Diagnostic efficiency of metagenomic next-generation sequencing for suspected infection in allogeneic hematopoietic stem cell transplantation recipients

Jiayu Huang; Yeqian Zhao; Chuanhe Jiang; Dongsheng Han; Zengkai Pan; Zilu Zhang; Luxiang Wang; Wei Chen; Su Li; Yanmin Zhao; Xiaoxia Hu

doi:10.3389/fcimb.2023.1251509

Diagnostic efficiency of metagenomic next-generation sequencing for suspected infection in allogeneic hematopoietic stem cell transplantation recipients

Front Cell Infect Microbiol. 2023 Sep 13:13:1251509. doi: 10.3389/fcimb.2023.1251509. eCollection 2023.

Authors

Jiayu Huang^{1

2}, Yeqian Zhao³, Chuanhe Jiang^{1

2}, Dongsheng Han⁴, Zengkai Pan^{1

2}, Zilu Zhang^{1

2}, Luxiang Wang^{1

2}, Wei Chen^{5

6}, Su Li⁷, Yanmin Zhao³, Xiaoxia Hu^{1

2}

Affiliations

¹ State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Collaborative Innovation Center of Hematology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
⁴ Centre of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
⁵ Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁷ GoBroad Medical Institute of Hematology (Shanghai Center), Liquan Hospital, Shanghai, China.

Abstract

Introduction: Immunosuppression predisposes allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients to infection. Prompt and accurate identification of pathogens is crucial to optimize treatment strategies. This multi-center retrospective study aimed to assess the ability of metagenomic next-generation sequencing (mNGS) to detect causative pathogens in febrile allo-HSCT recipients and examined its concordance with conventional microbiological tests (CMT).

Methods: We performed mNGS and CMT on samples obtained from 153 patients with suspected infection during allo-HSCT. Patients were grouped based on their neutropenic status at the time of sampling.

Results: The mNGS test was more sensitive than CMT (81.1% vs. 53.6%, P<0.001) for diagnosing clinically suspected infection, especially in the non-neutropenia cohort. mNGS could detect fungi and viruses better than bacteria, with a higher sensitivity than CMT. Immune events were diagnosed in 57.4% (35/61) of the febrile events with negative mNGS results, and 33.5% (48/143) with negative CMT results (P=0.002). The treatment success rate of the targeted anti-infection strategy was significantly higher when based on mNGS than on empirical antibiotics (85% vs. 56.5%, P=0.004).

Conclusion: The mNGS test is superior to CMT for identifying clinically relevant pathogens, and provides valuable information for anti-infection strategies in allo-HSCT recipients. Additionally, attention should be paid to immune events in patients with negative mNGS results.

Keywords: clinical infection; conventional microbiological tests; diagnostic efficiency; immune events; metagenomic next-generation sequencing.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents
Hematopoietic Stem Cell Transplantation* / adverse effects
High-Throughput Nucleotide Sequencing*
Humans
Immunosuppression Therapy
Metagenomics
Retrospective Studies
Sensitivity and Specificity

Substances

Anti-Bacterial Agents

Grants and funding

This work was supported by the National Natural Science Foundation (82170206 to XH, 82170210 to YMZ), Project of Disciplines of Excellence (20234Z0002 to XH), Shanghai Municipal Health Commission, the National Key Research and Development Program of China (2022YFA1103500 to YMZ), Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100 to WC).