Background: Infection during pregnancy with SARS-CoV-2 can have a serious impact on both maternal and foetal health. Clinical studies have shown that SARS-CoV-2 transmission from the mother to the foetus typically does not occur. However, there is evidence that SARS-CoV-2 can infect the placenta in utero. Here we sought to quantify the permissiveness of placental cells to SARS-CoV-2 infection and to determine if they support viral release.
Methods: By using publicly available single-cell RNA sequencing (scRNAseq) data sets and confocal microscopy we compared ACE2 transcript and protein expression across human first trimester and term placental cells. We also used in vitro infection assays to quantify the infection rates of a range of placenta-derived cells. Finally, we quantified the viral egress from these cells.
Results: ACE2 transcripts are found in a range of placental cell types across gestation, including trophoblast. However, ACE2 protein expression does not significantly change across placental cell types from first trimester to term. We find that 0.5±0.15 % of term trophoblast cells can be infected with SARS-CoV-2 while primary placental fibroblasts and macrophages, and JEG-3, JAR and HUVEC cell lines are resistant to infection. Furthermore, primary trophoblast cells poorly support viral release while JEG-3 cells allow relatively high levels of viral release.
Conclusions: The low level of viral release by primary placental cells provides insight into how the virus is impaired from crossing the placenta to the foetus.
Keywords: SARS-CoV-2; placenta; trophoblast.
The placenta is a fetal-derived organ that starts to form at 5 days post-conception. It forms the interface between the mother and foetus, mediating the transmission of oxygen and nutrients. The placenta also acts as an important physical barrier so that only select pathogens can cross to reach the foetus. Since the COVID pandemic in 2020 there has been discrepancy in the field over the permissiveness of placental cells to SARS-CoV-2. Infection with SARS-CoV-2 during pregnancy can have a serious impact on both the mother and the unborn child. While newborns infected with SARS-CoV2 have been identified, it remains unclear if infection can occur in utero. With this study the researchers evaluated if different placental cell types could be infected by SARS-CoV-2. The findings from this study will help researchers and medical professionals to understand how mother-to-child transmission is impaired in utero. We used a combination of relevant laboratory cell lines and primary samples from study participants (including trophoblast cells). As well as investigating infection levels, we also examined their expression of cellular proteins required for virus cell entry. The study found that these proteins are expressed at low levels in a range of placental cell types. However, their expression levels do not significantly change during pregnancy. About 0.5% of full-term trophoblast cells can be infected with SARS-CoV-2 and these cells release very few infectious virus particles. Other placental cell types are almost entirely resistant to infection. Together, these factors reduce the ability of this virus to infect the placenta and cross it to the foetus. This study provides further understanding of the rare cases where SARS-CoV-2 can be found in trophoblast cells but does not transmit further.
Copyright: © 2024 Yoshida N et al.