Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19

Nasna Nassir; Richa Tambi; Asma Bankapur; Saba Al Heialy; Noushad Karuvantevida; Hamda Hassan Khansaheb; Binte Zehra; Ghausia Begum; Reem Abdel Hameid; Awab Ahmed; Zulfa Deesi; Abdulmajeed Alkhajeh; K. M.Furkan Uddin; Hosneara Akter; Seyed Ali Safizadeh Shabestari; Omar Almidani; Amirul Islam; Mellissa Gaudet; Richard Kumaran Kandasamy; Tom Loney; Ahmad Abou Tayoun; Norbert Nowotny; Marc Woodbury-Smith; Proton Rahman; Wolfgang M. Kuebler; Mahmood Yaseen Hachim; Jean Laurent Casanova; Bakhrom K. Berdiev; Alawi Alsheikh-Ali; Mohammed Uddin

doi:10.1016/j.isci.2021.103030

Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19

Nasna Nassir, Richa Tambi, Asma Bankapur, Saba Al Heialy, Noushad Karuvantevida, Hamda Hassan Khansaheb, Binte Zehra, Ghausia Begum, Reem Abdel Hameid, Awab Ahmed, Zulfa Deesi, Abdulmajeed Alkhajeh, K. M.Furkan Uddin, Hosneara Akter, Seyed Ali Safizadeh Shabestari, Omar Almidani, Amirul Islam, Mellissa Gaudet, Richard Kumaran Kandasamy, Tom LoneyAhmad Abou Tayoun, Norbert Nowotny, Marc Woodbury-Smith, Proton Rahman, Wolfgang M. Kuebler, Mahmood Yaseen Hachim, Jean Laurent Casanova, Bakhrom K. Berdiev, Alawi Alsheikh-Ali, Mohammed Uddin^*

^*Corresponding author for this work

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

9 Citations (Scopus)

Abstract

Understanding host cell heterogeneity is critical for unraveling disease mechanism. Utilizing large-scale single-cell transcriptomics, we analyzed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAMs) where genes associated with severe COVID-19 comorbidities are significantly upregulated in bronchoalveolar lavage fluid of critical cases. FCGR3B consistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and in CCL3L1-upregulated cells from nasopharyngeal swabs. In silico findings were validated by upregulation of FCGR3B in nasopharyngeal swabs of severe ICU COVID-19 cases, particularly in older patients and those with comorbidities. Additional lines of evidence from transcriptomic data and in vivo of severe COVID-19 cases suggest that FCGR3B may identify a specific subtype of MoAM in patients with severe COVID-19 that may present a novel biomarker for screening and prognosis, as well as a potential therapeutic target.

Original language	English
Article number	103030
Journal	iScience
Volume	24
Issue number	9
DOIs	https://doi.org/10.1016/j.isci.2021.103030
Publication status	Published - Sept 24 2021
Externally published	Yes

Keywords

molecular biology
transcriptomics
virology

ASJC Scopus subject areas

General

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10.1016/j.isci.2021.103030

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Nassir, N., Tambi, R., Bankapur, A., Al Heialy, S., Karuvantevida, N., Khansaheb, H. H., Zehra, B., Begum, G., Hameid, R. A., Ahmed, A., Deesi, Z., Alkhajeh, A., Uddin, K. M. F., Akter, H., Safizadeh Shabestari, S. A., Almidani, O., Islam, A., Gaudet, M., Kandasamy, R. K., ... Uddin, M. (2021). Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19. iScience, 24(9), Article 103030. https://doi.org/10.1016/j.isci.2021.103030

Nassir, N, Tambi, R, Bankapur, A, Al Heialy, S, Karuvantevida, N, Khansaheb, HH, Zehra, B, Begum, G, Hameid, RA, Ahmed, A, Deesi, Z, Alkhajeh, A, Uddin, KMF, Akter, H, Safizadeh Shabestari, SA, Almidani, O, Islam, A, Gaudet, M, Kandasamy, RK, Loney, T, Tayoun, AA, Nowotny, N, Woodbury-Smith, M, Rahman, P, Kuebler, WM, Yaseen Hachim, M, Casanova, JL, Berdiev, BK, Alsheikh-Ali, A & Uddin, M 2021, 'Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19', iScience, vol. 24, no. 9, 103030. https://doi.org/10.1016/j.isci.2021.103030

