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

COVID-19 孕妇、母亲和儿童的流行病学和免疫发病机制

• 批准号: 10265666
• 负责人: MARY A STAAT
• 金额: $ 312.37万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265666
• 关键词: Address; Antibodies; Antigens; B-Lymphocytes; Blood; Breast Feeding; Child; Childhood; Cities; Clinical; Collection; Effectiveness; Elderly; Enrollment; Epitopes; Evaluation; Exposure to; Frequencies; Future; Genetic Programming; Genetic Variation; Goals; Human; Immune; Immune response; Immunity; Immunization; Immunologic Memory; Immunologics; Immunology; Individual; Infant; Infection; Infectious Disease Epidemiology; Influenza; Influenza A virus; Influenza vaccination; Infrastructure; Instruction; Knowledge; Life; Maintenance; Maternally-Acquired Immunity; Memory; Mexico; Milk; Mothers; Nature; Pediatric Hospitals; Population; Predisposition; Pregnant Women; Primary Infection; Reporting; Research Personnel; Sampling; Schedule; Shapes; Site; Symptoms; T memory cell; T-Lymphocyte; Umbilical Cord Blood; Vaccination; Vaccines; Variant; Viral; Viral Antigens; Virus; cohort; imprint; improved; infancy; influenza infection; influenza virus strain; influenza virus vaccine; influenzavirus; nasal swab; postnatal; recruit; response; seasonal influenza; secondary infection; stem; universal influenza vaccine; virology; virus genetics

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.

项目摘要摘要 尽管新颖的冠状病毒（Covid-19）大流行，但对关于的流行病学知之甚少 感染，传播和严重感染的敏感性。我们对Covid-19的了解在很大程度上是 基于感染后的严重疾病，以及患有合并症的成年人。很遗憾， 孕妇，婴儿和儿童的严重感染，伯恩伯恩和传播的敏感性 保持不确定。在有关感染易感性的知识中填补这些基本空白 这些基本的发展时间点需要能够简单筛查的产妇群体 临床症状和COVID-19病毒的获取。两种限制的基础设施已建立的基础设施 旨在对婴儿造成影响的前瞻性分析的同类群体（U01AI14673； 烙印）和呼吸道和肠感染（CDC赞助盛行； 可以利用https://www.cdc.gov/surveillance/nvsn/prevail.html）来调查事件，临床 孕妇共同19感染的表现，疾病的严重程度和免疫复合物，母亲 和他们的孩子。物流已经适用 并通过每周两次症状监测遵循婴儿感染的自然病史（通过文本 消息传递），每周的鼻拭子采样和通过快递网络实时识别病毒 辛辛那提都会区。通过此有关可用性的特别关注通知的补充资金 对2019年小说冠状病毒（2019-NCOV; NOT-AI-20-034）的研究的紧急竞争修订将 扩展此分析以包括对孕妇，母亲，婴儿的Covid-19流行病学监测 和儿童（AIM 1），以及在感染时的其他标本进行免疫评估的收集 与招募（感染前）和感染社区扩散分辨率（AIM 2）相比。流行病学 监视将包括分析感染严重程度和相对于产后年龄的病毒脱落的持续时间， 母亲和儿童之间的病毒传播以及其他家庭接触，以及潜在的影响 孕产妇的免疫力垂直和/或产后通过婴儿covid-19的母乳转移 感染敏感性。关键规格将包括可用于识别收益和损失的PBMC 每个细胞群，血浆/血清，用于分析病毒特异性抗体的定性/定量转移 每个时间点。另一个“ tempus”管，允许整个细胞的细胞内RNA稳定 在感染时，将收集血液以进行基因表达分析。我们认为这是COVID-19 免疫学测定正在开发并变得更具标准化，这些样本将Covid-19连接起来 感染节奏和每个人的严重程度将提供有吸引力的资源来调查 与孕妇，母亲和无症状到严重感染相关的免疫学变化 他们的孩子及其在每个含有母子的二元组中的关系。