The longer-term impact of prenatal exposure to SARS-CoV-2 infection and the COVID-19 vaccine on behavior, cognition, and brain functioning in the child

总结 严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）已感染超过2.33亿人 在全球仅美国就报告了约126，000例孕妇感染冠状病毒病-19（COVID-19）病例 个人，不包括很多无症状和未确诊的病例。因此，可能有数百万儿童 可能受到产前SARS-CoV-2暴露后遗症的影响。 动物研究表明，怀孕期间的各种母体病毒感染与受损的 神经系统发育。根据这些发现，流行病学研究表明，产前 暴露于感染与神经发育偏差和ASD风险升高有关。有一个 迫切需要前瞻性的、特征明确的出生队列来研究产前暴露于 SARS-CoV-2感染和儿童发育不良的风险，特别是在全球健康危机的背景下， 可能对孩子造成终身影响。此外，孕妇现在正在接种疫苗， COVID-19在大规模。疫苗引起短暂的免疫反应，从轻微到严重，发烧， 增加细胞因子水平。虽然研究表明，这些疫苗在怀孕期间是安全的，但长期- 长期对儿童大脑发育的影响尚不清楚。 本研究旨在探讨产前暴露于SARS-CoV-2感染与COVID-19的关系 接种疫苗对3岁儿童的行为、认知和大脑功能的影响。我们假设 SARS-CoV-2感染通过胎儿免疫系统的变化介导对儿童结局产生负面影响。我们 进一步假设COVID-19疫苗是安全的，对儿童几乎没有长期影响。 我们将利用我们在The Mount建立的持续前瞻性妊娠队列“C代” 在大流行的最初几周，纽约市的西奈卫生系统（超过2，800名妇女登记）。的 这一群体在种族/族裔和社会经济方面是多样化的。我们获得了以下结果：1）母血 妊娠期间和分娩时的样本; 2）每次抽血的母体SARS-CoV-2抗体滴度; 3） 人口统计学和临床数据;和4）新生儿干血斑（DBS）。在建议的计划中，我们会（i） 随访SARS-CoV-2暴露、疫苗暴露和未感染及未接种疫苗的母子二人组3 结合（ii）关于母亲SARS-CoV-2感染和COVID-19的现有信息， 怀孕期间的疫苗接种状况，以及（iii）新收集的SARS-CoV-2抗体和细胞因子水平数据 （iv）儿童期神经发育，包括行为、认知和运动发育，以及 (iv)脑功能的脑电图（EEG）。

SUMMARY The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 233 million people globally. The US alone has reported ~126,000 coronavirus disease-19 (COVID-19) cases in pregnant individuals, not including many asymptomatic and unconfirmed cases. Thus, potentially millions of children worldwide may be impacted by the sequelae of prenatal SARS-CoV-2 exposure. Animal research has shown that various maternal viral infections during pregnancy are associated with impaired neurodevelopment in offspring. In line with these findings, epidemiological studies suggest that prenatal exposure to infections is linked to neurodevelopmental deviations, and an elevated risk for ASD. There is an urgent need for prospective, well-characterized birth cohorts to study the link between prenatal exposure to SARS-CoV-2 infection and risk for adverse child development, particularly in light of a global health crisis with potentially lifelong consequences for the child. Moreover, pregnant women are now being vaccinated against COVID-19 on a large scale. Vaccines elicit a brief immune response, ranging from mild to severe, with fever and increased cytokine levels. While studies have shown that these vaccines are safe during pregnancy, the long- term effects on the child's developing brain are unknown. This study aims to investigate the association of prenatal exposure to SARS-CoV-2 infection and COVID-19 vaccination with behavior, cognition, and brain functioning in the child at 3 years of age. We hypothesize that SARS-CoV-2 infection negatively impact child outcomes, mediated by changes to the fetal immune system. We further hypothesize that COVID-19 vaccines are safe, with little to no long-term effects on the child. We will leverage our on-going prospective pregnancy cohort `Generation C', which we established at The Mount Sinai Health System in New York City (NYC) in the early weeks of the pandemic (> 2,800 women enrolled). The cohort is racially/ethnically and socio-economically diverse. We obtained the following: 1) maternal blood samples during pregnancy, and at delivery; 2) maternal SARS-CoV-2 antibody titers for each blood draw; 3) demographic and clinical data; and 4) neonatal dried blood spots (DBS). In the proposed project, we will (i) follow-up SARS-CoV-2 exposed, vaccine-exposed and non-infected and non-vaccinated mother-child dyads 3 years after birth, combining (ii) existing information on maternal SARS-CoV-2 infection and COVID-19 vaccination status during pregnancy, with (iii) newly collected data on SARS-CoV-2 antibody and cytokine levels in neonatal DBS; (iv) childhood neurodevelopment including behavior, cognition, and motor development, and (iv) brain functioning using electroencephalogram (EEG).