摘要：SummaryUnderstanding 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.FCGR3Bconsistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and inCCL3L1-upregulated cells from nasopharyngeal swabs.In silicofindings were validated by upregulation ofFCGR3Bin nasopharyngeal swabs of severe ICU COVID-19 cases, particularly in older patients and those with comorbidities. Additional lines of evidence from transcriptomic data andin vivoof severe COVID-19 cases suggest thatFCGR3Bmay 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.Graphical abstractDisplay OmittedHighlights•Association of MoAM subtype with severe COVID-19 cases presented with comorbidities•UpregulatedFCGR3BinCCL3L1positive MoAM cells in severe COVID-19 cases•UpregulatedFCGR3Bwithin MoAM subtype as a potential marker for COVID-19 severityMolecular biology; Transcriptomics; Virology
