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.

项目摘要 严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）是导致COVID-19大流行的原因。 缺乏诊断测试和目前的公共卫生政策限制了我们对SARS真正流行情况的了解- 二型冠状病毒SARS-CoV-2感染导致受感染宿主产生抗病毒抗体，但目前 目前尚不清楚这些抗体反应是否对随后的感染有保护作用。2003年的幸存者 SARS冠状病毒爆发降低了肺功能和生活质量， 疾病。后者与儿童喘息和哮喘的风险增加有关， 慢性和不同的疾病。数据还表明，有显著的种族/族裔差异， COVID-19结果的差异。病毒暴露风险的差异，对严重疾病的易感性， 获得保健的机会可能相互作用，加剧现有的保健不平等。怀孕提供了一个自然的 研究被动免疫的保护潜力的机制。母亲IgG是活跃的 通过胎盘运输，在没有产后暴露的情况下， 新生儿在生命的第一年。此外，伊加通过母乳从母亲传给孩子。我们 一个多学科小组将研究一组独特的波多黎各母亲和她们的婴儿， 在婴儿出生后五年内收集母乳、母亲和新生儿脐带血， 以及出生时、呼吸道疾病期间和每年临床评估时的新生儿/婴儿鼻上皮拭子。 我们将确定产前暴露于SARS-CoV-2，如从母亲和婴儿脐带血中测量的， 并调查这种病毒对儿童呼吸道疾病易感性的影响。我们将 对所有产前/产后母亲进行PCR检测和定性免疫检测，以检测SARS-CoV-2 感染在所有血清反应阳性的母亲中，我们将在第5天和第14天重复采集母乳样本， 在出生时、1个月、3个月、6个月和每年连续5年采集新生儿血斑样本。我们将测量伊加，IgG， 母亲母乳和血样中IgM和婴儿血清中IgG。我们将考察（目标1）被动语态 将SARS-CoV-2免疫力从血清阳性母亲转移到其新生儿，（目的2）是否早期生命SARS- CoV-2感染的严重程度和其他临床后遗症会因儿童免疫表型的改变而改变， 宿主遗传学，以及（目标3）社会环境因素如何影响孕产妇和婴儿接触COVID-19 并进一步影响儿童哮喘的发展。我们假设感染了 SARS-CoV-2产生中和抗体，保护他们的新生儿免受COVID-19疾病的侵害。与此相反， 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 和其他临床后遗症。我们进一步假设，这些协会是由宿主遗传和社会修改。 环境因素据我们所知，在美国境内或境外没有其他群体 需要和跟踪记录来执行这些分析。