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Single-cell immunophenotyping of the fetal immune response to maternal SARS-CoV-2 infection

ABSTRACT: Single-cell immunophenotyping of the fetal immune response to maternal SARS-CoV-2 infection

PROVIDER: PRJNA697969 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13582626.fastq.gz	Fastqsanger.gz
	SRR13582627.fastq.gz	Fastqsanger.gz
	SRR13582628.fastq.gz	Fastqsanger.gz
	SRR13582629.fastq.gz	Fastqsanger.gz
	SRR13582630.fastq.gz	Fastqsanger.gz

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Single-cell immunophenotyping of the fetal immune response to maternal SARS-CoV-2 infection

Project description:During the COVID-19 pandemic, thousands of pregnant women have been infected with SARS-CoV-2 worldwide. The short- and long-term implications of maternal SARS-CoV-2 infection on fetal and childhood well-being are unknown. To characterize the fetal immune response to maternal SARS-CoV-2 infection, we performed single-cell RNA sequencing and T cell receptor sequencing on cord blood mononuclear cells from infants born to mothers infected with SARS-CoV-2 in the third trimester. We identified widespread gene expression changes in cord blood leukocytes, including upregulation of interferon-stimulated genes (ISG) and of HLA genes in CD14+ monocytes; decreased activation of CD16+ monocytes; activation of plasmacytoid dendritic cells; and activation and exhaustion of NK cells and T CD8+ cells in the cord blood of infants born to SARS-CoV-2+ mothers. Lastly, we observed fetal TCR repertoire clonal expansion in cord blood T cells from pregnancies complicated by maternal SARS-CoV-2 infection. Our results suggest that even in the absence of vertical transmission, SARS-CoV-2 maternal infection in the third trimester modulates the fetal immune system.

2021-04-06 | GSE165193 | GEO

SARS-CoV-2 infection in pregnancy is associated with robust inflammatory response at the maternal-fetal interface

Project description:Pregnant women appear to be at increased risk for severe outcomes associated with COVID-19, but the pathophysiology underlying this increased morbidity and its potential impact on the developing fetus is not well understood. In this study of pregnant women with and without COVID-19, we assessed viral and immune dynamics at the placenta during maternal SARS-CoV-2 infection. Viral RNA was only rarely detected in the placentas from SARS-CoV-2-positive women in our cohort, with only 1/11 positive for infection at the maternal-fetal interface. Through bulk RNA transcriptomic analyses, we found that placentas from SARS-CoV-2-positive pregnancies exhibited inflammatory markers of immune activation, even in the majority of samples which did not show local invasion of the virus. These markers are associated with pregnancy complications such as preeclampsia and poor fetal outcomes. Overall, this study suggests that SARS-CoV-2 is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. While this likely represents a protective mechanism shielding the placenta from infection, inflammatory changes in the placenta may also contribute to poor pregnancy outcomes and thus warrant further investigation.

2021-04-14 | GSE171995 | GEO

SARS-CoV-2 infection in pregnancy is associated with robust inflammatory response at the maternal-fetal interface

Project description:Pregnant women appear to be at increased risk for severe outcomes associated with COVID-19, but the pathophysiology underlying this increased morbidity and its potential impact on the developing fetus is not well understood. In this study of pregnant women with and without COVID-19, we assessed viral and immune dynamics at the placenta during maternal SARS-CoV-2 infection. Amongst uninfected women, ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term. Term placentas from women infected with SARS-CoV-2, however, displayed a significant increase in ACE2 levels. Using immortalized cell lines and primary isolated placental cells, we determined the vulnerability of various placental cell types to direct infection by SARS-CoV-2 in vitro. Yet, despite the susceptibility of placental cells to SARS-CoV-2 infection, viral RNA was detected in the placentas of only a subset (∼13%) of women in this cohort. Through single cell transcriptomic analyses, we found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited markers associated with pregnancy complications, such as preeclampsia, and robust immune responses, including increased activation of placental NK and T cells and increased expression of interferon-related genes. Overall, this study suggests that SARS-CoV-2 is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. While this likely represents a protective mechanism shielding the placenta from infection, inflammatory changes in the placenta may also contribute to poor pregnancy outcomes and thus warrant further investigation.

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Project description:Here, we performed proteomic profiling of the maternal peripheral blood and umbilical cord blood from 6 pregnant women positive for SARS-CoV-2 and 6 pregnant women negative for SARS-CoV-2, and examined viral RNA and DNA copies of SARS-CoV-2 sequences in the umbilical cord and placental tissues.

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Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2

Project description:Peripheral and cord blood samples from SARS-CoV-2 positive or control pregnant women were profiled using paired-end DNBseq to evaluate transcriptomic changes associated with SARS-CoV-2 infection during pregnancy.

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Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2

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Project description:During pregnancy, the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent works show increased incidences of adverse pregnancy outcomes in COVID-19 patients; however, the mechanism remains unclear. Here, we analyzed the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from COVID-19 patients and control samples, we discovered aberrant immune activation and angiogenesis patterns in distinct cells from patients. Surprisingly, retrotransposons were also dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of Pregnancy-Specific Glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced significant changes to the epigenome and transcriptome at the maternal-fetal interface, which may be associated with pregnancy complications.

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A Retrospective Cohort Study for Main Postoperative Complications After SARS-CoV-2 Infection

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Global transcriptomic analysis of placenta from women with gestational SARS-CoV-2 infection during the 3rd trimester of pregnancy

Project description:Transcriptomic analysis of the placenta in both maternal and fetal compartments was performed to investigate the impact of maternal SARS-CoV-2 infection.

2024-02-14 | GSE233557 | GEO

SARS-CoV-2 Niches in Human Placenta Revealed by Spatial Transcriptomics

Project description:Diverse placental functions are compartmentalized to separate maternal-fetal antigens and restrict vertical transmission of pathogens. We hypothesized a high-resolution map, with single-cell and spatial resolution, would identify previously undetectable microbe immune microenvironments. To test this hypothesis, we utilized Visium Spatial Transcriptomics paired with H&E staining to generate 17,927 spatial transcriptomes and integrated these data with 273,944 published placenta single-cell and single-nuclei transcriptomes to generate a term placenta atlas of the maternal decidua, fetal chorionic villi, and chorioamniotic membranes. Comparisons of healthy control placentae (n=4), SARS-CoV-2 asymptomatic (n=4; no COVID-19 symptoms), and symptomatic (n=5; pneumonia, respiratory failure) placentae identified distinct thresholds of SARS-CoV-2 detection including (i) no detectable virus, (ii) sparse virus (limit of detection determined to be 1/7,000 cells), and (iii) highly positive SARS-CoV-2 in syncytiotrophoblasts, rigorously cross-validated by RT-qPCR, RNAscope, and immunohistochemistry. High levels of SARS-CoV-2 in placentae were associated with histiocytic intervillositis and perivillous fibrin deposition. Spatial transcriptomics revealed that this led to a significant shift from anti-inflammatory M2 macrophage populations toward intermediate pro-inflammatory M1 macrophages. In conclusion, we identified immune microenvironments representing host-pathogen battlegrounds where SARS-CoV-2 detection in the placenta was not dependent on maternal symptoms. Additional studies utilizing this approach are warranted, especially in the placenta.

2023-07-05 | GSE222987 | GEO

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