Molecular Pathology Demonstration of SARS-CoV-2 in Cytotrophoblast from Placental Tissue with Chronic Histiocytic Intervillositis, Trophoblast Necrosis and COVID-19

Abstract

A subset of placentas from pregnant women having the SARS-CoV-2 infection have been found to be infected with the coronavirus using molecular pathology methods including immunohistochemistry and RNA in situ hybridization. These infected placentas can demonstrate several unusual findings which occur together—chronic histiocytic intervillositis, trophoblast necrosis and positive staining of the syncytiotrophoblast for SARS-CoV-2. They frequently also have increased fibrin deposition, which can be massive in some cases. Syncytiotrophoblast is the most frequent fetal-derived cell type to be positive for SARS-CoV-2. It has recently been shown that in a small number of infected placentas, villous stromal macrophages, termed Hofbauer cells, and villous capillary endothelial cells can also stain positive for SARS-CoV-2. This report describes a placenta from a pregnant woman with SARS-CoV-2 that had chronic histiocytic intervillositis, trophoblast necrosis, increased fibrin deposition and positive staining of the syncytiotrophoblast for SARS-CoV-2. In addition, molecular pathology testing including RNAscope and immunohistochemistry for SARS-CoV-2 and double-staining immunohistochemistry using antibodies to E-cadherin and GATA3 revealed that cytotrophoblast cells stained intensely for SARS-CoV-2. All of the cytotrophoblast cells that demonstrated positive staining for SARS-CoV-2 were in direct physical contact with overlying syncytiotrophoblast that also stained positive for the virus. The pattern of cytotrophoblast staining for SARS-CoV-2 was patchy, and there were chorionic villi having diffuse positive staining of the syncytiotrophoblast for SARS-CoV-2, but without staining of cytotrophoblast. This first detailed description of cytotrophoblast involvement by SARS-CoV-2 adds another fetal cell type from infected placentas that demonstrate viral staining.

Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury

“…In those placentas where the virus was localized using either immunohistochemistry or RNA in situ hybridization, the syncytiotrophoblast was involved in all cases. Previous studies have indicated that although the syncytiotrophoblast is the most common placental type to be involved with SARS-CoV-2, 59 other villous cells including cytotrophoblast, 61 Hofbauer cells, 60 and endothelial cells 60 can also stain positively for the virus. In our series, cytotrophoblast, Hofbauer cells and villous stromal and endothelial cells were occasionally found to stain positively for SARS-CoV-2.…”

Detection of SARS-CoV-2 in Neonatal Autopsy Tissues and Placenta

“…In addition, SARS-CoV-2 RNA is rarely detected in the placenta, and electron microscopy has misidentified common subcellular structures as coronavirus particles ( 25 – 28 ). In this patient, we found neither evidence of placental SARS-CoV-2 infection by ISH or IHC ( 29 – 34 ) nor evidence of chronic histiocytic intervillositis, which has been identified as a relatively consistent pathologic feature associated with placental SARS-CoV-2 infection ( 32 – 34 ). Consequently, conventional RT-PCR positivity may represent maternal viremia.…”

Developmental Aspects of SARS-CoV-2, Potential Role of Exosomes and Their Impact on the Human Transcriptome

“…A recent study showed SARS-CoV-2 staining in the placental cellular layers during embryonic development [57]. Positive staining for SARS-CoV-2 was detected in the epithelial covering of the placental villi called the syncytiotrophoblast, as well as in the inner cellular layer that gives rise to it, called the cytotrophoblast [57].…”

“…A recent study showed SARS-CoV-2 staining in the placental cellular layers during embryonic development [57]. Positive staining for SARS-CoV-2 was detected in the epithelial covering of the placental villi called the syncytiotrophoblast, as well as in the inner cellular layer that gives rise to it, called the cytotrophoblast [57]. This study is the first to report the details of the participation of the cytotrophoblast in the SARS-CoV-2 infection process, which adds to the list of fetal cell types from the placentas of infected mothers where viral staining is detected [57].…”

“…Positive staining for SARS-CoV-2 was detected in the epithelial covering of the placental villi called the syncytiotrophoblast, as well as in the inner cellular layer that gives rise to it, called the cytotrophoblast [57]. This study is the first to report the details of the participation of the cytotrophoblast in the SARS-CoV-2 infection process, which adds to the list of fetal cell types from the placentas of infected mothers where viral staining is detected [57]. Another study has reported the positive immunohistochemistry of a SARS-CoV-2 nucleocapsid within fetal pulmonary endothelium, which indicates vertical transmission [58].…”