Great Ormond Street Institute of Child Health, University College London, UK.
EGA Institute for Women's Health, University College London, UK.
BJOG. 2022 Jan;129(2):256-266. doi: 10.1111/1471-0528.16974. Epub 2021 Nov 18.
Pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, but little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a prerequisite 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.
We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT-qPCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues.
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 also does not co-express the two proteins across the second trimester or at term.
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 gastrointestinal 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.
This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS-CoV-2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission.
孕妇已被确定为 COVID-19 感染的潜在高危群体，但对于胎儿易感染性知之甚少。ACE2 和 TMPRSS2 的共表达已被确定为感染的先决条件，并且已知儿童和成人之间不同组织的表达存在差异。然而，这些蛋白质在胎儿中的表达情况尚不清楚。
我们对单个细胞数据存储库进行了回顾性分析。然后，通过对来自第二个三个月的人类胎儿组织库进行 RT-qPCR 和双色免疫组织化学分析，在基因和蛋白质水平上对这些数据进行了验证。
在所分析的主要上皮胎儿组织中，TMPRSS2 在基因和蛋白质水平上均存在。ACE2 仅在胎儿肠和肾脏中以显著水平存在，而在胎儿肺中不存在。胎盘在整个第二个三个月或足月时也不会共同表达这两种蛋白质。
该数据集表明，肺部不太可能成为 SARS-CoV2 胎儿感染的可行途径。尽管胎儿肾脏具有感染所需的两种蛋白质，但由于其解剖结构上免受病毒暴露，因此具有保护作用。然而，由于其两种蛋白质的高共表达以及对可能受感染羊水的暴露，胃肠道很可能容易受到感染。
这项工作通过 scRNAseq 和 ACE2 和 TMPRSS2 的蛋白表达分析，为 SARS-CoV-2 感染胎儿和胎盘的相对保护和易感性提供了详细的机制见解。研究结果有助于解释垂直传播率低的原因。
