Abstract
Introduction: The contribution of SARS-CoV-2 infection to the severity of placental alterations in preeclampsia remains unclear. This study aimed to evaluate the morphological changes in placentas of women who experienced COVID-19 during pregnancy, with a focus on the presence or absence of preeclampsia. Materials and Methods: The study included placentas from: (1) patients with both COVID-19 during pregnancy and preeclampsia (n = 20, 2022); (2) patients with COVID-19 during pregnancy without preeclampsia (n = 20, 2022); (3) patients with preeclampsia but without COVID-19 (n = 5, 2019); (4) patients with physiological pregnancies without COVID-19 or gestational complications (n = 5, 2019). Histological and immunohistochemical examinations of the placentas were performed using antibodies against the SARS-CoV-2 spike protein, DPP4 (CD26), and VEGF. Results: Placentas from patients with both COVID-19 and preeclampsia demonstrated the most pronounced stromal and vascular alterations, including pseudo-infarctions and villous fibrosis. Chorangiosis, excessive fibrinoid deposition in the intervillous space, and accelerated villous maturation with an increased number of syncytial knots were more common in the preeclampsia groups, regardless of prior COVID-19 infection. Symptomatic forms of coronavirus infection were associated with more severe manifestations of malperfusion. Expression of the SARS-CoV-2 spike protein was detected in 78% of syncytiotrophoblast cells and 37% of decidual cells in 28 of 40 placentas from women with previous COVID-19, while its presence in the vascular endothelium, macrophages, and villous fibroblasts was focal, as was CD26 expression. VEGF expression did not differ significantly between patients with and without COVID-19. Conclusions: COVID-19 is associated with more pronounced stromal-vascular alterations in the placenta; however, not all of these changes are directly caused by the virus itself but rather reflect the severe course of preeclampsia. Inflammatory alterations are nonspecific for COVID-19, even though CD26 and the SARS-CoV-2 spike protein are detectable in nearly all placental structures, whereas VEGF levels remain comparable to those observed in placentas prior to the coronavirus pandemic.