Venturini, Cristina;
Colston, Julia M;
Charles, Oscar;
Lankina, Anastasia;
Best, Timothy;
Atkinson, Claire;
Forrest, Calum;
... Breuer, Judith; + view all
(2024)
Persistent Low-Level Variants in a Subset of Viral Genes Are Highly Predictive of Poor Outcome in Immunocompromised Patients With Cytomegalovirus Infection.
The Journal of Infectious Diseases
10.1093/infdis/jiae001.
(In press).
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Abstract
BACKGROUND: Human cytomegalovirus is the most common and serious opportunistic infection after solid organ and haematopoietic stem cell transplantation. In this study, we used whole-genome cytomegalovirus data to investigate viral factors associated with the clinical outcome. METHODS: We sequenced cytomegalovirus samples from 16 immunocompromised paediatric patients with persistent viraemia. 8/16 patients died of complications due to cytomegalovirus infection. We also sequenced samples from 35 infected solid organ adult recipients of whom one died with cytomegalovirus infection. RESULTS: We showed that samples from both groups have fixed variants at resistance sites and mixed infections. NGS sequencing also revealed non-fixed variants at resistance sites in most of the patients who died (6/9). A machine learning approach identified 10 genes with non-fixed variants in these patients. These genes formed a viral signature which discriminated patients with cytomegalovirus infection who died from those that survived with high accuracy (AUC=0.96). Lymphocyte numbers for a subset of patients showed no recovery post-transplant in the patients who died. CONCLUSIONS: We hypothesise that the viral signature identified in this study may be a useful biomarker for poor response to antiviral drug treatment and indirectly for poor T cell function, potentially identifying early, those patients requiring non-pharmacological interventions.
| Type: | Article |
|---|---|
| Title: | Persistent Low-Level Variants in a Subset of Viral Genes Are Highly Predictive of Poor Outcome in Immunocompromised Patients With Cytomegalovirus Infection |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/infdis/jiae001 |
| Publisher version: | http://dx.doi.org/10.1093/infdis/jiae001 |
| Language: | English |
| Additional information: | The Journal of Infectious Diseases® © The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. https://doi.org/10.1093/infdis/jiae001 |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Immunology, Infectious Diseases, Microbiology, cytomegalovirus infection, genomics, viral signature, transplant, STEM-CELL TRANSPLANTATION, MANAGEMENT, RESISTANCE, RECOVERY |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10188741 |
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