Evaluation of metagenomic next-generation sequencing diagnosis for invasive pulmonary aspergillosis in immunocompromised and immunocompetent patients

Mycoses. 2023 Apr;66(4):331-337. doi: 10.1111/myc.13557. Epub 2023 Jan 11.

Abstract

Background: Invasive pulmonary aspergillosis (IPA) can occur in both immunocompromised and non-immunocompromised hosts, and early diagnosis of IPA is difficult. Metagenomic next-generation sequencing (mNGS) is a novel non-migratory pathogen detection method; however, utilising this method for IPA diagnosis is challenging due to the current lack of a unified clinical interpretation standard following Aspergillus detection using mNGS.

Objectives: To investigate the accuracy of IPA diagnosis by positive bronchoalveolar lavage fluid (BALF) mNGS results in immunocompromised and immunocompetent patients.

Methods: We retrospectively included patients with confirmed pulmonary infections having a BALF mNGS result of Aspergillus reads ≥1. We compared the accuracy of using mNGS for IPA diagnosis in patients with different immune statuses based on the revised EORTC/MSG criteria.

Results: Overall, 62 mNGS Aspergillus-positive patients were divided into two groups: with (41) and without IPA (21). In univariate logistic regression analysis, immunocompromised function, fever, halo sign on CT image, and multiple masses or nodules were associated with mNGS Aspergillus-positive IPA diagnosis. In multivariate logistic regression analysis, immunocompromised function (OR = 6.68, 95% CI: 1.73-25.87, p = .006) and a halo sign (OR = 7.993, 95% CI: 2.07-30.40, p = .003) were independent risk factors. The concordance rate of IPA diagnosis was significantly higher in immunocompromised patients [82.1% (23/28)] than in non-immunocompromised patients [52.9% (18/34); p = .016].

Conclusions: For immunocompromised patients, a combination of mNGS testing and lung CT imaging can be used for IPA diagnosis. However, caution is required in IPA diagnosis based on positive mNGS results in non-immunocompromised patients.

Keywords: Aspergillus; fungal infection; halo sign; immunocompromised host; invasive pulmonary aspergillosis; mNGS.

MeSH terms

  • Aspergillus / genetics
  • Bronchoalveolar Lavage Fluid
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Invasive Pulmonary Aspergillosis* / diagnosis
  • Retrospective Studies
  • Sensitivity and Specificity