- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04590261
Myeloid Cells in Patients With Covid-19 Pneumonia (MyeloidCovid)
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.
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Pierre-Régis Burgel, MD, PhD
- Phone Number: +33 01 58 41 23 49
- Email: pierre-regis.burgel@cch.aphp.fr
Study Contact Backup
- Name: Marie BENHAMMANI-Godard
- Phone Number: +33 01 58 41 12 11
- Email: marie.godard@aphp.fr
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 )
Study Plan
How is the study designed?
Design Details
- Primary Purpose: SCREENING
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: group 1
Former mild SARS-Cov2 Pneumonia, 2 to 12 moths before, ≤ 5 L/mn Oxygen treatment
|
Peripheral Blood sampling, 25 mL
Nasal Brushing, facultative
|
OTHER: Group 2
Former severe SARS-Cov2 Pneumonia, 2 to 12 moths before, > 5 L/mn Oxygen treatment
|
Peripheral Blood sampling, 25 mL
Nasal Brushing, facultative
|
OTHER: Group 3
Physician examination in the Pneumology ward, Cochin Hospital
|
Peripheral Blood sampling, 25 mL
Nasal Brushing, facultative
|
OTHER: Group 4
Current hospitalization for Sars-Cov2 Pneumonia at Cochin Hospital
|
Peripheral Blood sampling, 25 mL
Nasal Brushing, facultative
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Month zero-month 36
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Myeloid cell functions
Time Frame: Month zero-month 36
|
Cell culture and cytometric and analyte analysis of their functions, including IFN production
|
Month zero-month 36
|
Myeloid cell transcriptomic and proteomic study
Time Frame: Month zero-month 36
|
Transcriptomic and proteomic analysis of the functions of myeloid cell subtypes
|
Month zero-month 36
|
Transcriptomic study of nasal epithelial cells
Time Frame: Month zero-month 36
|
Single cell RNA sequencing of the nasal brush products
|
Month zero-month 36
|
Plasma analyte concentration measurement
Time Frame: Month zero-month 36
|
High sensitivity detection by state-of-the art ELISA type methods
|
Month zero-month 36
|
Collaborators and Investigators
Investigators
- Principal Investigator: Pierre-Régis Burgel, MD, PhD, Cochin Hospital
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- APHP201138
- 2020-A02700-39 (OTHER: IDRCB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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