The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a “cytokine storm,” we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS. Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be potentially modulated by dexamethasone.
【저자키워드】 SARS-CoV-2, Translational research, viral infection, Molecular medicine, Acute inflammation, 【초록키워드】 COVID-19, Dexamethasone, Inflammation, ARDS, Gene Expression, Immunity, mechanical ventilation, host response, Viral pneumonia, Patient, Control, Mild, expression, ISG, host gene expression, acute respiratory distress, Signaling, Analysis, Lower respiratory tract, granulocyte, Critically ill patient, colony stimulating factor, causes, SARS-CoV-2 viral load, syndrome, interferon-stimulated gene, PTEN, immunological, feature, etiologies, transcriptional, observé, predicted, identify, elevated, reduced, characterized, modulate, cause, tracheal, reveal, dysregulated, modulated, expression of gene, candidate drug, lower airway, patients with COVID-19, proinflammatory gene, tracheal aspirate, 【제목키워드】 COVID-19, ARDS, RNA sequencing, immunological, feature, identify,