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While abnormal placental pathology resulting from COVID\u201019 is common, direct infection of the placenta is rare. This suggests that pathophysiology associated with maternal COVID\u201019, rather than direct placental infection, is responsible for placental dysfunction. We hypothesized that maternal circulating extracellular vesicles (EVs), altered by COVID\u201019 during pregnancy, contribute to placental dysfunction. To examine this hypothesis, we characterized circulating EVs from pregnancies complicated by COVID\u201019 and tested their effects on trophoblast cell physiology in vitro. Trophoblast exposure to EVs isolated from patients with an active infection (AI), but not controls, altered key trophoblast functions including hormone production and invasion. Thus, circulating EVs from participants with an AI, both symptomatic and asymptomatic cases, can disrupt vital trophoblast functions. EV cargo differed between participants with COVID\u201019, depending on the gestational timing of infection, and Controls, which may contribute to the disruption of the placental transcriptome and morphology. Our findings show that COVID\u201019 can have effects throughout pregnancy on circulating EVs, and circulating EVs are likely to participate in placental dysfunction induced by COVID\u201019.<\/jats:p>","DOI":"10.1002\/jev2.70051","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T04:08:12Z","timestamp":1744258092000},"source":"Crossref","is-referenced-by-count":4,"title":["Extracellular Vesicles Alter Trophoblast Function in Pregnancies Complicated by COVID\u201019"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7643-8944","authenticated-orcid":false,"given":"Thea N.","family":"Golden","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Center for Women's Health and Reproductive Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Center for Excellence in 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