Interventions:
    • Other: Blood sampling
    • Other: Nasal Brushing
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: October 15, 2020)		 120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age > 18 years
  • Sex : male or female
  • French Social Security insurance
  • Information and consent dated and signed *
  • Group 1 : inclusion 2 to 12 months after hospitalization for Covid-19 pneumonia with mild severity (oxygen treatment ≤5L/mn);
  • Group 2 : 2 to 12 months after hospitalization for Covid-19 pneumonia with high severity (oxygen treatment >5L/mn);
  • Group 3 : external visit at Cochin Hospital, age- and sex -matched with Groups 1, 2, 4.
  • Group 4 : inclusion during hospitalization for Covid-19, within the first month of symptoms.

Exclusion Criteria:

  • Tuberculosis or other evolutive bacterial infection
  • Chronic evolutive viral Infections (Hepatitis B or C, HIV)
  • Ongoing chemotherapy or radiotherapy
  • Participation in another research protocol with current exclusion period at the time of pre-inclusion (possible inclusion in an observational study
  • Vulnerable person (pregnant, parturient woman, breastfeeding woman, person Under tutorship, person under arrest through judiciary or administrative decision )
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Pierre-Régis Burgel, MD, PhD 01 58 41 23 49 ext +33 pierre-regis.burgel@cch.aphp.fr
Contact: Marie BENHAMMANI-Godard 01 58 41 12 11 ext +33 marie.godard@aphp.fr
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04590261
Other Study ID Numbers  ICMJE APHP201138
2020-A02700-39 ( Other Identifier: IDRCB )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Assistance Publique - Hôpitaux de Paris
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Institut National de la Santé Et de la Recherche Médicale, France
Investigators  ICMJE
Principal Investigator: Pierre-Régis Burgel, MD, PhD Cochin Hospital
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date October 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP