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

产前接触 SARS-CoV-2 感染和 COVID-19 疫苗对儿童行为、认知和大脑功能的长期影响

• 批准号: 10503708
• 负责人: Anna-Sophie Rommel
• 金额: $ 70.27万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-19 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10503708
• 关键词: 2019-nCoV; 3 year old; Accounting; Age; Animal Experimentation; Animals; Antibody titer measurement; Attention; Auditory Evoked Potentials; Behavior; Behavioral; Birth; Blood; Blood Circulation; Blood specimen; Brain; COVID-19; Child; Child Behavior Checklist; Child Development; Childhood; Clinical Data; Cognition; Cognitive; Data; Development; Disease; Electroencephalogram; Enrollment; Ethnic Origin; Event-Related Potentials; Exploratory Behavior; Exposure to; Face; Family history of; Fever; Foundations; Funding; Generations; Health system; Immune; Immune response; Immune system; Immunoglobulin G; Impairment; Individual; Individuation; Infection; Inflammation; Lead; Light; Link; Long-Term Effects; Measures; Mediating; Memory; Mothers; Motor; Neonatal; Neurodevelopmental Disorder; Neuropsychology; New York City; Outcome; Pattern; Perception; Persons; Pregnancy; Pregnant Women; Preschool Child; Questionnaires; Race; Reporting; Risk; SARS-CoV-2 antibody; SARS-CoV-2 exposure; SARS-CoV-2 infection; Severities; Social Interaction; Socioeconomic Status; Spottings; Symptoms; Testing; Vaccinated; Vaccination; Vaccines; Virus Diseases; Visual evoked cortical potential; Woman; autism spectrum disorder; cohort; coronavirus disease; cost effective; cytokine; epidemiology study; fetal; follow-up; global health; in utero; indexing; infection risk; neonate; neurodevelopment; neurophysiology; offspring; pandemic disease; pathogen; pregnant; prenatal; prenatal exposure; prospective; racial and ethnic; relating to nervous system; sex; social; social disparities; socioeconomics; unvaccinated

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).

概括 严重的急性呼吸综合症冠状病毒2（SARS-COV-2）已感染了超过2.33亿人 全球。仅美国就报告了约126,000个冠状病毒19（Covid-19）病例 个人，不包括许多无症状和未经证实的病例。因此，可能有数百万个孩子 全世界可能受到产前SARS-COV-2暴露的后遗症的影响。 动物研究表明，怀孕期间的各种母体病毒感染与受损 后代的神经发育。与这些发现一致，流行病学研究表明产前 接触感染与神经发育偏差有关，ASD的风险升高。有一个 迫切需要预期的，特征良好的出生队列，以研究产前暴露与 SARS-COV-2感染和发生不良儿童发展的风险，特别是鉴于全球健康危机 对孩子的可能终生后果。而且，孕妇现在正在接种疫苗 COVID-19大规模。疫苗引起短暂的免疫反应，从轻度到重度，发烧和 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，但很长 对孩子发育中的大脑的术语影响尚不清楚。 这项研究旨在调查产前暴露于SARS-COV-2感染和COVID-19 3岁儿童的行为，认知和大脑功能的疫苗接种。我们假设这一点 SARS-COV-2感染会对儿童结局产生负面影响，这是由胎儿免疫系统变化介导的。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。 我们将利用我们在山上建立的正在进行的前瞻性怀孕队列“ C代” 纽约市的西奈卫生系统（NYC）在大流行的早期（> 2800名女性入学）。这 队列在种族/种族和社会经济上都是多样的。我们获得了以下内容：1） 怀孕期间和分娩时的样品； 2）每次抽血的母体SARS-COV-2抗体滴度； 3） 人口统计和临床数据； 4）新生儿干血点（DBS）。在拟议的项目中，我们将（i） 随访SARS-COV-2暴露于疫苗暴露，未感染和未接种疫苗的母子Dyads 3 出生后几年，结合了（ii）有关母体SARS-COV-2感染和Covid-19的现有信息 怀孕期间的疫苗接种状态，（iii）新收集的SARS-COV-2抗体和细胞因子水平的数据 在新生儿DBS中； （iv）儿童神经发育，包括行为，认知和运动发展，以及 （iv）使用脑电图（EEG）进行大脑功能。