Calprotectin Involvement in Emergency Hematopoiesis Observed in Severe COVID-19
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Differential gene expression and epigenetic signature of COVID-19 or leukemic versus normal HSC using CITE-seq and ATAC-seq
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
COVID-19 patients (group 1)
Patients with a recent diagnosis (<7 days since first symptoms) of moderate or severe COVID-19
干预措施: Blood samples (Biological)
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
干预措施: Blood samples (Biological)
Control group (group 3)
Age-matched healthy donors
干预措施: Blood samples (Biological)
结局指标
主要结局
Differential gene expression and epigenetic signature of COVID-19 or leukemic versus normal HSC using CITE-seq and ATAC-seq
时间窗: 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.
次要结局
- Ex vivo testing of calprotectin-receptor interaction inhibitor(During the last 6 months of the study)