Acute Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Pregnancy Is Associated with Placental Angiotensin-Converting Enzyme 2 Shedding.

While the human placenta may be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rate of fetal transmission is low, suggesting a barrier at the maternal-fetal interface. Angiotensin-converting enzyme (ACE)2, the main receptor for SARS-CoV-2, is regulated by a metalloprotease cleavage enzyme, a disintegrin and metalloprotease domain 17 (ADAM17). ACE2 is expressed in the human placenta, but its regulation in relation to maternal SARS-CoV-2 infection in pregnancy is not well understood. This study evaluated ACE2 expression, ADAM17 activity, and serum ACE2 abundance in a cohort of matched villous placental and maternal serum samples from control pregnancies (SARS-CoV-2 negative, n = 8) and pregnancies affected by symptomatic maternal SARS-CoV-2 infections in the second trimester [2nd Tri coronavirus disease (COVID), n = 8] and third trimester (3rd Tri COVID, n = 8). In 3rd Tri COVID compared with control and 2nd Tri COVID villous placental tissues, ACE2 mRNA expression was remarkably elevated; however, ACE2 protein expression was significantly decreased with a parallel increase in ADAM17 activity. Soluble ACE2 was also significantly increased in the maternal serum from 3rd Tri COVID infections compared with control and 2nd Tri COVID pregnancies. These data suggest that in acute maternal SARS-CoV-2 infections, decreased placental ACE2 protein may be the result of ACE2 shedding and highlights the importance of ACE2 for studies on SARS-CoV-2 responses at the maternal-fetal interface.