Ignite Creation Date:
2024-05-06 @ 3:20 PM
Last Modification Date:
2024-10-26 @ 1:47 PM
Study NCT ID:
NCT04590261
Status:
NOT_YET_RECRUITING
Last Update Posted:
2022-10-25
First Post:
2020-10-15
Brief Title:
Myeloid Cells in Patients With Covid-19 Pneumonia
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Myeloid Cells in Patients With Covid-19 Pneumonia
Status:
NOT_YET_RECRUITING
Status Verified Date:
2022-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MyeloidCovid
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
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 neutrophillymphocyte 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
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 neutrophillymphocyte 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2020-A02700-39 | OTHER | IDRCB | None |