Evidence map›Paper›PMID 41299665›Full record

ArticleCell communication and signaling : CCS2025

Extracellular vesicles from long COVID patients promote RUNX2-mediated cellular stress via dysregulated miR-204 and p53 pathway activation.

Luca Dalle Carbonare, Arianna Minoia, Sharazed Zouari, Michele Braggio, Mattia Cominacini, Salvatore Calogero Gaglio, Francesca Cristiana Piritore, Pamela Lorenzi, Mirko Meneghel, Kevin Dervishi and 17 more

Abstract read
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In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Luca Dalle CarbonareDepartment of Engineering for Innovation Medicine and School of Medicine in Sports and Exercise, University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, 37134, Italy.
Arianna MinoiaDepartment of Engineering for Innovation Medicine and School of Medicine in Sports and Exercise, University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, 37134, Italy.
Sharazed ZouariDepartment of Engineering for Innovation Medicine and School of Medicine in Sports and Exercise, University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, 37134, Italy.
Michele BraggioDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Mattia CominaciniDepartment of Engineering for Innovation Medicine and School of Medicine in Sports and Exercise, University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, 37134, Italy.
Salvatore Calogero GaglioDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Francesca Cristiana PiritoreDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Pamela LorenziDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Mirko MeneghelDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Kevin DervishiDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Andrea CorsiDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Anna PedrinollaDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Gaia GiuriatoDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Alessandra FioreDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Adriana CelesiaDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Laura GuerricchioDepartment of Experimental Medicine (DIMES), University of Genova, Genova, 16132, Italy.
Massimo VenturelliDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Federico SchenaDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Massimo DonadelliDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Monica MottesDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Maria Grazia RomanelliDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Massimiliano PerducaDepartment of Biotechnology, University of Verona, Verona, 37134, Italy.
Daniele GuardavaccaroDepartment of Biotechnology, University of Verona, Verona, 37134, Italy.
Ernesto CrisafulliDepartment of Medicine, Respiratory Medicine Unit, University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, 37134, Italy.
Donato ZipetoDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy.
Lucio BarileFaculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, CH-6900, Switzerland.
Maria Teresa ValentiDepartment of Neurosciences, Biomedicines and Movement Medicine, University of Verona, Verona, 37134, Italy. mariateresa.valenti@univr.it.

Funding

MUR Excellence Project 2023-2027 of the Department of Neuroscience, Biomedicine and Movement Sciences of the University of VeronaMUR PRIN 2022 - Projects of Relevant National Interest, funded by the European Union - NextGenerationEU, PNRR, Mission 4, Component 2, Investment 1.1, project Title "Fine definition of systemic and mucosal response in SARS-CoV-2 vaccinated subjects" - CUP code B53D23003410006.
6 · The paper itself

Abstract

backgroundSubjects with Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), experience a wide range of symptoms, including fatigue and respiratory disturbances, affecting their quality of life. Despite the increasing prevalence of Long COVID, the underlying pathogenic mechanisms remain poorly understood. Extracellular vesicles (EVs) are known to be involved in various processes, such as tissue repair and the transmission of viral particles. However, the specific characteristics and functional roles of EVs derived- from patients with Long COVID (LC-EVs) are poorly characterized.

methodsTo uncover systemic mechanisms underlying Long COVID, we performed a comprehensive characterization of patient-derived extracellular vesicles (EVs) via Nanoparticle Tracking analysis (NTA), Atomic Force Microscopy (AFM), Transmission Electron Microscope (TEM) and flow cytometry. These EVs were applied to lung cells, Mesenchymal Stem Cell (MSCs), Human Umbilical Vein Endothelial Cells (HUVECs) and Aortic Smooth Muscle Cells (ASMCs), revealing stress responses through SESN1, SESN2, and p53 activation. We further assessed mitochondrial respiration to evaluate metabolic dysfunction, and conducted targeted transfection experiments to dissect the molecular pathways involved, shedding light on EV-driven cellular reprogramming.

resultsThus, we observed that Long COVID (LC) patients experienced breathlessness and leg discomfort during exertion. Our data highlighted that LC-EVs induce aberrant RUNX2 expression and activate the p53/p21 pathway in lung cells as well stress responses. Additionally, LC-EVs impair mitochondrial function and cellular adaptability under metabolic stress, reducing maximal respiration and ATP production at high cell densities. Protein interaction analysis showed RUNX2 involvement in key biological processes and post-transcriptional regulation by hsa-miR-204-5p was identified. Finally, LC-EVs also activated stress pathways and increased RUNX2, SESN, p53, and p21 levels in endothelial cells, aortic smooth muscle cells, and mesenchymal stem cells.

conclusionsIn conclusions, these findings provide new insights into the role of extracellular vesicles in Long COVID, revealing their involvement in cellular stress and impaired mitochondrial function.

Indexed as

Core Binding Factor Alpha 1 SubunitCOVID-19Extracellular VesiclesMicroRNAsTumor Suppressor Protein p53FemaleHumansHuman Umbilical Vein Endothelial CellsMaleMesenchymal Stem CellsSARS-CoV-2Signal TransductionStress, PhysiologicalCore Binding Factor Alpha 1 SubunitMicroRNAsMIRN204 microRNA, humanRUNX2 protein, humanTP53 protein, humanTumor Suppressor Protein p53Hsa-miR-204-5pLong covidMesenchymal stem cellsRUNX2SESN

Identifiers

PMID41299665
PMCPMC12659154

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.