iScience (May 2022)
Inflammatory responses in the placenta upon SARS-CoV-2 infection late in pregnancy
- Lissenya B. Argueta,
- Lauretta A. Lacko,
- Yaron Bram,
- Takuya Tada,
- Lucia Carrau,
- André Figueiredo Rendeiro,
- Tuo Zhang,
- Skyler Uhl,
- Brienne C. Lubor,
- Vasuretha Chandar,
- Cristianel Gil,
- Wei Zhang,
- Brittany J. Dodson,
- Jeroen Bastiaans,
- Malavika Prabhu,
- Sean Houghton,
- David Redmond,
- Christine M. Salvatore,
- Yawei J. Yang,
- Olivier Elemento,
- Rebecca N. Baergen,
- Benjamin R. tenOever,
- Nathaniel R. Landau,
- Shuibing Chen,
- Robert E. Schwartz,
- Heidi Stuhlmann
Affiliations
- Lissenya B. Argueta
- Department of Cell and Developmental Biology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
- Lauretta A. Lacko
- Department of Surgery, Weill Cornell Medicine, New York, NY 10065, USA
- Yaron Bram
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA
- Takuya Tada
- Department of Microbiology, NYU Grossman School of Medicine, New York, NY 10016, USA
- Lucia Carrau
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- André Figueiredo Rendeiro
- Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10065, USA
- Tuo Zhang
- Genomics Resources Facility, Weill Cornell Medicine, New York, NY 10065, USA
- Skyler Uhl
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Brienne C. Lubor
- Department of Cell and Developmental Biology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
- Vasuretha Chandar
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA
- Cristianel Gil
- Department of Surgery, Weill Cornell Medicine, New York, NY 10065, USA
- Wei Zhang
- Genomics Resources Facility, Weill Cornell Medicine, New York, NY 10065, USA
- Brittany J. Dodson
- Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY 10065, USA
- Jeroen Bastiaans
- Department of Cell and Developmental Biology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
- Malavika Prabhu
- Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY 10065, USA
- Sean Houghton
- Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA
- David Redmond
- Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA
- Christine M. Salvatore
- Department of Pediatrics, Division of Pediatric Infectious Diseases, Weill Cornell Medicine, New York, NY 10065, USA
- Yawei J. Yang
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA
- Olivier Elemento
- Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10065, USA
- Rebecca N. Baergen
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA
- Benjamin R. tenOever
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Nathaniel R. Landau
- Department of Microbiology, NYU Grossman School of Medicine, New York, NY 10016, USA
- Shuibing Chen
- Department of Surgery, Weill Cornell Medicine, New York, NY 10065, USA; Corresponding author
- Robert E. Schwartz
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA; Corresponding author
- Heidi Stuhlmann
- Department of Cell and Developmental Biology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 5
p. 104223
Abstract
Summary: 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.