COVID-19 and vertical transmission: assessing the expression of ACE2 / TMPRSS2 in the human fetus and placenta to assess the risk of SARS-CoV-2 infection.

Abstract

Background: While pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a pre-requisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. Methods: We performed a retrospective analysis of single cell data repositories. This data was then validated at both gene and protein level by performing qRT-PCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. Findings: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels, only in the fetal intestine and kidney and is not expressed in the fetal lung. The placenta is also negative for the two proteins both during development and at term. Interpretation: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the GI tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid. Funding: This work was made possible by an MRC / UKRI COVID-19 Rapid response initiative grant (MR/V028480/1).

Fetoplacental transmission and placental response to SARS-CoV-2: Evidence from the literature

“…This could be on account of the placentas included in Taglauer et al (18) study consist of a placenta cohort from the third trimester COVID-19 positive pregnancies. The finding of decreasing ACE2 receptors at the third trimester is consistent with other eligible studies found in our search (19,20). This might suggest that SARS-CoV-2 -placenta infection might have an alternative route, or placenta at term provides a remarkable protective role in developing fetus against SARS-CoV-2 infection.…”

“…Therefore, this path might be rare as well. Furthermore, there was no evidence of ACE2 and TMPRSS2 proteins co-expression in the placenta in the second trimester to term (20). The lack of evidence for ACE2 and TMPRSS2 co-expression in singlecell and single-nuclei transcriptomic analysis in these studies indicates a low likelihood of placenta infection and vertical transmission at term.…”

“…One study suggested the possibility of vertical transmission via the gastrointestinal tract (GIT) in the late second trimester. This was attributed to the co-expression of ACE2 and TMPRSS2 within the GIT and not in the placenta (20).…”

“…Beesley et al (20) analyzed the expression of ACE2 and TMPRSS2 on fetal samples at both transcriptional and translation levels; only two sample types (kidney and intestine) manifested co-expression of both proteins from the secondto-third trimester. These findings were comparable to the conclusion of using publicly available scRNA-seq data.…”

“…These findings were comparable to the conclusion of using publicly available scRNA-seq data. It is plausible that fetal SARS-CoV-2 infection might occur via the gastrointestinal tract since the fetal intestine is directly exposed to amniotic fluid via fetal swallowing (20). This can be possible only if there is a presence of SARS-CoV-2 in the amniotic fluid.…”