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

This record contains all the fully processed single cell RNA sequencing objects included in the paper Nyirenda et al (2024) 'Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population'. Abstract 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. Figure 3 COSMIC_Lung_Atlas.h5ad COSMIC_Lung_Stromal_Atlas.h5ad COSMIC_Lung_Immune_Atlas.h5ad Figure 4 COSMIC_HCLA_Integration.rds Figure 5 COSMIC_Nasal_Atlas.h5ad COSMIC_Blood_Atlas.h5ad Total Post-mortem COVID-19 Lung Autopsy Papers Integration This data object was generated whereby all publicly available fatal COVID-19 lung single cell cohorts were integrated together. We include this analysis to show that the observed interferon responses detailed in the paper are preserved in not only the HLCA, but also existing post-mortem lung cohorts. The codebase for this additional analysis can be found here: https://github.com/olympiahardy/Malawi_Integration COSMIC_Delorey_Melms_Integration.rds Imaging Mass Cytometry Analysis This Zenodo record can be accessed using the DOI here: 10.5281/zenodo.13899297 . The GitHub repository can be accessed here: https://github.com/joaolsf/Spatial_Single_Cell_Lung_Atlas_Malawi_COVID