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Nat Med
. 2024 Nov 20.
doi: 10.1038/s41591-024-03354-3. Online ahead of print. Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population
James Nyirenda # 1 2 3 , Olympia M Hardy # 1 , João Da Silva Filho # 1 4 , Vanessa Herder 5 , Charalampos Attipa 1 3 6 7 , Charles Ndovi 1 2 3 , Memory Siwombo 8 9 , Takondwa Rex Namalima 8 , Leticia Suwedi 3 10 , Georgios Ilia 5 , Watipenge Nyasulu 1 2 3 , Thokozile Ngulube 1 3 , Deborah Nyirenda 3 10 , Leonard Mvaya 3 , Joseph Phiri 3 , Dennis Chasweka 9 , Chisomo Eneya 9 , Chikondi Makwinja 9 , Chisomo Phiri 9 , Frank Ziwoya 9 , Abel Tembo 9 , Kingsley Makwangwala 9 , Stanley Khoswe 9 , Peter Banda 8 9 , Ben Morton 3 11 , Orla Hilton 12 , Sarah Lawrence 13 , Monique Freire Dos Reis 14 15 , Gisely Cardoso Melo 16 , Marcus Vinicius Guimaraes de Lacerda 16 17 18 , Fabio Trindade Maranhão Costa 19 , Wuelton Marcelo Monteiro 15 16 , Luiz Carlos de Lima Ferreira 15 16 , Carla Johnson 1 , Dagmara McGuinness 1 , Kondwani Jambo 3 11 , Michael Haley 20 , Benjamin Kumwenda 9 , Massimo Palmarini 5 , Donna M Denno 13 , Wieger Voskuijl 8 9 21 , Steve Bvuobvuo Kamiza 9 , Kayla G Barnes 3 22 23 24 25 , Kevin Couper 20 , Matthias Marti 26 27 , Thomas D Otto 28 , Christopher A Moxon 29 30 31 32 33
Affiliations
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.
. 2024 Nov 20.
doi: 10.1038/s41591-024-03354-3. Online ahead of print. Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population
James Nyirenda # 1 2 3 , Olympia M Hardy # 1 , João Da Silva Filho # 1 4 , Vanessa Herder 5 , Charalampos Attipa 1 3 6 7 , Charles Ndovi 1 2 3 , Memory Siwombo 8 9 , Takondwa Rex Namalima 8 , Leticia Suwedi 3 10 , Georgios Ilia 5 , Watipenge Nyasulu 1 2 3 , Thokozile Ngulube 1 3 , Deborah Nyirenda 3 10 , Leonard Mvaya 3 , Joseph Phiri 3 , Dennis Chasweka 9 , Chisomo Eneya 9 , Chikondi Makwinja 9 , Chisomo Phiri 9 , Frank Ziwoya 9 , Abel Tembo 9 , Kingsley Makwangwala 9 , Stanley Khoswe 9 , Peter Banda 8 9 , Ben Morton 3 11 , Orla Hilton 12 , Sarah Lawrence 13 , Monique Freire Dos Reis 14 15 , Gisely Cardoso Melo 16 , Marcus Vinicius Guimaraes de Lacerda 16 17 18 , Fabio Trindade Maranhão Costa 19 , Wuelton Marcelo Monteiro 15 16 , Luiz Carlos de Lima Ferreira 15 16 , Carla Johnson 1 , Dagmara McGuinness 1 , Kondwani Jambo 3 11 , Michael Haley 20 , Benjamin Kumwenda 9 , Massimo Palmarini 5 , Donna M Denno 13 , Wieger Voskuijl 8 9 21 , Steve Bvuobvuo Kamiza 9 , Kayla G Barnes 3 22 23 24 25 , Kevin Couper 20 , Matthias Marti 26 27 , Thomas D Otto 28 , Christopher A Moxon 29 30 31 32 33
Affiliations
- PMID: 39567718
- DOI: 10.1038/s41591-024-03354-3
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.