Abstract
A small number of neonates delivered to women with SARS-CoV-2 infection have been found to become infected through intrauterine transplacental transmission. These cases are associated with a group of unusual placental pathology abnormalities that include chronic histiocytic intervillositis, syncytiotrophoblast necrosis, and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Hofbauer cells constitute a heterogeneous group of immunologically active macrophages that have been involved in transplacental infections that include such viral agents as Zika virus and human immunodeficiency virus. The role of Hofbauer cells in placental infection with SARS-CoV-2 and maternal-fetal transmission is unknown. This study uses molecular pathology techniques to evaluate the placenta from a neonate infected with SARS-CoV-2 via the transplacental route to determine whether Hofbauer cells have evidence of infection. We found that the placenta had chronic histiocytic intervillositis and syncytiotrophoblast necrosis, with the syncytiotrophoblast demonstrating intense positive staining for SARS-CoV-2. Immunohistochemistry using the macrophage marker CD163, SARS-CoV-2 nucleocapsid protein, and double staining for SARS-CoV-2 with RNAscope and anti-CD163 antibody, revealed that no demonstrable virus could be identified within Hofbauer cells, despite these cells closely approaching the basement membrane zone of the infected trophoblast. Unlike some other viruses, there was no evidence from this transmitting placenta for infection of Hofbauer cells with SARS-CoV-2.
Highlights
At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, pregnant women in China were reported to develop an infection with the etiological agent—a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) [1]
The identification of increasing numbers of pregnant mothers with COVID-19 giving birth to neonates who were found to test positive for SARS-CoV-2 [3,4,5,6] raised the question of how and when these infants had acquired their infection, including whether they had become infected through vertical transmission, and whether the virus could be transmitted prior to delivery through the placenta [7,8,9]
In those cases where both pregnant mothers and their neonates test positive for COVID-19, Schwartz et al [16] have recommended criteria for diagnosing transplacental transmission of maternal-fetal of SARS-CoV-2
Summary
At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, pregnant women in China were reported to develop an infection with the etiological agent—a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) [1]. It has recently been demonstrated that intrauterine transplacental transmission of SARSCoV-2 to the fetus can occur in infected pregnant women [10,11,12,13,14,15] In those cases where both pregnant mothers and their neonates test positive for COVID-19, Schwartz et al [16] have recommended criteria for diagnosing transplacental transmission of maternal-fetal of SARS-CoV-2. These are based upon the pathological demonstration of the virus in fetal-derived tissues of the placenta, including syncytiotrophoblast, chorionic villus stromal and endothelial cells, using immunohistochemistry or in situ RNA hybridization methods [16,17]. In order to better understand the potential mechanisms of SARS-CoV-2 transplacental transmission, we utilized molecular pathology techniques to evaluate viral distribution within chorionic villi of a placenta having extensive syncytiotrophoblast infection from a maternal-fetal dyad testing positive for the virus, with particular attention to Hofbauer cell involvement, and discuss the findings in terms of mechanisms of intrauterine transmission
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