Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical
Nasna Nassir1, Richa Tambi1, Asma Bankapur1
1College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE.
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.
Insights
Researchers identified a specific monocyte-derived alveolar macrophage (MoAM) subtype linked to severe COVID-19. The gene FCGR3B marks these cells, suggesting it could be a biomarker for disease severity and a therapeutic target.
Area of Science:
- Immunology
- Virology
- Genomics
Background:
- Host cell heterogeneity influences disease mechanisms.
- COVID-19 pathogenesis involves complex cellular responses.
Purpose of the Study:
- To identify specific cell subtypes associated with severe COVID-19.
- To investigate the role of monocyte-derived alveolar macrophages (MoAMs) in critical COVID-19 cases.
- To explore potential biomarkers for COVID-19 severity.
Main Methods:
- Large-scale single-cell transcriptomics analysis of patient tissue specimens.
- Comparison of samples from critical COVID-19 patients and healthy controls.
- In silico analysis and in vivo validation of gene expression patterns.
Main Results:
- A distinct MoAM subtype was identified, with upregulated genes linked to severe COVID-19 comorbidities.
- The gene FCGR3B was consistently found to demarcate this MoAM subset in various severe COVID-19 samples.
- FCGR3B upregulation was validated in nasopharyngeal swabs of severe COVID-19 patients, especially older individuals and those with comorbidities.
Conclusions:
- FCGR3B may identify a specific MoAM subtype in severe COVID-19 patients.
- This MoAM subtype presents a potential novel biomarker for COVID-19 screening and prognosis.
- FCGR3B could represent a future therapeutic target for severe COVID-19.
