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Embryos may be susceptible to Covid-19 from two weeks old, say Cambridge and Caltech researchers



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Embryos could be susceptible to Covid-19 from as early as the second week if the mother has the virus, a study suggests.

A human embryo cultured in vitro through the implantation stages and stained to reveal OCT4 transcription factor, magenta; GATA6 transcription factor, white; F-actin, green; and DNA, blue. Analysis of patterns of gene expression in such embryos reveals that ACE2, the receptor for the SARS-CoV-2 virus, and the TMPRSS2 protease that facilitates viral infection are expressed in these embryos, which represent the very early stages of pregnancy. Picture: Zernicka-Goetz Lab (40113886)
A human embryo cultured in vitro through the implantation stages and stained to reveal OCT4 transcription factor, magenta; GATA6 transcription factor, white; F-actin, green; and DNA, blue. Analysis of patterns of gene expression in such embryos reveals that ACE2, the receptor for the SARS-CoV-2 virus, and the TMPRSS2 protease that facilitates viral infection are expressed in these embryos, which represent the very early stages of pregnancy. Picture: Zernicka-Goetz Lab (40113886)

Scientists at the University of Cambridge and the California Institute of Technology (Caltech) say this could affect the chances of a successful pregnancy or impact on the future health of the fetus.

They found that genes thought to play a role in how the SARS-CoV- 2 virus infects our cells are active in the developing embryo even at this very early stage in pregnancy.

While further research is needed, the researchers say those planning for a family should be mindful of the findings.

Bailey Weatherbee, a PhD student at the University of Cambridge, said: “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.”

Questions around the potential effects of the SARS-CoV-2 virus on the developing fetus have been largely unanswered to date.

While the virus is typically understood as causing respiratory disease, it also affects many other organs. Older age and obesity are known risk factors for complications.

Researchers used technology developed by Professor Magdalena Zernicka-Goetz at the University of Cambridge to culture human embryos through the stage they normally implant in the wall of the mother’s uterus and examined the expression, or activity, of key genes in the embryo.

To infect human cells, the large ‘spike’ proteins that surround the surface of the SARS-CoV-2 virus bind to a protein receptor called ACE2. This is found on the surface of cells in our body.

The spike protein and ACE2 are then ‘cleaved’, which allows genetic material from the virus to enter the host cell.

The virus then exploits the host cell’s machinery to allow the virus to replicate and spread.

The research has implications for those planning a family
The research has implications for those planning a family

In their experiments, the researchers found patterns of expression of the genes ACE2, which provide the genetic code for the SARS-CoV-2 receptor, and TMPRSS2, which provides the code for a molecule that cleaves the spike protein and the ACE2 receptor.

These genes were expressed during key stages of the embryo’s development and in parts of the embryo that develop into tissues that interact with the mother’s blood supply for the exchange of nutrients.

In gene expression, the DNA code is first transcribed into RNA and processed into messenger RNA (mRNA), before it is translated into an amino acid sequence. By this process, it directs the synthesis of the encoded protein.

The study, reported in the Royal Society’s journal Open Biology, reports the finding of the messenger RNA.

Prof Zernicka-Goetz, who holds positions at both the University of Cambridge and Caltech, said: “Our work suggests that the human embryo could be susceptible to Covid-19 as early as the second week of pregnancy if the mother gets sick.

“To know whether this really could happen, it now becomes very important to know whether the ACE2 and TMPRSS2 proteins are made and become correctly positioned at cell surfaces. If these next steps are also taking place, it is possible that the virus could be transmitted from the mother and infect the embryo’s cells.”

Professor David Glover, also from Cambridge and Caltech, added: “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 fetal health.”

But the team say further research using stem cell models and non-human primates would help to better understand the risk.

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