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Multi-omic spatial profiling reveals the unique virus-driven immune landscape of COVID-19 placentitis
Matthew Pugh; Eanna Fennel; Ciara I Leahy; Tracey Perry; Beata Hargitai; Tamas Marton; Kelly J Hunter; Graham Halford; Hale Onder Yilmaz; Zania Stamataki; Gary Reynolds; Harriet J Hill; Benjamin E Willcox; Neil M Steven; Catherine A Thornton; Stefan Dojcinov; Aedin Culhane; Paul G Murray; Graham S Taylor.
Affiliation
  • Matthew Pugh; University of Birmingham
  • Eanna Fennel; University of Limerick
  • Ciara I Leahy; University of Limerick
  • Tracey Perry; University of Birmingham
  • Beata Hargitai; Birmingham Womens and Childrens Hospital
  • Tamas Marton; Birmingham Womens and Childrens Hospital
  • Kelly J Hunter; University of Birmingham
  • Graham Halford; Birmingham Womens and Childrens Hospital
  • Hale Onder Yilmaz; University of Birmingham
  • Zania Stamataki; University of Birmingham
  • Gary Reynolds; University of Birmingham
  • Harriet J Hill; University of Birmingham
  • Benjamin E Willcox; University of Birmingham
  • Neil M Steven; University of Birmingham
  • Catherine A Thornton; University of Swansea
  • Stefan Dojcinov; University of Swansea
  • Aedin Culhane; University of Limerick
  • Paul G Murray; University of Limerick
  • Graham S Taylor; University of Birmingham
Preprint in En | PREPRINT-BIORXIV | ID: ppbiorxiv-516398
ABSTRACT
COVID-19 placentitis, a rare complication of maternal SARS-CoV-2 infection, only shows detectable virus in the placenta of a subset of cases. We provide a deep multi-omic spatial characterisation of placentitis from obstetrically complicated maternal COVID-19 infection. We found that SARS-CoV-2 infected placentas have a distinct transcriptional and immunopathological signature. This signature overlaps with virus-negative cases supporting a common viral aetiology. An inverse correlation between viral load and disease duration suggests viral clearance over time. Quantitative spatial analyses revealed a unique microenvironment surrounding virus-infected trophoblasts characterised by PDL1-expressing macrophages, T-cell exclusion, and interferon blunting. In contrast to uninfected mothers, ACE2 was localised to the maternal side of the placental trophoblast layer of almost all mothers with placental SARS-CoV-2 infection, which may explain variable susceptibility to placental infection. Our results demonstrate a pivotal role for direct placental SARS-CoV-2 infection in driving the unique immunopathology of COVID-19 placentitis. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY
License
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Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Type of study: Etiology_studies Language: En Year: 2022 Document type: Preprint
Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Type of study: Etiology_studies Language: En Year: 2022 Document type: Preprint