The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease


Autoři: Anneloes L. van Rijn aff001;  Sander van Boheemen aff001;  Igor Sidorov aff001;  Ellen C. Carbo aff001;  Nikos Pappas aff002;  Hailiang Mei aff002;  Mariet Feltkamp aff001;  Marianne Aanerud aff003;  Per Bakke aff004;  Eric C. J. Claas aff001;  Tomas M. Eagan aff003;  Pieter S. Hiemstra aff005;  Aloys C. M. Kroes aff001;  Jutte J. C. de Vries aff001
Působiště autorů: Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands aff001;  Sequencing Analysis Support Core, Department of Medical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands aff002;  Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway aff003;  Department of Clinical Science, University of Bergen, Bergen, Norway aff004;  Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223952

Souhrn

Introduction

Exacerbations are major contributors to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), and respiratory bacterial and viral infections are an important trigger. However, using conventional diagnostic techniques, a causative agent is not always found. Metagenomic next-generation sequencing (mNGS) allows analysis of the complete virome, but has not yet been applied in COPD exacerbations.

Objectives

To study the respiratory virome in nasopharyngeal samples during COPD exacerbations using mNGS.

Study design

88 nasopharyngeal swabs from 63 patients from the Bergen COPD Exacerbation Study (2006–2010) were analysed by mNGS and in-house qPCR for respiratory viruses. Both DNA and RNA were sequenced simultaneously using an Illumina library preparation protocol with in-house adaptations.

Results

By mNGS, 24/88 samples tested positive. Sensitivity and specificity, as compared with PCR, were 96% and 98% for diagnostic targets (23/24 and 1093/1120, respectively). Additional viral pathogens detected by mNGS were herpes simplex virus type 1 and coronavirus OC43. A positive correlation was found between Cq value and mNGS viral normalized species reads (log value) (p = 0.002). Patients with viral pathogens had lower percentages of bacteriophages (p<0.001). No correlation was found between viral reads and clinical markers.

Conclusions

The mNGS protocol used was highly sensitive and specific for semi-quantitative detection of respiratory viruses. Excellent negative predictive value implicates the power of mNGS to exclude any pathogenic respiratory viral infectious cause in one test, with consequences for clinical decision making. Reduced abundance of bacteriophages in COPD patients with viral pathogens implicates skewing of the virome during infection, with potential consequences for the bacterial populations, during infection.

Klíčová slova:

Bacteriophages – Chronic obstructive pulmonary disease – Metagenomics – Polymerase chain reaction – Respiratory infections – Rhinovirus infection – Sequence databases – Viral pathogens


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2019 Číslo 10