TY - JOUR
T1 - Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19
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
N1 - Funding Information:
We thank all the participatory severe/critical COVID-19 individuals in our cohort. We also thank John Tsang, Can Liu Andrew J Martins for sharing data and from COVID Human Genome Effort∗, Helen Su, Laurent Abel, Aurélie Cobat for critically commenting on the manuscript. This research was funded by including College of Medicine at Mohammed Bin Rashid University of Medicine and Health Sciences , grant number MBRU-CM-RG2018-04 , MBRU-CM-RG2018-05 , MBRU-CM-RG2020-02 , and MBRU-CM-RG2020-12 , Sandooq Al Watan Research & Development , grant number SWARD-F2018-002 , AlMahmeed Collaborative Research Awards ( ALM1801 , ALM20-0074 ) and Al Jalila Foundation , grant number AJF201763 . Dr. Nasna Nassir and Dr. Richa Tambi were supported by the MBRU Post-Doctoral Fellow Award ( MBRU-PD-2020-04 ).
Publisher Copyright:
© 2021 The Authors
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.
KW - molecular biology
KW - transcriptomics
KW - virology
UR - http://www.scopus.com/inward/record.url?scp=85122825334&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85122825334&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2021.103030
DO - 10.1016/j.isci.2021.103030
M3 - Article
C2 - 34458692
AN - SCOPUS:85122825334
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 9
M1 - 103030
ER -