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

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.

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Publication Details

Journal
Nature Medicine
Published
2024-11-20
DOI
https://doi.org/10.1038/s41591-024-03354-3
Citations
5
Primary Topic
Immune responses and vaccinations
Type
article
Field-Weighted Citation Impact
1.20

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article

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

Deborah Nyirenda, Monique Freire dos Reis, Marcus Lacerda, Christopher A. Moxon et al.
5 citations
Nature Medicine
Immune responses and vaccinations
1.20
article

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

Deborah Nyirenda, Monique Freire dos Reis, Marcus Lacerda, Christopher A. Moxon, Matthias Marti, Thomas D. Otto, Kayla G. Barnes, Charalampos Attipa, Stanley Khoswe, Takondwa Rex Namalima, Wuelton Marcelo Monteiro, James Nyirenda, Orla Hilton, Memory Siwombo, Frank Ziwoya, Benjamin Kumwenda, Luíz Carlos de Lima Ferreira, Massimo Palmarini, Dennis Chasweka, Fábio Trindade Maranhão Costa, Kevin N. Couper, Wieger P. Voskuijl, Joseph Phiri, Vanessa Herder, Olympia M Hardy, Dagmara McGuinness, Kondwani Jambo, Donna M. Denno, Ben Morton, Steve Kamiza, Michael Haley, Leonard Mvaya, Chisomo Phiri, João Luiz Silva‐Filho, Georgios Ilia, Watipenge Nyasulu, Chisomo Eneya, Chikondi Makwinja, Kingsley Makwangwala, Charles Ndovi, Leticia Suwedi, Sarah Lawrence, Gisely Cardoso de Melo, Peter Banda, Carla Johnson, Thokozile Ngulube, Abel Tembo
article en
5 citations

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.

Nature MedicineVol. 30(12)
Broad Institute (US), Roslin Institute (GB), Harvard University (US), University of Liverpool (GB), Universidade Estadual de Campinas (UNICAMP) (BR), Liverpool School of Tropical Medicine (GB), University of Washington (US), University of Zurich (CH), Malawi-Liverpool-Wellcome Trust Clinical Research Programme (MW), Kamuzu Central Hospital (MW), University of Manchester (GB), Fundação de Medicina Tropical (BR), Blantyre Institute for Community Ophthalmology (MW), MRC University of Glasgow Centre for Virus Research (GB), Universidade do Estado do Amazonas (BR), Amsterdam University Medical Centers (NL), Queen Elizabeth Central Hospital (MW), Kamuzu University of Health Sciences (MW), Imperial College London (GB), Fundação Oswaldo Cruz (BR), The University of Texas Medical Branch at Galveston (US), University of Glasgow (GB), University of Edinburgh (GB)
Wellcome, Medical Research Council, Biotechnology and Biological Sciences Research Council
Good health and well-being
Openalex Percentile: Top 20%
Immune responses and vaccinations
1.20
DOIOpen Access PDFOpenAlex
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