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Inflammatory responses in the placenta upon SARS-CoV-2 infection late in pregnancy.

ABSTRACT: The effect of SARS-CoV-2 infection on placental function is not well understood. Analysis of placentas from women who tested positive at delivery showed SARS-CoV-2 genomic and subgenomic RNA in 22 out of 52 placentas. Placentas from two mothers with symptomatic COVID-19 whose pregnancies resulted in adverse outcomes for the fetuses contained high levels of viral Alpha variant RNA. The RNA was localized to the trophoblasts that cover the fetal chorionic villi in direct contact with maternal blood. The intervillous spaces and villi were infiltrated with maternal macrophages and T cells. Transcriptome analysis showed an increased expression of chemokines and pathways associated with viral infection and inflammation. Infection of placental cultures with live SARS-CoV-2 and spike protein-pseudotyped lentivirus showed infection of syncytiotrophoblast and, in rare cases, endothelial cells mediated by ACE2 and Neuropilin-1. Viruses with Alpha, Beta, and Delta variant spikes infected the placental cultures at significantly greater levels.

SUBMITTER: Argueta LB

PROVIDER: S-EPMC8996470 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Inflammatory responses in the placenta upon SARS-CoV-2 infection late in pregnancy.

Argueta Lissenya B LB Lacko Lauretta A LA Bram Yaron Y Tada Takuya T Carrau Lucia L Rendeiro André Figueiredo AF Zhang Tuo T Uhl Skyler S Lubor Brienne C BC Chandar Vasuretha V Gil Cristianel C Zhang Wei W Dodson Brittany J BJ Bastiaans Jeroen J Prabhu Malavika M Houghton Sean S Redmond David D Salvatore Christine M CM Yang Yawei J YJ Elemento Olivier O Baergen Rebecca N RN tenOever Benjamin R BR Landau Nathaniel R NR Chen Shuibing S Schwartz Robert E RE Stuhlmann Heidi H

iScience 20220411 5

The effect of SARS-CoV-2 infection on placental function is not well understood. Analysis of placentas from women who tested positive at delivery showed SARS-CoV-2 genomic and subgenomic RNA in 22 out of 52 placentas. Placentas from two mothers with symptomatic COVID-19 whose pregnancies resulted in adverse outcomes for the fetuses contained high levels of viral Alpha variant RNA. The RNA was localized to the trophoblasts that cover the fetal chorionic villi in direct contact with maternal blood ...[more]

PMID: 35434541

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Project description:ObjectivesPregnant women are at increased risk for severe SARS-CoV-2 infection and adverse neonatal outcome, primarily preterm birth and stillbirth. Our study aimed to investigate to which extent SARS-CoV-2 affects placental tissue and if viral replication within the placenta is evident, thus if there is a correlation between placental damage and adverse pregnancy outcome such as stillbirth.MethodsWe prospectively collected placentas from 61 SARS-CoV-2 infected pregnant women and 10 controls. Histopathological, immunohistochemical, and in situ hybridization studies were performed on all placentas with antibodies for SARS-CoV-2 proteins, ACE2, various immune cells, and inflammatory markers or probes for SARS-CoV-2 genes and an antisense strand.ResultsThe measured scores of SARS-CoV-2 glycoprotein, nucleocapsid, and antisense strand indicating replication correlated with both the severity of maternal symptoms and presence of stillbirth. Specifically, 15/61 placentas exhibited replication, while the three cases with stillbirth had high or maximal replication scores. ACE2-H-score was significantly higher in COVID-19 patients, while the expression of various immune cells did not differ statistically. In multivariate analysis, presence of maternal comorbidities correlated with presence of severe COVID-19 infection.ConclusionWe report evidence of active in vivo SARS-CoV-2 replication in the placenta after maternal infection in pregnancy in a case-control setting in a large population. Intensity of placental viral replication as well as viral levels were higher in women with severe or critical COVID-19 disease, supporting the rationale that severity of maternal SARS-CoV-2 infection could correlate with the severity of placentitis. Replication was maximal in cases of stillbirth, which suggests direct placental involvement in the pathophysiology of this dramatic outcome. Continuing to advocate for preventive measures against COVID-19 during pregnancy, including (re)vaccination, as well as appropriately counseling women with diagnosed infection, are of utter importance.

Dataset Information

Inflammatory responses in the placenta upon SARS-CoV-2 infection late in pregnancy.

Publications

Inflammatory responses in the placenta upon SARS-CoV-2 infection late in pregnancy.

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