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Compartmental immunophenotyping in COVID-19 ARDS: A case series - 09/01/21

Doi : 10.1016/j.jaci.2020.09.009 
Andreas Ronit, MD, PhD a, Ronan M.G. Berg, MD, PhD b, c, d, Jakob T. Bay, MD, PhD e, Anna K. Haugaard, MD e, Magnus G. Ahlström, MD, PhD f, Kristoffer S. Burgdorf, MSc, PhD e, Henrik Ullum, MD, PhD e, Sara B. Rørvig, MD, PhD g, Klaus Tjelle, MD h, Nicolai B. Foss, MD, DMSc h, Thomas Benfield, MD, DMSc a, Hanne Vibeke Marquart, MD, PhD e, , Ronni R. Plovsing, MD, PhD h,
a Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark 
b Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark 
c Department of Clinical Physiology, Nuclear Medicine and PET and Centre for Physical Activity Research, University of Copenhagen, Copenhagen, Denmark 
d Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontypridd, United Kingdom 
e Department of Clinical Immunology, University of Copenhagen, Copenhagen, Denmark 
f Department of Clinical Microbiology, University of Copenhagen, Copenhagen, Denmark 
g Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 
h Department of Anesthesiology and Intensive Care, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark 

Corresponding author: Ronni R. Plovsing, MD, PhD, Department of Anesthesiology and Intensive Care, Hvidovre Hospital, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark.Department of Anesthesiology and Intensive CareHvidovre HospitalKettegaard Allé 30HvidovreDK-2650Denmark

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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.

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Graphical abstract




Il testo completo di questo articolo è disponibile in PDF.

Key words : Acute respiratory distress syndrome, bronchoalveolar lavage, COVID-19, cytokines, flow cytometry

Abbreviations used : ARDS, BALF, COVID-19, CTLA-4, ICU, IP-10, MCP-1, PD1, RTE, SARS-CoV-2, Treg


Mappa


 This study was supported by the Lundbeck Foundation (grant R349-2020-540).
 Disclosure of potential conflict of interest: T. Benfield reports personal fees and nonfinancial support from Bristol-Myers Squibb and Gilead. The rest of the authors declare that they have no relevant conflicts of interest.


© 2020  Pubblicato da Elsevier Masson SAS.
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