@article{Nyirenda_J-2024_189404,
title = {Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population},
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 Ilia, G. 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 Guimaraes de Lacerda, M. and Maranhão Costa, F. and 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 Denno, D. and Voskuijl, W. and Kamiza, S. and Barnes, K. and Couper, K. and Marti, M. and Otto, T. and Moxon, C.},
month = {nov},
year = {2024},
abstract = {Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTDs), including coronavirus disease 2019 (COVID-19), but there are minimal data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. In this study, we used histology and high-dimensional imaging to characterize fatal lung disease in Malawian adults with (n = 9) and without (n = 7) COVID-19, and we generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other cohorts showed a conserved COVID-19 histopathological signature, driven by contrasting immune and inflammatory mechanisms: in US, European and Asian cohorts, by type I/III interferon (IFN) responses, particularly in blood-derived monocytes, and in the Malawian cohort, by response to 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.},
journal = {Nature Medicine},
publisher = {Springer Nature},
url = {https://doi.org/10.1038/s41591-024-03354-3},
}
