Fetuses could become infected with SARS-CoV-2 via fetal intestine

The intestine is a likely infection route for COVID-19 in fetuses, although the placenta largely protects against infection.

Researchers from University College London (UCL) aimed to understand potential routes of fetal COVID-19 infection. They explicitly wanted to investigate viral spread from an infected mother to the fetus, known as vertical transmission. Recent studies have suggested increased fetal susceptibility to SARS-CoV-2, the virus responsible for COVID-19. So far, data has documented transmission around the time of birth. However, concerns remained about infection during the second trimester, as was seen with other similar viruses, and is also when fetuses begin to swallow amniotic fluid.

'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' said co-senior author, Dr Mattia Gerli from UCL Royal Free Hospital.

The researchers, who have published their results in BJOG – an International Journal of Obstetrics and Gynaecology, investigated the expression of ACE2 and TMPRSS2 receptors in various fetal organs and placenta tissue during the second trimester of pregnancy. Expression of both receptors is required for SARS-CoV-2 infection.

This study found that the only fetal organs expressing ACE2 and TMPRSS2 were the intestines and kidneys. Researchers explained that the kidneys are likely irrelevant regarding fetal COVID-19 infection as the kidneys are anatomically protected. Additionally, the placenta did not co-express the two receptor proteins during the second trimester or at term.

The researchers explained that due to the placenta acting as a protective shield, vertical transmission is extremely uncommon. The researchers concluded that SARS-CoV-2 could only infect the fetus via the intestine, through fetal swallowing of amniotic fluid, which is required for nutrition.

'However, many studies in maternity care have found that the amniotic fluid around the fetus does not usually contain the SARS-CoV-2 virus, even if the mother is infected with COVID-19,' added Dr Gerli.

This study also highlighted that the biggest risk to the fetus is severe maternal COVID-19 infection. In this instance, viral load in the amniotic fluid may be higher, potentially damaging the placenta, leading to preterm birth.

'Vaccination against COVID-19 is known to be safe in pregnancy and reduces the chance of SARS-CoV-2 infection to very low levels,' reminded co-author, Professor Anna David consultant in obstetrics and maternal/fetal medicine at UCL hospital. '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.'