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

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

doi:10.1038/s41591-024-03354-3

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

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

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Article number	13850
Pages (from-to)	3765-3777
Number of pages	42
Journal	Nature Medicine
Volume	30
Issue number	12
Early online date	20 Nov 2024
DOIs	https://doi.org/10.1038/s41591-024-03354-3
Publication status	Published - Dec 2024

Keywords / Materials (for Non-textual outputs)

Adult
COVID-19/immunology
Female
Humans
Interferon-gamma/metabolism
Lung/pathology
Macrophages/immunology
Malawi/epidemiology
Male
Middle Aged
Monocytes/immunology
SARS-CoV-2
Single-Cell Analysis
Transcriptome

Access to Document

10.1038/s41591-024-03354-3

s41591-024-03354-3Final published version, 21.7 MBLicence: Creative Commons: Attribution (CC-BY)

Cite this

Nyirenda, J., Hardy, O. M., Silva Filho, J. D., Herder, V., Attipa, C., Ndovi, C., Siwombo, M., Namalima, T. R., Suwedi, L., Ilia, G., Nyasulu, W., Ngulube, T., Nyirenda, D., Mvaya, L., Chasweka, D., Eneya, C., Makwinja, C., Phiri, C., Ziwoya, F., ... Moxon, C. A. (2024). Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population. Nature Medicine, 30(12), 3765-3777. Article 13850. https://doi.org/10.1038/s41591-024-03354-3

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

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.",

keywords = "Adult, COVID-19/immunology, Female, Humans, Interferon-gamma/metabolism, Lung/pathology, Macrophages/immunology, Malawi/epidemiology, Male, Middle Aged, Monocytes/immunology, SARS-CoV-2, Single-Cell Analysis, Transcriptome",

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

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doi = "10.1038/s41591-024-03354-3",

language = "English",

volume = "30",

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journal = "Nature Medicine",

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Nyirenda, J, Hardy, OM, Silva Filho, JD, Herder, V, Attipa, C, Ndovi, C, Siwombo, M, Namalima, TR, Suwedi, L, Ilia, G, Nyasulu, W, Ngulube, T, Nyirenda, D, Mvaya, L, Chasweka, D, Eneya, C, Makwinja, C, Phiri, C, Ziwoya, F, Tembo, A, Makwangwala, K, Khoswe, S, Banda, P, Morton, B, Hilton, O, Lawrence, S, Dos Reis, MF, Melo, GC, de Lacerda, MVG, Trindade Maranhão Costa, F, Monteiro, WM, Ferreira, LCDL, Johnson, C, McGuinness, D, Jambo, K, Haley, M, Kumwenda, B, Palmarini, M, Denno, DM, Voskuijl, W, Kamiza, SB, Barnes, KG, Couper, K, Marti, M, Otto, TD & Moxon, CA 2024, 'Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population', Nature Medicine, vol. 30, no. 12, 13850, pp. 3765-3777. https://doi.org/10.1038/s41591-024-03354-3

TY - JOUR

T1 - Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population

AU - Nyirenda, James

AU - Hardy, Olympia M

AU - Silva Filho, João Da

AU - Herder, Vanessa

AU - Attipa, Charalampos

AU - Ndovi, Charles

AU - Siwombo, Memory

AU - Namalima, Takondwa Rex

AU - Suwedi, Leticia

AU - Ilia, Georgios

AU - Nyasulu, Watipenge

AU - Ngulube, Thokozile

AU - Nyirenda, Deborah

AU - Mvaya, Leonard

AU - Chasweka, Dennis

AU - Eneya, Chisomo

AU - Makwinja, Chikondi

AU - Phiri, Chisomo

AU - Ziwoya, Frank

AU - Tembo, Abel

AU - Makwangwala, Kingsley

AU - Khoswe, Stanley

AU - Banda, Peter

AU - Morton, Ben

AU - Hilton, Orla

AU - Lawrence, Sarah

AU - Dos Reis, Monique Freire

AU - Melo, Gisely Cardoso

AU - de Lacerda, Marcus Vinicius Guimaraes

AU - Trindade Maranhão Costa, Fabio

AU - Monteiro, Wuelton Marcelo

AU - Ferreira, Luiz Carlos de Lima

AU - Johnson, Carla

AU - McGuinness, Dagmara

AU - Jambo, Kondwani

AU - Haley, Michael

AU - Kumwenda, Benjamin

AU - Palmarini, Massimo

AU - Denno, Donna M

AU - Voskuijl, Wieger

AU - Kamiza, Steve Bvuobvuo

AU - Barnes, Kayla G

AU - Couper, Kevin

AU - Marti, Matthias

AU - Otto, Thomas D

AU - Moxon, Christopher A

PY - 2024/12

Y1 - 2024/12

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.

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.

KW - Adult

KW - COVID-19/immunology

KW - Female

KW - Humans

KW - Interferon-gamma/metabolism

KW - Lung/pathology

KW - Macrophages/immunology

KW - Malawi/epidemiology

KW - Male

KW - Middle Aged

KW - Monocytes/immunology

KW - SARS-CoV-2

KW - Single-Cell Analysis

KW - Transcriptome

U2 - 10.1038/s41591-024-03354-3

DO - 10.1038/s41591-024-03354-3

M3 - Article

C2 - 39567718

SN - 1078-8956

VL - 30

SP - 3765

EP - 3777

JO - Nature Medicine

JF - Nature Medicine

IS - 12

M1 - 13850

ER -

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

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Keywords / Materials (for Non-textual outputs)

Access to Document

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