RAPID: Collaborative Research: COVID-19, human milk and infant feeding

新冠肺炎疫情给个人和公共卫生带来了难以估量的挑战，这主要是因为科学家和临床医生对导致疫情的病毒以及传播途径知之甚少。虽然已知呼吸道飞沫是一种主要的传播方式，但很可能还有其他来源。一种未被研究的可能性是通过母乳喂养从母亲传染给婴儿。尽管研究人员知道一些病毒可以通过这种方式从母亲传给婴儿，但对SARS-CoV-2(导致新冠肺炎的病毒)几乎一无所知。因此，在已知母亲被感染的情况下，母乳喂养是否安全和/或有益，存在很大的混乱。这项研究将提供有关SARS-CoV-2这一基本生物学特性的基本信息，这些信息将立即被妇女、医疗保健提供者和公共政策制定者使用。这项研究将调查是否可以在受感染妇女生产的母乳中检测到SARS-CoV-2和抗SARS-CoV-2抗体。与配方奶喂养的母亲和婴儿相比，结果将提供有关疾病在母乳喂养的母亲和婴儿之间潜在传播的必要信息。这一主题十分紧迫，因为在大流行期间，妇女仍在分娩和哺乳，迫切需要指导。该项目的更广泛影响包括向公众宣传母乳喂养的选择，以及对本科生和研究生进行教育。尽管呼吸道飞沫是SARS-CoV-2已知的传播来源，但可能存在其他模式。其中一种可能性是SARS-CoV-2在母乳喂养期间的垂直传播，但人们对这种类型的冠状病毒传播知之甚少。对于SARS-CoV-2，只有少数几项研究报告了对新冠肺炎+女性生产的牛奶的分析；除了三项研究外，所有研究都报告没有牛奶中含有病毒的证据。关于母乳抗体对婴儿免疫反应和症状严重程度的影响的研究也同样有限。因此，对于SARS-CoV-2+母亲母乳喂养的风险和好处，人们存在很大的困惑。这项拟议的研究是对25名母乳喂养的母亲和婴儿以及25名配方奶喂养的母亲和婴儿进行的纵向重复测量研究。将在产妇确诊后7天内招募DUADS，并跟踪2个月，在此期间将重复收集(从哺乳母亲那里)牛奶和乳拭子，并使用RT-qPCR分析SARS-CoV-2RNA；还将分析牛奶中SARS-CoV-2特异性抗体。还将收集和分析粪便样本，以评估病毒暴露/脱落；并收集和分析干血迹，以评估病毒血症和抗体(免疫球蛋白和免疫球蛋白A)滴度。结果将立即通知妇女、医疗保健提供者和公共政策制定者有关产后婴儿喂养选择的信息。这一快速奖项是由综合组织系统生物部的生理和结构系统集群利用冠状病毒援助、救济和经济安全(CARE)法案的资金颁发的。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The COVID-19 pandemic has resulted in untold challenges to personal and public health, largely because scientists and clinicians know very little about the virus that causes it and how transmission occurs. Whereas respiratory droplets are known to be a major mode of transmission, it is very likely that there are other sources. One understudied possibility is transmission from mother to infant via breastfeeding. Although researchers know that some viruses can be passed from mother to infant in this fashion, almost nothing is known about SARS-CoV-2 (the virus that causes COVID-19). For this reason, there is substantial confusion as to whether breastfeeding is safe and/or beneficial when a mother is known to be infected. This study will provide fundamental information about this basic biological property of SARS-CoV-2, information that will be immediately usable by women, healthcare providers, and public policy makers. This study will investigate whether SARS-CoV-2 and anti-SARS-CoV-2 antibodies can be detected in breast milk produced by infected women. Results will provide needed information about potential spread of the disease between breastfeeding mothers and infants as compared to formula-feeding mothers and infants. This topic is urgent because women continue to give birth and breastfeed during the pandemic, and guidance is critically needed. The Broader Impacts of this project include both outreach to the public to inform breastfeeding mothers about breast-feeding choices, and education of an undergraduate and graduate student.Although respiratory droplets are a known source of SARS-CoV-2 transmission, other modes likely exist. One such possibility is SARS-CoV-2 vertical transmission during breastfeeding, but little is known about this type of transfer for any coronaviruses. For SARS-CoV-2, there are only a handful of studies that report analysis of milk produced by COVID-19+ women; all but three report no evidence of virus in milk. There is similarly limited research on the effects of maternal milk antibodies on infant immune responses and severity of symptoms. As a result, there is substantial confusion as to the risks and benefits of breastfeeding for SARS-CoV-2+ mothers. This proposed research is a longitudinal, repeated-measures study of 25 breastfeeding mothers and infants and 25 formula-feeding mothers and infants. Dyads will be recruited within 7 days of maternal COVID-19 diagnosis and followed for 2 months during which time milk and breast swabs will be repeatedly collected (from breastfeeding mothers) and analyzed for SARS-CoV-2 RNA using an RT-qPCR; milk will also be analyzed for SARS-CoV-2-specific antibodies. Stool samples will also be collected and analyzed to assess viral exposure/shedding; and dried blood spots collected and analyzed to assess viremia and antibody (IgG and IgA) titers. Results will immediately inform women, healthcare providers, and public policy makers regarding infant feeding choices during the postpartum period. This RAPID award is made by the Physiological and Structural Systems Cluster in the BIO Division of Integrative Organismal Systems, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.