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，但显着的知识差距 对于疾病控制中心，尤其是指定高风险人群（例如孕妇）。的 高临床重要性是孕妇感染的敏感性，母亲和母亲的直接风险 疾病严重程度（包括早产和胎儿死亡）对怀孕的间接影响。虽然很多 正在从转化研究到Covid-19的干预试验进行研究，孕妇是 几乎普遍排除在干预和观察试验之外。对孕妇的研究是 最高优先级。了解哪些孕妇有严重的Covid-19疾病的风险，几周 如果不是在临床症状学之前的几个月，则可以为预防性提供新颖而重要的窗口 限制母体发病率和死亡率的干预措施。此外，如果出现大多数临床数据 与其他呼吸道病毒相比 了解怀孕的免疫学变化可能会提供有关调节疾病方法的见解 非怀孕人群的风险。为了解决所有这些差距，与 在Covid-19的高流行率领域中，生物测量和详细表型是。已建立 两个活跃的孕产妇队列的研究团队和研究基础设施专为前瞻性分析而设计 现在可以利用怀孕期间的孕产妇免疫力（R01-A1145840）来研究深度免疫 在获得Covid-19-19。我们将能够调查如何不同 免疫表型可以预测孕妇的共同感染。补充现有的专业知识 本研究为父型RO1的截骨学和免疫学增添了免疫学和病毒学专业知识 宾夕法尼亚大学。我们建议调查以下三个科学重要目标：1）是否是否 孕妇的免疫特征与孕妇的Covid19的获取和严重程度有关； 2） 活性covid19孕妇的免疫特征是否类似于非孕妇 疾病的严重程度和3）妊娠第二个三个月的免疫特征是否与不良 生殖结果。所有入学的妇女都将通过裁定COIVD-收集广泛的元数据。 19状态和严重程度以及产科结果的详细临床表型。深度免疫 表型将对先天和适应性免疫状态进行创新和严格的调查 怀孕，并将询问其与Covid19表型的关联。我们也会 在同一时间点研究母体抗体（IgG和针对SARS-COV-2）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 与400人队列一起在2年的时间内完成拟议的研究。这项研究解决了许多重要的 知识的差距，包括有关怀孕中免疫生物学的基本问题。