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

项目总结摘要 尽管新型冠状病毒新冠肺炎正在大范围传播，但人们对新冠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。我们对新冠肺炎的了解主要是 根据病情严重的老年人感染后，与成人并存的情况。不幸的是， 孕妇、婴儿和儿童对严重感染、疾病负担和传播的易感性 在很大程度上仍然是不确定的。填补关于感染易感性的这些基本知识空白 这些关键的发育时间点需要母婴队列能够同时进行筛查 临床症状和新冠肺炎病毒感染情况。为两个母婴建立的基础设施 为婴儿流感感染和免疫的前瞻性分析设计的队列(U01AI144673； 印记)和呼吸道和肠道感染(以疾控中心赞助的为准； 可以利用https://www.cdc.gov/surveillance/nvsn/prevail.html)来调查发病率、临床 孕妇、母亲新冠肺炎感染的临床表现、病情严重程度及免疫相关性 和他们的孩子。招募怀孕第三个月的女性的后勤工作已经到位， 并通过每周两次的症状监测跟踪婴儿感染的自然历史(通过文本 消息)，每周鼻拭子采样，并通过位于 辛辛那提大都市区。通过本特别利益通知提供的补充资金 2019年新型冠状病毒(2019-nCoV；Not-AI-20-034)研究的紧急竞争性修订将 将这一分析扩展到包括对孕妇、母亲、婴儿的新冠肺炎流行病学监测 和儿童(目标1)，外加在感染时用于免疫学分析的额外标本收集 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病毒脱落持续时间与出生后年龄的关系， 病毒在母婴之间以及其他家庭接触者之间的传播及其潜在影响 婴儿新冠肺炎母体免疫通过母乳垂直和/或产后转移 感染易感性。关键样本将包括可用于确定以下各项得失的PBMC 每个细胞群、血浆/血清用于分析病毒特异性抗体的质/量变化 每个时间点。一种额外的“坦普斯”管，可使细胞内的RNA整体稳定 感染时将采集血液进行基因表达分析。我们将其设想为新冠肺炎 免疫学分析正在开发中，并变得更加标准化，这些样本与新冠肺炎联系起来 每个人的感染速度和严重性将提供宝贵的资源来调查 与无症状到严重感染相关的免疫学变化 他们的孩子和他们在每个母婴二元组中的关系。

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.