@article{4691, keywords = {Immunopathogenesis, infection, Single-cell imaging, Viral infection}, author = {James Nyirenda and Olympia M. Hardy and João Da Silva Filho and Vanessa Herder and Charalampos Attipa and Charles Ndovi and Memory Siwombo and Takondwa Rex Namalima and Leticia Suwedi and Georgios Ilia and Watipenge Nyasulu and Thokozile Ngulube and Deborah Nyirenda and Leonard Mvaya and Joseph Phiri and Dennis Chasweka and Chisomo Eneya and Chikondi Makwinja and Chisomo Phiri and Frank Ziwoya and Abel Tembo and Kingsley Makwangwala and Stanley Khoswe and Peter Banda and Ben Morton and Orla Hilton and Sarah Lawrence and Monique Freire dos Reis and Gisely Cardoso Melo and Marcus Vinicius Guimaraes de Lacerda and Fabio Trindade Maranhão Costa and Wuelton Marcelo Monteiro and Luiz Carlos de Lima Ferreira and Carla Johnson and Dagmara McGuinness and Kondwani Jambo and Michael Haley and Benjamin Kumwenda and Massimo Palmarini and Donna M. Denno and Wieger Voskuijl and Steve Bvuobvuo Kamiza and Kayla G. Barnes and Kevin Couper and Matthias Marti and Thomas D. Otto and Christopher A. Moxon}, title = {Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population}, 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.}, year = {2024}, journal = {Nature Medicine}, pages = {1-13}, month = {2024-11-20}, issn = {1546-170X}, url = {https://www.nature.com/articles/s41591-024-03354-3}, doi = {10.1038/s41591-024-03354-3}, language = {en}, }