Development of Mucosal and Systemic Immunity and Risk of Food Allergy

背景：SARS-CoV-2病毒在母乳中的传播尚不清楚， 描述不佳的研究，报告说在总共36个母乳样本中只有1个检测到病毒。此外，本发明还 母亲在怀孕和哺乳期间感染SARS-CoV-2可能赋予一些特异性， 通过抗体进行保护。只有一项研究报告存在SARS-CoV-2的IgG 在HM。其他病毒感染的抗体依赖性增强的惊人例子说明了 关键是要了解HM中这些抗体的特征和活性。因此， 了解母婴传播的风险和保护因素， 母乳喂养。 设计：我们提出了一项COVID-19+母亲的纵向队列研究，以确定 传播（婴儿通过母乳喂养暴露于病毒，存在于人乳和乳晕皮肤上） 和保护性因素（在HM中的SARS-CoV-2特异性抗体应答、特征和中和 母乳喂养的能力。纵向样本将使我们能够评估疾病的时间变化 当然了 方法：我们将招募50名哺乳期前3个月的COVID+母亲，25名有症状的母亲和25名 无症状。我们将同时从两个地点收集样本：罗切斯特大学 医学和牙科学院和纽约纽约大学。这些网站将提供强大的， 交错接触病人我们将通过当地医院和社交媒体平台进行招募。母亲 将提供知情同意书。已收到IRB批准。所有样本将在 在医院（如果入院）或家中。研究工作人员之间不得有身体接触 和参与者。母亲将在第0天（入组）、第3天、第10天、第19天、 28和90，第0和3天的乳房皮肤拭子和第0和90天的手指针刺全血。他们 还将指导其提供第-7天的冷冻人乳样本（如可用）。 分析：将在Jarvinen-Seppo实验室从HM和乳房皮肤拭子中提取RNA。SARS- 将使用基于RT-qPCR三扩增子探针的系统定量CoV-2基因组RNA 根据CDC的建议。我们将通过重复的方法比较HM中SARS-CoV-2的存在和变化。 措施分析我们将评估母亲手指中SARS-CoV-2和其他冠状病毒抗体 用Luminex对SARS 1、SARS 2、HKU 1、229 E、NL 63和OC 43的S蛋白和N蛋白进行了特异性检测， 由Zand实验室开发和验证的mPLEX-CoV系统。重复测量分析将 用于比较HM抗SARS-CoV-2抗体浓度随时间的变化 疾病进展之间的关系，以及轻度至重度症状的女性之间的关系。 影响：这些结果对于了解母乳喂养的风险和益处至关重要， COVID-19感染，并有必要制定以证据为基础的政策，并照顾这些家庭。

Background: Transmission of the SARS-CoV-2 virus in human milk (HM) is unknown with only 11 poorly-described studies, reporting detectable virus in just 1 of the total 36 breastmilk samples. Further, it is possible that maternal SARS-CoV-2 infection during pregnancy and lactation confers some specific protection through antibodies. Only one study reports the presence of IgG to SARS-CoV-2 in HM. Alarming examples of antibody-dependent enhancement of other viral infections illustrate how critical it is to understand both the profile and activity of these antibodies in HM. It is critical then to understand the transmission risks and protective factors between mother and child through breastfeeding. Design: We propose a longitudinal cohort study of COVID-19+ mothers to determine risks of transmission (viral exposure of infants through breastfeeding by presence in HM and on areolar skin) and protective factors (SARS-CoV-2-specific antibody response in HM, profile and neutralization capacity) of breastfeeding. Longitudinal samples will allow us to assess temporal changes over disease course. Methods: We will enroll 50 COVID+ mothers in the first 3 months of lactation, 25 symptomatic and 25 asymptomatic. We will concurrently collect samples from two locations: The University of Rochester School of Medicine and Dentistry and New York University, NY. These sites will provide robust and staggered access to patients. We will recruit through local hospitals and social media platforms. Mothers will provide informed eConsent. IRB approval has been received. All samples will be self-collected in the hospital (if admitted) or in the home. There will be no physical contact between study staff and participants. Mothers will express and collect whole breastmilk on Days 0 (enrollment), 3, 10, 19, 28, and 90, breast skin swabs on Days 0 and 3 and whole blood by fingerstick on days 0 and 90. They will also be instructed to provide a frozen HM sample from Day -7, if available. Analysis: RNA will be extracted from HM and breast skin swabs in the Jarvinen-Seppo lab. SARS- CoV-2 genomic RNA will be quantitated using RT-qPCR three amplicon probe-based system as recommended by CDC. We will compare presence and changes in SARS-CoV-2 in HM via repeated measures analysis. We will assess SARS-CoV-2 and other coronavirus antibodies in maternal finger prick and HM to S and N proteins of SARS1, SARS2, HKU1, 229E, NL63 and OC43 by Luminex on the mPLEX-CoV system developed and validated by the Zand lab. Repeated measures analysis will be used to compare the changes in concentration of HM anti-SARS-CoV-2 antibodies over the time-course of disease progression and also between women with mild to severe symptoms. Impact: These results are critical to understand the risks and benefits of breastfeeding in the context of COVID-19 infection, and are necessary to make evidence-based policies, and to care for these families.