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title = "Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19",

abstract = "Understanding host cell heterogeneity is critical for unraveling disease mechanism. Utilizing large-scale single-cell transcriptomics, we analyzed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAMs) where genes associated with severe COVID-19 comorbidities are significantly upregulated in bronchoalveolar lavage fluid of critical cases. FCGR3B consistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and in CCL3L1-upregulated cells from nasopharyngeal swabs. In silico findings were validated by upregulation of FCGR3B in nasopharyngeal swabs of severe ICU COVID-19 cases, particularly in older patients and those with comorbidities. Additional lines of evidence from transcriptomic data and in vivo of severe COVID-19 cases suggest that FCGR3B may identify a specific subtype of MoAM in patients with severe COVID-19 that may present a novel biomarker for screening and prognosis, as well as a potential therapeutic target.",

keywords = "molecular biology, transcriptomics, virology",

author = "Nasna Nassir and Richa Tambi and Asma Bankapur and {Al Heialy}, Saba and Noushad Karuvantevida and Khansaheb, {Hamda Hassan} and Binte Zehra and Ghausia Begum and Hameid, {Reem Abdel} and Awab Ahmed and Zulfa Deesi and Abdulmajeed Alkhajeh and Uddin, {K. M.Furkan} and Hosneara Akter and {Safizadeh Shabestari}, {Seyed Ali} and Omar Almidani and Amirul Islam and Mellissa Gaudet and Kandasamy, {Richard Kumaran} and Tom Loney and Tayoun, {Ahmad Abou} and Norbert Nowotny and Marc Woodbury-Smith and Proton Rahman and Kuebler, {Wolfgang M.} and {Yaseen Hachim}, Mahmood and Casanova, {Jean Laurent} and Berdiev, {Bakhrom K.} and Alawi Alsheikh-Ali and Mohammed Uddin",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = sep,

day = "24",

doi = "10.1016/j.isci.2021.103030",

language = "English",

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AU - Nassir, Nasna

AU - Tambi, Richa

AU - Bankapur, Asma

AU - Al Heialy, Saba

AU - Karuvantevida, Noushad

AU - Khansaheb, Hamda Hassan

AU - Zehra, Binte

AU - Begum, Ghausia

AU - Hameid, Reem Abdel

AU - Ahmed, Awab

AU - Deesi, Zulfa

AU - Alkhajeh, Abdulmajeed

AU - Uddin, K. M.Furkan

AU - Akter, Hosneara

AU - Safizadeh Shabestari, Seyed Ali

AU - Almidani, Omar

AU - Islam, Amirul

AU - Gaudet, Mellissa

AU - Kandasamy, Richard Kumaran

AU - Loney, Tom

AU - Tayoun, Ahmad Abou

AU - Nowotny, Norbert

AU - Woodbury-Smith, Marc

AU - Rahman, Proton

AU - Kuebler, Wolfgang M.

AU - Yaseen Hachim, Mahmood

AU - Casanova, Jean Laurent

AU - Berdiev, Bakhrom K.

AU - Alsheikh-Ali, Alawi

AU - Uddin, Mohammed

PY - 2021/9/24

Y1 - 2021/9/24

N2 - Understanding host cell heterogeneity is critical for unraveling disease mechanism. Utilizing large-scale single-cell transcriptomics, we analyzed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAMs) where genes associated with severe COVID-19 comorbidities are significantly upregulated in bronchoalveolar lavage fluid of critical cases. FCGR3B consistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and in CCL3L1-upregulated cells from nasopharyngeal swabs. In silico findings were validated by upregulation of FCGR3B in nasopharyngeal swabs of severe ICU COVID-19 cases, particularly in older patients and those with comorbidities. Additional lines of evidence from transcriptomic data and in vivo of severe COVID-19 cases suggest that FCGR3B may identify a specific subtype of MoAM in patients with severe COVID-19 that may present a novel biomarker for screening and prognosis, as well as a potential therapeutic target.

AB - Understanding host cell heterogeneity is critical for unraveling disease mechanism. Utilizing large-scale single-cell transcriptomics, we analyzed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAMs) where genes associated with severe COVID-19 comorbidities are significantly upregulated in bronchoalveolar lavage fluid of critical cases. FCGR3B consistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and in CCL3L1-upregulated cells from nasopharyngeal swabs. In silico findings were validated by upregulation of FCGR3B in nasopharyngeal swabs of severe ICU COVID-19 cases, particularly in older patients and those with comorbidities. Additional lines of evidence from transcriptomic data and in vivo of severe COVID-19 cases suggest that FCGR3B may identify a specific subtype of MoAM in patients with severe COVID-19 that may present a novel biomarker for screening and prognosis, as well as a potential therapeutic target.

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KW - transcriptomics

KW - virology

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DO - 10.1016/j.isci.2021.103030

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SN - 2589-0042

VL - 24

JO - iScience

JF - iScience

IS - 9

M1 - 103030

ER -

Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19

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