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: 10445499
• 负责人: Maria De Las Mercedes Perez Rodriguez
• 金额: $ 84.28万
• 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/10445499
• 关键词: 2019-nCoV; Acute; Age; Antibodies; Attention; Autoantibodies; Autoimmune Process; Blood; Blood specimen; COVID-19; Centers for Disease Control and Prevention (U.S.); Cerebrospinal Fluid; Cognition; Cognitive; Cognitive deficits; Cohort Studies; Data; Development; Dimensions; Exposure to; Funding; General Population; Generations; Goals; Gold; Immunoassay; Immunoglobulin G; Impaired cognition; Infection; Inflammation; Inflammatory; Lead; Link; Long-Term Effects; Longitudinal Studies; Measures; Mediating; Mediator of activation protein; Memory; Mental Health; Neuraxis; Neurons; New York; Nucleocapsid; Outcome; Performance; Peripheral; Phenotype; Play; 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; base; 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; peripheral blood; 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.

全世界很大一部分孕妇（在我们CDC资助的C代人群中占21%， n= 2，545）最近暴露于严重急性呼吸综合征冠状病毒-2（SARS-CoV-2） 育龄妇女尽管普遍接种疫苗，但仍继续受到感染。然而，急性 SARS-CoV-2感染在妊娠和产后脆弱期的亚急性影响是 还不清楚。怀孕和产后是冠状病毒病19（COVID-19）的高风险时期， 出现神经精神症状。感染和炎症过程的失调 外周和中枢神经系统（CNS）被认为在这种脆弱性中起作用。我们现在知道 SARS-CoV-2在一般人群中导致亚急性和长期精神和认知后遗症的发生率很高 人口还需要了解SARS-CoV-2感染对心理健康的长期影响 孕妇和产后妇女的弱势群体，特别是因为他们往往 被排除在大型队列研究之外。我们建议研究先前SARS-CoV-2的长期影响 感染对产后精神和认知后遗症的影响及中枢和外周的介导作用 炎症我们将利用把握度良好的妊娠队列（C代队列，目标n> 3，000） 2020年4月在纽约成立，21%的队列先前暴露于SARS-CoV-2 感染至今。在该队列的一个子集（n=500）中，我们建议收集配对的血液和脑脊液， 液体（CSF）样本，这将提供独特的机会，研究亚急性和长期的 SARS-CoV-2感染对中枢神经系统（CNS）炎症过程的影响。我们 假设先前SARS-CoV-2感染可导致外周和中枢炎症调节异常， 怀孕期间的过程，这有助于引起精神症状和认知 产后脆弱时期的功能障碍。目标1将描述以下方面的亚急性和长期影响： 先前暴露于SARS-CoV-2对孕妇中枢和外周炎症的影响，包括 测量SARS-CoV-2 IgG抗体，使用高灵敏度多路复用技术表征炎症特征 免疫测定CSF和血液中的11种炎症标志物，并检查神经元 自身抗体目标2将研究既往SARS-CoV-2暴露、中枢神经系统和 妊娠期外周炎症和产后精神症状。目标3将审查 既往SARS-CoV-2暴露与妊娠期间中枢和外周炎症之间的相关性，以及 产后注意力、记忆力和执行功能的认知缺陷。