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

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.

Five cases of pulmonary Aspergillus nodules diagnosed at surgery and by pathology in immunocompetent patients, with a literature review

“…mNGS has higher sensitivity than traditional culture methods and is more accurate in diagnosing tuberculosis, fungi, viruses and anaerobes. 12 , 13 The diagnostic accuracy of BALF mNGS positive for Aspergillus in immunocompromised IPA patients reached 82.3%, 14 but its diagnostic value in CPA lacks relevant research data. Due to limitations in conditions and high costs, our group of cases were unable to undergo preoperative BALF mNGS testing.…”

Metagenomic Next-Generation Sequencing (mNGS) for the Diagnosis of Pulmonary Aspergillosis

“…Therefore, mNGS detection combined with pulmonary CT imaging can be used for IPA diagnosis in patients with immunocompromised function. However, the diagnosis of IPA based on positive mNGS results in non-immunocompromised patients should be approached with caution [24].…”

Clinical performance of metagenomic next-generation sequencing for diagnosis of pulmonary Aspergillus infection and colonization

“…In some cases, it can even detect fungal pathogens that are difficult to diagnose using conventional methods ( Liu et al., 2022 ; Chen et al., 2023a ). Furthermore, research has investigated the diagnostic utility of mNGS in non-neutropenic patients, those with COVID-19, and immunocompromised patients with pulmonary Aspergillus infection ( Bao et al., 2022 ; Hoenigl et al., 2023 ; Zhan et al., 2023 ). However, there is still a dearth of studies on differentiating between Aspergillus infection and colonization.…”