Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infecting Pregnant Women and the Fetus, Intrauterine Transmission, and Placental Pathology During the Coronavirus Disease 2019 (COVID-19) Pandemic: It's Complicated

Abstract

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

“…The mononuclear cells that composed the majority of the inflammatory infiltrate in the intervillous space stained positive with antibody to CD163, confirming their identity as histiocytes (Figure 2). Similar to other reported placentas infected with SARS-CoV-2 having chronic histiocytic intervillositis and trophoblast necrosis [26][27][28], the syncytiotrophoblast stained diffusely positive for SARS-CoV-2 using immunohistochemistry for viral antigen and RNAscope for viral mRNA. However, unlike previously reported placentas, some cytotrophoblast cells also stained positive for SARS-CoV-2 (Figure 3).…”

“…Double-staining using antibodies to CD163 and SARS-CoV-2 nucleocapsid protein staining revealed chorionic villous macrophages (Hofbauer cells) in the stroma beneath the cytotrophoblast cells (Figure 4); the cytotro-phoblast stained intensely positive for the virus but was negative for CD163, while the Hofbauer cells stained positive for CD163 but were negative for viral staining. Similar to other reported placentas infected with SARS-CoV-2 having chronic histiocytic intervillositis and trophoblast necrosis [26][27][28], the syncytiotrophoblast stained diffusely positive for SARS-CoV-2 using immunohistochemistry for viral antigen and RNAscope for viral mRNA. However, unlike previously reported placentas, some cytotrophoblast cells also stained positive for SARS-CoV-2 (Figure 3).…”

“…These include chronic histiocytic intervillositis, trophoblast necrosis, and using molecular pathology methods, positivity of the syncytiotrophoblast for SARS-CoV-2 [26,27]. Among all placental cell types, the syncytiotrophoblast appears to be the most frequently involved cell type that stains for SARS-CoV-2 antigens or RNA [28]. To a much lesser extent, recent research has identified SARS-CoV-2 staining in placental stromal macrophages, termed Hofbauer cells [29], and endothelial cells of the villous capillaries in a small number of infected placentas [29].…”

Prioritizing the Continuing Global Challenges to Emerging and Reemerging Viral Infections

“…Public health agencies including the World Health Organization (WHO) have warned that infectious diseases have been emerging at alarming rates that had not been previously seen (11), and since the 1970s there have been approximately 40 In addition to these newly identified agents, such previously recognized viral infections including pandemic influenza, yellow fever, measles, and others continue to pose a threat through the occurrence of new epidemics. The dengue virus is notable as the most significant and widespread flavivirus disease to have emerged globally, including a formerly rare form of the disease termed dengue hemorrhagic fever and its fatal counterpart-dengue shock syndrome (12).…”

“…Besides these agents there are two pathogenic coronaviruses-MERS-CoV and SARS-CoVthat were first identified in the last 20 years and have also caused this concern (38). These two emergent coronaviruses caused illness and death of pregnant women well as well as perinatal deaths, but there were no confirmed cases of placental infection or vertical transmission identified (39,40). The most recent example of vertical transmission of an emerging virus has been the identification of transplacental infection of fetuses as well as postpartum infection of neonates with SARS-CoV-2 (40,41), where the virus can infect not only the mother but also the placenta, fetus, and newborn.…”