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.

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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DOI:
10.1111/1471-0528.16974
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发表时间:
2022-01
期刊:
BJOG : an international journal of obstetrics and gynaecology
影响因子:
--
通讯作者:
Gerli M
Gerli M
中科院分区:
其他
文献类型:
--
作者:
Beesley MA;Davidson JR;Panariello F;Shibuya S;Scaglioni D;Jones BC;Maksym K;Ogunbiyi O;Sebire NJ;Cacchiarelli D;David AL;De Coppi P;Gerli M

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孕妇已被确定为COVID-19感染的潜在风险群体,但关于胎儿对感染的易感性知之甚少。ACE 2和TMPRSS 2的共表达已被确定为感染的先决条件,并且已知不同组织中的表达在儿童和成人之间存在差异。然而,这些蛋白质在胎儿中的表达是未知的。我们对单细胞数据库进行了回顾性分析。然后通过对中期妊娠人胎儿组织文库进行RT-qPCR和双色免疫组织化学,在基因和蛋白质水平上验证数据。TMPRSS 2在分析的主要为上皮的胎儿组织中以基因和蛋白质水平存在。ACE 2仅在胎儿肠和肾脏中以显著水平存在,并且在胎儿肺中不表达。胎盘在妊娠中期或足月时也不共表达这两种蛋白质。该数据集表明肺部不太可能是SARS-CoV 2胎儿感染的可行途径。尽管胎儿肾脏同时提供了感染所需的两种蛋白质,但在解剖学上受到保护,不会暴露于病毒。然而,胃肠道可能容易感染,因为它的两种蛋白质的高共表达,以及它暴露于潜在感染的羊水。这项工作通过对ACE 2和TMPRSS 2的scRNAseq和蛋白表达分析,为胎儿和胎盘对SARS-CoV-2感染的相对保护和脆弱性提供了详细的机制见解。这些发现有助于解释垂直传播率低的原因。这项工作通过对ACE 2和TMPRSS 2的scRNAseq和蛋白表达分析,为胎儿和胎盘对SARS-CoV-2感染的相对保护和脆弱性提供了详细的机制见解。这些发现有助于解释垂直传播率低的原因。
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. 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.
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