Shen Huili, Zhang Xiaolei, Xu Junfeng, Ma Weike, Chen Weiming, Wang Yixue, Zhang Caiyan, Fan Panpan, Zhu Xuemei, He Liming, Yan Huiyuan, Shen Meili, Lu Guoping, Yan Gangfeng
Department of Critical Care Medicine, and Department of Emergency, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Department of Critical Care Medicine, and Department of Emergency, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Children's Hospital of Fudan University (Xiamen Branch), Xiamen Children's Hospital, Fujian, China.
J Infect Public Health. 2025 Aug;18(8):102823. doi: 10.1016/j.jiph.2025.102823. Epub 2025 May 11.
Study on the clinical pathogen diagnosis in large cohort of critically ill children using metagenomic next-generation sequencing (mNGS) with different enrichment strategies has been limited.
763 samples were enrolled and we summarized the clinical pathogen diagnosis and compared the performance between mNGS and clinical microbial tests (CMTs) in different sample types, as well as between shotgun-based (S-mNGS) and hybrid capture-based mNGS (C-mNGS).
A total of 93 clinical diagnosed pathogens were identified from763 samples with suspected infections, with a positive rate of 60.16 %. Respiratory specimens had the highest positive rate (90.73 %, 235/259), while the lowest was cerebrospinal fluid (26.94 %, 59/219). mNGS showed higher sensitivity (90.85 % vs. 83.66 %, P = 0.001), specificity (77.30 % vs. 67.43 %, P = 0.007), positive predictive value (PPV, 85.80 % vs. 79.50 %, P = 0.01), negative predictive value (NPV, 84.84 % vs. 73.21 %, P < 0.001), and accuracy (85.45 % vs. 77.20 %, P < 0.001) than CMTs. The corrected true positive rate of mNGS was higher than CMTs (83.88 % vs. 75.60 %, P = 0.002), and its advantage in virus detection was more obvious (OR=1.39, 95 %CI: 1.08-1.78, P = 0.010). S-mNGS and C-mNGS shown significantly higher sensitivity and accuracy than CMTs. However, the total true positive rate between S-mNGS and C-mNGS were close (83.15 % vs. 85.00 %, P = 0.600). According to the mNGS results, the adjusted pathogen diagnosis rate was 45.48 % (417/763), and the adjusted anti-infection strategy ratio was 42.86 % (327/763).
mNGS provided an efficient pathogen diagnosis method for critically ill children with suspected infection. Different enrichment strategies of mNGS can play their respective advantages in clinical practice.
使用宏基因组下一代测序（mNGS）结合不同富集策略对大量危重症儿童进行临床病原体诊断的研究有限。
纳入763份样本，总结临床病原体诊断情况，并比较mNGS与临床微生物检测（CMTs）在不同样本类型中的性能，以及基于鸟枪法（S-mNGS）和基于杂交捕获法的mNGS（C-mNGS）之间的性能。
从763份疑似感染样本中总共鉴定出93种临床诊断病原体，阳性率为60.16%。呼吸道标本的阳性率最高（90.73%，235/259），而脑脊液的阳性率最低（26.94%，59/219）。mNGS显示出比CMTs更高的敏感性（90.85%对83.66%，P = 0.001）、特异性（77.30%对67.43%，P = 0.007）、阳性预测值（PPV，85.80%对79.50%，P = 0.01）、阴性预测值（NPV，84.84%对73.21%，P < 0.001）和准确性（85.45%对77.20%，P < 0.001）。mNGS的校正真阳性率高于CMTs（83.88%对75.60%，P = 0.002），其在病毒检测方面的优势更明显（OR = 1.39，95%CI：1.08 - 1.78，P = 0.010）。S-mNGS和C-mNGS显示出比CMTs显著更高的敏感性和准确性。然而，S-mNGS和C-mNGS之间的总真阳性率接近（83.15%对85.00%，P = 0.600）。根据mNGS结果，调整后的病原体诊断率为45.48%（417/763），调整后的抗感染策略比例为42.86%（327/763）。
mNGS为疑似感染的危重症儿童提供了一种有效的病原体诊断方法。mNGS的不同富集策略在临床实践中可以发挥各自的优势。
