- Chen J. et al. (2023). A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts.Nat Cell Biol (2023).
In contrast to non-pregnant women, pregnant women have an increased risk of contracting a viral infection. If pregnant women become infected with SARS-CoV-2, this also increases the risk of stillbirths or premature births. These negative birth outcomes are particularly pronounced if the SARS-CoV-2 infection occurred at an early stage of pregnancy. Compared to non-vaccinated women, vaccinated women benefit from significant protection against stillbirths and infant deaths in the first month of life.1
SARS-CoV-2 can infect human cells via ACE2, transmembrane serine protease 2 (TMPRSS2) or via endocytosis. In addition to the respiratory tract, many other organs can also be infected. This is partly due to the broad expression of ACE2 and TMPRSS2. In addition to the heart, kidneys and intestines, there is scientific evidence that the placenta also expresses ACE2 and TMPRSS.
The effects of SARS-CoV-2 infection in the early stages of embryonic and foetal development and placentation are still largely unclear. Several studies have shown that SARS-CoV-2 infection of the placental tissue of infected pregnant women was associated with placentitis. Pregnancy losses were observed more frequently in infected pregnant women, particularly in the first trimester.
The primary target of SARS-CoV-2 infection is villous syncytiotrophoblasts. This is confirmed by histopathological examinations. However, these cells are essential for the production of beta-hCG. This hormone is responsible for maintaining pregnancy.
Using a placenta in vitro model, the Australian research group was able to investigate the mechanisms that could underlie SARS-CoV-2 infection during placentation and early pregnancy. In their model, they were able to observe that syncytiotrophoblasts can be infected by the angiotensin-converting enzyme 2 (ACE2).
Using a co-culture model of vertical transmission, the research group was able to show that SARS-CoV-2 has the ability to infect syncytiotrophoblasts through prior infection of endometrial cells. Within the syncytiotrophoblasts, cellular processes were impaired, which ultimately led to reduced beta-hCG secretion and morphological changes in these cells. The function of the syncytiotrophoblasts was negatively influenced by this.
However, there is also good news: the cellular impairment of syncytiotrophoblasts can be restored by antibody strategies and antiviral drugs. The research group investigated the effectiveness of the antiviral compounds Remdesivir or Molnupiravir against the replication of the SARS-CoV-2 virus in their placenta in vitro model. They observed that both antiviral compounds were effective against SARS-CoV-2 infection within the syncytiotrophoblast at a concentration of 1 µM.