Multi-omic spatial profiling reveals the unique virus-driven immune landscape of COVID-19 placentitis

Pugh, M.; Fennel, E.; Leahy, C. I.; Perry, T.; Hargitai, B.; Marton, T.; Hunter, K. J.; Halford, G.; Yilmaz, H. O.; Stamataki, Z.; Reynolds, G.; Hill, H. J.; Willcox, B. E.; Steven, N. M.; Thornton, C. A.; Dojcinov, S.; Culhane, A.; Murray, P. G.; Taylor, G. S.

doi:10.1101/2022.11.14.516398

bioRxiv · 10.1101/2022.11.14.516398

Multi-omic spatial profiling reveals the unique virus-driven immune landscape of COVID-19 placentitis

Pugh, M.·Fennel, E.·Leahy, C. I.·Perry, T.·Hargitai, B.·Marton, T.·Hunter, K. J.·Halford, G.·Yilmaz, H. O.·Stamataki, Z.·Reynolds, G.·Hill, H. J.·Willcox, B. E.·Steven, N. M.·Thornton, C. A.·Dojcinov, S.·Culhane, A.·Murray, P. G.·Taylor, G. S.

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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

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Pugh, M., Fennel, E., Leahy, C. I., Perry, T., Hargitai, B., Marton, T., Hunter, K. J., Halford, G., Yilmaz, H. O., Stamataki, Z., Reynolds, G., Hill, H. J., Willcox, B. E., Steven, N. M., Thornton, C. A., Dojcinov, S., Culhane, A., Murray, P. G., Taylor, G. S.. 2022-11-14. Multi-omic spatial profiling reveals the unique virus-driven immune landscape of COVID-19 placentitis. https://doi.org/10.1101/2022.11.14.516398

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