EV Sepsis Natural History

这项研究，新生儿肠道病毒和人类副病毒病毒败血症：自然史和预测因素 发病率和死亡率，由Mark Abzug医学博士科学领导。新生儿病毒性败血症是一种临床综合征 以一系列器官受累为特征的，包括肝炎、凝血障碍(血小板减少症 有或没有凝血时间紊乱)和/或心肌炎，有时与 脑膜脑炎或肺炎。尽管许多病毒可以导致新生儿病毒性败血症，包括 单纯疱疹病毒(HSV)、巨细胞病毒(CMV)和腺病毒是最常见的两种原因 肠道病毒(EVS)和人类副病毒(HPeV)。新生儿EV或HPeV败血症的抗病毒治疗 是需要的，但还没有商业化。新生儿病毒性败血症未来抗病毒试验的设计 如果更好地了解这种严重但罕见的疾病的自然历史，将大大受益。 更准确地定义与新生儿EV和HPeV相关的长期发病率和死亡率 脓毒症，以及更好地描述可预测不良后果的临床和实验室参数， 对于指导治疗试验的最佳设计很重要，包括适当的终点、 样本量和纳入标准。定量聚合酶链式反应(QPCR)或其他实验室的潜在用途 预测这些疾病的严重程度、长期后遗症或死亡率的生物标志物目前 未知。如果定量聚合酶链式反应被证明是临床结果的有用预测因子或替代物，这将极大地 促进治疗试验的开展。最后，到目前为止的研究表明，一部分儿童 临床表现为新生儿病毒性败血症，没有EVS、HPeV或其他已知病毒。这很重要 使用最先进的病原体发现工具更好地了解病原体的全谱。 这项拟议的研究旨在填补我们对新生儿病毒败血症知识的这些空白，以推动 为这一疾病的抗病毒治疗疗法的预期发展做好试验准备。这将是 通过评估以下具体目标来完成：1)估计以下疾病的发病率和死亡率 新生儿EV败血症和新生儿HPeV败血症；2)确定临床和实验室参数，包括 定量聚合酶链式反应(QPCR)，预测新生儿EV和 新生儿HPeV败血症；以及3)确定非EV、HPeV、HSV、 CMV，以及使用下一代测序技术发现病原体的腺病毒。系统的远景 对新生儿病毒性败血症的多中心评估，包括EV和HPeV败血症，将产生可以 用于设计未来的第一、第二和第三阶段治疗研究，目前正在开发中的抗病毒药物 由制药公司，如Kyorin制药有限公司和Vaxart，Inc.

This study, Neonatal Enterovirus and Human Parechovirus Viral Sepsis: Natural History and Predictors of Morbidity and Mortality, is scientifically led by Mark Abzug, MD. Neonatal viral sepsis is a clinical syndrome characterized by a constellation of organ involvement that includes hepatitis, coagulopathy (thrombocytopenia with or without derangement of clotting times), and/or myocarditis, sometimes occurring in concert with meningoencephalitis or pneumonitis. Although a number of viruses can cause neonatal viral sepsis, including herpes simplex virus (HSV), cytomegalovirus (CMV), and adenovirus, two of the most frequent causes are enteroviruses (EVs) and human parechoviruses (HPeVs). Antiviral treatment for neonatal EV or HPeV sepsis is needed, but not yet commercially available. The design of future antiviral trials for neonatal viral sepsis would greatly benefit from a better understanding of the natural history of this serious, but rare, condition. More precise definition of rates of long-term morbidity and mortality associated with neonatal EV and HPeV sepsis, and better delineation of clinical and laboratory parameters that are predictive of adverse outcomes, are important to inform the optimal design of therapeutic trials, including issues such as appropriate endpoints, sample size, and inclusion criteria. The potential utility of quantitative PCR (qPCR) or other laboratory biomarkers to predict severity of illness, long-term sequelae, or mortality in these illnesses is currently unknown. If qPCR was shown to be a useful predictor of or surrogate for clinical outcomes, this could greatly facilitate the performance of therapeutic trials. Finally, studies to date suggest that a portion of children presenting clinically with neonatal viral sepsis do not have EVs, HPeVs, or other known viruses. It is important to better understand the full spectrum of etiologic agents using state-of-the-art tools for pathogen discovery. The proposed study is designed to fill in these gaps in our knowledge about neonatal viral sepsis to advance trial readiness for the anticipated development of antiviral treatment therapy for this condition. This will be accomplished by evaluating the following specific aims: 1) to estimate the morbidity and mortality rates of neonatal EV sepsis and neonatal HPeV sepsis; 2) to identify clinical and laboratory parameters, including quantitative polymerase chain reaction (qPCR), predictive of morbidity and mortality from neonatal EV and neonatal HPeV sepsis; and 3) to determine the etiologies of neonatal viral sepsis not due to EV, HPeV, HSV, CMV, and adenovirus using next-gen sequencing for pathogen discovery. The systematic prospective multicenter assessment of neonatal viral sepsis, including EV and HPeV sepsis, will produce data that can be used in the design of future Phase I, II, and III treatment studies with antiviral drugs currently in development by pharmaceutical companies, such as KYORIN Pharmaceutical Co., Ltd., and Vaxart, Inc.