Progesterone induced immune modulation during pregnancy – supplemental research in COVID-19

怀孕期间黄体酮诱导的免疫调节 — COVID-19 的补充研究

• 批准号: 10344851
• 负责人: Sing Sing Way
• 金额: $ 53.81万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10344851
• 关键词: 2019-nCoV; Address; Age; Area; Biology; COVID-19; COVID-19 severity; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Data; Cohort Studies; Complement; Data; Disease; Enrollment; Exposure to; Fetal Death; High Prevalence; Immune; Immune response; Immunity; Immunoglobulin G; Immunoglobulin M; Immunologics; Immunology; Infection; Institution; Intervention; Intervention Trial; Investigation; Knowledge; Logistics; Maternal Mortality; Maternal antibody; Maternally-Acquired Immunity; Metadata; Mothers; Parents; Patients; Pennsylvania; Perinatology; Persons; Phenotype; Population; Postpartum Period; Pre-Eclampsia; Predisposition; Pregnancy; Pregnancy Trimesters; Pregnant Women; Premature Birth; Progesterone; Research; Research Infrastructure; Risk; SARS-CoV-2 infection; SARS-CoV-2 positive; Second Pregnancy Trimester; Serology test; Severities; Severity of illness; Specimen; Time; Translational Research; Umbilical Cord Blood; Universities; Woman; Work; adjudication; adverse pregnancy outcome; clinical phenotype; cohort; design; disorder risk; embryo/fetus antigen; ethnic diversity; fetal; high risk population; immunoregulation; innovation; insight; maternal comorbidity; maternal morbidity; novel; novel coronavirus; obstetric outcomes; pandemic disease; parity; patient population; pregnant; preventive intervention; prospective; racial diversity; recruit; reproductive; reproductive outcome; respiratory virus; severe COVID-19; social health determinants; symptomatology; translational study; virology

Project Summary: Despite pandemic spread of the novel coronavirus, COVID-19, significant knowledge gaps remain especially for Center for Disease Control designated high risk populations such as pregnant women. Of high clinical importance is the susceptibility of pregnant women to infection, the direct risk to the mother and the indirect impact of disease severity (including preterm delivery and fetal death) on the pregnancy. While much research is being pursued from translational research to intervention trials for COVID-19, pregnant women are almost universally excluded from intervention and observational trials. Research in pregnant women is of the highest priority. The ability to understand which pregnant women are at risk for severe COVID-19 disease, weeks if not months prior to clinical symptomatology, could provide novel and important windows for preventative interventions to limit maternal morbidity and mortality. Additionally, if clinical data emerges that the majority of pregnant women may actually be more tolerant of SARS-CoV-2 compared to other respiratory viruses, understanding the immunological changes of pregnancy may provide insights as to ways to modulate disease risk in non-pregnant populations. To address all of these gaps in knowledge, large maternal cohorts with biospecimens and detailed phenotyping in areas of high prevalence of COVID-19 are required. The established investigative team and research infrastructure for two active maternal cohorts designed for prospective analysis of maternal immunity during pregnancy (R01-A1145840) can now be leveraged to investigate deep immune phenotyping of pregnant women prior to acquisition of COVID-19. We will be able to investigate how different immune phenotypes predict COVID-19 infection in pregnant women. Complementing the existing expertise in perinatology and immunology for the parent RO1, this study add the immunology and virology expertise at the University of Pennsylvania. We propose to investigate the following three scientifically important aims: 1) whether maternal immune profiles are associated with acquisition and severity of COVID19 in pregnant women; 2) whether immune profiles in pregnant women with active COVID19 are similar to non-pregnant women with similar disease severity and 3) whether immune profiles in the 2nd trimester of pregnancy are associated with adverse reproductive outcomes. All women enrolled will have extensive metadata collected with adjudication of COIVD- 19 status and severity as well as detailed clinical phenotyping of obstetrical outcomes. Deep immune phenotyping will provide innovative and rigorous investigation of innate and adaptive immune states during pregnancy and will be interrogated regarding their association with COVID19 phenotypes. We will also investigate the presence of maternal antibodies (IgG and IgM against SARS-CoV-2) at the same time point as immune profiling. We have the necessary expertise, the research infrastructure and the patient population to complete the proposed study in the 2 year time line with a 400 person cohort. This study address many significant gaps in knowledge including essential questions regarding the immune biology in pregnancy.

项目摘要：尽管新型冠状病毒（COVID-19）大流行，但仍存在重大知识差距 尤其是对于疾病控制中心指定的高危人群，例如孕妇。的 具有高度临床重要性的是孕妇对感染的易感性、对母亲和胎儿的直接风险 疾病严重程度（包括早产和胎儿死亡）对妊娠的间接影响。虽然很多 研究正在进行从转化研究到针对 COVID-19 的干预试验，孕妇 几乎普遍被排除在干预和观察试验之外。针对孕妇的研究是 最高优先级。了解哪些孕妇有患严重 COVID-19 疾病的风险的能力，周数 如果不是在临床症状出现前几个月，可以为预防提供新颖且重要的窗口 限制孕产妇发病率和死亡率的干预措施。此外，如果临床数据出现，大多数 与其他呼吸道病毒相比，孕妇实际上可能对 SARS-CoV-2 更耐受， 了解妊娠期的免疫变化可能为调节疾病的方法提供见解 非怀孕人群的风险。为了解决所有这些知识差距，大量母亲群体 需要在 COVID-19 高发地区进行生物样本和详细表型分析。已成立的 为前瞻性分析而设计的两个活跃母亲队列的调查团队和研究基础设施 现在可以利用怀孕期间母体免疫力的影响（R01-A1145840）来研究深层免疫 在感染 COVID-19 之前对孕妇进行表型分析。我们将能够研究如何不同 免疫表型可预测孕妇感染 COVID-19。补充现有的专业知识 母体 RO1 的围产期学和免疫学，本研究增加了母体 RO1 的免疫学和病毒学专业知识 宾夕法尼亚大学。我们建议研究以下三个具有科学意义的重要目标：1）是否 母体免疫特征与孕妇感染新冠病毒及其严重程度相关； 2） 患有活动性新冠病毒的孕妇的免疫特征是否与患有类似疾病的非孕妇相似 疾病严重程度以及 3) 妊娠第二个月的免疫特征是否与不良反应相关 生殖结果。所有登记的女性都将获得根据 COIVD 裁决收集的大量元数据 - 19 产科结果的状态和严重程度以及详细的临床表型。深度免疫 表型分析将为先天性和适应性免疫状态提供创新和严格的研究 怀孕并将被询问其与 COVID19 表型的关系。我们还将 在同一时间点调查母体抗体（针对 SARS-CoV-2 的 IgG 和 IgM）的存在 免疫分析。我们拥有必要的专业知识、研究基础设施和患者群体 在 2 年时间内完成 400 人队列的拟议研究。这项研究涉及许多重要的 知识差距，包括有关妊娠期免疫生物学的基本问题。