Infant Immunologic and Neurologic Development following Maternal Infection in Pregnancy during Recent Epidemics

摘要/概要 2019年新出现的冠状病毒病（COVID-19）大规模爆发，全球范围内迅速 传播，导致大流行感染和前所未有的全球卫生紧急情况。只是 几年前，我们目睹了寨卡病毒（ZIKV）对未出生的胎儿的毁灭性影响， 美洲.这项建议是为了填补在理解《公约》方面的重大空白， 产前感染如ZIKV和SARS-CoV-2感染对孕妇的临床影响 通过评估婴儿的细胞和免疫系统， 母体感染后的体液免疫应答与临床和神经发育结局 免疫激活（MIA）在这个脆弱的人群。我们的研究团队 在过去的7年里，我们一直在合作，以表征子宫内的临床和细胞效应。 寨卡病毒（ZIKV）的传播，从数百名母亲那里收集标本， 来自巴西的婴儿对。我们报告了多个产科和临床结果的婴儿， 先天性ZIKV感染，包括ZIKV垂直传播率至少为 65%，感染的儿童不会产生ZIKV特异性中和抗体，尽管早期 IgM反应，母体体液免疫反应往往是强大的， 中和活性在COVID-19大流行期间，我们建立了一个母婴队列， 在加州大学洛杉矶分校和里约热内卢的Fiocruz和对照组的母婴配对登记， 在这两个地方约会。我们正在利用现有的基础设施和开发的科学方法 在ZIKV流行之后，进一步评估临床、细胞体液和 炎症参数可预测暴露于以下物质的婴儿和儿童的免疫结果： 母亲ZIKV和SARS Cov 2感染。拟议研究的主要目标是 全面表征MIA对婴儿免疫发育和临床的影响 结果，重点是免疫发病机制。我们纳入了200名母亲的纵向队列- 美国和巴西的COVID-19感染婴儿对和100对健康对照母婴对， 在巴西的200对ZIKV母婴对和在相同临床研究中心的100对健康对照对 来实现这些目标。本RO 1建议评估MIA对婴儿的影响， 存在和免疫发展。最先进的技术被用来解决科学目标， 由免疫学、传染病和先天性疾病领域的专家领导的研究 感染的人都有持续的成功的、富有成效的伙伴关系。呈现的数据将是 对于了解产前病毒感染儿童人群的免疫发病机制至关重要 暴露。

Abstract/Summary The massive outbreak of newly emerged coronavirus disease 2019 (COVID-19) saw rapid global spread, leading to a pandemic infection and an unprecedented global health emergency. Just years before, we witnessed the devastating impact of Zika virus (ZIKV) to unborn fetuses in the Americas. This proposal responds to the need to fill critical gaps in the understanding of the clinical repercussions of antenatal infections such as ZIKV and SARS-CoV-2 infection in pregnant women to the developing immune system of their infants, through the evaluation of cellular and humoral immune responses and clinical and neurodevelopmental outcomes following maternal immune activation (MIA) in this vulnerable population. Our team of researchers has been collaborating over the last 7 years to characterize the clinical and cellular effects of in utero transmission of Zika virus (ZIKV), with the collection of specimens from over hundreds of mother- infant pairs from Brazil. We reported on multiple obstetrical and clinical outcomes of infants with congenital ZIKV infection in the literature, including that ZIKV vertical transmission rate is at least 65%, that infected children do not develop ZIKV specific neutralizing antibodies despite an early IgM response, and that maternal humoral immune responses tend to be robust with highly neutralizing activity. During the COVID-19 pandemic we established a cohort of mother-infant pairs at UCLA and Fiocruz, Rio de Janeiro and controls with mother-infant dyads enrolled to date in both places. We are utilizing the existing infrastructure and scientific methods developed in the aftermath of the ZIKV epidemic to further evaluate clinical, cellular humoral and inflammatory parameters predicting immunologic outcomes in infants and children exposed to either maternal ZIKV and SARS Cov2 infection. The main goal of the proposed research is to comprehensively characterize repercussions of MIA on infant immune development and clinical outcomes, with a focus on immune pathogenesis. We include a longitudinal cohort of 200 mother- infant pairs with COVID-19 and 100 healthy control mother-infant pairs in the US and Brazil and 200 mother-infant pairs with ZIKV in Brazil and 100 healthy control pairs at the same clinical sites to address these goals. This RO1 proposes to evaluate the repercussions of MIA on infant well- being and immune development. State of the art technology is used to address the scientific aims, with the research led by experts in the field of immunology, infectious diseases & congenital infections who have ongoing successful, productive partnerships. The data rendered will be crucial for the knowledge of immune pathogenesis in pediatric populations with antenatal viral exposures.