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DAMP Laden Extracellular Vesicles From the Airways of Patients With Severe SARS‐CoV‐2 Respiratory Infection Compromise Inflammation and Cellular Metabolism

April Rees Orcid Logo, Oliver Richards Orcid Logo, Molly Raikes, Megan Chambers, Sophie Reed Orcid Logo, Ceri Battle, Hannah Toghill, Luke Newey, Tyler Joseph, Haiyan An, Hui Zhang, Iain Perry Orcid Logo, Jason Webber Orcid Logo, Nick Jones Orcid Logo, Cathy Thornton Orcid Logo

Journal of Extracellular Vesicles, Volume: 15, Issue: 6, Start page: e70288

Swansea University Authors: April Rees Orcid Logo, Oliver Richards Orcid Logo, Molly Raikes, Megan Chambers, Sophie Reed Orcid Logo, Tyler Joseph, Haiyan An, Iain Perry Orcid Logo, Jason Webber Orcid Logo, Nick Jones Orcid Logo, Cathy Thornton Orcid Logo

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DOI (Published version): 10.1002/jev2.70288

Abstract

Highly inflammatory mononuclear phagocytes (MNPs) cause tissue damage across the respiratory tract and other organs in response to infections such as SARS-CoV-2. Extracellular vesicles (EVs) can metabolically and phenotypically reprogram target cells, suggesting a potential role in COVID-19 patholog...

