The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect the human placenta. The normal vascular pattern of the placenta includes vasculogenesis and angiogenesis, which are associated with the physiological expression of vascular endothelial growth factor (VEGF). Since the infection with SARS-CoV-2 seriously affects the vasculature of multiple organs, including the lungs, heart, and brain, the authors from Ukraine and the United States investigated whether and how the SARS-CoV-2 affects placental arteries in women who were infected during pregnancy and gave birth to live full-term newborns.
Of note, a recent immunohistochemical study of markers involved in vascular damage and the autophagic process in the placental tissue of unvaccinated women infected with SARS-CoV-2 demonstrated the increased expression of VEGF and the endothelial cell marker CD34 in the placentas of SARS-CoV-2 positive women, which indicates alterations, disarrangements, or remodeling of normal vasculature, associated with vascular endothelial injury and inflammation, presumably endothelitis. https://discovermednews.com/colocalization-of-sars-cov-2-spike-protein-with-markers-of-vascular-damage-and-autophagy-in-placentas/
About the study
This study enrolled 85 women who were infected with SARS-CoV-2 and had symptoms of COVID-19 between 28 and 36 weeks of pregnancy. In all participants, infection with SARS-CoV-2 was diagnosed by reverse transcription polymerase chain reaction of nasopharyngeal swabs. The majority (68%) of women who tested positive for SARS-CoV-2 had mild COVID-19, whereas 32% experienced a severe disease with pneumonia. The exclusion criteria were the following: preeclampsia, hypertension, diabetes, large fetus (>5kg), smoking during pregnancy, and the human immunodeficiency virus 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 performed immunohistochemistry with the antibodies against α-smooth muscle actin, a marker of pericytes and myofibroblastic cells, and morphometric analysis of the placental arterial wall thickness and 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
Severe vascular remodeling, with histological features of vessel wall thickening and lumen narrowing, was found in the placental arteries of all women who tested positive for COVID-19 during pregnancy, regardless of whether they had COVID-19 symptoms. Mothers not infected with SARS-CoV-2 during pregnancy had no signs of the placental vessel wall thickening.
The morphometric analysis of the placental arterial walls revealed significant differences between 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.
The morphometric analysis also demonstrated a significantly smaller (5-fold) arterial lumen in women with COVID-19 than in healthy controls. Importantly, Masson’s trichrome staining showed not only a quantitative thickening of placental vessels in women infected with SARS-CoV-2 during pregnancy but also a fibrosis of the vessel walls.
In thickened placental vessels of women infected with SARS-CoV-2 during pregnancy, the immunohistochemistry with the antibodies against α-smooth muscle actin demonstrated a dramatic increase in smooth muscle mass. According to the authors, the placental arteries of women with COVID-19 during pregnancy very likely underwent smooth muscle cell proliferation.
Vascular wall thickening in the placentas of women who contracted COVID-19 during pregnancy
The original figure from the article by Gychka SG, Brelidze TI, Kuchyn IL, et al. PLoS ONE, 2022.
Masson’s trichrome staining.
The original figure from the article by Gychka SG, Brelidze TI, Kuchyn IL, et al. PLoS ONE, 2022.
Conclusion
This study demonstrated severe vascular remodeling of placental arteries, including severe thickening and fibrosis of the vessel walls, and the occlusion of the vessel lumen in women infected with SARS-CoV-2 during pregnancy. Although the narrowing of the placental arterial lumen alters the blood flow between the mother and the fetus, the newborns’ health in this study cohort was not significantly affected. The same research group 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%, which is 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
