The management of hand-foot-and-mouth disease(HFMD) epidemic is difficult due to the frequent emergence of non-EV71 and non-CVA16 enteroviruses and some cases testing negative for HFMD-associated causative agents. To clarify the virus spectrum of mild and severe HFMD, a comprehensive virome analysis of 238 samples was performed using next-generation sequencing (NGS). The data revealed total thirteen mammalian- and plant- virus families and diverse viral populations including enteroviruses, common respiratory viruses, diarrhea-related viruses, plant viruses and anelloviruses. A total of 18 viruses from 7 virus families were identified in severe cases, versus 37 viruses from 12 virus families in mild cases. Moreover, complicated mixed-infections of enteroviruses with common respiratory viruses were mainly found in severe cases(P = 0.013), while diarrhea-related viruses were mainly found in mild cases(P < 0.001). This study provides the preliminary understanding of viromes both in mild and severe cases, which may benefit the detection of etiologic agents and prevention of HFMD.

由于非EV71和非CVA16肠病毒的频繁出现，并且手足口病（HFMD）流行的管理很困难，并且某些情况下HFMD相关病原体呈阴性。为了阐明轻度和重度手足口病的病毒谱，使用下一代测序（NGS）对238个样品进行了全面的病毒学分析。数据揭示了总共13个哺乳动物和植物病毒家族以及各种病毒种群，包括肠道病毒，普通呼吸道病毒，腹泻相关病毒，植物病毒和网膜病毒。在严重病例中，总共鉴定出来自7个病毒家族的18种病毒，而在轻度病例中，鉴定出来自12个病毒家族的37种病毒。此外，在严重病例中主要发现肠道病毒与普通呼吸道病毒的复杂混合感染（P  = 0.013），而腹泻相关病毒主要见于轻度病例（P  <0.001）。这项研究为轻度和重度病例提供了病毒学的初步了解，这可能有助于病原体的发现和手足口病的预防。