Researchers at the University of Cambridge and the California Institute of Technology (Caltech) have identified genes active in early embryonic development that could increase their susceptibility to SARS-CoV-2 infection.
Since December 2019, SARS-CoV-2 has rapidly spread across the world. It has infected millions of people and caused a huge number of deaths. The consequences of infection for unborn children have largely been unaddressed. There have been several conflicting reports regarding vertical transmission of the virus. However, these studies have looked at pregnancy during the third trimester. Little is known about vertical transmission during earlier stages of pregnancy.
In this study, published in Open Biology, researchers address the earliest stage of development at which SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), is expressed. In other words, when is the human embryo first at risk of infection? Using a culture platform developed by scientists at Cambridge, the researchers explored gene expression patterns in vitro beyond implantation stage.
SARS-CoV-2 enters the host cell by binding to ACE2 which is cleaved by the transmembrane protease serine 2 (TMPRSS2). By blocking this protease activity, ACE2-mediated entry is blocked. This suggests that co-expression of both these genes is required for infection. Therefore, the team also sought to look at the expression patterns of these genes using integrated single-cell RNA-sequencing data.
Vertical transmission of SARS-CoV-2?
The team identified expression and co-expression of ACE2 and TMPRSS2 in key stages of early embryonic development. They also identified this in embryonic regions that develop into tissues which interact with maternal blood supply for nutrient exchange. This raises the possibility of vertical transmission of SARS-CoV-2.
Professor David Glover, from the University of Cambridge and Caltech, stated:
“Genes encoding proteins that make cells susceptible to infection by this novel coronavirus become expressed very early on in the embryo’s development. This is an important stage when the embryo attaches to the mother’s womb and undertakes a major remodelling of all of its tissues and for the first time starts to grow. COVID-19 could affect the ability of the embryo to properly implant into the womb or could have implications for future foetal health.”
The researchers indicated that further investigation using stem cells models of the embryo and non-human primate is required. This will allow researchers to understand the potential effects of SARS-CoV-2 infection on early embryos. These results also reinforce the importance for women planning a family to try and reduce their risk of infection.
Bailey Weatherbee, PhD student at the University of Cambridge, stated:
“We don’t want women to be unduly worried by these findings, but they do reinforce the importance of doing everything they can to minimise their risk of infection.”