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 James, Hardy Olympia, Da Silva Filho João, Herder Vanessa, Attipa Charalampos, Ndovi Charles, Siwombo Memory, Namalima Takondwa, Suwedi Leticia, Nyasulu Watipenge, Ngulube Thokozile, Nyirenda Deborah, Mvaya Leonard, Phiri Joseph, Chasweka Dennis, Eneya Chisomo, Makwinja Chikondi, Phiri Chisomo, Ziwoya Frank, Tembo Abel, Makwangwala Kingsley, Khoswe Stanley, Banda Peter, Morton BenORCID, Hilton Orla, Lawrence Sarah, dos Reis Monique Freire, Melo Gisely Cardoso, de Lacerda Marcus Vinicius Guimaraes, Costa Fabio Trindade Maranhão, Monteiro Wuelton Marcelo, de Lima Ferreira Luiz Carlos, Johnson Carla, McGuinness Dagmara, Jambo KondwaniORCID, Haley Michael, Kumwenda Benjamin, Palmarini Massimo, Barnes Kayla G., Denno Donna M., Voskuijl WiegerORCID, Kamiza Steve, Couper Kevin, Marti Matthias, Otto Thomas, Moxon Christopher A.ORCID
Abstract
ABSTRACTPostmortem 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.
Publisher
Cold Spring Harbor Laboratory
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