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Published in: Journal of Extracellular Vesicles
ISSN: 2001-3078 2001-3078
Published: Wiley 2026
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URI: https://cronfa.swan.ac.uk/Record/cronfa71957
first_indexed 2026-05-20T08:46:06Z
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Extracellular vesicles (EVs) can metabolically and phenotypically reprogram target cells, suggesting a potential role in COVID-19 pathology. We hypothesised that EVs drive inflammatory changes in COVID-19 and investigated their cargo and effects on MNPs. EVs and MNPs were isolated from matched peripheral blood and airways of ventilated patients with and without severe COVID-19, alongside healthy volunteer blood samples. Characterisation was performed using flow cytometry, microscopy, transcriptomics, PCR, proteomics, mass spectrometry, and bioenergetic profiling. We found that airway EVs from severe COVID-19 patients carried altered cargo, notably reduced miRNAs and enriched mitochondrial DNA and ATP, a difference absents in the circulation. These DAMP-rich EVs impaired healthy MNP function, suppressing cytokine production (e.g., IL-6, IFN&#x3B1;2), and inflammatory programs identified in the monocyte proteomic profile, while also disrupting oxidative phosphorylation&#x2014;features matching airway MNPs in severe disease. Interaction of COVID-19 airway EVs with monocytes was diminished and these EVs had altered phosphatidylcholine/ lysophosphatidylcholine content. 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spelling 2026-06-12T14:35:09.8271214 v2 71957 2026-05-20 DAMP Laden Extracellular Vesicles From the Airways of Patients With Severe SARS‐CoV‐2 Respiratory Infection Compromise Inflammation and Cellular Metabolism ae088f7f8609d2b2ea4666f9b52b3c15 0000-0002-4408-634X April Rees April Rees true false 93c672d7c4bf8ebe19916d432f0ec7bb 0000-0002-5824-2745 Oliver Richards Oliver Richards true false 826fd42de9a60f65e393abf738f7c95c Molly Raikes Molly Raikes true false 7df677285443d1a8c1b5aab4474fa4b4 Megan Chambers Megan Chambers true false c290e7a868f816083ed0255168bd1917 0000-0001-8099-3847 Sophie Reed Sophie Reed true false d7932ff3df05439115a4c4d2b9ba60db Tyler Joseph Tyler Joseph true false 983c922392c6b16ae0618f38dd408234 Haiyan An Haiyan An true false 7d630cc1fa34fdcd873711c80a874322 0000-0001-8530-4086 Iain Perry Iain Perry true false 25d1a26f9b8bb556bd9412080e40351d 0000-0003-4772-3014 Jason Webber Jason Webber true false 0fce0f7ddbdbfeb968f4e2f1e3f86744 0000-0003-4846-5117 Nick Jones Nick Jones true false c71a7a4be7361094d046d312202bce0c 0000-0002-5153-573X Cathy Thornton Cathy Thornton true false 2026-05-20 MEDS Highly inflammatory mononuclear phagocytes (MNPs) cause tissue damage across the respiratory tract and other organs in response to infections such as SARS-CoV-2. Extracellular vesicles (EVs) can metabolically and phenotypically reprogram target cells, suggesting a potential role in COVID-19 pathology. We hypothesised that EVs drive inflammatory changes in COVID-19 and investigated their cargo and effects on MNPs. EVs and MNPs were isolated from matched peripheral blood and airways of ventilated patients with and without severe COVID-19, alongside healthy volunteer blood samples. Characterisation was performed using flow cytometry, microscopy, transcriptomics, PCR, proteomics, mass spectrometry, and bioenergetic profiling. We found that airway EVs from severe COVID-19 patients carried altered cargo, notably reduced miRNAs and enriched mitochondrial DNA and ATP, a difference absents in the circulation. These DAMP-rich EVs impaired healthy MNP function, suppressing cytokine production (e.g., IL-6, IFNα2), and inflammatory programs identified in the monocyte proteomic profile, while also disrupting oxidative phosphorylation—features matching airway MNPs in severe disease. Interaction of COVID-19 airway EVs with monocytes was diminished and these EVs had altered phosphatidylcholine/ lysophosphatidylcholine content. Our findings reveal a distinct EV cargo that reprograms immune metabolism, identifying a novel immunomodulatory mechanism exploited by SARS-CoV-2. Journal Article Journal of Extracellular Vesicles 15 6 e70288 Wiley 2001-3078 2001-3078 aspirates, blood, extracellular vesicles, macrophages, monocytes, SARS-CoV-2 1 6 2026 2026-06-01 10.1002/jev2.70288 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University SU Library paid the OA fee (TA Institutional Deal) This work was funded by the Medical Research Council (MRC), Tackling COVID-19 project under grant MR/V037013/1. 2026-06-12T14:35:09.8271214 2026-05-20T09:40:42.5814025 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science April Rees 0000-0002-4408-634X 1 Oliver Richards 0000-0002-5824-2745 2 Molly Raikes 3 Megan Chambers 4 Sophie Reed 0000-0001-8099-3847 5 Ceri Battle 6 Hannah Toghill 7 Luke Newey 8 Tyler Joseph 9 Haiyan An 10 Hui Zhang 11 Iain Perry 0000-0001-8530-4086 12 Jason Webber 0000-0003-4772-3014 13 Nick Jones 0000-0003-4846-5117 14 Cathy Thornton 0000-0002-5153-573X 15 71957__36960__4d37b5569fed4aaba8396b982fa33095.pdf 71957.VOR.pdf 2026-06-12T14:32:26.0931548 Output 2903328 application/pdf Version of Record true © 2026 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. This is an open access article under the terms of the Creative Commons Attribution License. true eng http://creativecommons.org/licenses/by/4.0/
