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DNA and RNA viruses of the blood virome of allogeneic hematopoietic stem cell transplant recipients: a longitudinal observational study during a one-year period after transplantation - the Geneva Blood Virome Project (the GeBVir Project)

English title DNA and RNA viruses of the blood virome of allogeneic hematopoietic stem cell transplant recipients: a longitudinal observational study during a one-year period after transplantation - the Geneva Blood Virome Project (the GeBVir Project)
Applicant Kaiser Laurent
Number 179507
Funding scheme Project funding
Research institution Laboratoire de Virologie Service des Maladies Infectieuses Hôpitaux Universitaires de Genève
Institution of higher education University of Geneva - GE
Main discipline Internal Medicine
Start/End 01.04.2018 - 31.03.2022
Approved amount 287'696.00
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All Disciplines (2)

Discipline
Internal Medicine
Medical Microbiology

Keywords (9)

Virus; Virology; Blood; Blood-based test; Virome; Survival; Hematopoietic stem cell transplantation; Real time PCR ; Longitudinal study

Lay Summary (French)

Lead
Le Geneva Blood Virome Project est une étude observationnelle longitudinale décrivant la charge virale plasmatique de 21 virus ADN et ARN du virome sanguin de patients transplantés allogéniques de cellules souches hématopoïétiques, sur une période d'un an après la transplantation.
Lay summary
Le Geneva Blood Virome Project est une étude observationnelle longitudinale. L’objectif principal consiste en la description de la cinétique de la charge virale plasmatique d’une sélection de 21 virus ADN et ARN du virome sanguin (Herpesviridae Polyomaviridae, Adenoviridae, Parvoviridae, Anelloviridae, Picornaviridae et Flaviviridae) chez des patients adultes transplantés allogéniques de cellules souches hématopoïétiques, sur une période d’un an après la transplantation. Ces virus ADN et ARN sont susceptibles de faire des infections aiguës, chroniques ou des réactivations après la transplantation. Les objectifs secondaires sont : l’étude de potentielles associations entre la charge virale plasmatique de certains virus, à des temps spécifiques depuis la transplantation, 1) avec les caractéristiques des receveurs et de la transplantation, et 2) avec des issues cliniques après la transplantation (y.c. la survie globale et sans récidive, la maladie greffe-contre-hôte et la reconstitution immune). La population de l’étude consiste en des patients adultes transplantés allogéniques de cellules souches hématopoïétiques aux Hôpitaux Universitaires des Genève, inclus dans une cohorte monocentrique genevoise existante ("Cohort of infectious disease in hematopoietic stem cell transplant patients"), pour laquelle des échantillons cliniques sont prélevés à différents temps après la transplantation. Nous inclurons dans ce projet un total de 120 patients depuis mars 2017 et utiliserons les échantillons plasmatiques collectés le jour de la transplantation et après la transplantation pour réaliser le screening de virus ADN et ARN par PCR et RT-PCR en temps réel qualitatives et quantitatives. Une analyse interim sera faite avec les résultats des 50 premiers patients et l’analyse définitive sera réalisée vers la fin de l’année 2020. 
Direct link to Lay Summary Last update: 18.04.2018

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Publications

Publication
Unmasking viral sequences by metagenomic next-generation sequencing in adult human blood samples during steroid-refractory/dependent graft-versus-host disease
Zanella M. C., Cordey S., Laubscher F., Docquier M., Vieille G., Van Delden C., Braunersreuther V., TA Mc Kee, Lobrinus J. A., Masouridi-Levrat S., Chalandon Y., Kaiser L., Vu D. L. (2021), Unmasking viral sequences by metagenomic next-generation sequencing in adult human blood samples during steroid-refractory/dependent graft-versus-host disease, in Microbiome, 9(1), 28-28.

Abstract

Areas of shadow persist concerning the composition of the blood virome and the role of commensal viruses. Next-generation sequencing (NGS) has been used as a discovery tool reporting countless viral or microbial sequences but with little systematic or classical approach and has only provided an overview of the blood virome. Viral infections and reactivations after transplantation are probably not innocent even if some of them are asymptomatic. Among highly immunosuppressed patients, such as hematopoietic stem cell (HSCT) recipients, there is a need to improve our comprehension of factors associated with clinical outcomes. Some DNA or RNA viruses of the blood virome could be part of these factors. For this purpose there is a need to perform at first a description of the blood virome’s composition and dynamics after transplantation. The Geneva Blood Virome Project is a longitudinal observational study. The main objective is to describe the kinetics of the blood viral load of a selection of DNA and RNA viruses of the blood virome (viruses belonging to Herpesviridae, Polyomaviridae, Adenoviridae, Parvoviridae, Papillomaviridae, Anelloviridae, Cycloviridae, Picornaviridae and Flaviviridae families), among adult allogeneic HSCT recipients over a one-year period after transplantation. The secondary objectives of are: 1) to assess if the blood viral load of some viral species, at a relevant time point (at the time or after transplantation), is associated with HSCT recipients’ and/or transplant’s characteristics, 2) and to assess if the blood viral load of some viral species, at a relevant time point, is associated with clinical outcomes at one year after transplantation, such as overall and relapse-free survival, and composite outcome graft-versus-host-disease free survival. The population of the study will consist in adult patients receiving allogeneic stem cell transplantation at University Hospitals of Geneva and who are enrolled in an already existing monocentric cohort named "Cohort of infectious disease in hematopoietic stem cell transplant patients" and for which clinical specimens are collected and stored at the time and after transplantation. We plan to include 120 patients whose plasma samples are collected from March 2017. We will systematically use plasma samples collected at 5 time points (the day of transplantation, 30 days, 3 months, 6 months, and one year after transplantation) to perform qualitative and quantitative real-time r(RT)-PCR assays for the screening of DNA and RNA viruses. The real time PCR assays will consist either in PCR specifically designed for the purpose of the project, commercial kit PCR or available in house PCR assays. Design and validation experiments of PCR assays have already started and we expect to start the analysis of the plasma samples in November 2017, realize an interim analysis of the first 50 patients’ results one year after study’s start and the definitive analysis by the end of 2020.The Geneva Blood Virome project will provide a description of the virome’s composition and dynamics, the number and types of co-infections, and the potential associations of some viruses with clinical outcomes after transplantation. Furthermore, the technical aspects of this project could lead to a change in the current research practice, with the use of real-time PCR r(RT)-PCR as a "low-tech" but robust benchmark technique and as a complementary method of NGS results. Most importantly, the results obtained with this technique will provide meaningful information for clinicians involved in HSCT routine care. This project could also lead to further projects dedicated to the study of the immunological and genetic factors associated with components of the virome. It is too early to speculate on the possible impact in terms of clinical management of HSCT recipients but in the long term we may envision a change in our diagnostic and therapeutic approaches by considering strategies that favor the restoration of an equilibrium of the virome and microbiome in general. This is of particular importance in patients such as transplant recipients and patients with hematologic conditions who are under the influence of numerous treatments and blood products, and since there is a thin line between the immune balance that controls infections or promote complications.
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