Metagenomics next-generation sequencing for diagnosis of invasive fungal diseases in patients with hematological diseases

Abstract

Objectives

To investigate the clinical characteristics and risk factors of invasive fungal disease (IFD) in patients with hematological disorders.

Methods

From January 2023 to January 2025, 67 patients with blood diseases hospitalized at the Hematology Department who were suspected of infection with IFD underwent metagenomic next-generation sequencing (mNGS) and fungal pathogen detection. Their clinical characteristics and laboratory examinations were retrospectively analyzed.

Results

A cohort of 67 patients was enrolled in the study, among which 32 cases were diagnosed with IFD through mNGS and etiological culture, while no fungal pathogens were detected in the remaining 35 cases. The diagnostic yield of mNGS for fungal infection detection (47.76%) demonstrated superior sensitivity compared to conventional pathogenic microbial culture (14.93%), β-D-glucan assay (11.94%), and galactomannan assay (2.99%). Within the IFD cohort, Candida species constituted the most prevalent etiology (46.88%, n = 15), followed by Aspergillus (18.75%, n = 6), Penumocystis (12.5%, n = 4), and Rhizomucor (12.5%, n = 4), with other fungal species accounting for the remaining cases (9.37%, n = 3). Multivariate logistic regression analysis revealed six independent risk factors associated with IFD in patients with hematological disorders: cluster of differentiation 4+ T cell count <400 cells/µL (odds ratio [OR] = 9.45, P = 8.9×10^–5), elevated C-reactive protein (OR = 3.18, P = 0.027), elevated interleukin (IL)-6 (OR = 5.75, P = 0.001), elevated IL-10 (OR = 3.31, P = 0.033), hypoproteinemia (OR = 42.17, P = 0.013), and neutropenia lasting for more than 10 days (OR = 4.11, P = 0.015).

Conclusions

mNGS has high sensitivity in detecting IFD in patients with hematological diseases. Cluster of differentiation 4+ cell count below 400/uL, increased level of C-reactive protein, IL-6, and IL-10, hypoproteinemia, and neutropenia lasting for more than 10 days are independent risk factors for IFD in patients with hematological diseases.