Background Many studies have described the blood immune profile of severe COVID-19 patients but few have elucidated the cellular composition and organisation in lung tissue. Method We used tissue-based single cell mass cytometry and a suite of mathematical tools to generate a spatial analytical pipeline which searched for statistically significant cell-level co-location of immune cells and specified lung microstructures, without a priori specification of neighborhood environment. Lung samples from fatal COVID-19 patients (n=12) were stained with a 35-metal-tagged antibody panel and imaged with the Tissue Hyperion system. Results 677,931 single segmented cells were derived and 38 immune and structural cell types annotated. Monocytes, macrophages and immature neutrophils showed highest abundance across all histopathology stages of injury and repair. A striking cluster of cells was observed, comprising immature neutrophils and cytotoxic CD8 with high expression of Granzyme B, IFN-? and IFN-?. These were spatially co-located with proliferating alveolar epithelium in areas with diffuse alveolar damage. Network analysis showed that these inflammatory foci connected other immature neutrophil and monocyte subsets across all histopathology stages.Conclusion The cellular map of fatal COVID-19 lungs is marked by highly active clusters of immature neutrophils and cytotoxic CD8 T cells, spatially linked with alveolar progenitor cells, and temporally with the diffuse alveolar damage stage. These findings provide new insights into how immune cells interact in the lungs of severe COVID-19 disease.