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Severe vascular remodeling of placental arteries in women infected with SARS-CoV-2 during pregnancy

The infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can have serious effects not only on the pulmonary vasculature but also on the vasculature of multiple organs, including the heart and brain. In this study, the authors from Ukraine and the United States examined the remodeling of placental arteries of women who were infected with SARS-CoV-2 during pregnancy and gave birth to live full-term newborns

 

About the study

Infection with SARS-CoV-2 was diagnosed in all participants 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 HIV infection. Researchers used as controls the archived placental tissues from 28 women who gave birth to live full-term newborns in 2018, before the COVID-19 pandemic.

The authors used several techniques, immunohistochemistry with the antibodies against α-smooth muscle actin and the Kv11.1 potassium channels and morphometric analysis of the placental arterial wall thickness 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. 

The placental arteries of all women who tested positive for COVID-19 during pregnancy, regardless of whether they had COVID-19 symptoms, showed severe vascular remodeling, with histological features of vessel wall thickening and lumen narrowing.  Notably, the placental vessels of mothers not infected with SARS-CoV-2 during pregnancy had no signs of vessel wall thickening.

The morphometric analysis of the placental arterial walls showed 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. Also, the morphometric analysis demonstrated a 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 infected with SARS-CoV-2 during pregnancy but also a 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 the antibodies against a smooth muscle cell marker α-smooth muscle actin demonstrated a dramatic increase in smooth muscle mass in thickened placental vessels of women with COVID-19. The authors stated that placental arteries in women with COVID-19 very likely underwent smooth muscle cell proliferation.

Conclusion

This study demonstrated severe vascular remodeling of placental arteries, including severe thickening of the vessel walls and the occlusion of the vessel lumen, of 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%, 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

 

 

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