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 journalArticlepeer-review

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 languageEnglish
Article number103030
JournaliScience
Volume24
Issue number9
DOIs
Publication statusPublished - Sep 24 2021
Externally publishedYes

Keywords

  • molecular biology
  • transcriptomics
  • virology

ASJC Scopus subject areas

  • General

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