Molecular Insights into the Thrombotic and Microvascular Injury in Placental Endothelium of Women with Mild or Severe COVID-19
Arturo Flores‐Pliego, Jael Miranda, Sara Vega-Torreblanca, María Yolotzín Valdespino-Vázquez, Addy Cecilia Helguera‐Repetto, Aurora Espejel-Núñez, Héctor Borboa-Olivares, Salvador Espino y Sosa, Paloma Mateu-Rogell, Moisés León‐Juárez, Víctor Hugo Ramírez-Santes, Arturo Cardona-Pérez, Maria Isabel Villegas-Mota, Johnatan Torres‐Torres, Ángeles Juárez-Reyes, Thelma Rizo-Pica, Rosa O. González, Lorenza González‐Mariscal, Guadalupe Estrada‐Gutiérrez
Abstract
Clinical manifestations of coronavirus disease 2019 (COVID-19) in pregnant women are diverse, and little is known of the impact of the disease on placental physiology. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been detected in the human placenta, and its binding receptor ACE2 is present in a variety of placental cells, including endothelium. Here, we analyze the impact of COVID-19 in placental endothelium, studying by immunofluorescence the expression of von Willebrand factor (vWf), claudin-5, and vascular endothelial (VE) cadherin in the decidua and chorionic villi of placentas from women with mild and severe COVID-19 in comparison to healthy controls. Our results indicate that: (1) vWf expression increases in the endothelium of decidua and chorionic villi of placentas derived from women with COVID-19, being higher in severe cases; (2) Claudin-5 and VE-cadherin expression decrease in the decidua and chorionic villus of placentas from women with severe COVID-19 but not in those with mild disease. Placental histological analysis reveals thrombosis, infarcts, and vascular wall remodeling, confirming the deleterious effect of COVID-19 on placental vessels. Together, these results suggest that placentas from women with COVID-19 have a condition of leaky endothelium and thrombosis, which is sensitive to disease severity.