The effect of SARS-CoV-2 on the susceptibility of respiratory outcomes in a Puerto Rican Birth Cohort

SARS-CoV-2 对波多黎各出生队列呼吸结局易感性的影响

• 批准号: 10277300
• 负责人: LUISA N BORRELL
• 金额: $ 64.63万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10277300
• 关键词: 2019-nCoV; 21 year old; 5 year old; Active Biological Transport; Address; Admixture; Adult Respiratory Distress Syndrome; Affect; Antibody Response; Asthma; Biological; Biological Assay; Birth; Blood; Blood specimen; Businesses; COVID-19; COVID-19 detection; COVID-19 morbidity; COVID-19 mortality; COVID-19 pandemic; COVID-19 severity; Cessation of life; Child; Childhood; Childhood Asthma; Chronic; Chronic Disease; Clinic Visits; Clinical; Cohort Studies; Contracts; Data; Development; Diagnostic tests; Disease; Disease Outbreaks; Ethnic Origin; Exposure to; Future; Genetic; Genetic Variation; Health Policy; Health Services Accessibility; Human Milk; Immune; Immunity; Immunoassay; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologics; Immunophenotyping; Individual; Infant; Infection; Knowledge; Latino; Life; Link; Lung diseases; Maternal Exposure; Measures; Metagenomics; Minority; Mothers; Multisystem Inflammatory Syndrome in Children; Nasal Epithelium; Neonatal; New York City; Newborn Infant; Outcome; Participant; Passive Immunity; Peripheral Blood Mononuclear Cell; Placenta; Play; Population; Positioning Attribute; Postpartum Period; Predisposition; Pregnancy; Pregnant Women; Prevalence; Production; Public Health; Puerto Rican; Puerto Rico; Quality of life; Race; Recruitment Activity; Risk; Role; SARS coronavirus; SARS-CoV-2 antibody; SARS-CoV-2 exposure; SARS-CoV-2 immunity; SARS-CoV-2 infection; SARS-CoV-2 positive; Sampling; Schools; Seasonal Variations; Serology; Serum; Severities; Social Environment; Socioeconomic Status; Spottings; Survivors; Swab; Testing; Time; Umbilical Cord Blood; Viral; Viral Antibodies; Viral Respiratory Tract Infection; Virus; Wheezing; Woman; antibody transfer; base; clinical risk; cohort; design; disease disparity; epidemiology study; family structure; genome-wide; health care availability; health inequalities; high risk; infant infection; minority children; mortality; multidisciplinary; neonatal immunity; neonate; neutralizing antibody; pandemic disease; peripheral blood; postnatal; pregnant; prenatal exposure; prospective; pulmonary function; racial and ethnic; racial and ethnic disparities; recruit; research clinical testing; respiratory; respiratory health; screening; seropositive; socioeconomics; socioenvironmental factor

PROJECT SUMMARY Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. The lack of diagnostic tests and current public health policies limit our knowledge of the true prevalence of SARS- CoV-2. Infection with SARS-CoV-2 results in production of anti-viral antibodies in infected hosts, yet it is currently unknown whether these antibody responses are protective against subsequent infection. Survivors of the 2003 SARS coronavirus outbreak had reduced lung function and quality of life, and more frequent viral respiratory illnesses. The latter are associated with increased risk for childhood wheeze and asthma, the most common chronic and disparate disease among children. Data also indicate that there are significant racial/ethnic disparities in COVID-19 outcomes. Disparities in risk of viral exposure, susceptibility to severe disease, and access to health care may interact to exacerbate existing health inequalities. Pregnancy provides a natural mechanism by which to examine the protective potential of passive immunity. Maternal IgG is actively transported across the placenta and in the absence of postnatal exposure wane to undetectable levels in the neonate over the first year of life. Furthermore, IgA is passed from mother to child through breastmilk. Our multidisciplinary team will study a unique cohort of Puerto Rican mothers and their infants prospectively following the infants through their first five years of life collecting maternal breastmilk, maternal and neonatal cord blood, and neonatal/infant nasal epithelium swabs at birth, during respiratory illness, and at yearly clinical evaluations. We will determine prenatal exposure to SARS-CoV-2 as measured from maternal and infant cord blood at time of birth and investigate the effect this virus has on the susceptibility of respiratory disease in children. We will screen all pre/postpartum mothers with a PCR assay and qualitative immunoassay to detect SARS-CoV-2 infection. Among all seropositive mothers, we will collect repeated breast milk samples at 5 and 14 days and serial newborn blood spot samples at birth, 1, 3, 6 months, and yearly for 5 years. We will measure IgA, IgG, and IgM in maternal breastmilk and blood samples, and IgG in infant serum. We will examine (Aim 1) the passive transfer of SARS-CoV-2 immunity from seropositive mothers to their neonates, (Aim 2) whether early life SARS- CoV-2 infection severity and other clinical sequelae is modified by altered childhood immunophenotypes and host genetics, and (Aim 3) how socio-environmental factors affect maternal and infant exposure to COVID-19 and further affect the development of childhood asthma. We hypothesize that pregnant women infected with SARS-CoV-2 produce neutralizing antibodies, which protect their newborns from COVID-19 disease. In contrast, infants who contract SARS-CoV-2 after birth are at increased risk for later respiratory disease including asthma and other clinical sequelae. We further postulate that these associations are modified by host genetic and socio- environmental factors. To our knowledge, there are no other groups within or outside the U.S. with the population needed and track record to perform these analyses.

