Summary 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. Graphical abstract Highlights • Association of MoAM subtype with severe COVID-19 cases presented with comorbidities • Upregulated FCGR3B in CCL3L1 positive MoAM cells in severe COVID-19 cases • Upregulated FCGR3B within MoAM subtype as a potential marker for COVID-19 severity Molecular biology; Transcriptomics; Virology
【저자키워드】 Virology, Molecular biology, transcriptomics, 【초록키워드】 COVID-19, Biomarker, severe COVID-19, Prognosis, Pneumonia, COVID-19 severity, Comorbidity, heterogeneity, ICU, Nasopharyngeal swab, older patient, Bronchoalveolar lavage fluid, nasopharyngeal swabs, Patient, understanding, transcriptomic data, disease, Critical, mechanism, single-cell, alveolar macrophage, marker, Evidence, COVID-19 cases, critical cases, host cell, Abstract, life-threatening, upregulation, healthy controls, positive, potential therapeutic target, Cell, FCGR3B, analyzed, identify, significantly, upregulated, subset, CCL3L1, multiple tissue specimen, severe COVID-19 cohort, those with comorbidities, 【제목키워드】 COVID-19, Transcriptome, Patient, Critical, alveolar macrophage, FCGR3B, identify, upregulated,