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1., Introduction: This study investigates the impact of SARS-CoV-2 infection on placental histopathology in pregnant women, comparing outcomes between vaccinated and non-vaccinated individuals. Despite known adverse pregnancy outcomes linked to SARS-CoV-2 infection, the specific effects on the placenta remain unclear. Although vaccination has demonstrated a substantial reduction in infection severity, its impact on placental health requires more insight. 2., Methods: Between March 2021 and July 2022, 387 COVID-19-positive women were admitted for delivery. Of these, 98 with non-severe symptoms were analyzed: 35 vaccinated during pregnancy, and 63 non-vaccinated. Two independent pathologists evaluated all placental specimens. 3., Results: The only differing obstetrical characteristic between groups was the mode of delivery (p 0.047), lacking clinical implications. Over 85% of placentas exhibited microscopic abnormalities, predominantly maternal vascular supply disorders (vaccinated 89.1%; unvaccinated 85.5%). Comparing vaccinated and unvaccinated groups revealed statistically significant differences, notably in increased focal perivillous fibrin deposits (IFPFD) [17.1% vs. 33.3% (p 0.04)] and avascular fibrotic villi (AFV) [0% vs. 11.1% (p 0.04)]. Binomial logistic regression confirmed the vaccine's protective role against IFPFD (aOR 0.36; 95%CI 013-0.99) and AVF (aOR 0.06, 95% CI 0.003-0.98). A sub-analysis in vaccinated women showed a positive correlation between the timing of the first dose and IFPFD presence (p 0.018). 4., Discussion: The lower incidence of maternal and fetal vascular malperfusion placental features in vaccinated women, coupled with the timing correlation, supports the vaccine's protective effect on placental tissue in COVID-19-infected pregnant patients. Notably, no side effects were reported post-vaccination, emphasizing the vaccine's safety and advocating for its secure administration in pregnant populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)