Placental vascular remodeling in pregnant women with COVID-19

Abstract

Severe acute respiratory syndrome coronavirus 2 has been causing the pandemic of coronavirus disease 2019 (COVID-19) that has so far resulted in over 450 million infections and six million deaths. This respiratory virus uses angiotensin-converting enzyme 2 as a receptor to enter host cells and affects various tissues in addition to the lungs. The present study reports that the placental arteries of women who gave birth to live full-term newborns while developing COVID-19 during pregnancy exhibit severe vascular wall thickening and the occlusion of the vascular lumen. A morphometric analysis of the placental arteries stained with hematoxylin and eosin suggests a 2-fold increase in wall thickness and a 5-fold decrease in the lumen area. Placental vascular remodeling was found to occur in all of SARS-CoV-2-positive mothers as defined by RT-PCR. Immunohistochemistry with α-smooth muscle actin and the Kv11.1 channel as well as Masson’s trichrome staining showed that such placental vascular remodeling in COVID-19 is associated with smooth muscle proliferation and fibrosis. Placental vascular remodeling may represent a response mechanism to the clinical problems associated with childbirth in COVID-19 patients.

The effects of COVID-19 on placental morphology

“…In addition to the morphological changes mentioned above in the placenta as a result of COVID-19, a study conducted last year found an abnormality in the umbilical cord of COVID-19 pregnancies to be high, whereby it attached to the margin of the placenta resulting in altered functioning and blood flow [ 82 ]. In addition, vascular remodelling in the arteries of the placenta in COVID-19 pregnancies have now been identified through histological examinations and documented [ 85 ]. Therefore, it can be speculated that in COVID-19 pregnancies the oxygen demand increases, however this demand is not met.…”

KCNH2 encodes a nuclear-targeted polypeptide that mediates hERG1 channel gating and expression

“…Pancreatic beta cells express KCNH2 , and loss-of-function KCNH2 variants are associated with hyperinsulinemia and diabetes ( 58 , 59 ). KCNH2 is also expressed in smooth muscle tissues, where it regulates contractile function ( 60 , 61 ), and is associated with vascular remodeling ( 62 , 63 ).…”

SARS-CoV-2 Footprints in the Placenta: What We Know after Three Years of the Pandemic

“…The placental arterial lumen area was found to be significantly smaller (5-fold) in SARS-CoV-2 patients than in the controls (p < 0.01). In addition, immunohistochemistry using the smooth muscle cell marker α-smooth muscle actin clearly indicated a dramatic increase in smooth muscle mass in the placental arteries of SARS-CoV-2 patients, with quantitatively thickened placental vessels [50]. Another recent case-control study reported significant pathological alterations in the placenta and umbilical cord [51].…”

“…Gychka et al [50] provided a morphometric and immunohistochemistry analysis of placental tissue. Interestingly, the authors observed significant remodeling of vessels in the placentas of SARS-CoV-2-positive women.…”

“…Table 1 provides an overview of the main entry factors and other molecules investigated for their likely involvement in SARS-CoV-2's capacity to infect placental tissue [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52]55]. (Omicron).…”