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

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: https://doi.org/10.1038/s41591-024-03354-3

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.

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Cite as

Nyirenda, J., Hardy, O., Da Silva Filho, J., Herder, V., Attipa, C., Ndovi, C., Siwombo, M., Namalima, T., Suwedi, L., Ilia, G., Nyasulu, W., Ngulube, T., Nyirenda, D., Mvaya, L., Phiri, J., Chasweka, D., Eneya, C., Makwinja, C., Phiri, C., Ziwoya, F., Tembo, A., Makwangwala, K., Khoswe, S., Banda, P., Morton, B., Hilton, O., Lawrence, S., Freire dos Reis, M., Cardoso Melo, G., Guimaraes de Lacerda, M., Maranhão Costa, F., Monteiro, W., Carlos de Lima Ferreira, L., Johnson, C., McGuinness, D., Jambo, K., Haley, M., Kumwenda, B., Palmarini, M., Denno, D., Voskuijl, W., Kamiza, S., Barnes, K., Couper, K., Marti, M., Otto, T. & Moxon, C. 2024, 'Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population', Nature Medicine. https://doi.org/10.1038/s41591-024-03354-3

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DOI: https://doi.org/10.1038/s41591-024-03354-3

Repository URI: https://eprints.gla.ac.uk/340663/