Single-Cell RNA-seq Identifies Cell Subsets in Human Placenta That Highly Expresses Factors to Drive Pathogenesis of SARS-CoV-2

Nancy Ashray; Anshul Bhide; Priyanka Chakarborty; Stacy Colaco; Anuradha Mishra; Karisma Chhabria; Mohit Kumar Jolly; Deepak Modi

doi:10.20944/preprints202005.0195.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 8 May 2020 / Approved: 11 May 2020 / Online: 11 May 2020 (12:50:48 CEST)

Infection by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) results in the novel coronavirus disease COVID-19, which has posed a serious threat globally. Infection of SARS-CoV-2 during pregnancy is associated with complications like preterm labor and premature rupture of membranes; a proportion of neonates born to the infected mothers are also positive for the virus. During pregnancy, the placental barrier protects the fetus from pathogens and ensures healthy development. However, whether or not SARS-CoV-2 can infect the placenta is unknown. Herein, utilizing single-cell RNA-seq data, we report that the SARS-CoV-2 binding receptor ACE2 and the S protein priming protease TMPRSS2 are co-expressed by a subset of syncytiotrophoblasts (STB) in the first trimester and extra villous trophoblasts (EVT) in the second trimester human placenta. The ACE2- and TMPRSS2-positive (ACE2+TMPRSS2+) placental subsets express mRNA for proteins involved in viral budding and replication. These cells also express mRNA for proteins that interact with SARS-CoV-2 structural and non-structural proteins in the host cells. We also discovered unique signatures of genes in ACE2+TMPRSS2+ STBs and EVTs. The ACE2+TMPRSS2+ STBs are highly differentiated cells and express genes involved mitochondrial metabolism and glucose transport. The second trimester ACE2+TMPRSS2+ EVTs are enriched for markers of endovascular trophoblasts. Further, both these subtypes abundantly expressed genes in Toll like receptor pathway, the second trimester EVTs (but not first trimester STBs) are also enriched for component of the JAK-STAT pathway that drive inflammation. To conclude, herein we uncovered the cellular targets for SARS-CoV-2 entry and show that these cells can potentially drive viremia in the developing human placenta. Our results provide a basic framework towards understanding the paraphernalia involved in SARS-CoV-2 infections in pregnancy.

Placenta; trophoblast; SARS-CoV-2; Coronaviruses; COVID-19; Single cell RNAseq; scRNA-seq; ACE2;TMPRSS2; CD147; CTSL; inflammation

LIFE SCIENCES, Cell & Developmental Biology

Comment 1

Received: 12 May 2020
Commenter: Dr. Ashutosh Kumar
The commenter has declared there is no conflict of interests.

Comment: Very comprehensive study with robust molecular level evidence for potential SARS-CoV-2 invasion of placental cells.

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Comment 2

Received: 19 May 2020
Commenter: Chris Mozi
The commenter has declared there is no conflict of interests.

Comment: Too my speculation and over overstretching of data that dilutes the problem. Further the title seems very misleading as if the authors themselves performed the scRNA Seq. They need to mention clearly even on title that it is just an analysis of an already published data, which unless someone read the methods wont even find out. I suppose they should change their title in the first place.
Also lot of issue with analysis when some transcripts are very low abundant in the Placenta as they mention themselves.

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Comment 3

Received: 25 May 2020
Commenter: Nathan
The commenter has declared there is no conflict of interests.

Comment: https://www.biorxiv.org/content/10.1101/2020.05.18.101485v1
https://www.news-medical.net/news/20200520/Main-receptors-used-by-SARS-CoV-2-for-cell-entry-are-absent-in-the-human-placenta.aspx

Confusing with these contradictory reports

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Single-Cell RNA-seq Identifies Cell Subsets in Human Placenta That Highly Expresses Factors to Drive Pathogenesis of SARS-CoV-2

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