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Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19.
Saris, Anno; Reijnders, Tom D Y; Nossent, Esther J; Schuurman, Alex R; Verhoeff, Jan; Asten, Saskia van; Bontkes, Hetty; Blok, Siebe; Duitman, Janwillem; Bogaard, Harm-Jan; Heunks, Leo; Lutter, Rene; van der Poll, Tom; Garcia Vallejo, Juan J.
  • Saris A; Center for Experimental and Molecular Medicine, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands a.saris@amsterdamumc.nl.
  • Reijnders TDY; Infectious Disease, Leiden Universitair Medisch Centrum, Leiden, The Netherlands.
  • Nossent EJ; Center for Experimental and Molecular Medicine, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.
  • Schuurman AR; Department of Pulmonary Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
  • Verhoeff J; Amsterdam Cardiovascular Sciences Research Institute, Amsterdam UMC, Amsterdam, The Netherlands.
  • Asten SV; Center for Experimental and Molecular Medicine, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.
  • Bontkes H; Department of Molecular Cell Biology & Immunology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
  • Blok S; Amsterdam institute for infection and immunity, Amsterdam, Netherlands.
  • Duitman J; Department of Molecular Cell Biology & Immunology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
  • Bogaard HJ; Amsterdam institute for infection and immunity, Amsterdam, Netherlands.
  • Heunks L; Medical Immunology Laboratory, Department of Clinical Chemistry, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
  • Lutter R; Department of Pulmonary Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
  • van der Poll T; Center for Experimental and Molecular Medicine, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.
  • Garcia Vallejo JJ; Department of Pulmonary Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
Thorax ; 76(10): 1010-1019, 2021 10.
Article in English | MEDLINE | ID: covidwho-1180971
Preprint
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Semantic information from SemMedBD (by NLM)
1. Critical Illness PROCESS_OF Patients
Subject
Critical Illness
Predicate
PROCESS_OF
Object
Patients
2. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
3. Blood PART_OF Patients
Subject
Blood
Predicate
PART_OF
Object
Patients
4. Airway structure PART_OF Patients
Subject
Airway structure
Predicate
PART_OF
Object
Patients
5. Flow Cytometry MEASURES Bronchoalveolar Lavage Fluid
Subject
Flow Cytometry
Predicate
MEASURES
Object
Bronchoalveolar Lavage Fluid
6. Flow Cytometry MEASURES Plasma
Subject
Flow Cytometry
Predicate
MEASURES
Object
Plasma
7. T-Lymphocyte PRODUCES T-Cell Receptor
Subject
T-Lymphocyte
Predicate
PRODUCES
Object
T-Cell Receptor
8. T-Cell Surface Glycoprotein CD PREDISPOSES C0392674
Subject
T-Cell Surface Glycoprotein CD
Predicate
PREDISPOSES
Object
C0392674
9. Critical Illness PROCESS_OF Patients
Subject
Critical Illness
Predicate
PROCESS_OF
Object
Patients
10. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
11. Blood PART_OF Patients
Subject
Blood
Predicate
PART_OF
Object
Patients
12. Airway structure PART_OF Patients
Subject
Airway structure
Predicate
PART_OF
Object
Patients
13. Flow Cytometry MEASURES Bronchoalveolar Lavage Fluid
Subject
Flow Cytometry
Predicate
MEASURES
Object
Bronchoalveolar Lavage Fluid
14. Flow Cytometry MEASURES Plasma
Subject
Flow Cytometry
Predicate
MEASURES
Object
Plasma
15. T-Lymphocyte PRODUCES T-Cell Receptor
Subject
T-Lymphocyte
Predicate
PRODUCES
Object
T-Cell Receptor
16. T-Cell Surface Glycoprotein CD4, human|CD4 PREDISPOSES Exhaustion
Subject
T-Cell Surface Glycoprotein CD4, human|CD4
Predicate
PREDISPOSES
Object
Exhaustion
ABSTRACT

BACKGROUND:

Knowledge of the pathophysiology of COVID-19 is almost exclusively derived from studies that examined the immune response in blood. We here aimed to analyse the pulmonary immune response during severe COVID-19 and to compare this with blood responses.

METHODS:

This was an observational study in patients with COVID-19 admitted to the intensive care unit (ICU). Mononuclear cells were purified from bronchoalveolar lavage fluid (BALF) and blood, and analysed by spectral flow cytometry; inflammatory mediators were measured in BALF and plasma.

FINDINGS:

Paired blood and BALF samples were obtained from 17 patients, four of whom died in the ICU. Macrophages and T cells were the most abundant cells in BALF, with a high percentage of T cells expressing the ƴδ T cell receptor. In the lungs, both CD4 and CD8 T cells were predominantly effector memory cells (87·3% and 83·8%, respectively), and these cells expressed higher levels of the exhaustion marker programmad death-1 than in peripheral blood. Prolonged ICU stay (>14 days) was associated with a reduced proportion of activated T cells in peripheral blood and even more so in BALF. T cell activation in blood, but not in BALF, was higher in fatal COVID-19 cases. Increased levels of inflammatory mediators were more pronounced in BALF than in plasma.

INTERPRETATION:

The bronchoalveolar immune response in COVID-19 has a unique local profile that strongly differs from the immune profile in peripheral blood. Fully elucidating COVID-19 pathophysiology will require investigation of the pulmonary immune response.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Inflammation Mediators / COVID-19 / Immunity, Cellular Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Thorax Year: 2021 Document Type: Article Affiliation country: Thoraxjnl-2020-216256

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Inflammation Mediators / COVID-19 / Immunity, Cellular Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Thorax Year: 2021 Document Type: Article Affiliation country: Thoraxjnl-2020-216256