Metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection

PLoS One

Michael Greiner¹  Cornelia Bayard¹  Nicolas J. Mueller¹  Peter W. Schreiber¹  Christian Benden²  Macé M. Schuurmans²  Alexandra Trkola³  Fabienne D. Geissberger³  Riccarda Capaul³  Osvaldo Zagordi³  Bettina Ruehe³  Michael Huber³  Dagmara W. Lewandowska³  Jürg Böni³  Andrea Zbinden³ 

[1] Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland;Division of Pulmonary Medicine, University Hospital Zurich, Zurich, Switzerland;Institute of Medical Virology, University of Zurich, Zurich, Switzerland

关键词: Lung transplantation;    Metagenomics;    Respiratory infections;    Rhinovirus infection;    Etiology;    Polymerase chain reaction;    Viral pathogens;    Respiratory physiology;   

DOI  :  10.1371/journal.pone.0177340

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background Lung transplant patients are a vulnerable group of immunosuppressed patients that are prone to frequent respiratory infections. We studied 60 episodes of respiratory symptoms in 71 lung transplant patients. Almost half of these episodes were of unknown infectious etiology despite extensive routine diagnostic testing. Methods We re-analyzed respiratory samples of all episodes with undetermined etiology in order to detect potential viral pathogens missed/not accounted for in routine diagnostics. Respiratory samples were enriched for viruses by filtration and nuclease digestion, whole nucleic acids extracted and randomly amplified before high throughput metagenomic virus sequencing. Viruses were identified by a bioinformatic pipeline and confirmed and quantified using specific real-time PCR. Results In completion of routine diagnostics, we identified and confirmed a viral etiology of infection by our metagenomic approach in four patients (three Rhinovirus A, one Rhinovirus B infection) despite initial negative results in specific multiplex PCR. Notably, the majority of samples were also positive for Torque teno virus (TTV) and Human Herpesvirus 7 (HHV-7). While TTV viral loads increased with immunosuppression in both throat swabs and blood samples, HHV-7 remained at low levels throughout the observation period and was restricted to the respiratory tract. Conclusion This study highlights the potential of metagenomic sequencing for virus diagnostics in cases with previously unknown etiology of infection and in complex diagnostic situations such as in immunocompromised hosts.

【 授权许可】

CC BY