TY - UNPB
T1 - Multi-omic spatial profiling reveals the unique virus-driven immune landscape of COVID-19 placentitis
AU - Pugh, Matthew
AU - Fennell, Eanna
AU - Leahy, Ciara I
AU - Perry, Tracey
AU - Hargitai, Beata
AU - Marton, Tamas
AU - Hunter, Kelly
AU - Halford, Graham
AU - Yilmaz, Hale Onder
AU - Stamataki, Zania
AU - Reynolds, Gary
AU - Hill, Harriet J.
AU - Willcox, Benjamin E.
AU - Steven, Neil
AU - Thornton, Catherine A
AU - Dojcinov, Stefan D.
AU - Culhane, Aedin
AU - Murray, Paul G.
AU - Taylor, Graham S.
PY - 2022/11/14
Y1 - 2022/11/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85146567659&partnerID=MN8TOARS
U2 - 10.1101/2022.11.14.516398
DO - 10.1101/2022.11.14.516398
M3 - Preprint
BT - Multi-omic spatial profiling reveals the unique virus-driven immune landscape of COVID-19 placentitis
PB - bioRxiv
ER -