Invasive Pulmonary Aspergillosis Diagnosis via Peripheral Blood Metagenomic Next-Generation Sequencing

Abstract

Invasive pulmonary aspergillosis (IPA) is one of the major causes of morbidity and mortality in immunocompromised patients such as hematological malignancies, hematopoietic stem cell transplantation, and solid organ transplantation. The diagnosis of IPA in these patients is still difficult because it has no obvious specificity in clinical symptoms, signs and imaging, and test sensitivity of blood 1,3-β-d-glucan test, galactomannan are low. Therefore, we still need to explore more diagnostic methods. In our study, via peripheral blood metagenomic next-generation sequencing (mNGS), five patients were tested positive for Aspergillus DNA and then quickly diagnosed as IPA. Out of the 5 cases, 1 was proven and 4 were probable IPA. The underlying diseases of the 5 patients were myelodysplastic syndrome (2 cases), acute myeloid leukemia (2 cases), and renal transplantation (1 case). Then they were diagnosed as IPA using other methods such as lung histopathology, bronchoalveolar lavage fluid (BALF) mNGS, and sputum culture or sputum mNGS. In case 1, sputum culture suggested Aspergillus flavus. In case 2, both Grocott methenamine silver (GMS) stain of lung histopathology and lung tissue mNGS suggested Aspergillus infection. In cases 3 and 4, BALF-mNGS suggested Aspergillus infection. In case 5, sputum mNGS suggested Aspergillus infection. In conclusion, detecting the cfDNA of Aspergillus via peripheral blood mNGS can be used to diagnose IPA and is a rapid and non-invasive diagnosis method.

Metagenomic next-generation sequencing for the diagnosis of pulmonary aspergillosis in non-neutropenic patients: a retrospective study

“…Mixed infections and co-pathogens in 13 non-neutropenic pulmonary aspergillosis cases identified using mNGS. and the diagnosis of pulmonary aspergillosis (He et al, 2019;Zhang et al, 2020;Chen et al, 2021;Ma et al, 2022). In these studies, Chen et al (Chen et al, 2021) and Zhang et al (Zhang et al, 2020) reported the application of NGS in diagnosing coinfection of Aspergillus and P. jirovecii, which supports the results of this study.…”

“…To date, mNGS has been clinically used. There are only few studies that have investigated the association between mNGS and the diagnosis of pulmonary aspergillosis ( He et al., 2019 ; Zhang et al., 2020 ; Chen et al., 2021 ; Ma et al., 2022 ). In these studies, Chen et al.…”

Application Value of Metagenomics Next-Generation Sequencing (mNGS) in Detection of Mucormycosis after Chemotherapy in Childhood Acute Leukemia

“…However, the early diagnosis of pulmonary trichomycosis lacks speci city and relies mainly on histopathology and fungal culture, with long lead times and low positive rates [7]. In recent years, with the advent of mNGS assays, the detection rate of pathogenic organisms in children with postchemotherapy coinfection in leukemia has improved [8]. In this study, we retrospectively analyzed seven children with acute leukemia who had early infection detected by the mNGS method after chemotherapy for leukemia from January 2020 to December 2021, and analyzed the clinical characteristics, treatment, and outcome of these children [9].…”

Invasive pulmonary aspergillosis with candidiasis: usefulness of molecular and ultrastructural morphological analysis on FFPE tissue for invasive fungal infections

“…The most severe form of Aspergillus infection is invasive aspergillosis (IA), which affects more than 300,000 people worldwide every year [ 10 ]. IPA accounts for more than 90% of cases of IA, and viral infections such as infections with SARS-CoV-2 and influenza viruses have recently been reported to be risks for IPA [ 7 , 11 ]. Influenza virus infection is known to induce 'influenza-associated pulmonary aspergillosis (IAPA)', which can progress to IPA, and the incidence of IAPA has been increasing [ 5 , 6 ].…”