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

Myelodysplastic Syndromes Clinical Trial

— CALPRO  

Official title:

Calprotectin Involvement in Emergency Hematopoiesis Observed in Severe COVID-19

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04953312
• Other study ID #: APHP210522
• Secondary ID: 2021-A00674-37
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2023
• Est. completion date: July 2024

Study information

• Verified date: October 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Michaela FONTENAY, PhD
• Phone: +33 1 58 41 20 04
• Email: michaela.fontenay[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 55
• Est. completion date: July 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Myelomonocytic Leukemia
• COVID-19
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndromes
• Old Age

Intervention

Biological:
• Blood samples
blood

Locations

Country	Name	City	State
France	Gustave Roussy Institut	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Gustave Roussy, Cancer Campus, Grand Paris

Country where clinical trial is conducted

France, 

References & Publications (8)

Abers MS, Delmonte OM, Ricotta EE, Fintzi J, Fink DL, de Jesus AAA, Zarember KA, Alehashemi S, Oikonomou V, Desai JV, Canna SW, Shakoory B, Dobbs K, Imberti L, Sottini A, Quiros-Roldan E, Castelli F, Rossi C, Brugnoni D, Biondi A, Bettini LR, D'Angio' M, Bonfanti P, Castagnoli R, Montagna D, Licari A, Marseglia GL, Gliniewicz EF, Shaw E, Kahle DE, Rastegar AT, Stack M, Myint-Hpu K, Levinson SL, DiNubile MJ, Chertow DW, Burbelo PD, Cohen JI, Calvo KR, Tsang JS; NIAID COVID-19 Consortium, Su HC, Gallin JI, Kuhns DB, Goldbach-Mansky R, Lionakis MS, Notarangelo LD. An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCI Insight. 2021 Jan 11;6(1). pii: 144455. doi: 10.1172/jci.insight.144455. — View Citation

Bauer W, Diehl-Wiesenecker E, Ulke J, Galtung N, Havelka A, Hegel JK, Tauber R, Somasundaram R, Kappert K. Outcome prediction by serum calprotectin in patients with COVID-19 in the emergency department. J Infect. 2021 Apr;82(4):84-123. doi: 10.1016/j.jinf.2020.11.016. Epub 2020 Nov 17. — View Citation

Kaya T, Yaylaci S, Nalbant A, Yildirim I, Kocayigit H, Çokluk E, Sekeroglu MR, Köroglu M, Güçlü E. Serum calprotectin as a novel biomarker for severity of COVID-19 disease. Ir J Med Sci. 2022 Feb;191(1):59-64. doi: 10.1007/s11845-021-02565-8. Epub 2021 Feb 27. — View Citation

Luis García de Guadiana Romualdo, Mulero MDR, Olivo MH, Rojas CR, Arenas VR, Morales MG, Abellán AB, Conesa-Zamora P, García-García J, Hernández AC, Morell-García D, Dolores Albaladejo-Otón M, Consuegra-Sánchez L. Circulating levels of GDF-15 and calprotectin for prediction of in-hospital mortality in COVID-19 patients: A case series. J Infect. 2021 Feb;82(2):e40-e42. doi: 10.1016/j.jinf.2020.08.010. Epub 2020 Aug 12. — View Citation

Mahler M, Meroni PL, Infantino M, Buhler KA, Fritzler MJ. Circulating Calprotectin as a Biomarker of COVID-19 Severity. Expert Rev Clin Immunol. 2021 May;17(5):431-443. doi: 10.1080/1744666X.2021.1905526. Epub 2021 Apr 13. Review. — View Citation

Shi H, Zuo Y, Yalavarthi S, Gockman K, Zuo M, Madison JA, Blair C, Woodward W, Lezak SP, Lugogo NL, Woods RJ, Lood C, Knight JS, Kanthi Y. Neutrophil calprotectin identifies severe pulmonary disease in COVID-19. J Leukoc Biol. 2021 Jan;109(1):67-72. doi: 10.1002/JLB.3COVCRA0720-359R. Epub 2020 Sep 1. — View Citation

Silvin A, Chapuis N, Dunsmore G, Goubet AG, Dubuisson A, Derosa L, Almire C, Hénon C, Kosmider O, Droin N, Rameau P, Catelain C, Alfaro A, Dussiau C, Friedrich C, Sourdeau E, Marin N, Szwebel TA, Cantin D, Mouthon L, Borderie D, Deloger M, Bredel D, Mouraud S, Drubay D, Andrieu M, Lhonneur AS, Saada V, Stoclin A, Willekens C, Pommeret F, Griscelli F, Ng LG, Zhang Z, Bost P, Amit I, Barlesi F, Marabelle A, Pène F, Gachot B, André F, Zitvogel L, Ginhoux F, Fontenay M, Solary E. Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19. Cell. 2020 Sep 17;182(6):1401-1418.e18. doi: 10.1016/j.cell.2020.08.002. Epub 2020 Aug 5. — View Citation

Udeh R, Advani S, de Guadiana Romualdo LG, Dolja-Gore X. Calprotectin, an Emerging Biomarker of Interest in COVID-19: A Systematic Review and Meta-Analysis. J Clin Med. 2021 Feb 15;10(4). pii: 775. doi: 10.3390/jcm10040775. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differential gene expression and epigenetic signature of COVID-19 or leukemic versus normal HSC using CITE-seq and ATAC-seq	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.	12 months
Secondary	Ex vivo testing of calprotectin-receptor interaction inhibitor	Expression of targeted receptors will be monitored by flow cytometry. Clinically developed compounds that could inhibit calprotectin effects will be tested in vitro.	During the last 6 months of the study

External Links

•   Groupe Francophone des Myélodysplasies: GFM is a cooperative group of the French Society of Hematology