SARS-CoV-2 in Pregnancy: Comparison of Natural Infection and Hybrid Immunity in Mother-Infant Pairs

项目摘要/摘要 虽然妊娠期间感染SARS-CoV-2的临床范围从无症状到危重疾病， 怀孕本身增加了严重和危重新冠肺炎的风险。美国领先的产科学会。 建议孕期接种新冠肺炎信使核糖核酸疫苗，预防严重疾病。 此外，通过胎盘转移免疫球蛋白G(IgG)对新生儿的被动免疫至关重要 在生命的前六个月很重要，特别是因为新冠肺炎疫苗只被批准用于儿童 &gt；六个月大。混合免疫，定义为在自然感染之前或之后疫苗诱导的免疫 SARS-CoV-2病毒在非怀孕人群中产生的反应比隔离时的任何一种类型更强烈。这个 妊娠期SARS-CoV-2混合免疫的长期炎症和免疫学反应 以严密调控的T细胞控制和免疫调节为标志，与自然感染相比尚不清楚。 随着SARS-CoV-2变得流行，这项提议将解决文献中主要关注的一个空白 孕期自然感染SARS-CoV-2与疫苗诱导免疫的比较。利用现有的 新冠肺炎母婴结局(COMP)研究--一项纵向队列研究 二人在怀孕期间被诊断为SARS-CoV-2感染，该提案旨在更好地了解长期- 孕期SARS-CoV-2混合免疫的妊娠结局。我们推测SARS-CoV-2混合病毒 与自然感染相比，孕期免疫提供了对产后并发症的保护 以减少母亲的全身炎症，并导致母婴配对更强大的免疫反应。 本研究的目的是：1)评估围产期和产后延迟的患病率和危险因素 新冠肺炎在SARS-CoV-2混合免疫者和SARS-CoV-2混合免疫者中的并发症 自然感染；2)比较全身性炎症情况，如通过细胞因子谱测量 具有SARS-CoV-2混合免疫和自然感染的孕妇在分娩时和产后一年； 以及3)评估对祖代和奥米克龙(BA.5)菌株的细胞和体液免疫反应 SARS-CoV-2杂交母婴在分娩时和产后6个月内的新冠肺炎 与自然感染相比具有免疫力。K23将支持坎布博士在1)应用程序中发展高级技能 免疫学，2)围产期感染，3)细胞因子分析，以便成为有效的翻译 医生兼科学家。卡琳·尼尔森博士，世界著名的围产期儿童传染病(ID)专家 感染，将作为主要的导师。共同导师奥托·O·杨博士和格雷斯·奥德罗万迪博士， 病毒免疫学，拥有超过20年的NIH连续资助和成功的跟踪记录 师徒关系。联合导师Debika Bhattacharya博士将作为成人ID临床研究员在围产期提供指导 病毒感染。K23将使坎布博士在多学科研究的融合中开辟出一个独特的利基市场 为了开始她作为一名独立调查员的职业生涯，她在怀孕期间对病毒感染进行了免疫学研究。

PROJECT SUMMARY/ABSTRACT While the clinical spectrum of SARS-CoV-2 infection in pregnancy ranges from asymptomatic to critical disease, pregnancy itself augments the risk of severe and critical COVID-19. The leading obstetrical societies in the U.S. recommend COVID-19 messenger RNA (mRNA) vaccination in pregnancy to prevent severe disease. Furthermore, passive immunity to the neonate via transplacental transfer of immunoglobulin G (IgG) is critically important during the first six months of life, particularly as the COVID-19 vaccines are approved only for children >six months of age. Hybrid immunity, defined as vaccine-induced immunity before or after natural infection with SARS-CoV-2, produces a more robust response in non-pregnant populations than either type in isolation. The long-term inflammatory and immunologic responses to SARS-CoV-2 hybrid immunity in pregnancy, a state marked by tightly regulated T cell control and immune modulation, compared to natural infection are unknown. As SARS-CoV-2 becomes endemic, this proposal will address a gap in the literature that has focused primarily on natural SARS-CoV-2 infection in pregnancy compared to vaccine-induced immunity. Leveraging the existing COVID-19 Outcomes in Mother-Infant Pairs (COMP) study, a longitudinal cohort that follows 225 mother-infant dyads diagnosed with SARS-CoV-2 infection in pregnancy, the proposal seeks to better understand the long- term consequences of SARS-CoV-2 hybrid immunity in pregnancy. We hypothesize that SARS-CoV-2 hybrid immunity compared to natural infection in pregnancy confers protection against postpartum complications, leads to less maternal systemic inflammation, and results in more robust immune responses in mother-infant pairs. The study aims are: 1) to estimate the prevalence and risk factors of peripartum and delayed postpartum complications of COVID-19 in pregnancy between those with SARS-CoV-2 hybrid immunity, and those with natural infection; 2) to compare the systemic inflammatory landscapes, as measured by cytokine profiles, of pregnant women with SARS-CoV-2 hybrid immunity and natural infection at delivery and one year postpartum; and 3) to evaluate cellular and humoral immune responses to the ancestral and Omicron (BA.5) strains following COVID-19 in pregnancy at delivery and six months postpartum in mother-infant dyads with SARS-CoV-2 hybrid immunity compared to natural infection. The K23 will support Dr. Cambou to develop advanced skills in 1) applied immunology, 2) perinatal infections, and 3) cytokine analysis, in order to become an effective translational physician-scientist. Dr. Karin Nielsen, a world-renowned pediatric infectious diseases (ID) expert in perinatal infections, will serve as the primary mentor. Co-mentors Drs. Otto O. Yang and Grace Aldrovandi, experts in viral immunology, have over 20 years of continuous NIH funding and proven track records of successful mentorship. Co-mentor Dr. Debika Bhattacharya will offer guidance as an adult ID clinical researcher in perinatal viral infections. The K23 will allow Dr. Cambou to carve out a unique niche of multidisciplinary research blending immunology with viral infections in pregnancy, in order to launch her career as an independent investigator.