Vuppussetty, C. (Chaitanya)

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    Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs
    (2023) Clelland, C. (Colin); Whalley, J. (Justin); Sims, D. (David); Weeratunga, P. (Praveen); Bull, J. (Joshua); Sergeant, M. (Martin); Klenerman, P. (Paul); Monaco, C. (Claudia); Gamez, E.C. (Eddie C.); Issa, F. (Fadi); Antanaviciute, A. (Agne); Etherington, R.E. (Rachel E.); Denney, L. (Laura); Byrne, H.M. (Helen M.); McGowan, S. (Simon); Richards, D. (Duncan); Ahern, D.J. (David J.); Udalova, I.A. (Irina A.); Zurke, Y.X. (Yasemin Xiomara); Turner, G.D.H. (Gareth D.H.); Melero, I. (Ignacio); Repapi, E. (Emmanouela); Ogg, G. (Graham); Cross, A.R. (Amy R.); Ho, L.P. (Ling-Pei); Andrea, C.E. (Carlos Eduardo) de; Taylor, S. (Stephen); Knight, J.C. (Julian C.); Vuppussetty, C. (Chaitanya); Dong, T. (Tao); Woo, J. (Jeongmin)
    Single cell spatial interrogation of the immune-structural interactions in COVID -19 lungs is challenging, mainly because of the marked cellular infiltrate and architecturally distorted microstructure. To address this, we develop a suite of mathematical tools to search for statistically significant co-locations amongst immune and structural cells identified using 37-plex imaging mass cytometry. This unbiased method reveals a cellular map interleaved with an inflammatory network of immature neutrophils, cytotoxic CD8 T cells, megakaryocytes and monocytes co-located with regenerating alveolar progenitors and endothelium. Of note, a highly active cluster of immature neutrophils and CD8 T cells, is found spatially linked with alveolar progenitor cells, and temporally with the diffuse alveolar damage stage. These findings offer further insights into how immune cells interact in the lungs of severe COVID-19 disease. We provide our pipeline [Spatial Omics Oxford Pipeline (SpOOx)] and visual-analytical tool, Multi-Dimensional Viewer (MDV) software, as a resource for spatial analysis. Mathematical tools can be used to help identify pathological features from images of diseased lungs. Here, the authors used mathematical tools combined with high resolution multiplex imaging mass cytometry to show an association between immature neutrophils, CD8 T cells and proliferating alveolar epithelial cells in areas of maximal alveolar damage in COVID-19 lungs.