项目总结 严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是新冠肺炎大流行的罪魁祸首。 缺乏诊断测试和当前的公共卫生政策限制了我们对SARS真实流行情况的了解- CoV-2。感染SARS-CoV-2会导致受感染的宿主产生抗病毒抗体，但目前 尚不清楚这些抗体反应是否对后续感染具有保护作用。2003年的幸存者 SARS冠状病毒暴发降低了肺功能和生活质量，并使呼吸道病毒感染更加频繁 疾病。后者与儿童喘息和哮喘的风险增加有关，这是最常见的 儿童中的慢性和不同疾病。数据还表明，有很大的种族/民族 新冠肺炎成果的差异。暴露于病毒的风险、对严重疾病的易感性以及 获得医疗保健可能会相互作用，加剧现有的健康不平等。怀孕提供了一种自然的 检测被动免疫保护潜力的机制。母体免疫球蛋白是活跃的 在没有出生后暴露的情况下，通过胎盘运输到无法检测到的水平 一岁以上的新生儿。此外，免疫球蛋白A通过母乳从母亲传给孩子。我们的 多学科团队将研究一个独特的波多黎各母亲和她们的婴儿队列，前瞻性地跟踪 婴儿在他们生命的头五年收集母亲的母乳、母亲和新生儿的脐带血， 新生儿/婴儿出生时、呼吸道疾病期间和每年临床评估时拭子。 我们将确定孕妇和婴儿脐带血在产前接触SARS-CoV-2病毒的情况 并调查这种病毒对儿童呼吸道疾病易感性的影响。我们会 应用聚合酶链式反应和定性免疫分析对所有产前/产后母亲进行SARS-CoV-2检测 感染。在所有血清呈阳性的母亲中，我们将在第5天和第14天收集重复的母乳样本，并 新生儿出生时、出生后1、3、6个月连续抽血，每年抽血5年。我们会检测免疫球蛋白A，免疫球蛋白， 母乳和血样中的IgM和婴儿血清中的Ig G。我们将检查(目标1)被动语态 SARS-CoV-2免疫从血清阳性母亲向其新生儿的转移(目标2)早期SARS-CoV-2是否 CoV-2感染严重程度和其他临床后遗症通过改变儿童免疫表型和 宿主遗传学，以及(目标3)社会环境因素如何影响母婴接触新冠肺炎 并进一步影响儿童哮喘的发展。我们假设孕妇感染了 SARS-CoV-2会产生中和抗体，保护他们的新生儿免受新冠肺炎疾病的侵袭。相比之下， 出生后感染SARS-CoV-2的婴儿日后患包括哮喘在内的呼吸道疾病的风险增加 以及其他临床后遗症。我们进一步假设，这些联系是由宿主的遗传和社会- 环境因素。据我们所知，在美国国内外没有其他群体的人口 执行这些分析所需的和跟踪记录。