Abstract
Background: Severe immunopathology may drive the deleterious manifestations that are observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood.
Objective: Our aim was to phenotype leukocyte subpopulations and the cytokine milieu in the lungs and blood of critically ill patients with COVID-19 acute respiratory distress syndrome (ARDS).
Methods: We consecutively included patients less than 72 hours after intubation following informed consent from their next of kin. Bronchoalveolar lavage fluid was evaluated by microscopy; bronchoalveolar lavage fluid and blood were assessed by 10-color flow cytometry and a multiplex cytokine panel.
Results: Four mechanically ventilated patients (aged 40-75 years) with moderate-to-severe COVID-19 ARDS were included. Immature neutrophils dominated in both blood and lungs, whereas CD4 and CD8 T-cell lymphopenia was observed in the 2 compartments. However, regulatory T cells and T H 17 cells were found in higher fractions in the lung. Lung CD4 and CD8 T cells and macrophages expressed an even higher upregulation of activation markers than in blood. A wide range of cytokines were expressed at high levels both in the blood and in the lungs, most notably, IL-1RA, IL-6, IL-8, IP-10, and monocyte chemoattactant protein-1, consistent with hyperinflammation.
Conclusion: COVID-19 ARDS exhibits a distinct immunologic profile in the lungs, with a depleted and exhausted CD4 and CD8 T-cell population that resides within a heavily hyperinflammatory milieu.
Keywords: Acute respiratory distress syndrome; COVID-19; bronchoalveolar lavage; cytokines; flow cytometry.
【저자키워드】 COVID-19, Cytokines, acute respiratory distress syndrome, flow cytometry, Bronchoalveolar lavage, 【초록키워드】 coronavirus disease, Macrophage, ARDS, IL-6, neutrophil, IP-10, lung, intubation, cytokine, immunopathology, CD4, flow cytometry, monocyte, lymphopenia, Regulatory T cell, Bronchoalveolar lavage fluid, hyperinflammation, Lungs, Patient, IL-8, phenotype, multiplex, Blood, acute respiratory distress, marker, distress, Deleterious, CD8 T cell, manifestation, leukocyte, Critically ill patient, Activation, moderate-to-severe COVID-19, syndrome, Stage, IL-1ra, upregulation, fraction, subpopulation, Hyperinflammatory, Cell, bronchoalveolar, evaluated, less, expressed, were expressed, exhibit, CD8 T-cell, mechanically ventilated patient, were assessed, with COVID-19, 【제목키워드】 case sery,