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If and how SARS\u2010CoV\u20102\u2010specific immune cells negatively affect placenta functionality is still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>We stimulated peripheral blood mononuclear cells (PBMCs) from women of reproductive age with SARS\u2010CoV\u20102 peptides and cocultured them with trophoblast spheroids (HTR\u20108\/SVneo and JEG\u20103) to dissect if SARS\u2010CoV\u20102\u2010activated immune cells can interfere with trophoblast functionality. The activation and cytokine profile of the PBMCs were determined using multicolor flow cytometry. The functionality of trophoblast spheroids was assessed using microscopy, enzyme\u2010linked immunosorbent assay (ELISA), and RT\u2010qPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SARS\u2010CoV\u20102 S and M peptides significantly activated PBMCs (monocytes, NK cells, and T cells with memory subsets) and induced the upregulation of proinflammatory cytokines, such as IFN\u03b3. The activated PBMCs did not impact the viability, growth rate, and invasion capabilities of trophoblast spheroids. Furthermore, the hormonal production of hCG by JEG\u20103 spheroids was not compromised upon coculture with the activated PBMCs. mRNA transcript levels of genes involved in trophoblast spheroid functional pathways were also not dysregulated after coculture.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Together, the findings of our in vitro coculture model, although not fully representative of in vivo conditions, strongly support the claim that the interaction of SARS\u2010CoV\u20102\u2010activated peripheral blood immune cells with trophoblast cells at the fetal\u2013maternal interface does not negatively affect trophoblast functionality. This goes in hand with the recommendation of vaccinating pregnant women in their first trimester.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.70039","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T14:56:25Z","timestamp":1736261785000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SARS\u2010CoV\u20102 Activated Peripheral Blood Mononuclear Cells (PBMCs) Do Not Provoke Adverse Effects in Trophoblast Spheroids"],"prefix":"10.1111","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9245-6811","authenticated-orcid":false,"given":"Humblenoble Stembridge","family":"Ayuk","sequence":"first","affiliation":[{"name":"Department of Environmental Immunology Helmholtz Centre for Environmental Research  Leipzig Saxony Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of 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