多微生物相互作用对人类偏肺病毒感染儿童的临床影响：一项基于下一代测序的有针对性的回顾性研究

摘要(中文译文)

（）是儿童急性呼吸道感染的重要病原体。既往研究依赖传统诊断方法，低估了复杂的多重微生物相互作用，而本研究旨在利用靶向下一代测序（tNGS）全面描绘其共定植或共感染病原谱的动态变化及其对疾病严重程度的影响，从而为临床风险分层提供依据。本回顾性研究纳入526例（）感染的住院儿童。采用靶向下一代测序（tNGS）按年龄、性别、标本来源、免疫缺陷和免疫接种状态分层，全面分析共定植或共感染谱。采用多因素logistic回归评估其与宿主因素及严重临床结局（ICU[重症监护病房]入住、机械通气、感染性休克、影像学肺炎）的独立相关性。住院患者中位年龄为36个月，15.6%需要入住ICU。由于我们在tNGS现有结果中至少鉴定出一种病原体，队列中共检出的总体流行率为100%。共定植或共感染病原谱呈现出显著的年龄特异性、时间动态变化和标本类型依赖性。多因素分析确定了数种与严重结局独立相关的病原体。具体而言，机会性和非典型病原体（如[患病率：7.22%]、[1.71%]、[0.76%]和[1.90%]）是ICU入住、有创通气和感染性休克的强危险因素（校正比值比[aOR]范围为4.57至28.69）。相反，[25.67%]始终表现出保护作用（例如，ICU入住的aOR=0.43）。[12.93%]是影像学肺炎的独立危险因素（aOR=2.25），而[1.14%]显示出显著的保护性关联（aOR=0.09）。尽管存在局限性，包括单中心回顾性设计和缺乏hMPV阴性对照组，（）感染儿童的共定植或共感染病原谱仍然复杂，且与宿主特征密切相关。通过tNGS早期识别高风险共感染病原体（如CMV或）应触发强化临床监测。未来需要前瞻性对照研究来验证这些发现并确认因果关系。

Abstract

() is a significant pathogen of acute respiratory infection in children. While previous studies have relied on conventional diagnostics that underestimate complex polymicrobial interactions, this study aimed to utilize targeted next-generation sequencing (tNGS) to comprehensively profile the dynamics of its co-colonization or co-infection pathogen spectrum and their impact on disease severity, thereby informing clinical risk stratification. This retrospective study enrolled 526 hospitalized children with infection. Targeted next-generation sequencing (tNGS) was used to comprehensively analyze the co-colonization or co-infection spectrum stratified by age, gender, sample origin, immune deficiency, and immunization status. Multivariable logistic regression was employed to assess independent associations with host factors and severe clinical outcomes (ICU [intensive care unit] admission, mechanical ventilation, septic shock, pneumonia on imaging). The median age of the inpatients was 36 months, and 15.6% required ICU admission. The overall prevalence of co-detection among the cohort was 100% since we identified at least one pathogen in the existing results from tNGS. The co-colonization or co-infection pathogen spectrum demonstrated significant age specificity, temporal dynamics, and sample type dependency. Multivariable analysis identified several pathogens independently associated with severe outcomes. Specifically, opportunistic and atypical pathogens (such as [prevalence: 7.22%], [1.71%], [0.76%], and [1.90%]) were strong risk factors for ICU admission, invasive ventilation, and septic shock (adjusted Odds Ratios [aOR] ranging from 4.57 to 28.69). Conversely, (25.67%) consistently exhibited a protective effect (eg, aOR=0.43 for ICU admission). (12.93%) was an independent risk factor for pneumonia on imaging (aOR=2.25), while (1.14%) showed a significant protective association (aOR=0.09). Despite limitations including a single-center retrospective design and the absence of an hMPV-negative control group, the co-colonization or co-infection pathogen spectrum in children with infection is complex and closely related to host characteristics. Early identification of high-risk co-pathogens (eg, CMV or ) via tNGS should trigger intensified clinical monitoring. Future prospective controlled studies are needed to validate these findings and confirm causality.

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