@article{Nyirenda_J-2023_180783,
title = {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},
author = {Nyirenda, J. and Hardy, O. and Da Silva Filho, J. and Herder, V. and Attipa, C. and Ndovi, C. and Siwombo, M. and Namalima, T. and Suwedi, L. and Nyasulu, W. and Ngulube, T. and Nyirenda, D. and Mvaya, L. and Phiri, J. and Chasweka, D. and Eneya, C. and Makwinja, C. and Phiri, C. and Ziwoya, F. and Tembo, A. and Makwangwala, K. and Khoswe, S. and Banda, P. and Morton, B. and Hilton, O. and Lawrence, S. and Freire dos Reis, M. and Cardoso Melo, G. and Vinicius Guimaraes de Lacerda, M. and Trindade Maranhão Costa, F. and Marcelo Monteiro, W. and Carlos de Lima Ferreira, L. and Johnson, C. and McGuinness, D. and Jambo, K. and Haley, M. and Kumwenda, B. and Palmarini, M. and Barnes, K. and Denno, D. and Voskuijl, W. and Kamiza, S. and Couper, K. and Marti, M. and Otto, T. and Moxon, C.},
month = {dec},
year = {2023},
abstract = {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 interferon-gamma (IFN-γ) 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.},
journal = {bioRxiv},
publisher = {BioRxiv },
url = {https://doi.org/10.1101/2023.11.16.566964},
}
