TY - JOUR
AU - Nyirenda, James
AU - Hardy, Olympia
AU - Da Silva Filho, João
AU - Herder, Vanessa
AU - Attipa, Charalampos
AU - Ndovi, Charles
AU - Siwombo, Memory
AU - Namalima, Takondwa
AU - Suwedi, Leticia
AU - Nyasulu, Watipenge
AU - Ngulube, Thokozile
AU - Nyirenda, Deborah
AU - Mvaya, Leonard
AU - Phiri, Joseph
AU - Chasweka, Dennis
AU - Eneya, Chisomo
AU - Makwinja, Chikondi
AU - Phiri, Chisomo
AU - Ziwoya, Frank
AU - Tembo, Abel
AU - Makwangwala, Kingsley
AU - Khoswe, Stanley
AU - Banda, Peter
AU - Morton, Ben
AU - Hilton, Orla
AU - Lawrence, Sarah
AU - Freire dos Reis, Monique
AU - Cardoso Melo, Gisely
AU - Vinicius Guimaraes de Lacerda, Marcus
AU - Trindade Maranhão Costa, Fabio
AU - Marcelo Monteiro, Wuelton
AU - Carlos de Lima Ferreira, Luiz
AU - Johnson, Carla
AU - McGuinness, Dagmara
AU - Jambo, Kondwani C.
AU - Haley, Michael
AU - Kumwenda, Benjamin
AU - Palmarini, Massimo
AU - Barnes, Kayla G.
AU - Denno, Donna M.
AU - Voskuijl, Wieger
AU - Kamiza, Steve
AU - Couper, Kevin
AU - Marti, Matthias
AU - Otto, Thomas D.
AU - Moxon, Christopher
PY - 2023
DA - December
TI - 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
JO - bioRxiv
DO - https://doi.org/10.1101/2023.11.16.566964
AB - 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.
PB - BioRxiv 
UR - https://eprints.gla.ac.uk/323712/
KW - Coronavirus (COVID-19)
ER