Compartmental immunophenotyping in COVID-19 ARDS: A case series

J Allergy Clin Immunol. 2021 Jan;147(1):81-91. doi: 10.1016/j.jaci.2020.09.009. Epub 2020 Oct 23.

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 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.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • Cross-Sectional Studies
  • Cytokines / immunology
  • Female
  • Humans
  • Immunophenotyping
  • Lung / immunology*
  • Lung / pathology
  • Lymphopenia / immunology*
  • Lymphopenia / pathology
  • Male
  • Middle Aged
  • Respiratory Distress Syndrome / immunology*
  • Respiratory Distress Syndrome / pathology
  • SARS-CoV-2 / immunology*
  • Th17 Cells / immunology*
  • Th17 Cells / pathology

Substances

  • Cytokines