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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

Study Description
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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.

Condition or disease Intervention/treatment Phase
Covid-19; SARS-Cov2 Other: Blood sampling Other: Nasal Brushing Not Applicable

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Myeloid Cells in Patients With Covid-19 Pneumonia
Estimated Study Start Date : December 2022
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
group 1
Former mild SARS-Cov2 Pneumonia, 2 to 12 moths before, ≤ 5 L/mn Oxygen treatment
 Other: Blood sampling
Peripheral Blood sampling, 25 mL

Other: Nasal Brushing
Nasal Brushing, facultative
Group 2
Former severe SARS-Cov2 Pneumonia, 2 to 12 moths before, > 5 L/mn Oxygen treatment
 Other: Blood sampling
Peripheral Blood sampling, 25 mL

Other: Nasal Brushing
Nasal Brushing, facultative
Group 3
Physician examination in the Pneumology ward, Cochin Hospital
 Other: Blood sampling
Peripheral Blood sampling, 25 mL

Other: Nasal Brushing
Nasal Brushing, facultative
Group 4
Current hospitalization for Sars-Cov2 Pneumonia at Cochin Hospital
 Other: Blood sampling
Peripheral Blood sampling, 25 mL

Other: Nasal Brushing
Nasal Brushing, facultative


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Myeloid cell functions [ Time Frame: Month zero-month 36 ]
    Cell culture and cytometric and analyte analysis of their functions, including IFN production

  2. Myeloid cell transcriptomic and proteomic study [ Time Frame: Month zero-month 36 ]
    Transcriptomic and proteomic analysis of the functions of myeloid cell subtypes

  3. Transcriptomic study of nasal epithelial cells [ Time Frame: Month zero-month 36 ]
    Single cell RNA sequencing of the nasal brush products

  4. Plasma analyte concentration measurement [ Time Frame: Month zero-month 36 ]
    High sensitivity detection by state-of-the art ELISA type methods


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 )
Contacts and Locations
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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): NCT04590261


Contacts
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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

Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
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Principal Investigator: Pierre-Régis Burgel, MD, PhD Cochin Hospital
More Information
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Additional Information:

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04590261    
Other Study ID Numbers: APHP201138
2020-A02700-39 ( Other Identifier: IDRCB )
First Posted: October 19, 2020    Key Record Dates
Last Update Posted: October 25, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Covid-19
Neutrophils
Dendritic cells
Monocytes
Macrophages
 Interferons
Nasal mucosa
Peripheral blood
Pneumonia
Additional relevant MeSH terms:
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COVID-19
Pneumonia
Respiratory Tract Infections
Infections
Pneumonia, Viral
Virus Diseases
 Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases