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 - Repository

Full text

: https://doi.org/10.1101/2023.11.16.566964

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.

Rights

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. http://creativecommons.org/licenses/by-nc-nd/4.0/

Cite as

Nyirenda, J., Hardy, O., Da Silva Filho, J., Herder, V., Attipa, C., Ndovi, C., Siwombo, M., Namalima, T., Suwedi, L., 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., Vinicius Guimaraes de Lacerda, M., Trindade Maranhão Costa, F., Marcelo Monteiro, W., Carlos de Lima Ferreira, L., Johnson, C., McGuinness, D., Jambo, K., Haley, M., Kumwenda, B., Palmarini, M., Barnes, K., Denno, D., Voskuijl, W., Kamiza, S., Couper, K., Marti, M., Otto, T. & Moxon, C. 2023, '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', bioRxiv. https://doi.org/10.1101/2023.11.16.566964

Downloadable citations

HTML BIB RIS

Identifiers

DOI: https://doi.org/10.1101/2023.11.16.566964

Repository URI: https://eprints.gla.ac.uk/323712/