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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
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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
Journal of Extracellular Vesicles, Volume: 15, Issue: 6, Start page: e70288
Swansea University Authors:
April Rees , Oliver Richards , Molly Raikes, Megan Chambers, Sophie Reed , Tyler Joseph, Haiyan An, Iain Perry , Jason Webber , Nick Jones , Cathy Thornton
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PDF | Version of Record
© 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.
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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...
| Published in: | Journal of Extracellular Vesicles |
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| ISSN: | 2001-3078 2001-3078 |
| Published: |
Wiley
2026
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| Online Access: |
Check full text
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa71957 |
| 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 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. |
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| Keywords: |
aspirates, blood, extracellular vesicles, macrophages, monocytes, SARS-CoV-2 |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
This work was funded by the Medical Research Council (MRC), Tackling COVID-19 project under grant MR/V037013/1. |
| Issue: |
6 |
| Start Page: |
e70288 |