TY - JOUR
KW - Immunopathogenesis
KW - infection
KW - Single-cell imaging
KW - Viral infection
AU - James Nyirenda
AU - Olympia M. Hardy
AU - João Da Silva Filho
AU - Vanessa Herder
AU - Charalampos Attipa
AU - Charles Ndovi
AU - Memory Siwombo
AU - Takondwa Rex Namalima
AU - Leticia Suwedi
AU - Georgios Ilia
AU - Watipenge Nyasulu
AU - Thokozile Ngulube
AU - Deborah Nyirenda
AU - Leonard Mvaya
AU - Joseph Phiri
AU - Dennis Chasweka
AU - Chisomo Eneya
AU - Chikondi Makwinja
AU - Chisomo Phiri
AU - Frank Ziwoya
AU - Abel Tembo
AU - Kingsley Makwangwala
AU - Stanley Khoswe
AU - Peter Banda
AU - Ben Morton
AU - Orla Hilton
AU - Sarah Lawrence
AU - Monique Freire dos Reis
AU - Gisely Cardoso Melo
AU - Marcus Vinicius Guimaraes de Lacerda
AU - Fabio Trindade Maranhão Costa
AU - Wuelton Marcelo Monteiro
AU - Luiz Carlos de Lima Ferreira
AU - Carla Johnson
AU - Dagmara McGuinness
AU - Kondwani Jambo
AU - Michael Haley
AU - Benjamin Kumwenda
AU - Massimo Palmarini
AU - Donna M. Denno
AU - Wieger Voskuijl
AU - Steve Bvuobvuo Kamiza
AU - Kayla G. Barnes
AU - Kevin Couper
AU - Matthias Marti
AU - Thomas D. Otto
AU - Christopher A. Moxon
AB - 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.
BT - Nature Medicine
DA - 2024-11-20
DO - 10.1038/s41591-024-03354-3
LA - en
N2 - 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.
PY - 2024
SP - 1
EP - 13
T2 - Nature Medicine
TI - Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population
UR - https://www.nature.com/articles/s41591-024-03354-3
Y2 - 2024-11-26
SN - 1546-170X
ER -