title DAMP Laden Extracellular Vesicles From the Airways of Patients With Severe SARS‐CoV‐2 Respiratory Infection Compromise Inflammation and Cellular Metabolism
spellingShingle DAMP Laden Extracellular Vesicles From the Airways of Patients With Severe SARS‐CoV‐2 Respiratory Infection Compromise Inflammation and Cellular Metabolism
April Rees
Oliver Richards
Molly Raikes
Megan Chambers
Sophie Reed
Tyler Joseph
Haiyan An
Iain Perry
Jason Webber
Nick Jones
Cathy Thornton
title_short DAMP Laden Extracellular Vesicles From the Airways of Patients With Severe SARS‐CoV‐2 Respiratory Infection Compromise Inflammation and Cellular Metabolism
title_full DAMP Laden Extracellular Vesicles From the Airways of Patients With Severe SARS‐CoV‐2 Respiratory Infection Compromise Inflammation and Cellular Metabolism
title_fullStr DAMP Laden Extracellular Vesicles From the Airways of Patients With Severe SARS‐CoV‐2 Respiratory Infection Compromise Inflammation and Cellular Metabolism
title_full_unstemmed DAMP Laden Extracellular Vesicles From the Airways of Patients With Severe SARS‐CoV‐2 Respiratory Infection Compromise Inflammation and Cellular Metabolism
title_sort DAMP Laden Extracellular Vesicles From the Airways of Patients With Severe SARS‐CoV‐2 Respiratory Infection Compromise Inflammation and Cellular Metabolism
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author_id_fullname_str_mv ae088f7f8609d2b2ea4666f9b52b3c15_***_April Rees
93c672d7c4bf8ebe19916d432f0ec7bb_***_Oliver Richards
826fd42de9a60f65e393abf738f7c95c_***_Molly Raikes
7df677285443d1a8c1b5aab4474fa4b4_***_Megan Chambers
c290e7a868f816083ed0255168bd1917_***_Sophie Reed
d7932ff3df05439115a4c4d2b9ba60db_***_Tyler Joseph
983c922392c6b16ae0618f38dd408234_***_Haiyan An
7d630cc1fa34fdcd873711c80a874322_***_Iain Perry
25d1a26f9b8bb556bd9412080e40351d_***_Jason Webber
0fce0f7ddbdbfeb968f4e2f1e3f86744_***_Nick Jones
c71a7a4be7361094d046d312202bce0c_***_Cathy Thornton
author April Rees
Oliver Richards
Molly Raikes
Megan Chambers
Sophie Reed
Tyler Joseph
Haiyan An
Iain Perry
Jason Webber
Nick Jones
Cathy Thornton
author2 April Rees
Oliver Richards
Molly Raikes
Megan Chambers
Sophie Reed
Ceri Battle
Hannah Toghill
Luke Newey
Tyler Joseph
Haiyan An
Hui Zhang
Iain Perry
Jason Webber
Nick Jones
Cathy Thornton
format Journal article
container_title Journal of Extracellular Vesicles
container_volume 15
container_issue 6
container_start_page e70288
publishDate 2026
institution Swansea University
issn 2001-3078
2001-3078
doi_str_mv 10.1002/jev2.70288
publisher Wiley
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
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description Highly inflammatory mononuclear phagocytes (MNPs) cause tissue damage across the respiratory tract and other organs in response to infections such as SARS-CoV-2. Extracellular vesicles (EVs) can metabolically and phenotypically reprogram target cells, suggesting a potential role in COVID-19 pathology. We hypothesised that EVs drive inflammatory changes in COVID-19 and investigated their cargo and effects on MNPs. EVs and MNPs were isolated from matched peripheral blood and airways of ventilated patients with and without severe COVID-19, alongside healthy volunteer blood samples. Characterisation was performed using flow cytometry, microscopy, transcriptomics, PCR, proteomics, mass spectrometry, and bioenergetic profiling. We found that airway EVs from severe COVID-19 patients carried altered cargo, notably reduced miRNAs and enriched mitochondrial DNA and ATP, a difference absents in the circulation. These DAMP-rich EVs impaired healthy MNP function, suppressing cytokine production (e.g., IL-6, IFNα2), and inflammatory programs identified in the monocyte proteomic profile, while also disrupting oxidative phosphorylation—features matching airway MNPs in severe disease. Interaction of COVID-19 airway EVs with monocytes was diminished and these EVs had altered phosphatidylcholine/ lysophosphatidylcholine content. Our findings reveal a distinct EV cargo that reprograms immune metabolism, identifying a novel immunomodulatory mechanism exploited by SARS-CoV-2.
published_date 2026-06-01T06:02:38Z
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