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: 10213945
• 负责人: MARY A STAAT
• 金额: $ 253.01万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-18 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10213945
• 关键词: 2019-nCoV; Adult; Age; Antibodies; Area; Biological; COVID-19; Cells; Centers for Disease Control and Prevention (U.S.); Child; Clinical; Collection; Communities; Development; Disease; Elderly; Epidemiologic Monitoring; Epidemiology; Event; Funding; Gene Expression Profiling; Goals; Household; Human; Human Milk; Immune; Immune response; Immunity; Immunologics; Immunology procedure; Incidence; Individual; Infant; Infection; Influenza; Infrastructure; Knowledge; Life; Link; Logistics; Mothers; Natural History; Nose; Pathogenesis; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Population; Predisposition; Pregnancy; Pregnant Women; RNA; Research; Resolution; Resources; Respiratory Tract Infections; Sampling; Severities; Severity of illness; Specimen; Standardization; Swab; Symptoms; Testing; Text Messaging; Third Pregnancy Trimester; Time; Tube; Virus; Virus Shedding; Whole Blood; Woman; base; burden of illness; cohort; comorbidity; design; enteric infection; epidemiology study; high risk; interest; lens; novel coronavirus; novel therapeutics; novel vaccines; pandemic disease; postnatal; preservation; prospective; recruit; sample collection; screening; transmission process; viral transmission; virus identification

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.

项目概要摘要 尽管新型冠状病毒（COVID-19）大流行，但人们对它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 基于老年人和患有合并症的成年人感染后的严重疾病。很遗憾， 孕妇、婴儿和儿童对严重感染、疾病负担和传播的易感性 很大程度上仍然是未定义的。填补有关感染易感性的这些基本知识空白 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。为两名母婴建立的基础设施 旨在对婴儿流感获得和免疫进行前瞻性分析的队列（U01AI144673； IMPRINT）和呼吸道和肠道感染（CDC 赞助的 PREVAIL； https://www.cdc.gov/surveillance/nvsn/prevail.html）可用于调查发病率、临床 孕妇、母亲感染 COVID-19 的表现、疾病严重程度和免疫相关性 和他们的孩子。招募处于第三个妊娠期的女性的后勤工作已经到位， 并通过每周两次的症状监测来跟踪婴儿感染的自然史（通过文本 消息传递），每周鼻拭子采样，并通过快递网络实时识别病毒 辛辛那提都会区。通过本关于可用性的特别兴趣通知提供补充资金 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 扩大这一分析范围，将孕妇、母亲、婴儿的 COVID-19 流行病学监测纳入其中 和儿童（目标 1），加上感染时额外收集样本进行免疫学检测 与招募（感染前）和感染社区传播解决（目标 2）进行比较。流行病学 监测将包括分析感染严重程度以及相对于产后年龄的病毒排出持续时间， 病毒在母婴以及其他家庭接触者之间的传播，以及潜在的影响 母体免疫力通过母乳垂直和/或产后转移到婴儿 COVID-19 感染易感性。关键样本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/定量变化 每个时间点。额外的“Tempus”管可稳定整个细胞的细胞内 RNA 将在感染时收集血液用于基因表达分析。我们预计，随着 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 相关 每个人的感染速度和严重程度将为调查提供宝贵的资源 孕妇、母亲和儿童中与无症状到严重感染相关的免疫学变化 他们的孩子以及母婴二元组中的关系。