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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.
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  • Max Beesley,
  • Joseph Davidson,
  • Francesco Panariello,
  • Soichi Shibuya,
  • Dominic Scaglioni,
  • Brendan Jones,
  • Kasia Maksym,
  • Olumide Ogunbiyi,
  • Neil Sebire,
  • Davide Cacchiarelli,
  • Anna David,
  • Paolo De Coppi,
  • Mattia Gerli
Max Beesley
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Joseph Davidson
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Francesco Panariello
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Soichi Shibuya
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Dominic Scaglioni
University College London
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Brendan Jones
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Kasia Maksym
UCL
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Olumide Ogunbiyi
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Neil Sebire
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Davide Cacchiarelli
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Anna David
University College London
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Paolo De Coppi
Great Ormond Street Hospital For Children NHS Foundation Trust
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Mattia Gerli
University College London
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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).

Peer review status:IN REVISION

09 Jul 2021Submitted to BJOG: An International Journal of Obstetrics and Gynaecology
11 Jul 2021Assigned to Editor
11 Jul 2021Submission Checks Completed
12 Jul 2021Reviewer(s) Assigned
23 Aug 2021Review(s) Completed, Editorial Evaluation Pending
12 Sep 2021Editorial Decision: Revise Major