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Here, we provide a molecular basis for the breastfeeding recommendation through mass spectrometry (MS)-based proteomics and glycosylation analysis of immune-related proteins in both colostrum and mature breastmilk collected from COVID-19 patients and healthy donors. The total protein amounts in the COVID-19 colostrum group were significantly higher than in the control group. While casein proteins in COVID-19 colostrum exhibited significantly lower abundances, immune-related proteins, especially whey proteins with antiviral properties against SARS-CoV-2, were upregulated. These proteins were detected with unique site-specific glycan structures and improved glycosylation diversity that are beneficial for recognizing epitopes and blocking viral entry. Such adaptive differences in milk from COVID-19 mothers tended to fade in mature milk from the same mothers one month postpartum. These results suggest that feeding infants colostrum from COVID-19 mothers confers both nutritional and immune benefits, and provide molecular-level insights that aid breastmilk feeding decisions in cases of active infection.<\/jats:p>","DOI":"10.3390\/nu14122513","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T05:25:11Z","timestamp":1655443511000},"page":"2513","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Proteomic Analysis of Human Milk Reveals Nutritional and Immune Benefits in the Colostrum from Mothers with COVID-19"],"prefix":"10.3390","volume":"14","author":[{"given":"Juanjuan","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Zhongnan Hospital of Wuhan University, Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minjie","family":"Tan","sequence":"additional","affiliation":[{"name":"Institute for Cell Analysis, Shenzhen Bay Laboratory, Shenzhen 518132, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8451-9173","authenticated-orcid":false,"given":"Jing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology and Health, Beijing Academy of Science and Technology, Beijing 100089, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Tian","sequence":"additional","affiliation":[{"name":"Institute for Cell Analysis, Shenzhen Bay Laboratory, Shenzhen 518132, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Zhongnan Hospital of Wuhan University, Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianbin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7297-1266","authenticated-orcid":false,"given":"Yanyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute for Cell Analysis, Shenzhen Bay Laboratory, Shenzhen 518132, China"},{"name":"Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanzhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Zhongnan Hospital of Wuhan University, Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan 430071, China"},{"name":"Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuexin","family":"Yang","sequence":"additional","affiliation":[{"name":"National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5468-8993","authenticated-orcid":false,"given":"Guanbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Cell Analysis, Shenzhen Bay Laboratory, Shenzhen 518132, China"},{"name":"Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41590-018-0294-9","article-title":"Memory CD4(+) T cells are generated in the human fetal intestine","volume":"20","author":"Li","year":"2019","journal-title":"Nat. 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