COVID-19 Epidemiology and Immune-Pathogenesis in Pregnant Women, Mothers and Children

项目摘要 尽管新型冠状病毒COVID-19大流行，但人们对这种病毒的流行病学知之甚少。 感染、传播和对严重感染的易感性。我们对COVID-19的了解主要是 根据老年人感染后病情严重，以及成年人有合并症。不幸的是， 孕妇、婴儿和儿童对严重感染的易感性、疾病负担和传播 在很大程度上是不确定的。填补这些关于感染易感性知识的根本空白， 这些重要的发育时间点需要能够同时筛查的母婴队列 临床症状和COVID-19病毒感染。为两个母婴建立的基础设施 设计用于婴儿流感感染和免疫力前瞻性分析的队列（U 01 AI 144673; IMPRINT）和呼吸道和肠道感染（CDC申办的PREVAIL; https：//www.cdc.gov/surveillance/nvsn/patientail.html）可用于研究发生率、临床 COVID-19感染在孕妇、母亲中的表现、疾病严重程度和免疫相关性 还有他们的孩子招募怀孕晚期妇女的后勤工作已经到位， 并通过每周两次的症状监测（通过文本）跟踪婴儿的自然感染史 消息），每周鼻拭子采样，并通过快递网络实时识别病毒。 辛辛那提市区。通过本特别关注通知提供补充资金， 2019年新型冠状病毒研究的紧急竞争修订（2019-nCoV; NOT-AI-20-034）将 扩大分析范围，包括对孕妇、母亲、婴儿的COVID-19流行病学监测 和儿童（目标1），并在感染时额外采集标本进行免疫学检测 与招募（感染前）和感染-社区传播解决（目标2）相比。流行病学 监测将包括分析感染严重程度和相对于出生后年龄的病毒脱落持续时间， 母婴及其他家庭接触者之间的病毒传播，以及 母亲免疫力通过婴儿COVID-19垂直和/或产后母乳转移 感染易感性关键标本将包括PBMC，可用于识别 用于分析病毒特异性抗体定性/定量变化的各细胞群、血浆/血清 每个时间点。一个额外的“Tempus”管，允许稳定来自整个细胞的细胞内RNA 将在感染时收集血液用于基因表达分析。我们设想，作为COVID-19 免疫学检测正在开发中，并变得更加标准化，这些样本与COVID-19 每个人的感染克里思和严重程度将为调查 与孕妇、母亲和孕妇中无症状至严重感染相关的免疫学变化 他们的孩子和他们在每一个母婴二元体中的关系。

PROJECT SUMMARY ABSTRACT Despite pandemic spread of the novel coronavirus, COVID-19, too little is known about the epidemiology of infection, transmission, and susceptibility to severe infection. What we do know about COVID-19 is largely based on severe disease after infection in the elderly, and adults with co-morbid conditions. Unfortunately, susceptibility to severe infection, disease burden, and transmission in pregnant women, infants and children remain largely undefined. Filling these fundamental gaps in knowledge regarding infection susceptibility in these essential developmental time points require maternal-infant cohorts capable of simultaneously screening clinical symptoms and COVID-19 virus acquisition. The established infrastructure for two maternal-infant cohorts designed for prospective analysis of infant influenza acquisition and immunity (U01AI144673; IMPRINT) and respiratory and enteric infection (CDC sponsored PREVAIL; https://www.cdc.gov/surveillance/nvsn/prevail.html) can be leveraged to investigate the incidence, clinical manifestations, disease severity and immune correlates of COVID-19 infection in pregnant women, mothers and their children. The logistics are already in place for recruiting women during their third pregnancy trimester, and following the natural history of infection in infants through twice weekly symptom surveillance (by text messaging), weekly nasal swab sampling, and virus identification in real-time through a courier network in the Cincinnati metro area. Supplemental funding through this Notice of Special Interest regarding the availability of Urgent Competitive Revision for Research on the 2019 Novel Coronavirus (2019-nCoV; NOT-AI-20-034) will expand this analysis to include COVID-19 epidemiological surveillance for pregnant women, mothers, infants and children (Aim 1), plus additional collection of specimens for immunological assays at the time of infection compared with recruitment (pre-infection) and infection-community spread resolution (Aim 2). Epidemiological surveillance will include analysis of infection severity and duration of virus shedding relative to postnatal age, transmission of virus between mother and child plus other household contacts, and the potential impacts of maternal immunity transferred either vertically and/or postnatally through breast milk on infant COVID-19 infection susceptibility. Key specimens will include PBMCs that could be used to identify gains and losses of each cell population, plasma/serum for analysis of qualitative/quantitative shifts in virus-specific antibodies at each time point. An additional “Tempus” tube allowing stabilization of intracellular RNA from cells in whole blood will be collected at the time of infection for gene expression analysis. We envision that as COVID-19 immunological assays are being developed and become more standardized, these samples that link COVID-19 infection tempo and severity of each individual will provide an invaluable resource to investigate the immunological changes associated with asymptomatic to severe infection in pregnant women, mothers and their children and their relationship in each maternal-infant dyad.