Multi-omic spatial profiling reveals the unique virus-driven immune landscape of COVID-19 placentitis
Summary 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 <jats:fig id="ufig1" position="anchor" orientation="portrait" fig-type="figure"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="516398v1_ufig1" position="float" orientation="portrait" /></jats:fig>.
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 12. März Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pugh, Matthew [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2022.11.14.516398 |
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| PPN (Katalog-ID): |
XBI037879979 |
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| 245 | 1 | 0 | |a Multi-omic spatial profiling reveals the unique virus-driven immune landscape of COVID-19 placentitis |
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| 520 | |a Summary 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 <jats:fig id="ufig1" position="anchor" orientation="portrait" fig-type="figure"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="516398v1_ufig1" position="float" orientation="portrait" /></jats:fig> | ||
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| 700 | 1 | |a Perry, Tracey |4 aut | |
| 700 | 1 | |a Hargitai, Beata |4 aut | |
| 700 | 1 | |a Marton, Tamas |4 aut | |
| 700 | 1 | |a Hunter, Kelly J. |4 aut | |
| 700 | 1 | |a Halford, Graham |4 aut | |
| 700 | 1 | |a Yilmaz, Hale Onder |4 aut | |
| 700 | 1 | |a Stamataki, Zania |0 (orcid)0000-0003-3823-4497 |4 aut | |
| 700 | 1 | |a Reynolds, Gary |4 aut | |
| 700 | 1 | |a Hill, Harriet J. |4 aut | |
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| 700 | 1 | |a Steven, Neil |4 aut | |
| 700 | 1 | |a Thornton, Catherine A. |4 aut | |
| 700 | 1 | |a Dojcinov, Stefan D. |4 aut | |
| 700 | 1 | |a Culhane, Aedin |4 aut | |
| 700 | 1 | |a Murray, Paul G. |4 aut | |
| 700 | 1 | |a Taylor, Graham S. |4 aut | |
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