Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
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.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:76 |
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| Enthalten in: |
Thorax - 76(2021), 10 vom: 14. Okt., Seite 1010-1019 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Saris, Anno [VerfasserIn] |
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| Links: |
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| Themen: |
COVID-19 |
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| Anmerkungen: |
Date Completed 29.09.2021 Date Revised 29.09.2021 published: Print-Electronic CommentIn: Thorax. 2021 Oct;76(10):961. - PMID 34088785 Citation Status MEDLINE |
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| doi: |
10.1136/thoraxjnl-2020-216256 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19 |
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| 500 | |a Date Completed 29.09.2021 | ||
| 500 | |a Date Revised 29.09.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Thorax. 2021 Oct;76(10):961. - PMID 34088785 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a pneumonia | |
| 650 | 4 | |a respiratory infection | |
| 650 | 4 | |a viral infection | |
| 650 | 7 | |a Inflammation Mediators |2 NLM | |
| 700 | 1 | |a Reijnders, Tom D Y |e verfasserin |4 aut | |
| 700 | 1 | |a Nossent, Esther J |e verfasserin |4 aut | |
| 700 | 1 | |a Schuurman, Alex R |e verfasserin |4 aut | |
| 700 | 1 | |a Verhoeff, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Asten, Saskia van |e verfasserin |4 aut | |
| 700 | 1 | |a Bontkes, Hetty |e verfasserin |4 aut | |
| 700 | 1 | |a Blok, Siebe |e verfasserin |4 aut | |
| 700 | 1 | |a Duitman, Janwillem |e verfasserin |4 aut | |
| 700 | 1 | |a Bogaard, Harm-Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Heunks, Leo |e verfasserin |4 aut | |
| 700 | 1 | |a Lutter, Rene |e verfasserin |4 aut | |
| 700 | 1 | |a van der Poll, Tom |e verfasserin |4 aut | |
| 700 | 1 | |a Garcia Vallejo, Juan J |e verfasserin |4 aut | |
| 700 | 0 | |a ArtDECO consortium and the Amsterdam UMC COVID study group |e verfasserin |4 aut | |
| 700 | 1 | |a Nossent, Esther J |e investigator |4 oth | |
| 700 | 1 | |a Duitman, Janwillem |e investigator |4 oth | |
| 700 | 1 | |a Saris, Anno |e investigator |4 oth | |
| 700 | 1 | |a Vries, Heder De |e investigator |4 oth | |
| 700 | 1 | |a Meijboom, Lilian J |e investigator |4 oth | |
| 700 | 1 | |a Bos, Lieuwe D |e investigator |4 oth | |
| 700 | 1 | |a Blok, Siebe G |e investigator |4 oth | |
| 700 | 1 | |a Schuurman, Alex R |e investigator |4 oth | |
| 700 | 1 | |a Reijnders, Tom Dy |e investigator |4 oth | |
| 700 | 1 | |a Hugenholtz, F |e investigator |4 oth | |
| 700 | 1 | |a Vallejo, Juan Garcia |e investigator |4 oth | |
| 700 | 1 | |a Bontkes, Hetty |e investigator |4 oth | |
| 700 | 1 | |a Vlaar, Alexander Pj |e investigator |4 oth | |
| 700 | 1 | |a Wiersinga, Joost |e investigator |4 oth | |
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| 700 | 1 | |a Poll, Tom van der |e investigator |4 oth | |
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