Calprotectin, a Biomarker of COVID-19 Severity (CALPRO)

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04953312

Collaborator

Gustave Roussy, Cancer Campus, Grand Paris (Other)

Enrollment

Location

Arms

17.9

Anticipated Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to provide new insights into the pathophysiology of emergency hematopoiesis detected in severe COVID-19 patients. The investigators aim to explore the ability of calprotectin to induce an immunosuppressive myeloid program at the hematopoietic stem and progenitor cell (HSPC) level, and to identify the receptor(s) involved in this effect. Since patients with a hematological malignancy demonstrate a very high propensity to develop a severe COVID-19, the investigators will explore how HSPCs collected from patients with a myeloid malignancy respond to calprotectin.

Condition or Disease	Intervention/Treatment	Phase
Severe/Moderate Coronavirus Chronic Myelomonocytic Leukemia Myelodysplastic Syndromes Old Age	Biological: Blood samples	N/A

Detailed Description

Emergency myelopoiesis in response to SARS-CoV-2 infection produce immunosuppressive myeloid cells with accumulation of immature granulocytes and loss of non-classical monocytes. Excessive release of calprotectin, the dimer of S100A8/A9 alarmins, by immature granulocytes and activated monocytes reflects this situation. A role of calprotectin has been previously described in the initiation and progression of chronic hematological malignancies such as myelodysplastic syndromes.

To provide a rationale for the targeting of alarmin-driven signaling pathways and limit the pathogenic inflammatory response to SARS-CoV-2 infection, the role of calprotectin in the production of immunosuppressive cells from the bone marrow hematopoietic stem and progenitors cells needs to be investigated in patients with severe COVID-19 in comparison with patients with chronic myeloid malignancies (such as chronic myelomonocytic leukemia and myelodysplastic syndromes) and with age-mached healthy controls.

A comprehensive and integrated multiomics approach will be used to decipher the features of immunosuppressive cells and identify therapeutic targets in deregulated pathways.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

55 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Calprotectin Involvement in Emergency Hematopoiesis Observed in Severe COVID-19

Anticipated Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: COVID-19 patients (group 1) Patients with a recent diagnosis (<7 days since first symptoms) of moderate or severe COVID-19	Biological: Blood samples blood
Experimental: Chronic myeloid malignancies (group 2) Adults with chronic myeloid malignancies including myelodysplastic syndromes with low risk MDS ; high risk MDS according to IPSS-R or with dysplastic or proliferative chronic myelomonocytic leukemia according to WHO2016	Biological: Blood samples blood
Other: Control group (group 3) Age-matched healthy donors	Biological: Blood samples blood

Arm

Intervention/Treatment

Experimental: COVID-19 patients (group 1)

Patients with a recent diagnosis (<7 days since first symptoms) of moderate or severe COVID-19

Biological: Blood samples

blood

Experimental: Chronic myeloid malignancies (group 2)

Adults with chronic myeloid malignancies including myelodysplastic syndromes with low risk MDS ; high risk MDS according to IPSS-R or with dysplastic or proliferative chronic myelomonocytic leukemia according to WHO2016

Biological: Blood samples

blood

Other: Control group (group 3)

Age-matched healthy donors

Biological: Blood samples

blood

Outcome Measures

Primary Outcome Measures

Differential gene expression and epigenetic signature of COVID-19 or leukemic versus normal HSC using CITE-seq and ATAC-seq [12 months]
Hematopoietic stem and progenitor cells from patients with severe or moderate COVID-19 or chronic myeloid malignancies or controls will be purified for analyses of transcriptome and chromatin conformation, and also functionally characterized using in vitro culture systems. Results will be compared between the three groups.

Secondary Outcome Measures

Ex vivo testing of calprotectin-receptor interaction inhibitor [During the last 6 months of the study]
Expression of targeted receptors will be monitored by flow cytometry. Clinically developed compounds that could inhibit calprotectin effects will be tested in vitro.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Criteria for all groups:

Adults ≥ 18 years
Dated and signed inform consent *
- : written informed consent of relative (trusted person, close family) in case of emergency procedure, by default emergency inclusion notified in medical file and pursuance consent sought.
Affiliation with a social security scheme

Criteria for control group:

Age-matched healthy donors

Criteria for chronic myeloid malignancies:

A diagnosis of low or high-risk myelodysplastic syndromes according to the WHO 2016 classification
A diagnosis of dysplastic or proliferative chronic myelomonocytic leukemia according to WHO 2016

Criteria for COVID-19 patients:

Patients with a recent diagnosis (<7 days since first symptoms) of moderate or severe COVID-19

Exclusion Criteria:

Pregnant women
Minor patient or major under protection
Patients with COVID-19 infection and active cancer or a history of cancer within the last 6 months
Patients with COVID-19 and severe comorbidities including cardiovascular or respiratory diseases, unbalanced diabetes, obesity (IMC >29)
Patient on AME (state medical aid)