SARS-CoV-2 Transplacental Transmission: A Rare Occurrence? An Overview of the Protective Role of the Placenta

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic, caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global public health crisis, causing substantial concern especially to the pregnant population. Pregnant women infected with SARS-CoV-2 are at greater risk of devastating pregnancy complications such as premature delivery and stillbirth. Irrespective of the emerging reported cases of neonatal COVID-19, reassuringly, confirmatory evidence of vertical transmission is still lacking. The protective role of the placenta in limiting in utero spread of virus to the developing fetus is intriguing. The short- and long-term impact of maternal COVID-19 infection in the newborn remains an unresolved question. In this review, we explore the recent evidence of SARS-CoV-2 vertical transmission, cell-entry pathways, placental responses towards SARS-CoV-2 infection, and its potential effects on the offspring. We further discuss how the placenta serves as a defensive front against SARS-CoV-2 by exerting various cellular and molecular defense pathways. A better understanding of the placental barrier, immune defense, and modulation strategies involved in restricting transplacental transmission may provide valuable insights for future development of antiviral and immunomodulatory therapies to improve pregnancy outcomes.

SARS-CoV-2 Transplacental Transmission: A Rare Occurrence? An Overview of the Protective Role of the Placenta.

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic, caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global public health crisis, causing substantial concern especially to the pregnant population. Pregnant women infected with SARS-CoV-2 are at greater risk of devastating pregnancy complications such as premature delivery and stillbirth. Irrespective of the emerging reported cases of neonatal COVID-19, reassuringly, confirmatory evidence of vertical transmission is still lacking. The protective role of the placenta in limiting in utero spread of virus to the developing fetus is intriguing. The short- and long-term impact of maternal COVID-19 infection in the newborn remains an unresolved question. In this review, we explore the recent evidence of SARS-CoV-2 vertical transmission, cell-entry pathways, placental responses towards SARS-CoV-2 infection, and its potential effects on the offspring. We further discuss how the placenta serves as a defensive front against SARS-CoV-2 by exerting various cellular and molecular defense pathways. A better understanding of the placental barrier, immune defense, and modulation strategies involved in restricting transplacental transmission may provide valuable insights for future development of antiviral and immunomodulatory therapies to improve pregnancy outcomes.

SARS-CoV-2 Infection in Pregnancy: Placental Histomorphological Patterns, Disease Severity and Perinatal Outcomes.

The association between maternal COVID-19 infection, placental histomorphology and perinatal outcomes is uncertain. The published studies on how placental structure is affected after SARS-CoV-2 virus in COVID-19-infected pregnant women are lacking. We investigated the effects of maternal SARS-CoV-2 infection on placental histomorphology and pregnancy outcomes. A retrospective cohort study on 47 pregnant women with confirmed SARS-CoV-2 infection, matched with non-infected controls, was conducted. Relevant clinicopathological data and primary birth outcomes were recorded. Histomorphology and SARS-CoV-2 immunohistochemistry analyses of placental tissues were performed. Only 1 of 47 cases showed SARS-CoV-2 immunoreactivity in the syncytiotrophoblasts. Histologically, decidual vasculopathy (n = 22/47, p = 0.004), maternal vascular thrombosis (n = 9/47, p = 0.015) and chronic histiocytic intervillositis (n = 10/47, p = 0.027) were significantly higher in the COVID-19-infected placentas when compared to the control group. Maternal vascular thrombosis was a significant feature in the active COVID-19 group. A significant lower gestational age (p < 0.001)) at delivery and a higher caesarean section rate (p = 0.007) were observed in the active SARS-CoV-2-infected cases, resulting in a significant lower fetal-placental weight ratio (p = 0.022) and poorer Apgar score (p < 0.001). Notably, active (p = 0.027), symptomatic (p = 0.039), severe-critical (p = 0.002) maternal COVID-19 infection and placental inflammation (p = 0.011) were associated with an increased risk of preterm delivery. Altered placental villous maturation and severe-critical maternal COVID-19 infection were associated with an elevated risk of poor Apgar scores at birth (p = 0.018) and maternal mortality (p = 0.023), respectively.

Loss of CXC-Chemokine Receptor 1 Expression in Chorioamnionitis Is Associated with Adverse Perinatal Outcomes.

BACKGROUND: Chorioamnionitis complicates about 1-5% of deliveries at term and causes about one-third of stillbirths. CXC-chemokine receptor 1 (CXCR1) binds IL-8 with high affinity and regulates neutrophil recruitment. We aimed to determine the immunoexpression of CXCR1 in placentas with chorioamnionitis, and its association with adverse perinatal outcomes. METHODS: A total of 101 cases of chorioamnionitis and 32 cases of non-chorioamnionitis were recruited over a period of 2 years. CXCR1 immunohistochemistry was performed, and its immunoexpression in placentas was evaluated. The adverse perinatal outcomes included intrauterine death, poor APGAR score, early neonatal death, and respiratory complications. RESULTS: Seventeen cases (17/101, 16.8%) with chorioamnionitis presented as preterm deliveries. Lung complications were more common in mothers who were >35 years (p = 0.003) and with a higher stage in the foetal inflammatory response (p = 0.03). Notably, 24 cases (23.8%) of histological chorioamnionitis were not detected clinically. Interestingly, the loss of CXCR1 immunoexpression in the umbilical cord endothelial cells (UCECs) was significantly associated with foetal death (p = 0.009). CONCLUSION: The loss of CXCR1 expression in UCECs was significantly associated with an increased risk of adverse perinatal outcomes and could be used as a biomarker to predict adverse perinatal outcomes in chorioamnionitis. Further study is warranted to study the pathophysiology involved in the failure of CXCR1 expression in these cells.

The Effects of COVID-19 on Placenta and Pregnancy: What Do We Know So Far?

The current coronavirus disease 2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has inflicted a serious health crisis globally. This virus is associated with a spectrum of respiratory illness ranging from asymptomatic, mild to severe pneumonia, and acute respiratory distress syndrome. Accumulating evidence supports that COVID-19 is not merely a respiratory illness per se, but potentially affects other organ systems including the placenta. SARS-CoV-2 gains access to human cells via angiotensin-converting enzyme 2 (ACE-2). The abundance of ACE-2 on the placental cell surface, especially the syncytiotrophoblasts, could potentially contribute to vertical transplacental transmission to the fetus following maternal COVID-19 infection. Intriguingly, despite the placentas being tested positive for SARS-CoV-2, there are very few newborns that manifest virus-induced diseases. The protective effects of the placental barrier to viral infection, limiting the spread of the virus to newborn infants, remain a mystery. The detrimental role of COVID-19 in pregnancies is largely debatable, although COVID-19 maternal infection has been implicated in unfavorable pregnancy outcomes. In this review, we summarize the pathological features manifested in placenta due to COVID-19 maternal infection that have been previously reported, and relate them to the possible disease manifestation. The potential mechanistic pathways associated with transplacental viral transmission and adverse pregnancy outcomes are also discussed.