Codebase for the spatially resolved single-cell atlas of the post-mortem lung in fatal COVID-19, non- and lower respiratory diseases in an African population.
Spatially resolved single-cell atlas of the lung in fatal Covid19 in an African population reveals a distinct cellular signature and an interferon gamma dominated response
James Nyirenda*, Olympia Hardy*, João Da Silva Filho*, Vanessa Herder, Charalampos Attipa, Charles Ndovi, Memory Siwombo, Takondwa Namalima, Leticia Suwedi, Watipenge Nyasulu, Thokozile Ngulube, Deborah Nyirenda, Leonard Mvaya, Joseph Phiri, Dennis Chasweka, Chisomo Eneya, Chikondi Makwinja, Chisomo Phiri, Frank Ziwoya, Abel Tembo, Kingsley Makwangwala, Stanley Khoswe, Peter Banda, Ben Morton, Orla Hilton, Sarah Lawrence, Monique Freire dos Reis, Gisely Cardoso Melo, Marcus Vinicius Guimaraes de Lacerda, Fabio Trindade Maranhão Costa, Wuelton Marcelo Monteiro, Luiz Carlos de Lima Ferreira, Carla Johnson, Dagmara McGuinness, Kondwani Jambo, Michael Haley, Benjamin Kumwenda, Massimo Palmarini, Kayla G. Barnes+, Donna M. Denno+, Wieger Voskuijl+ , Steve Kamiza+, Kevin Couper+, Matthias Marti+, Thomas Otto+, Christopher A. Moxon+,**
[https://www.biorxiv.org/content/10.1101/2023.11.16.566964v1]
Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTD) including Covid19 but there is almost no 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 the Malawi cohort, by response to interferongamma (IFN-) in lung-resident alveolar macrophages, in USA, European and Asian cohorts by type I/III interferon responses, particularly in blood-derived monocytes. HIV status had minimal impact on histology or immunopathology. Our study provides data resources and highlights the importance of studying the cellular mechanisms of disease in underrepresented populations, indicating shared and distinct targets for treatment.
Check out the interactive single cell atlas hosted on the cellxgeneVIP platform hosted by the University of Glasgow, by clicking on the URL below:
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.