Coronavirus disease 2019 (COVID-19) in pregnancy: pathomorphological ultrastructural changes of the placenta

Abstract

Aim. To investigate ultrastructural changes in the placenta of pregnant women with COVID-19 during the second and third trimesters of gestation.

Materials and methods. A total of 128 placentas from pregnant women with a confirmed positive PCR test for SARS-CoV-2 RNA were examined. Group I – placentas after live births (n = 94; gestational age 40 ± 2 weeks). Group II – placentas after antenatal fetal death (n = 34; gestational age 33 ± 4 weeks). Based on the post-COVID interval (the time between maternal COVID-19 diagnosis and delivery), the following subgroups were formed: in I.1 (n = 54) and II.1 (n = 12), the post-COVID interval was 5–16 weeks; and in I.2 (n = 40) and II.2 (n = 22), it was 1–4 weeks. For comparison, placentas from physiological deliveries before the COVID-19 pandemic were analyzed (n = 50; gestational age 39 ± 1 week). Macroscopic, microscopic, electron microscopic, morphometric, and statistical analyses were performed.

Results. Results. In 100 % of cases, placentitis, endothelial dysfunction, and microcirculatory damage were observed. During the acute phase of COVID-19, cytoplasmic edema of endothelial cells, disruption of cell membranes, and nuclear apoptosis were detected, along with stromal edema of chorionic villi, narrowing of vascular lumina, and destructive changes in telocytes (TCs). With a longer post-COVID interval, Group I showed a decrease in placentitis and stromal edema, as well as restoration of endothelial function and vascular lumina. In Group II, however, arteriolosclerosis, stromal fibrosis, and impaired villous maturation were identified.

Conclusions. The effect of SARS-CoV-2 in all groups caused edema and irreversible changes in the endothelial cells of chorionic villous vessels during the acute phase of the disease. The morphogenesis of SARS-CoV-2-induced placental dysfunction involved endothelial dysfunction, impaired microcirculation, inflammatory infiltration, stromal edema of terminal villi followed by fibrosis, narrowing of vascular lumina, and a reduction in the proportion of free intervillous space. Microcirculatory disturbances and stromal villous edema in COVID-19 led to destructive changes in TCs, thereby limiting adequate angiogenesis and regulation of vascular tone in immature intermediate villi. Irreversible alterations of TCs, their fibroblastic differentiation, and subsequent stromal fibrosis of stem and intermediate villi resulted in a reduced number of terminal villi and a dissociated disordered villous maturation.