Dataset Information

Persistent Low-Level Variants in a Subset of Viral Genes Are Highly Predictive of Poor Outcome in Immunocompromised Patients With Cytomegalovirus Infection.

ABSTRACT:

Background

Human cytomegalovirus (HCMV) is the most common and serious opportunistic infection after solid organ and hematopoietic stem cell transplantation. In this study, we used whole-genome HCMV data to investigate viral factors associated with the clinical outcome.

Methods

We sequenced HCMV samples from 16 immunocompromised pediatric patients with persistent viremia. Eight of the 16 patients died of complications due to HCMV infection. We also sequenced samples from 35 infected solid organ adult recipients, of whom 1 died with HCMV infection.

Results

We showed that samples from both groups have fixed variants at resistance sites and mixed infections. Next-generation sequencing also revealed nonfixed variants at resistance sites in most of the patients who died (6/9). A machine learning approach identified 10 genes with nonfixed variants in these patients. These genes formed a viral signature that discriminated patients with HCMV infection who died from those who survived with high accuracy (area under the curve = 0.96). Lymphocyte numbers for a subset of patients showed no recovery posttransplant in the patients who died.

Conclusions

We hypothesize 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 nonpharmacological interventions.

SUBMITTER: Venturini C

PROVIDER: S-EPMC11326829 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Persistent Low-Level Variants in a Subset of Viral Genes Are Highly Predictive of Poor Outcome in Immunocompromised Patients With Cytomegalovirus Infection.

Venturini Cristina C Colston Julia M JM Charles Oscar O Lankina Anastasia A Best Timothy T Atkinson Claire C Forrest Calum C Williams Charlotte A CA Rao Kanchan K Worth Austen A Thorburn Doug D Harber Mark M Griffiths Paul P Breuer Judith J

The Journal of infectious diseases 20240801 2

<h4>Background</h4>Human cytomegalovirus (HCMV) is the most common and serious opportunistic infection after solid organ and hematopoietic stem cell transplantation. In this study, we used whole-genome HCMV data to investigate viral factors associated with the clinical outcome.<h4>Methods</h4>We sequenced HCMV samples from 16 immunocompromised pediatric patients with persistent viremia. Eight of the 16 patients died of complications due to HCMV infection. We also sequenced samples from 35 infect ...[more]

PMID: 38181168

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Project description:BackgroundMost patients with SARS-CoV-2 are non-infectious within 2 weeks, though viral RNA may remain detectable for weeks. However there are reports of persistent SARS-CoV-2 infection, with viable virus and ongoing infectivity months after initial detection. Beyond individuals, viral evolution during persistent infections may be accelerated, driving emergence of mutations associated with viral variants of concern. These patients often do not meet inclusion criteria for clinical trials, meaning clinical and virologic characteristics, and optimal management strategies are poorly evidence-based.MethodsWe analysed cases of SARS-CoV-2 infection from a regional testing laboratory in South-West England between March 2020 and December 2021, with at least two SARS-CoV-2 positive samples separated by ≥ 56 days were identified. Excluding those with confirmed or likely re-infection, we identified patients with persistent infection, characterised by an ongoing clinical syndrome consistent with COVID-19 alongside monophyletic viral lineage of SARS-CoV-2. We examined clinical and virologic characteristics, treatment, and outcome. We further performed a literature review investigating cases of persistent SARS-CoV-2 infection, reviewing patient characteristics and treatment.ResultsWe identified six patients with persistent SARS-CoV-2 infection. All were hypogammaglobulinaemic and had underlying haematological malignancy, with four having received B-cell depleting therapy. Evidence of viral evolution, including accrual of mutations associated with variants of concern, was demonstrated in five cases. Four patients ultimately cleared SARS-CoV-2. In two patients, clearance followed treatment with casirivimab/imdevimab. Both survived beyond thirty days following viral clearance, having experienced infections of 305- and 269-days duration respectively, after failed attempts at clearance with alternative therapies. We found 60 cases of confirmed persistent infection in the literature, with a further 31 probable cases. Of those, 80% of patients treated with monoclonal antibodies cleared SARS-CoV-2, and none died.ConclusionHaematological malignancy and patients receiving B-cell depleting therapies represent key groups at risk of persistent SARS-CoV-2 infection. Throughout persistent infection, SARS-CoV-2 can evolve rapidly, giving rise to significant mutations, including those implicated in variants of concern. Monoclonal antibodies appear to be a promising therapeutic option, potentially in combination with antivirals, crucial for individuals, and for public health.

Dataset Information

Persistent Low-Level Variants in a Subset of Viral Genes Are Highly Predictive of Poor Outcome in Immunocompromised Patients With Cytomegalovirus Infection.

Background

Methods

Results

Conclusions

Publications

Persistent Low-Level Variants in a Subset of Viral Genes Are Highly Predictive of Poor Outcome in Immunocompromised Patients With Cytomegalovirus Infection.

Similar Datasets

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