The authors from Ukraine and the United States examined the placental arteries of women who were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy and gave birth to live full-term newborns. The morphometric analysis revealed severe vascular remodeling of the placental arteries, including severe thickening of the vessel walls and occlusion of the vessel lumen in women with COVID-19 during pregnancy.
In all included women, infection with SARS-CoV-2 was diagnosed by reverse transcription polymerase chain reaction of nasopharyngeal swabs. In women who tested positive for SARS-CoV-2, the majority (68%) had a mild disease, whereas 32% experienced a severe disease with pneumonia. The exclusion criteria were: preeclampsia, hypertension, diabetes, large fetus (>5kg), smoking during pregnancy, and HIV infection. The archived placental tissues from 28 women who gave birth to live full-term newborns in 2018, before the COVID-19 pandemic, were used as controls.
The authors employed several techniques, such as immunohistochemistry with the antibodies against α-smooth muscle actin and the Kv11.1 potassium channels, and morphometric analysis that included the evaluation of the thickness of the placental arterial wall and the placental arterial lumen index (the ratio of the internal vessel area to the external vessel area). All sample preparations were randomized, and the data analysis was performed in a blinded manner.
Results
This study included 85 women who were infected with SARS-CoV-2 and had symptoms of COVID-19 between 28 and 36 weeks of pregnancy.
In all women who tested positive for COVID-19 during pregnancy, the placental arteries displayed severe vascular remodeling, with histological features of vessel wall thickening and lumen narrowing, regardless of whether they had COVID-19 symptoms. There were no signs of vessel wall thickening in the placental vessels of mothers who were not infected with SARS-CoV-2 during pregnancy.
The morphometric analysis of the thickness of the placental arterial wall showed a significant difference between the results obtained in women who had COVID-19 during pregnancy and healthy controls. The median value of placental arterial wall thickness in women with COVID-19 was approximately 30 μm, while in controls it was approximately 15 μm. According to these results, the arterial wall thickness in placentas of women with COVID-19 was twice as high as that of women without COVID-19. Also, the morphometric analysis showed significantly smaller (5-fold) arterial lumen in women with COVID-19 than in the control subjects. The Masson’s trichrome staining showed not only a quantitative thickening of placental vessels in women who had contracted SARS-CoV-2 during pregnancy but also fibrosis of the vessel walls.
Original figure from the article by Gychka SG, Brelidze TI, Kuchyn IL, et al. PLoS ONE, 2022. Vascular wall thickening in the placentas of women who contracted COVID-19 during pregnancy
Original figure from the article by Gychka SG, Brelidze TI, Kuchyn IL, et al. PLoS ONE, 2022. Masson’s trichrome staining.
Immunohistochemistry with a smooth muscle cell marker, α-smooth muscle actin, clearly demonstrated the dramatic increase in smooth muscle mass in thickened placental vessels of women with COVID-19. In addition, the expression of Kv11.1 potassium channels was increased in the placental vessels of women who had COVID-19 during pregnancy. According to the authors, the placental arteries in women with COVID-19 most likely underwent smooth muscle cell proliferation.
In conclusion, this study demonstrated severe vascular remodeling of placental arteries, including severe thickening of the vessel walls and the occlusion of the vessel lumen, in women with COVID-19 during pregnancy. The narrowing of the placental arterial lumen should alter the blood flow between the mother and the fetus. However, the newborns’ health in this study cohort was not significantly affected, despite severe placental vascular remodeling. The same research group has previously reported 20 cases of prenatal fetal death in the group of 414 women infected with SARS-CoV-2 during pregnancy. This corresponds to a rate of almost 5%, significantly higher than the population average.
Therefore, the authors emphasized that further studies are needed to determine the effects of placental vascular remodeling on neonatal well-being and development.
This article was published in Plos One.
Journal Reference
Gychka SG, Brelidze TI, Kuchyn IL, et al. (2022) Placental vascular remodeling in pregnant women with COVID-19. PLoS ONE 17(7): e0268591. (Open Access) https://doi.org/10.1371/journal.pone.0268591
