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

摘要 严重急性呼吸综合征冠状病毒-2(SARS-CoV-2)已感染超过2.33亿人 全球范围内。仅在美国就报告了约126,000例冠状病毒病-19例孕妇(新冠肺炎) 个人，不包括许多无症状和未经确认的病例。因此，可能会有数百万儿童 全世界可能受到产前接触SARS-CoV-2的后遗症的影响。 动物研究表明，怀孕期间的各种母体病毒感染与受损有关 子代的神经发育。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有关，并增加了患自闭症的风险。有一个 迫切需要对具有良好特征的预期出生队列进行研究，以研究产前暴露于 SARS-CoV-2感染和儿童发育不良风险，特别是在全球卫生危机的背景下 可能会给孩子带来终身的后果。此外，孕妇现在正在接种疫苗，以防止 大规模的新冠肺炎。疫苗会引起从轻度到重度的短暂免疫反应，表现为发热和 细胞因子水平升高。虽然研究表明，这些疫苗在怀孕期间是安全的，但长期的- 对孩子发育中的大脑的长期影响尚不清楚。 本研究旨在探讨产前接触SARS-CoV-2感染与新冠肺炎的关系。 对3岁儿童的行为、认知和大脑功能进行疫苗接种。我们假设 SARS-CoV-2感染通过胎儿免疫系统的变化对儿童结局产生负面影响。我们 进一步的假设是新冠肺炎疫苗是安全的，对儿童几乎没有长期影响。 我们将利用我们在山顶建立的正在进行的预期怀孕队列‘C世代’ 纽约(NYC)的西奈卫生系统(NYC)在大流行的最初几周(&GT；2800名妇女参加)。这个 这一群体在种族/民族和社会经济方面是多样化的。我们获得了以下结果：1)母血 孕期和分娩时的样本；2)每次抽血的孕妇SARS-CoV-2抗体滴度；3) 人口学和临床资料；4)新生儿血斑(DBS)。在拟议的项目中，我们将：(I) SARS-CoV-2暴露、疫苗暴露、未感染和未接种母婴二人组3的随访 出生后数年，结合(Ii)有关产妇感染SARS-CoV-2的现有信息和新冠肺炎 孕期疫苗接种情况，(Iii)新收集的SARS-CoV-2抗体和细胞因子水平数据 (Iv)儿童神经发育，包括行为、认知和运动发育，以及 (4)使用脑电(EEG)检测大脑功能。

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).