Acute respiratory distress syndrome (ARDS) is a life-threatening syndrome, constituted by respiratory failure and diffuse alveolar damage that results from dysregulated local and systemic immune activation, causing pulmonary vascular, parenchymal, and alveolar damage. SARS-CoV-2 infection has become the dominant cause of ARDS worldwide, and emerging evidence implicates neutrophils and their cytotoxic arsenal of effector functions as central drivers of immune-mediated lung injury in COVID-19 ARDS. However, key outstanding questions are whether COVID-19 drives a unique program of neutrophil activation or effector functions that contribute to the severe pathogenesis of this pandemic illness and whether this unique neutrophil response can be targeted to attenuate disease. Using a combination of high-dimensional single-cell analysis and ex vivo functional assays of neutrophils from patients with COVID-19 ARDS, compared with those with non-COVID ARDS (caused by bacterial pneumonia), we identified a functionally distinct landscape of neutrophil activation in COVID-19 ARDS that was intrinsically programmed during SARS-CoV-2 infection. Furthermore, neutrophils in COVID-19 ARDS were functionally primed to produce high amounts of neutrophil extracellular traps. Surprisingly, this unique pathological program of neutrophil priming escaped conventional therapy with dexamethasone, thereby revealing a promising target for adjunctive immunotherapy in severe COVID-19.
【저자키워드】 Neutrophils, immunology, Innate immunity, Infectious disease, 【초록키워드】 COVID-19, Dexamethasone, ARDS, pandemic, therapy, Pathogenesis, Respiratory failure, severe COVID-19, Pneumonia, Neutrophil extracellular traps, Immunotherapy, SARS-COV-2 infection, neutrophil, Local, Lung injury, immune activation, Diffuse alveolar damage, disease, single-cell, function, Immune-mediated, Bacterial, Evidence, Combination, Analysis, distress, neutrophil activation, alveolar damage, Ex vivo, Vascular, syndrome, life-threatening, priming, dominant, neutrophil response, caused, functional, question, contribute, unique, dysregulated, intrinsically, attenuate, driver, escaped, parenchymal, patients with COVID-19, 【제목키워드】 therapy, severe COVID-19, neutrophil, reveal,