Rapid whole genome sequencing (rWGS) of peripheral blood has been used to detect microbial DNA in acute infections. Cytomegalovirus (CMV) is a herpesvirus capable of causing severe disease in neonates and immunocompromised patients. We identified CMV in patients undergoing diagnostic rWGS by matching reads that did not align to the human reference genome to a database of microbial genomes. rWGS was conducted on peripheral blood obtained from ill pediatric patients (age 1 day to 18 years). Reads not aligning to the human genome were analyzed using an in-house pipeline to identify DNA consistent with CMV infection. Of 669 patients who received rWGS from July 2016 through July 2019, we identified 28 patients (4.2%) with reads that aligned to the CMV reference genome. Six of these patients had clinical findings consistent with symptomatic CMV infection. Positive results were highly correlated (R² > 0.99, p < 0.001) to a CMV-qPCR assay conducted on DNA isolated from whole blood samples. In acutely ill children receiving rWGS for diagnosis of genetic disease, we propose analysis of patient genetic data to identify CMV, which could impact treatment of up to 4% of children in the intensive care unit.

外周血的快速全基因组测序 (rWGS) 已用于检测急性感染中的微生物 DNA。巨细胞病毒 (CMV) 是一种疱疹病毒，能够在新生儿和免疫功能低下的患者中引起严重疾病。我们通过将与人类参考基因组不一致的读数与微生物基因组数据库进行匹配，在接受诊断性 rWGS 的患者中识别出 CMV。rWGS 是对从生病的儿科患者（1 天到 18 岁）获得的外周血进行的。使用内部管道分析与人类基因组不对齐的读数，以识别与 CMV 感染一致的 DNA。在 2016 年 7 月至 2019 年 7 月期间接受 rWGS 的 669 名患者中，我们确定了 28 名患者 (4.2%) 的读数与 CMV 参考基因组对齐。其中 6 名患者的临床表现与有症状的 CMV 感染一致。阳性结果高度相关（R²  > 0.99，p  < 0.001) 对从全血样本中分离的 DNA 进行的 CMV-qPCR 测定。在接受 rWGS 诊断遗传病的急病儿童中，我们建议分析患者的遗传数据以识别 CMV，这可能会影响重症监护病房中多达 4% 的儿童的治疗。