Wang Di, Lai Min, Song Hua, Zhang Jing-Ying, Zhao Fen-Ying, Liang Juan, Xu Wei-Qun, Tang Yong-Min, Xu Xiao-Jun
Division/Center of Hematology-Oncology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.
The Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou, China.
Front Microbiol. 2022 Mar 8;13:819467. doi: 10.3389/fmicb.2022.819467. eCollection 2022.
The performance of metagenomic next-generation sequencing (mNGS) in identifying pathogens in immunocompromised children was not very clear. The purpose of this study is to assess the performance of mNGS in this population and to investigate whether the integration of serum cytokines and mNGS assay could improve diagnostic accuracy. We retrospectively collected the clinical data of pediatric patients who suffered febrile diseases and underwent mNGS determination simultaneously in the department of hematology/oncology between January 2019 and March 2021. Specimens were sent for conventional microbiological test (CMT), mNGS, and serum cytokine measurement in parallel. A total of 258 episodes of febrile diseases were enrolled, mNGS was positive in 224 cases, while CMT was positive in 78 cases. mNGS and CMT were both positive in 70 (27.1%) cases and were both negative in 26 (10.1%) cases. There were 154 (59.7%) cases positive by mNGS only while 8 (3.1%) were positive by CMT only. It was common that two or more pathogens were simultaneously detected by mNGS in a single specimen, with only 61 tests identified a single organism. Whether the organisms reported by mNGS were the microbiological etiology of infection was evaluated. Of the 224 cases with positive mNGS results, 135 (58.4%), 30 (13.0%), and 59 (28.6%) were considered as "probable," "possible," and "unlikely," respectively. Patients with high IL-6 (≥ 390 pg/ml) were likely to be bacterial infection. Although mNGS reported mixed pathogens, 84.6% (33/39) and 83.3% (10/12) of patients presenting high IL-6 were confirmed as bacterial infection in the training and validation cohort, respectively. In conclusion, mNGS analysis demonstrates promising diagnostic potential in rapidly identifying clinically relevant pathogens. Given the detection of many clinically irrelevant organisms, the integration of IL-6 improves the precision of mNGS results interpretation.
宏基因组下一代测序（mNGS）在识别免疫功能低下儿童病原体方面的表现尚不清楚。本研究旨在评估mNGS在该人群中的表现，并探讨血清细胞因子与mNGS检测相结合是否能提高诊断准确性。我们回顾性收集了2019年1月至2021年3月期间在血液科/肿瘤科患有发热性疾病并同时接受mNGS检测的儿科患者的临床资料。标本同时送去进行传统微生物检测（CMT）、mNGS检测和血清细胞因子测量。共纳入258例发热性疾病发作病例，mNGS检测阳性224例，而CMT检测阳性78例。mNGS和CMT均阳性70例（27.1%），均阴性26例（10.1%）。仅mNGS检测阳性154例（59.7%），仅CMT检测阳性8例（3.1%）。mNGS在单个标本中同时检测到两种或更多病原体的情况很常见，只有61次检测鉴定出单一病原体。评估了mNGS报告的生物体是否为感染的微生物病因。在mNGS结果阳性的224例病例中，分别有135例（58.4%）、30例（13.0%）和59例（28.6%）被认为是“可能的”、“可能的”和“不太可能的”。白细胞介素-6（IL-6）水平高（≥390 pg/ml）的患者可能是细菌感染。尽管mNGS报告有混合病原体，但在训练队列和验证队列中，IL-6水平高的患者分别有84.6%（33/39）和83.3%（10/12）被确认为细菌感染。总之，mNGS分析在快速识别临床相关病原体方面显示出有前景的诊断潜力。鉴于检测到许多临床不相关的生物体，IL-6的整合提高了mNGS结果解读的准确性。
