Article ; Online: Clinical and in Vitro Evidence against Placenta Infection at Term by Severe Acute Respiratory Syndrome Coronavirus 2.
The American journal of pathology
2021 Volume 191, Issue 9, Page(s) 1610–1623
Abstract: ... coronavirus 2 (SARS-CoV-2) during pregnancy, the question of placental infection and its consequences ... Despite occasional reports of vertical transmission of severe acute respiratory syndrome ... As a mechanism of defense, we hypothesized that trophoblasts at term do not express angiotensin-converting enzyme 2 and ...
Abstract | 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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MeSH term(s) | Adult ; Angiotensin-Converting Enzyme 2/biosynthesis ; COVID-19/enzymology ; COVID-19/pathology ; Female ; Gene Expression Regulation, Enzymologic ; Humans ; Placenta Diseases/enzymology ; Placenta Diseases/pathology ; Pregnancy ; Pregnancy Complications, Infectious/enzymology ; Pregnancy Complications, Infectious/pathology ; SARS-CoV-2/metabolism ; Serine Endopeptidases/biosynthesis ; Trophoblasts/enzymology ; Trophoblasts/pathology ; Virus Internalization | |||||
Chemical Substances | ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-) | |||||
Language | English | |||||
Publishing date | 2021-06-08 | |||||
Publishing country | United States | |||||
Document type | Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't | |||||
ZDB-ID | 2943-9 | |||||
ISSN | 1525-2191 ; 0002-9440 | |||||
ISSN (online) | 1525-2191 | |||||
ISSN | 0002-9440 | |||||
DOI | 10.1016/j.ajpath.2021.05.009 | |||||
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Database | MEDical Literature Analysis and Retrieval System OnLINE |
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