Impact of SARS-CoV-2 infection during pregnancy on the placenta and fetus

Abstract

Pregnant people and their fetuses are vulnerable to adverse health outcomes from coronavirus 2019 disease (COVID-19) due to infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has been associated with higher rates of maternal mortality, preterm birth, and stillbirth. While SARS-CoV-2 infection of the placenta and vertical transmission is rare, this may be due to the typically longer time interval between maternal infection and testing of the placenta and neonate. Placental injury is evident in cases of SARS-CoV-2-associated stillbirth with massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. Maternal COVID-19 can also polarize fetal immunity, which may have long-term effects on neurodevelopment. Although the COVID-19 pandemic continues to evolve, the impact of emerging SARS-CoV-2 variants on placental and perinatal injury/mortality remains concerning for maternal and perinatal health. Here, we highlight the impact of COVID-19 on the placenta and fetus and remaining knowledge gaps.

Keywords: COVID-19; Coronavirus; Fetus; Immune response; Maternal mortality; Placenta; Pregnancy; Preterm birth; SARS-CoV-2; Stillbirth; Vertical transmission.

Figure 1.. Histopathology of SARS-CoV-2 placentitis.

Photomicrographs of placental tissues are shown for uninfected (A) and SARS-CoV-2 infected (B-D) placental tissues using hematoxylin and eosin staining (A-C) or immunohistochemical staining for the SARS-CoV-2 nucleocapsid protein (D). Normal histology is shown in panel A (20X). In panel B, we show a case of SARS-CoV-2 placentitis with massive perivillous fibrin deposition (10X). In this case, the intervillous space is completely obstructed with fibrin and the villi demonstrate necrosis. In panel C, we show a placenta with SARS-CoV-2 placentitis that has necrosis of the syncytiotrophoblast cell layer and chronic histiocytic intervillositis (20X). Mononuclear inflammatory cells stained positively in this case using immunohistochemistry and an antibody to CD168 (data not shown). In panel D, we show a case with SARS-CoV-2 placentitis that demonstrates coronavirus infection of the chorionic villi using immunohistochemistry targeting the SARS-CoV-2 nucleocapsid protein. This image reveals widespread circumferential staining of the syncytiotrophoblast cell layer (20X). In addition, punctate staining is present within cells of the villous stroma, which represent Hofbauer cells and fetal endothelial cells (DAB, brown staining). Background morphology also reveals trophoblast necrosis, one of the features of SARS-CoV-2 placentitis.

Figure 2.. Conceptual model for activation of fetal NK cell.

The figure depicts a fetal NK cell in the center that is becoming activated through two different pathways: 1) indirectly via exposure to maternal cytokines (i.e., IL-2, IL-15, IL-18, IL-21, IFN-α; right side), or 2) directly via vertical transmission and infection of neonatal cells (left side).