Compartmental immunophenotyping in COVID-19 ARDS: A case series
Authors: Andreas Ronit, Ronan M.G. Berg, Jakob T. Bay, Anna K. Haugaard, Magnus G. Ahlström, Kristoffer S. Burgdorf, Henrik Ullum, Sara B. Rørvig, Klaus Tjelle, Nicolai B. Foss, Thomas Benfield, Hanne Vibeke Marquart, Ronni R. Plovsing
Journal: Journal of Allergy and Clinical Immunology (2020)

BackgroundSevere immunopathology may drive the deleterious manifestations that are observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood.ObjectiveOur 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).MethodsWe 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.ResultsFour 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 TH17 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.ConclusionCOVID-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. Severe immunopathology may drive the deleterious manifestations that are observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood. 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). 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. 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 TH17 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. 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.