How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we perform single-cell deep-immune profiling of bronchoalveolar lavage (BAL) samples from 5 patients with mild and 26 with critical COVID-19 in comparison to BALs from non-COVID-19 pneumonia and normal lung. We use pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them. In mild COVID-19, CD8 + resident-memory (T RM ) and CD4 + T-helper-17 (T H17 ) cells undergo active (presumably antigen-driven) expansion towards the end of the trajectory, and are characterized by good effector functions, while in critical COVID-19 they remain more naïve. Vice versa, CD4 + T-cells with T-helper-1 characteristics (T H1 -like) and CD8 + T-cells expressing exhaustion markers (T EX -like) are enriched halfway their trajectories in mild COVID-19, where they also exhibit good effector functions, while in critical COVID-19 they show evidence of inflammation-associated stress at the end of their trajectories. Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19, while alveolar macrophages, otherwise characterized by anti-inflammatory and antigen-presenting characteristics, are depleted. In critical COVID-19, monocytes contribute to an ATP-purinergic signaling-inflammasome footprint that could enable COVID-19 associated fibrosis and worsen disease-severity. Finally, viral RNA-tracking reveals infected lung epithelial cells, and a significant proportion of neutrophils and macrophages that are involved in viral clearance.
【저자키워드】 Innate immunity, bioinformatics, Genome-wide analysis of gene expression, 【초록키워드】 COVID-19, Macrophage, Gene Expression, adaptive, Stress, Anti-inflammatory, Pneumonia, neutrophil, lung, fibrosis, immunopathology, CD4, CD8, monocyte, BAL, Characteristics, Patient, Mild, trajectory, T-cell, change, Critical, single-cell, Lung epithelial cells, marker, Evidence, Bronchoalveolar lavage, Alveolar macrophages, Trajectories, Non-COVID-19, naïve, host immune system, functions, clearance, vice, Hyperinflammatory, Cell, involved, proportion, characterized, undergo, contribute, in viral, reveal, expressing, build, 【제목키워드】 COVID-19, adaptive, immune, Mild, Critical, single-cell, Bronchoalveolar lavage,