Cerebrospinal fluid (CSF) and peripheral markers of the neuropsychiatric sequelae of COVID-19: The Generation C-SF pregnancy study

COVID-19 神经精神后遗症的脑脊液 (CSF) 和外周标志物：C-SF 一代妊娠研究

• 批准号: 10595028
• 负责人: Maria De Las Mercedes Perez Rodriguez
• 金额: $ 84.49万
• 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: 2022-04-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10595028
• 关键词: 2019-nCoV; Acute; Age; Antibodies; Attention; Autoantibodies; Autoimmune Process; Blood; Blood specimen; COVID-19; Central Nervous System; Cerebrospinal Fluid; Cognition; Cognitive; Cognitive deficits; Cohort Studies; Data; Development; Diagnostic; Dimensions; Exclusion; Exposure to; Funding; General Population; Generations; Goals; Immunoassay; Immunoglobulin G; Impaired cognition; Infection; Inflammation; Inflammatory; Link; Long-Term Effects; Longitudinal Studies; Measures; Mediating; Mediator; Memory; Mental Health; Neurons; New York; Nucleocapsid; Outcome; Performance; Peripheral; Phenotype; Postpartum Depression; Postpartum Period; Postpartum Women; Pregnancy; Pregnant Women; Process; Risk Factors; Role; SARS-CoV-2 antibody; SARS-CoV-2 exposure; SARS-CoV-2 infection; Sampling; Vaccination; Vulnerable Populations; Woman; cognitive performance; cognitive testing; cohort; executive function; fetal; high risk; inflammatory marker; long term consequences of COVID-19; neuropsychiatric sequelae of COVID-19; neuropsychiatric symptom; neuropsychiatry; pathogen; personalized medicine; post SARS-CoV-2 infection; postpartum outcome; psychiatric symptom; reproductive

A large proportion of pregnant women worldwide (21% in our CDC-funded Generation C cohort, current n=2,545) has been recently exposed to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and women of reproductive age continue to be infected despite widespread vaccination. However, the acute and subacute effects of SARS-CoV-2 infection during the vulnerable period of pregnancy and postpartum are not yet clear. Pregnancy and the postpartum are high-risk periods for coronavirus disease 19 (COVID-19) and for developing neuropsychiatric symptoms. Infections and dysregulation of inflammatory processes in the periphery and central nervous system (CNS) are thought to play a role in this vulnerability. We now know that SARS-CoV-2 causes high rates of subacute and long-term psychiatric and cognitive sequelae in the general population. There is a need to also understand the long-term effects of SARS-CoV-2 infection on mental health and cognition in the vulnerable population of pregnant and postpartum women, especially because they often are excluded from large cohort studies. We propose to study the long-term effects of prior SARS-CoV-2 infection on psychiatric and cognitive sequelae postpartum, with a mediating role of central and peripheral inflammation. We will leverage a well-powered pregnancy cohort (Generation C cohort, target n>3,000) established in April 2020 in New York, with 21% of the cohort previously exposed to SARS-CoV-2 infection to date. In a subset of this cohort (n=500), we propose to collect paired blood and cerebrospinal fluid (CSF) samples, which will provide the unique opportunity to investigate the subacute and long-term impacts of SARS-CoV-2 infection on inflammatory processes in the central nervous system (CNS). We hypothesize that prior SARS-CoV-2 infection can lead to dysregulation of peripheral and central inflammatory processes during pregnancy, and that this contributes to causing psychiatric symptoms and cognitive dysfunction in the vulnerable post-partum period. Aim 1 will characterize the subacute and long-term impact of prior exposure to SARS-CoV-2 on central and peripheral inflammation in pregnant women, including measuring SARS-CoV-2 IgG antibodies, characterizing inflammatory profiles using a high-sensitivity multiplex immunoassay for 11 inflammatory markers in CSF and blood, and examining the presence of neuronal autoantibodies. Aim 2 will examine the association between prior SARS-CoV-2 exposure, central and peripheral inflammation during pregnancy, and psychiatric symptoms postpartum. Aim 3 will examine the association between prior SARS-CoV-2 exposure, central and peripheral inflammation during pregnancy, and cognitive deficits in attention, memory and executive functioning postpartum.

全球很大比例的孕妇(目前在我们疾控中心资助的C世代队列中占21% N=2545)最近接触到严重急性呼吸综合征冠状病毒2(SARS-CoV-2) 尽管广泛接种疫苗，但育龄妇女仍继续受到感染。然而，急性 孕期和产后感染SARS-CoV-2的亚急性影响为 还不清楚。怀孕和产后是冠状病毒病19(新冠肺炎)和 出现神经精神症状。炎症过程中的感染和失调 外周和中枢神经系统(CNS)被认为在此漏洞中发挥了作用。我们现在知道了， SARS-CoV-2在一般情况下会导致较高的亚急性和长期精神和认知后遗症 人口。还有必要了解SARS-CoV-2感染对精神健康的长期影响 在孕妇和产后妇女的弱势群体中的认知，特别是因为她们经常 被排除在大型队列研究之外。我们建议研究以前的SARS-CoV-2的长期影响 感染对产后精神和认知后遗症的影响，具有中枢和外周调节作用 发炎。我们将利用一个强大的怀孕队列(C世代队列，目标n&gt；3000) 于2020年4月在纽约成立，21%的队列以前接触过SARS-CoV-2 到目前为止的感染。在这个队列的一个子集(n=500)中，我们建议收集配对的血液和脑脊液 体液(CSF)样本，这将提供独特的机会来调查亚急性和长期 SARS-CoV-2感染对中枢神经系统炎症过程的影响我们 假设先前感染SARS-CoV-2可导致外周和中枢炎症调节失调 在怀孕过程中，这会导致精神症状和认知 易受感染的产后期功能障碍。目标1将描述亚急性和长期影响 先前接触SARS-CoV-2对孕妇中枢和外周炎症的影响，包括 检测SARS-CoV-2免疫球蛋白抗体，用高灵敏度多重分析表征炎症特征 脑脊液和血液中11种炎症标志物的免疫测定及神经元的存在 自身抗体。目标2将研究以前接触SARS-CoV-2、中央和 妊娠期间的外周炎症和产后的精神症状。目标3将研究 既往SARS-CoV-2暴露、孕期中枢和外周炎症与 产后注意力、记忆力和执行功能方面的认知缺陷。