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

Author(s):Show less -

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

• Document type: Journal article
• Source: Nature Medicine; v. N/A, p. 42-pg., 2024-11-20.

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-gamma 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. A single-cell study integrating data from lung tissues from patients with fatal COVID-19 from Malawi, the United States and Europe identifies shared and distinct immune and inflammatory mechanisms of response. (AU)

• FAPESP's process: 16/12855-9 - Mechanism of action of lipoxin in the protection against experimental cerebral malaria
• Grantee: João Luiz da Silva Filho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/05369-6 - Artificial inteligence driven drug repositioning strategy for COVID-19
• Grantee: Fabio Trindade Maranhão Costa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/18611-7 - Development of new tools for search and validation of molecular targets for therapy against Plasmodium vivax
• Grantee: Fabio Trindade Maranhão Costa
• Support Opportunities: Research Projects - Thematic Grants