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https://www.arca.fiocruz.br/handle/icict/69173
SPATIALLY RESOLVED SINGLE-CELL ATLAS UNVEILS A DISTINCT CELLULAR SIGNATURE OF FATAL LUNG COVID-19 IN A MALAWIAN POPULATION
Author
Nyirenda, James
Hardy, Olympia M.
Silva Filho, João 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
Reis, Monique Freire dos
Melo, Gisely Cardoso
Lacerda, Marcus Vinicius Guimaraes de
Costa, Fabio Trindade Maranhão
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
Matthias Marti, Matthias Marti
Otto, Thomas D.
Moxon, Christopher A.
Hardy, Olympia M.
Silva Filho, João 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
Reis, Monique Freire dos
Melo, Gisely Cardoso
Lacerda, Marcus Vinicius Guimaraes de
Costa, Fabio Trindade Maranhão
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
Matthias Marti, Matthias Marti
Otto, Thomas D.
Moxon, Christopher A.
Affilliation
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
Queen Elizabeth Central Hospital. Blantyre, Malawi.
Queen Elizabeth Central Hospital. Blantyre, Malawi.
Malawi-Liverpool-Wellcome Programme, Kamuzu University of Health Sciences. Blantyre, Malawi.
MRC-University of Glasgow Centre for Virus Research. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
Malawi-Liverpool-Wellcome Programme, Kamuzu University of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Malawi-Liverpool-Wellcome Programme, Kamuzu University of Health Sciences. Blantyre, Malawi.
Department of Infectious Diseases, Imperial College London. London, UK.
Department of Global Health and Pediatrics, University of Washington. Seattle, WA, USA.
Oncology Control Centre of Amazonas State (FCECON). Manaus, AM, Brazil.
Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Leônidas & Maria Deane. Manaus, AM, Brasil.
Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
Malawi-Liverpool-Wellcome Programme, Kamuzu University of Health Sciences. Blantyre, Malawi.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
Queen Elizabeth Central Hospital. Blantyre, Malawi.
Queen Elizabeth Central Hospital. Blantyre, Malawi.
Malawi-Liverpool-Wellcome Programme, Kamuzu University of Health Sciences. Blantyre, Malawi.
MRC-University of Glasgow Centre for Virus Research. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
Malawi-Liverpool-Wellcome Programme, Kamuzu University of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Kamuzu University of Science of Health Sciences. Blantyre, Malawi.
Malawi-Liverpool-Wellcome Programme, Kamuzu University of Health Sciences. Blantyre, Malawi.
Department of Infectious Diseases, Imperial College London. London, UK.
Department of Global Health and Pediatrics, University of Washington. Seattle, WA, USA.
Oncology Control Centre of Amazonas State (FCECON). Manaus, AM, Brazil.
Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Leônidas & Maria Deane. Manaus, AM, Brasil.
Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
Malawi-Liverpool-Wellcome Programme, Kamuzu University of Health Sciences. Blantyre, Malawi.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow. Glasgow, UK.
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.
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