Compartmental immunophenotyping in COVID-19 ARDS: a case series

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paper: Ronit, A., Berg, R. M., Bay, J. T., Haugaard, A. K., Ahlström, M. G., Burgdorf, K. S., ... & Plovsing, R. R. (2020). Compartmental immunophenotyping in COVID-19 ARDS: A case series. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2020.09.009
contributor: Ronni R. Plovsing
contributor_organization: Hvidovre Hospital, University of Copenhagen, Denmark
contributor_email: ronni.thermann.reitz.plovsing.01@regionh.dk
    • description: The cellular immune response of COVID-19 acute respiratory distress syndrome (ARDS) is dominated by immature neutrophils in both the blood and the lungs, with concomitant CD4 and CD8 T-cell lymphopenia and elevated inflammatory chemokine and cytokine levels.
    • exact_source: Figure 2; Figure 5; Figure E4; Figure E10
    • tissue: Bronchoalveolar lavage fluid (BALF); Whole blood
    • immune_exposure: COVID-19 infection
    • cohort: Adults (40-75 years)
    • comparison: Observational and cross-sectional study on severe COVID-19 infection
    • repository_id: -
    • platform: -
    • response_components: -
    • response_behavior: -
      • description: The T-cell profile in the lungs of patients with COVID-19 ARDS is substantially different from that in blood, with expression of much higher levels of activation and higher frequency of Treg cells and TH17 cells.
      • exact_source: Figure 4; Figure E3; Figure E7; Figure E8; Figure E9
      • tissue: Bronchoalveolar lavage fluid (BALF); Whole blood
      • immune_exposure: COVID-19 infection
      • cohort: Adults (40-75 years)
      • comparison: Observational and cross-sectional study on severe COVID-19 infection
      • repository_id: -
      • platform: -
      • response_components: -
      • response_behavior: -
      PMID
      cord_uid k33aeh3s
      authors
      Ronit, Andreas et al
      abstract
      BACKGROUND: Severe immunopathology may drive the deleterious manifestations observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood. OBJECTIVE: 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 <72 hours after intubation following informed consent from next of kin. Bronchoalveolar lavage fluid (BALF) was evaluated by microscopy and BALF and blood was assessed by 10-colored flow cytometry and a multiplex cytokine panel. RESULTS: Four mechanically ventilated patients (40-75 yr.) with moderate to severe COVID-19 ARDS were included. Immature neutrophils dominated in both blood and lungs, while CD4 and CD8 T cell lymphopenia were observed in the two compartments. However, T regulatory 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 blood and in the lungs, most notably IL-1RA, IL-6, IL-8, IP-10, and MCP-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. TRIAL REGISTRATION: clinicaltrials.gov/ct2/show/NCT04354584.
      status
      available
      journal
      J. allergy clin. immunol