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. <i>FCGR3B</i> consistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and in <i>CCL3L1</i>-upregulated cells from nasopharyngeal swabs. <i>In silico</i> findings were validated by upregulation of <i>FCGR3B</i> 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 <i>in vivo</i> of severe COVID-19 cases suggest that <i>FCGR3B</i> 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.