SARS-CoV-2 Infects Syncytiotrophoblast and Activates Inflammatory Responses in the Placenta.

TitleSARS-CoV-2 Infects Syncytiotrophoblast and Activates Inflammatory Responses in the Placenta.
Publication TypeJournal Article
Year of Publication2021
AuthorsArgueta LB, Lacko LA, Bram Y, Tada T, Carrau L, Zhang T, Uhl S, Lubor BC, Chandar V, Gil C, Zhang W, Dodson B, Bastiaans J, Prabhu M, Salvatore CM, Yang YJ, Baergen RN, tenOever BR, Landau NR, Chen S, Schwartz RE, Stuhlmann H
Date Published2021 Jun 17

SARS-CoV-2 infection during pregnancy leads to an increased risk of adverse pregnancy outcomes. Although the placenta itself can be a target of virus infection, most neonates are virus free and are born healthy or recover quickly. Here, we investigated the impact of SARS-CoV-2 infection on the placenta from a cohort of women who were infected late during pregnancy and had tested nasal swab positive for SARS-CoV-2 by qRT-PCR at delivery. SARS-CoV-2 genomic and subgenomic RNA was detected in 23 out of 54 placentas. Two placentas with high virus content were obtained from mothers who presented with severe COVID-19 and whose pregnancies resulted in adverse outcomes for the fetuses, including intrauterine fetal demise and a preterm delivered baby still in newborn intensive care. Examination of the placental samples with high virus content showed efficient SARS-CoV-2 infection, using RNA in situ hybridization to detect genomic and replicating viral RNA, and immunohistochemistry to detect SARS-CoV-2 nucleocapsid protein. Infection was restricted to syncytiotrophoblast cells that envelope the fetal chorionic villi and are in direct contact with maternal blood. The infected placentas displayed massive infiltration of maternal immune cells including macrophages into intervillous spaces, potentially contributing to inflammation of the tissue. infection of placental cultures with SARS-CoV-2 or with SARS-CoV-2 spike (S) protein pseudotyped lentivirus targeted mostly syncytiotrophoblast and in rare events endothelial cells. Infection was reduced by using blocking antibodies against ACE2 and against Neuropilin 1, suggesting that SARS-CoV-2 may utilize alternative receptors for entry into placental cells.

Alternate JournalbioRxiv
PubMed ID34100019
PubMed Central IDPMC8183016
Grant ListR33 AI122390 / AI / NIAID NIH HHS / United States
K08 AI120898 / AI / NIAID NIH HHS / United States
R01 DK119667 / DK / NIDDK NIH HHS / United States
R01 CA234614 / CA / NCI NIH HHS / United States
F32 HD096810 / HD / NICHD NIH HHS / United States
R21 AI122390 / AI / NIAID NIH HHS / United States
R01 DK121072 / DK / NIDDK NIH HHS / United States
DP1 DA046100 / DA / NIDA NIH HHS / United States
R01 AI107301 / AI / NIAID NIH HHS / United States
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Yawei (Jenny) Yang, M.D., Ph.D.

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