{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:42:52Z","timestamp":1789429372726,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:00:00Z","timestamp":1739577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Good Ventures Foundation and the NIH\/NIAID","award":["U01AI144673"],"award-info":[{"award-number":["U01AI144673"]}]},{"name":"Good Ventures Foundation and the NIH\/NIAID","award":["S10OD02671"],"award-info":[{"award-number":["S10OD02671"]}]},{"name":"National Institutes of Health Shared Instrumentation Grant Program","award":["U01AI144673"],"award-info":[{"award-number":["U01AI144673"]}]},{"name":"National Institutes of Health Shared Instrumentation Grant Program","award":["S10OD02671"],"award-info":[{"award-number":["S10OD02671"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Human milk-derived extracellular vesicles (HMEVs) are key components in breast milk, promoting infant health and development. Maternal conditions could affect HMEV cargo; however, the impact of SARS-CoV-2 infection on HMEVs remains unknown. This study investigated the influence of SARS-CoV-2 infection during pregnancy on postpartum HMEV molecules. The median duration from SARS-CoV-2 test positivity to milk collection was 3 months. After defatting and casein micelle disaggregation, HMEVs were isolated from milk samples of nine mothers with prenatal SARS-CoV-2 and six controls by sequential centrifugation, ultrafiltration, and qEV-size exclusion chromatography. The presence of HMEV was confirmed via transmission electron microscopy. Nanoparticle tracking analysis demonstrated particle diameters of &lt;200 nm and yields of &gt;1 \u00d7 1011 particles per mL of milk. Western immunoblots detected ALIX, CD9, and HSP70, supporting the presence of HMEVs in the isolates. Cargo from thousands of HMEVs were analyzed using a multi-omics approach, including proteomics and microRNA sequencing, and predicted that mothers with prenatal SARS-CoV-2 infection produced HMEVs with enhanced functionalities involving metabolic reprogramming, mucosal tissue development, and immunomodulation. Our findings suggest that SARS-CoV-2 infection during pregnancy boosts mucosal site-specific functions of HMEVs, potentially protecting infants against viral infections. Further prospective studies should be pursued to reevaluate the short- and long-term benefits of breastfeeding in the post-COVID era.<\/jats:p>","DOI":"10.3390\/cells14040284","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T07:48:22Z","timestamp":1739778502000},"page":"284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Prenatal SARS-CoV-2 Infection Alters Human Milk-Derived Extracellular Vesicles"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6398-5626","authenticated-orcid":false,"given":"Somchai","family":"Chutipongtanate","sequence":"first","affiliation":[{"name":"Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supasek","family":"Kongsomros","sequence":"additional","affiliation":[{"name":"Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"},{"name":"Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatice","family":"Cetinkaya","sequence":"additional","affiliation":[{"name":"Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7371-4085","authenticated-orcid":false,"given":"Xiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damaris","family":"Kuhnell","sequence":"additional","affiliation":[{"name":"Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7953-6793","authenticated-orcid":false,"given":"Desir\u00e9e","family":"Benefield","sequence":"additional","affiliation":[{"name":"Center for Advanced Structural Biology, Department of Molecular & Cellular Biosciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy D.","family":"Haffey","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-2250","authenticated-orcid":false,"given":"Michael A.","family":"Wyder","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Kwatra","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45267, USA"},{"name":"Department of Clinical Microbiology, Christian Medical College, Vellore 632004, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon C.","family":"Conrey","sequence":"additional","affiliation":[{"name":"Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison R.","family":"Burrell","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Langevin","sequence":"additional","affiliation":[{"name":"Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6851-1198","authenticated-orcid":false,"given":"Leyla","family":"Esfandiari","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Newburg","sequence":"additional","affiliation":[{"name":"Department of Environmental and Public Health Sciences, University 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