Viral Infection of HSPC Impacts Hematopoiesis

SARS-CoV-2 Clinical Trial

— MEGAHOST  

Official title:

Virus-induced Immunosuppression Via Infection of Hematopoietic Progenitors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06458504
• Other study ID #: APHP240419
• Secondary ID: 2024-A00117-40
• Status: Not yet recruiting
• Start date: June 2024
• Est. completion date: February 2026

Study information

• Verified date: June 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Claude CAPRON, MD, PhD
• Phone: + 33 01 49 09 58 47
• Email: claude.capron[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 45
• Est. completion date: February 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

-

Related Conditions & MeSH terms

• HIV-1
• Infections
• SARS-CoV-2

Locations

Country	Name	City	State
France	Hematology and interne medicine department, Ambroise Paré hospital - APHP	Boulogne-Billancourt

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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