Viral Infection of HSPC Impacts Hematopoiesis (MEGAHOST)

Virus-induced Immunosuppression Via Infection of Hematopoietic Progenitors

We propose to demonstrate that HIV-1 and SARS-CoV-2 are capable of targeting long-lived HSPC with self-renewal capacities. These progenitors, thus transformed into host cells, can give rise to a durable source of infected cells with an impact on hematopoiesis.

Study Overview

• Status: Recruiting
• Conditions: SARS-CoV-2; HIV-1

Detailed Description

Virus-induced immunosuppression is the transient or persistent decline of immune cell counts and/or function caused by a virus, favouring its persistence in the host organisms. When sustained, triggered by acute viral replication or maintained by chronic viral infections, virus-induced immunosuppression is a life-threatening condition. It is notoriously observed in chronic HIV-1 infection and even in a considerable fraction of antiretroviral-treated HIV-infected individuals. It is also observed in some individuals recovering from severe and mild-to-moderate COVID-19. Its mechanisms are elusive and efficient therapeutic options are not available. Virus-induced immunosuppression may occur in the periphery (affecting circulating immune cells) or in the bone marrow, affecting hematopoietic stem and progenitor cells (HSPC) and hematopoiesis. Several viruses can infect HSPCs. HIV-1 can directly infect HSC, negatively impacting HSC function and the whole stem cell environment of the bone marrow. Whether HSC can be productively infected by SARS-CoV-2 or just targeted and modulated by it remains uncertain and further studies are required to determine HSPC susceptibility or viral sensing for SARS-CoV-2. Therefore, we will i) Evaluate which hematopoietic stem and progenitor cells (HSPC) are targeted by HIV-1 (in vivo and ex vivo) and SARS-CoV-2 (ex vivo); ii) Evaluate whether these infected HSPC would modulate the bone marrow environment by upregulating inflammatory cytokines detrimental to lymphopoiesis.

• Study Type: Observational
• Enrollment (Estimated): 45

Contacts and Locations

• Study Contact: Name: Claude CAPRON, MD, PhD; Phone Number: + 33 01 49 09 58 47; Email: claude.capron@aphp.fr
• Study Contact Backup: Name: Fernando REAL, PhD; Phone Number: + 33 03 20 87 12 01; Email: fernando.real@cnrs.fr

Study Locations

• France
  • Boulogne-Billancourt, France, 92100
    • Recruiting
    • Hematology and interne medicine department, Ambroise Paré hospital - APHP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

• adult patients.
• patients able to read and understand the information note.
• no opposition to the use of biological samples. 45 subjects are required in our study:

(A) 20 patients with FFPE osteomedullary biopsy prior to COVID-19 pandemic. Including :

• 10 HIVpos patients selected based on biopsy results (normal, subnormal/minor lesion).
• 10 HIVneg patients selected to match HIVpos patients, considering age and biological sex.

(B) 25 HIVneg patients asymptomatic for COVID-19 for whom a myelogram or BM biopsy is prescribed as part of a search for haematological pathology or as part of lymphoma extension investigations.

Description

Inclusion Criteria:

HIV patients :

• HIV-positive patients with a negative or positive viral load.
• managed at Ambroise Paré Hospital.
• patients with a bone marrow biopsy or myelogram performed as part of their care.

Healthy subjects without HIV - patients with a BM biopsy or myelogram performed as part of their care for a suspected hematological pathology.

Management at Ambroise Paré Hospital.

Exclusion Criteria:

-

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate if infected HSPC would modulate the bone marrow environment	Evaluate whether these infected HSPC would modulate the bone marrow environment by upregulating inflammatory cytokines detrimental to lymphopoiesis.	at 1 year

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Claude CAPRON, MD, PhD, Laboratory of Immunology, Ambroise Paré hospital - APHP; Study Director: Fernando REAL, PhD, Center for Infection and Immunity of Lille, INSERM U1019 - CNRS UMR9017, Institut Pasteur de Lille

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: June 10, 2024
• First Submitted That Met QC Criteria: June 10, 2024
• First Posted (Actual): June 13, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Immunosuppression; HIV-1; Hematopoietic Progenitors; Virus-induced
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: APHP240419; 2024-A00117-40 (Registry Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No