Spatially resolved single-cell atlas unveils A distinct cellular signature of fatal lung COVID-19 in a Malawian population

Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTD) including Covid19, but there is minimal data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. We used histology and high-dimensional imaging to characterise fatal lung disease in Malawian adults with (n=9) and without (n=7) Covid19, and generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other  cohorts showed a conserved Covid19 histopathological signature, driven by contrasting immune and inflammatory mechanisms:  in USA, European and Asian cohorts by type I/III interferon responses, particularly in blood-derived monocytes, in the Malawi cohort, by response to interferon-gamma (IFN-γ) in lung-resident macrophages. HIV status had minimal impact on histology or immunopathology. Our study provides a data resource and highlights the importance of studying the cellular mechanisms of disease in underrepresented populations, indicating shared and distinct targets for treatment. 

Here, there are scripts containing pre-processing, image denoise, cell segmentation, single-cell and spatial statistics analysis as well as visualisation plots for the Imaging Mass Cytometry of the post-mortem lung sections. 

Check out the interactive single cell atlas hosted on the cellxgeneVIP platform hosted by the University of Glasgow, by clicking on https://cellatlas-cxg.mvls.gla.ac.uk/COSMIC/view/COSMIC_IMC_Lung.h5ad/