Clinical trial NCT04953312: Calprotectin, a Biomarker of COVID-19 Severity (CALPRO)
Official title: Calprotectin Involvement in Emergency Hematopoiesis Observed in Severe COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Severe/Moderate Coronavirus
Chronic Myelomonocytic Leukemia
Myelodysplastic Syndromes
Old Age
Keywords: Calprotectin
hematopoiesis
COVID-19
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Gustave Roussy, Cancer Campus, Grand Paris
First posted: 2021-07-07
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Differential gene expression and epigenetic signature of COVID-19 or leukemic versus normal HSC using CITE-seq and ATAC-seq
timeFrame: 12 months
Secondary outcomes:
measure: Ex vivo testing of calprotectin-receptor interaction inhibitor
timeFrame: During the last 6 months of the study
Other outcomes:
Locations:
city: Villejuif
country: France
facility: Gustave Roussy Institut
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Michaela FONTENAY, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gustave Roussy Institut
name: Eric SOLARY, MD
role: STUDY_DIRECTOR
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