Clinical and in Vitro Evidence against Placenta Infection at Term by Severe Acute Respiratory Syndrome Coronavirus 2.

Clinical and in Vitro Evidence against Placenta Infection at Term by Severe Acute Respiratory Syndrome Coronavirus 2.
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DOI:
10.1016/j.ajpath.2021.05.009
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发表时间:
2021-09
期刊:
The American journal of pathology
影响因子:
--
通讯作者:
Debiève F
Debiève F
中科院分区:
其他
文献类型:
--
作者:
Colson A;Depoix CL;Dessilly G;Baldin P;Danhaive O;Hubinont C;Sonveaux P;Debiève F

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尽管偶尔有报道称严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 在怀孕期间垂直传播,但胎盘感染及其对新生儿的影响问题仍未得到解答。在此,我们通过逆转录酶 PCR、免疫组织化学和原位杂交分析了 31 名 2019 冠状病毒病阳性母亲的胎盘。仅检测到1例胎盘感染,该感染与胎儿宫内死亡有关。然后从足月非病理人类胎盘中分离分化的初级滋养层,进行分化,并暴露于 SARS-CoV-2 病毒体。与阳性对照细胞Vero E6不同,感染后4天细胞滋养层和合体滋养层内或上清液中的病毒检测不到。作为一种防御机制,我们假设足月滋养层不表达血管紧张素转换酶 2 和跨膜蛋白酶丝氨酸 2 (TMPRSS2),这是 SARS-CoV-2 进入的两个主要宿主膜受体。怀孕期间胎盘中这些蛋白质的定量证实了合胞体表面不存在 TMPRSS2。令人惊讶的是,瞬时诱导的 TMPRSS2 实验表达不允许病毒进入分化的滋养层细胞或在分化的滋养层细胞中复制。总而言之,这些结果强调滋养层细胞在足月时不太可能被 SARS-CoV-2 感染,但引起了人们对早产感染的担忧。
Despite occasional reports of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy, the question of placental infection and its consequences for the newborn remain unanswered. Herein, we analyzed the placentas of 31 coronavirus disease 2019–positive mothers by reverse transcriptase PCR, immunohistochemistry, and in situ hybridization. Only one case of placental infection was detected, which was associated with intrauterine demise of the fetus. Differentiated primary trophoblasts were then isolated from nonpathologic human placentas at term, differentiated, and exposed to SARS-CoV-2 virions. Unlike for positive control cells Vero E6, the virus inside cytotrophoblasts and syncytiotrophoblasts or in the supernatant 4 days after infection was undetectable. As a mechanism of defense, we hypothesized that trophoblasts at term do not express angiotensin-converting enzyme 2 and transmembrane protease serine 2 (TMPRSS2), the two main host membrane receptors for SARS-CoV-2 entry. The quantification of these proteins in the placenta during pregnancy confirmed the absence of TMPRSS2 at the surface of the syncytium. Surprisingly, a transiently induced experimental expression of TMPRSS2 did not allow the entry or replication of the virus in differentiated trophoblasts. Altogether, these results underline that trophoblasts are not likely to be infected by SARS-CoV-2 at term, but raise concern about preterm infection.
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