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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.

Sec. Clinical and Diagnostic Microbiology and Immunology

Targeted next-generation sequencing for respiratory infections in patients with hematological malignancies

Provisionally accepted
Xiaoxia  HuXiaoxia Hu1*Jiayu  HuangJiayu Huang1Su  LiSu Li2Chuanhe  JiangChuanhe Jiang1Luxiang  WangLuxiang Wang1Zengkai  PanZengkai Pan1Zilu  ZhangZilu Zhang1Jun  ZhuJun Zhu2Wei  ChenWei Chen3*
  • 1Department of Hematolgy, Ruijin Hospital, Shanghai, China
  • 2Shanghai Liquan Hospital, Shanghai, China
  • 3Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China

The final, formatted version of the article will be published soon.

Background: Patients with hematological malignancies are immunocompromised and prone to respiratory infections, but identification of causative pathogens is challenging. The aim of this study was to analyze the ability of targeted next-generation sequencing (tNGS) to detect pathogens in immunocompromised patients. Methods: tNGS and conventional microbiological tests (CMT) were performed on samples from the respiratory tract of 99 patients with suspected respiratory infections. Metagenomic next-generation sequencing (mNGS) was conducted in parallel in 43 patients. Comparative analysis was conducted using the Pearson χ2 test and Fisher’s exact test, as appropriate. Results: The overall microbial detection rates for tNGS were 100% (23/23) in the upper respiratory tract and 96.1% (99/103) in the lower respiratory tract. Microorganism colonization was detected by tNGS in 80.8% (97/120) of cases. The sensitivity of tNGS was 30% greater than that of CMT (87.7% vs. 52.5%; P < 0.001), but tNGS had a lower specificity (33.3% vs. 83.3%; P = 0.242). tNGS improved the overall treatment success rate by 69.7% (69/99 cases) in CMT true-negative or CMT-partially matched cases. In the paired respiratory tNGS and mNGS cases, tNGS verified 73.3% (11/15) cases of infection, while mNGS only verified 40% (P=0.139). Conclusions: Most immunosuppressed patients are colonized by microorganisms, and require prompt identification of the cause of any infections. tNGS has promising diagnostic potential and offers valuable information for optimizing antibiotic therapy, especially when compared to CMT.

Keywords: Targeted next-generation sequencing, metagenomic next-generation sequencing, diagnosticefficiency, conventional microbiological tests, treatment efficacy

Received: 03 Aug 2025; Accepted: 03 Nov 2025.

Copyright: © 2025 Hu, Huang, Li, Jiang, Wang, Pan, Zhang, Zhu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Xiaoxia Hu, hu_xiaoxia@126.com
Wei Chen, cw11242@rjh.com.cn

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.