tetano
Editor, Senior Moderator
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[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Olympia M Hardy[SUP] #[/SUP][SUP] 1 [/SUP], João Da Silva Filho[SUP] #[/SUP][SUP] 1 4 [/SUP], Vanessa Herder[SUP] 5 [/SUP], Charalampos Attipa[SUP] 1 3 6 7 [/SUP], Charles Ndovi[SUP] 1 2 3 [/SUP], Memory Siwombo[SUP] 8 9 [/SUP], Takondwa Rex Namalima[SUP] 8 [/SUP], Leticia Suwedi[SUP] 3 10 [/SUP], Georgios Ilia[SUP] 5 [/SUP], Watipenge Nyasulu[SUP] 1 2 3 [/SUP], Thokozile Ngulube[SUP] 1 3 [/SUP], Deborah Nyirenda[SUP] 3 10 [/SUP], Leonard Mvaya[SUP] 3 [/SUP], Joseph Phiri[SUP] 3 [/SUP], Dennis Chasweka[SUP] 9 [/SUP], Chisomo Eneya[SUP] 9 [/SUP], Chikondi Makwinja[SUP] 9 [/SUP], Chisomo Phiri[SUP] 9 [/SUP], Frank Ziwoya[SUP] 9 [/SUP], Abel Tembo[SUP] 9 [/SUP], Kingsley Makwangwala[SUP] 9 [/SUP], Stanley Khoswe[SUP] 9 [/SUP], Peter Banda[SUP] 8 9 [/SUP], Ben Morton[SUP] 3 11 [/SUP], Orla Hilton[SUP] 12 [/SUP], Sarah Lawrence[SUP] 13 [/SUP], Monique Freire Dos Reis[SUP] 14 15 [/SUP], Gisely Cardoso Melo[SUP] 16 [/SUP], Marcus Vinicius Guimaraes de Lacerda[SUP] 16 17 18 [/SUP], Fabio Trindade Maranhão Costa[SUP] 19 [/SUP], Wuelton Marcelo Monteiro[SUP] 15 16 [/SUP], Luiz Carlos de Lima Ferreira[SUP] 15 16 [/SUP], Carla Johnson[SUP] 1 [/SUP], Dagmara McGuinness[SUP] 1 [/SUP], Kondwani Jambo[SUP] 3 11 [/SUP], Michael Haley[SUP] 20 [/SUP], Benjamin Kumwenda[SUP] 9 [/SUP], Massimo Palmarini[SUP] 5 [/SUP], Donna M Denno[SUP] 13 [/SUP], Wieger Voskuijl[SUP] 8 9 21 [/SUP], Steve Bvuobvuo Kamiza[SUP] 9 [/SUP], Kayla G Barnes[SUP] 3 22 23 24 25 [/SUP], Kevin Couper[SUP] 20 [/SUP], Matthias Marti[SUP] 26 27 [/SUP], Thomas D Otto[SUP] 28 [/SUP], Christopher A Moxon[SUP] 29 30 31 32 33 [/SUP]
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[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Olympia M Hardy[SUP] #[/SUP][SUP] 1 [/SUP], João Da Silva Filho[SUP] #[/SUP][SUP] 1 4 [/SUP], Vanessa Herder[SUP] 5 [/SUP], Charalampos Attipa[SUP] 1 3 6 7 [/SUP], Charles Ndovi[SUP] 1 2 3 [/SUP], Memory Siwombo[SUP] 8 9 [/SUP], Takondwa Rex Namalima[SUP] 8 [/SUP], Leticia Suwedi[SUP] 3 10 [/SUP], Georgios Ilia[SUP] 5 [/SUP], Watipenge Nyasulu[SUP] 1 2 3 [/SUP], Thokozile Ngulube[SUP] 1 3 [/SUP], Deborah Nyirenda[SUP] 3 10 [/SUP], Leonard Mvaya[SUP] 3 [/SUP], Joseph Phiri[SUP] 3 [/SUP], Dennis Chasweka[SUP] 9 [/SUP], Chisomo Eneya[SUP] 9 [/SUP], Chikondi Makwinja[SUP] 9 [/SUP], Chisomo Phiri[SUP] 9 [/SUP], Frank Ziwoya[SUP] 9 [/SUP], Abel Tembo[SUP] 9 [/SUP], Kingsley Makwangwala[SUP] 9 [/SUP], Stanley Khoswe[SUP] 9 [/SUP], Peter Banda[SUP] 8 9 [/SUP], Ben Morton[SUP] 3 11 [/SUP], Orla Hilton[SUP] 12 [/SUP], Sarah Lawrence[SUP] 13 [/SUP], Monique Freire Dos Reis[SUP] 14 15 [/SUP], Gisely Cardoso Melo[SUP] 16 [/SUP], Marcus Vinicius Guimaraes de Lacerda[SUP] 16 17 18 [/SUP], Fabio Trindade Maranhão Costa[SUP] 19 [/SUP], Wuelton Marcelo Monteiro[SUP] 15 16 [/SUP], Luiz Carlos de Lima Ferreira[SUP] 15 16 [/SUP], Carla Johnson[SUP] 1 [/SUP], Dagmara McGuinness[SUP] 1 [/SUP], Kondwani Jambo[SUP] 3 11 [/SUP], Michael Haley[SUP] 20 [/SUP], Benjamin Kumwenda[SUP] 9 [/SUP], Massimo Palmarini[SUP] 5 [/SUP], Donna M Denno[SUP] 13 [/SUP], Wieger Voskuijl[SUP] 8 9 21 [/SUP], Steve Bvuobvuo Kamiza[SUP] 9 [/SUP], Kayla G Barnes[SUP] 3 22 23 24 25 [/SUP], Kevin Couper[SUP] 20 [/SUP], Matthias Marti[SUP] 26 27 [/SUP], Thomas D Otto[SUP] 28 [/SUP], Christopher A Moxon[SUP] 29 30 31 32 33 [/SUP]
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.