Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Clin Chem. 2022 Jul 27;68(8):1031-1041. doi: 10.1093/clinchem/hvac067.
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.
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.
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).
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.
宏基因组下一代测序（mNGS）有可能成为某些临床情况下的补充检测方法，甚至是必要检测方法。然而，mNGS 在患有各种类型感染性疾病（ID）的大量儿童患者中的临床应用尚未得到评估。
2019 年 4 月至 2021 年 4 月，在一家儿科医院采集了 640 份样本，根据最终临床诊断将其分为 ID [479（74.8%）]、非 ID（NID；156（24.4%）]和未知病例[5（0.8%）]。我们比较了 mNGS 和标准参考检测在病原体检测中的诊断性能。
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%）。在区分 ID 和 NID 方面，mNGS 的敏感性比标准检测高出约 45.0%（75.0%比 30.0%；P<0.001）。对于真菌检测，mNGS 阳性结果占 93.0%，而标准检测阳性结果占 43.7%（P<0.001）。通过添加 meta 转录组测序，可增加呼吸系统样本的诊断信息。进一步分析还表明，无论感染是由单一或多种病原体引起，测序数据的读取计数与临床诊断高度相关（Kendall tau b=0.484，P<0.001）。
对于疑似感染处于危急状态的儿科患者，mNGS 检测可以提供有价值的诊断信息，解决常规检测阴性或不确定的问题，区分 ID 和 NID 病例，并有助于准确和有效地进行临床治疗决策。
