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

Nyirenda, James, Hardy, Olympia, Filho, João Da Silva, Herder, Vanessa, Attipa, Charalampos, Ndovi, Charles, Siwombo, Memory, Namalima, Takondwa Rex, Suwedi-Kapesa, Leticia, Ilia, Georgios, Nyasulu, Watipenge, Ngulube, Thokozile, Nyirenda, Deborah, Mvaya, Leonard, Phiri, Joseph, Chaswek, Dennis, Eneya, Chisomo, Makwinja, Chikondi, Phiri, Chisomo, Ziwoya, Frank, Tembo, Abel, Makwangwala, Kingsley, Khoswe, Stanley, Banda, Peter, Morton, Ben ORCID: https://orcid.org/0000-0002-6164-2854, Hilton, Orla, Lawrence, Sarah, Freire dos Reis, Monique, Melo, Gisely Cardoso, Guimaraes de Lacerda, Marcus Vinicius, Costa, Fabio Trindade Maranhão, Monteiro, Wuelton Marcelo, Carlos de Lima Ferreira, Luiz, Johnson, Carla, McGuinness, Dagmara, Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Haley, Michael, Kumwenda, Benjamin, Palmarini, Massimo, Denno, Donna, Voskuijl, Wieger, Kamiza, Steve Bvuobvuo, Barnes, Kayla, Couper, Kevin, Marti, Matthias, Otto, Thomas and Moxon, Christopher (2024) 'Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population'. Nature Medicine. (In Press)

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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.

Item Type:	Article
Subjects:	QU Biochemistry > Cells and Genetics > QU 350 Cellular structures QU Biochemistry > Cells and Genetics > QU 375 Cell physiology QY Clinical Pathology > QY 25 Laboratory techniques and procedure WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 506 COVID-19
Faculty: Department:	Biological Sciences > Vector Biology Department Biological Sciences > Department of Tropical Disease Biology Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI):	https://doi.org/10.1038/s41591-024-03354-3
Depositing User:	Ben Morton
Date Deposited:	27 Nov 2024 11:07
Last Modified:	27 Nov 2024 11:24
URI:	https://archive.lstmed.ac.uk/id/eprint/25655

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