BACKGROUND Metagenomic next-generation sequencing (mNGS) has the potential to become a complementary, if not essential, test in some clinical settings. However, the clinical application of mNGS in a large population of children with various types of infectious diseases (IDs) has not been previously evaluated. METHODS From April 2019 to April 2021, 640 samples were collected at a single pediatric hospital and classified as ID [479 (74.8%)], non-ID [NID; 156 (24.4%)], and unknown cases [5 (0.8%)], according to the final clinical diagnosis. We compared the diagnostic performance in pathogen detection between mNGS and standard reference tests. RESULTS According to final clinical diagnosis, the sensitivity and specificity of mNGS were 75.0% (95% CI: 70.8%-79.2%) and 59.0% (95% CI: 51.3%-66.7%), respectively. For distinguishing ID from NID, the sensitivity of mNGS was approximately 45.0% higher than that of standard tests (75.0% vs 30.0%; P < 0.001). For fungal detection, mNGS showed positive results in 93.0% of cases, compared to 43.7% for standard tests (P < 0.001). Diagnostic information was increased in respiratory system samples through the addition of meta-transcriptomic sequencing. Further analysis also showed that the read counts in sequencing data were highly correlated with clinical diagnosis, regardless of whether infection was by single or multiple pathogens (Kendall's tau b = 0.484, P < 0.001). CONCLUSIONS For pediatric patients in critical condition with suspected infection, mNGS tests can provide valuable diagnostic information to resolve negative or inconclusive routine test results, differentiate ID from NID cases, and facilitate accurate and effective clinical therapeutic decision-making.

中文翻译：

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儿科患者宏基因组下一代测序的诊断性能：大型儿童医疗中心的回顾性研究。

背景 宏基因组下一代测序 (mNGS) 有可能成为一些临床环境中的补充（如果不是必需的）测试。然而，之前尚未评估 mNGS 在患有各种类型传染病 (ID) 的大量儿童中的临床应用。方法 2019 年 4 月至 2021 年 4 月，在一家儿科医院采集 640 份样本，分类为 ID [479 (74.8%)]、非 ID [NID；156 (24.4%)] 和未知病例 [5 (0.8%)]，根据最终临床诊断。我们比较了 mNGS 和标准参考测试在病原体检测中的诊断性能。结果根据最终临床诊断，mNGS的敏感性和特异性分别为75.0%（95% CI：70.8%-79.2%）和59.0%（95% CI：51.3%-66.7%）。为了区分 ID 和 NID，mNGS 的灵敏度比标准测试高约 45.0%（75.0% vs 30.0%；P < 0.001）。对于真菌检测，mNGS 在 93.0% 的病例中显示阳性结果，而标准检测为 43.7%（P < 0.001）。通过添加元转录组测序，增加了呼吸系统样本中的诊断信息。进一步的分析还表明，无论感染是由单一病原体还是多种病原体引起的，测序数据中的读取计数与临床诊断高度相关（Kendall's tau b = 0.484，P < 0.001）。结