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Compartmental immunophenotyping in COVID-19 ARDS: a case series

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Ronit, Andreas ; Berg, Ronan M G ; Bay, Jakob T ; Haugaard, Anna K ; Ahlström, Magnus G ; Burgdorf, Kristoffer S ; Ullum, Henrik ; Rørvig, Sara B ; Tjelle, Klaus ; Foss, Nicolai B ; Benfield, Thomas ; Marquart, Hanne Vibeke ; Plovsing, Ronni R. / Compartmental immunophenotyping in COVID-19 ARDS : a case series. I: The Journal of allergy and clinical immunology. 2021 ; Bind 147, Nr. 1. s. 81-91.

Bibtex

@article{b8a72013a7f547dabede0ab53a08f627,
title = "Compartmental immunophenotyping in COVID-19 ARDS: a case series",
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 H17 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 = "Adult, Aged, CD8-Positive T-Lymphocytes/immunology, COVID-19/immunology, Cross-Sectional Studies, Cytokines/immunology, Female, Humans, Immunophenotyping, Lung/immunology, Lymphopenia/immunology, Male, Middle Aged, Respiratory Distress Syndrome/immunology, SARS-CoV-2/immunology, Th17 Cells/immunology, Acute respiratory distress syndrome, COVID-19, cytokines, flow cytometry, bronchoalveolar lavage",
author = "Andreas Ronit and Berg, {Ronan M G} and Bay, {Jakob T} and Haugaard, {Anna K} and Ahlstr{\"o}m, {Magnus G} and Burgdorf, {Kristoffer S} and Henrik Ullum and R{\o}rvig, {Sara B} and Klaus Tjelle and Foss, {Nicolai B} and Thomas Benfield and Marquart, {Hanne Vibeke} and Plovsing, {Ronni R}",
note = "Copyright {\textcopyright} 2020 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2021",
month = jan,
doi = "10.1016/j.jaci.2020.09.009",
language = "English",
volume = "147",
pages = "81--91",
journal = "The Journal of allergy and clinical immunology",
issn = "0091-6749",
publisher = "Mosby, Inc",
number = "1",

}

RIS

TY - JOUR

T1 - Compartmental immunophenotyping in COVID-19 ARDS

T2 - a case series

AU - Ronit, Andreas

AU - Berg, Ronan M G

AU - Bay, Jakob T

AU - Haugaard, Anna K

AU - Ahlström, Magnus G

AU - Burgdorf, Kristoffer S

AU - Ullum, Henrik

AU - Rørvig, Sara B

AU - Tjelle, Klaus

AU - Foss, Nicolai B

AU - Benfield, Thomas

AU - Marquart, Hanne Vibeke

AU - Plovsing, Ronni R

N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2021/1

Y1 - 2021/1

N2 - 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 H17 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.

AB - 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 H17 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.

KW - Adult

KW - Aged

KW - CD8-Positive T-Lymphocytes/immunology

KW - COVID-19/immunology

KW - Cross-Sectional Studies

KW - Cytokines/immunology

KW - Female

KW - Humans

KW - Immunophenotyping

KW - Lung/immunology

KW - Lymphopenia/immunology

KW - Male

KW - Middle Aged

KW - Respiratory Distress Syndrome/immunology

KW - SARS-CoV-2/immunology

KW - Th17 Cells/immunology

KW - Acute respiratory distress syndrome

KW - COVID-19

KW - cytokines

KW - flow cytometry

KW - bronchoalveolar lavage

UR - http://www.scopus.com/inward/record.url?scp=85094108829&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2020.09.009

DO - 10.1016/j.jaci.2020.09.009

M3 - Journal article

C2 - 32979342

VL - 147

SP - 81

EP - 91

JO - The Journal of allergy and clinical immunology

JF - The Journal of allergy and clinical immunology

SN - 0091-6749

IS - 1

ER -

ID: 60934399