An unborn baby could become infected with Covid-19 if their gut is exposed to the SARS-CoV-2 virus, finds a new study led by UCL researchers with Great Ormond Street Hospital for Children and the NIHR Great Ormond Street Biomedical Research Centre.
Although the study did not look specifically at mothers with Covid-19 and whether their infection was transmitted to an unborn baby, it found that certain fetal organs, such as the intestine, are more susceptible to infection than others.
However, researchers say, that opportunities for the Covid-19 virus infecting the fetus are extremely limited, as the placenta acts as a highly effective and protective shield, and evidence suggests fetal infection, known as vertical transmission, is extremely uncommon.
For the study, published in BJOG - An International Journal of Obstetrics & Gynaecology, researchers set out to understand how newborn babies could have developed Covid-19 antibodies, as has been reported in a small number of cases.
Specifically, they wanted to know if and how the virus could be passed from an infected mother to the unborn fetus.
To answer this question, researchers examined various fetal organs and placenta tissue to see if there was any presence of the cell surface protein receptors, ACE2 and TMPRSS2. These two receptors sit on the outside of cells and both are needed for the SARS-Cov-2 virus to infect and spread.
Researchers found the only fetal organs* to feature both the ACE2 and TMPRSS2 were the intestines (gut) and the kidney; however the fetal kidney is anatomically protected from exposure to the virus and is therefore less at risk of infection.
Therefore, the team concluded that the SARS-CoV-2 virus could only infect the fetus via the gut and through fetal swallowing of amniotic fluid, which the unborn baby does naturally for nutrients.
After birth ACE2 and TMPRSS2 receptors are known to be present in combination on the surface of cells in the human intestine as well as the lung. The gut and lung are suspected to be the main routes for Covid-19 infection, but in younger children, the intestine appears to be most important for virus infection.
Senior author, Dr Mattia Gerli (UCL Division of Surgery and Interventional Science & the Royal Free Hospital) explained: "The fetus is known to begin swallowing the amniotic fluid in the second half of pregnancy. To cause infection, the SARS-CoV-2 virus would need to be present in significant quantities in the amniotic fluid around the fetus.
"However, many studies in maternity care have found that the amniotic fluid around the fetus does not usually contain the SARS-CoV2 virus, even if the mother is infected with Covid-19. Our findings therefore explain that clinical infection of the fetus during pregnancy is possible but uncommon and that is reassuring for parents-to-be."
The study, funded by the Medical Research Council (MRC) and UKRI COVID-19 rapid response initiative, provides the most definitive information, to date, regarding the susceptibility of the human fetus to COVID-19 infection.
Fetal organs and tissues were made available via the Human Developmental Biology Resource (HDBR) biobank, which assists embryonic/fetal research. None of the organs and tissues from donated fetuses were from Covid-19-infected mothers and, in line with ethical guidelines, the research team did not test for Covid-19 antibodies.
Co-senior author Professor Paolo De Coppi (UCL Great Ormond Street Institute of Child Health and NIHR Great Ormond Street Hospital) said: "We have shown that the fetal intestine, which is in contact with amniotic fluids swallowed by the baby, is susceptible to SARS-CoV-2 virus. However, the placenta acts as a natural barrier, and with the limited evidence of amniotic fluid containing the virus, our study should provide reassurance to mothers."
The authors highlight that the biggest risk to the fetus during pregnancy is if the mother becomes very unwell with Covid-19 infection. In this instance the virus may be present in high concentration in the amniotic fluid. In addition, it could damage the placenta, which can lead to preterm birth.
Co-author, Professor Anna David (UCL Elizabeth Garrett Anderson Institute for Women’s Health and UCLH NIHR Biomedical Research Centre) added: "Vaccination against Covid-19 is known to be safe in pregnancy and reduces the chance of Sars-CoV2 infection to very low levels. The results of this study provide definitive information regarding the susceptibility of the human fetus to Covid-19 infection. Our findings support current healthcare policy that vaccination in pregnancy is the best way for mothers to protect their unborn baby from Covid-19 infection."
*The researchers did not find evidence of the receptors ACE2 and TMPRSS2 in the fetal lung or placenta in the middle or last trimester of pregnancy. The results were confirmed using a number of different techniques, including looking for both gene and protein expression.
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