MyeloidCovid: Myeloid Cells in Patients With Covid-19 Pneumonia

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04590261

Collaborator

Institut National de la Santé Et de la Recherche Médicale, France (Other)

120

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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	N/A

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

Study Type:

Interventional

Anticipated 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

Anticipated Study Start Date :

Nov 1, 2020

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

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

Primary Outcome Measures

Myeloid cell sub-population phenotype [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

Myeloid cell functions [Month zero-month 36]
Cell culture and cytometric and analyte analysis of their functions, including IFN production
Myeloid cell transcriptomic and proteomic study [Month zero-month 36]
Transcriptomic and proteomic analysis of the functions of myeloid cell subtypes
Transcriptomic study of nasal epithelial cells [Month zero-month 36]
Single cell RNA sequencing of the nasal brush products
Plasma analyte concentration measurement [Month zero-month 36]
High sensitivity detection by state-of-the art ELISA type methods

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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,

Group 4 : inclusion during hospitalization for Covid-19, within the first month of symptoms.
: If the clinical status of a patient from Group 4 does not allow immediate consent in ethically acceptable conditions, consent will be obtained from the patient's trusted person, or by default from a family member, if present. If not, the patient can still be included. He or she will be informed later an consent will be sought for potential pursuit of the research and for use of the data (law 2004-806, August 09 2004-article L1122-1-2).

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 )