Journal of Extracellular Vesicles · Published 2026-05-28 · DOI 10.1002/jev2.70288
April Rees, Oliver Richards, Molly E Raikes, Megan Chambers, Sophie G Reed, Ceri Battle, Hannah Toghill, Luke Newey, Tyler J Joseph, Haiyan An, Hui Zhang, Iain Perry, Jason Webber, Nicholas Jones, Catherine A Thornton
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.
Abstract from DOAJ. Public domain (CC0 1.0).
Read the article at the publisher →
Rees, A., Richards, O., Raikes, M., et al. (2026). DAMP Laden Extracellular Vesicles From the Airways of Patients With Severe SARS‐CoV‐2 Respiratory Infection Compromise Inflammation and Cellular Metabolism. Journal of Extracellular Vesicles. https://doi.org/10.1002/jev2.70288