Molecular Insights into the Thrombotic and Microvascular Injury in Placental Endothelium of Women with Mild or Severe COVID-19

Cells. 2021 Feb 10;10(2):364. doi: 10.3390/cells10020364.

Abstract

Clinical manifestations of coronavirus disease 2019 (COVID-19) in pregnant women are diverse, and little is known of the impact of the disease on placental physiology. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been detected in the human placenta, and its binding receptor ACE2 is present in a variety of placental cells, including endothelium. Here, we analyze the impact of COVID-19 in placental endothelium, studying by immunofluorescence the expression of von Willebrand factor (vWf), claudin-5, and vascular endothelial (VE) cadherin in the decidua and chorionic villi of placentas from women with mild and severe COVID-19 in comparison to healthy controls. Our results indicate that: (1) vWf expression increases in the endothelium of decidua and chorionic villi of placentas derived from women with COVID-19, being higher in severe cases; (2) Claudin-5 and VE-cadherin expression decrease in the decidua and chorionic villus of placentas from women with severe COVID-19 but not in those with mild disease. Placental histological analysis reveals thrombosis, infarcts, and vascular wall remodeling, confirming the deleterious effect of COVID-19 on placental vessels. Together, these results suggest that placentas from women with COVID-19 have a condition of leaky endothelium and thrombosis, which is sensitive to disease severity.

Keywords: COVID-19; VE-cadherin; claudin-5; endothelium; placenta; von Willebrand factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / analysis
  • COVID-19 / complications*
  • COVID-19 / pathology
  • COVID-19 / virology
  • Cadherins / analysis
  • Claudin-5 / analysis
  • Endothelium / blood supply
  • Endothelium / pathology
  • Endothelium / virology
  • Female
  • Humans
  • Infant, Newborn
  • Microvessels / pathology
  • Microvessels / virology
  • Placenta / blood supply*
  • Placenta / pathology*
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / etiology*
  • Pregnancy Complications, Cardiovascular / pathology
  • Pregnancy Complications, Cardiovascular / virology
  • Pregnancy Complications, Infectious / etiology*
  • Pregnancy Complications, Infectious / pathology
  • Pregnancy Complications, Infectious / virology
  • SARS-CoV-2 / isolation & purification
  • Thrombosis / etiology*
  • Thrombosis / pathology
  • Thrombosis / virology
  • Young Adult
  • von Willebrand Factor / analysis

Substances

  • Antigens, CD
  • CLDN5 protein, human
  • Cadherins
  • Claudin-5
  • cadherin 5
  • von Willebrand Factor