@article{86be7f885711478c970607540a39a795,
title = "Extracellular vesicle-mediated endothelial apoptosis and EV-associated proteins correlate with COVID-19 disease severity",
abstract = "Coronavirus disease-2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has lead to a global pandemic with a rising toll in infections and deaths. Better understanding of its pathogenesis will greatly improve the outcomes and treatment of affected patients. Here we compared the inflammatory and cardiovascular disease-related protein cargo of circulating large and small extracellular vesicles (EVs) from 84 hospitalized patients infected with SARS-CoV-2 with different stages of disease severity. Our findings reveal significant enrichment of proinflammatory, procoagulation, immunoregulatory and tissue-remodelling protein signatures in EVs, which remarkably distinguished symptomatic COVID-19 patients from uninfected controls with matched comorbidities and delineated those with moderate disease from those who were critically ill. Specifically, EN-RAGE, followed by TF and IL-18R1, showed the strongest correlation with disease severity and length of hospitalization. Importantly, EVs from COVID-19 patients induced apoptosis of pulmonary microvascular endothelial cells in the order of disease severity. In conclusion, our findings support a role for EVs in the pathogenesis of COVID-19 disease and underpin the development of EV-based approaches to predicting disease severity, determining need for patient hospitalization and identifying new therapeutic targets.",
keywords = "SARS-CoV-2, endothelial injury, inflammation, thrombosis",
author = "Balaji Krishnamachary and Christine Cook and Ashok Kumar and Leslie Spikes and Prabhakar Chalise and Dhillon, {Navneet K.}",
note = "Funding Information: We acknowledge Huiqing Yin‐DeClue and Ling Chen, Department of Internal Medicine, KUMC, for their help in processing blood specimens. We also acknowledge the significant amount of time and effort Maggie Y. Chen, a second‐year medical student, has devoted to maintaining the clinical data and registry for this study. We would also like to thank medical student, Hien Tran, for his assistance with bio‐specimen collection. We thank Luigi Boccardi, Department of Internal Medicine, KUMC, for his assistance in the preparation of IRB protocols, consent forms and other regulatory documents for COVID‐19 biorepository. We acknowledge Electron Microscope Research Laboratory (NIH/NIGMS COBRE grant P20GM104936 and NIH grant 1S10RR027564) for the TEM analysis. We also acknowledge the Flow Cytometry Core Laboratory, which is sponsored, in part, by the NIH/NIGMS COBRE grant P30GM103326 and the NIH/ NCI Cancer Center grant P30 CA168524. The funds to carry out the study were supported by National Institute of Health (NIH) grants R01 DA042715 and R01 HL129875 awarded to Navneet K. Dhillon and intramural R&D funds to Leslie Spikes. Funding Information: We acknowledge Huiqing?Yin-DeClue and Ling Chen, Department of Internal Medicine, KUMC, for their help in processing blood specimens. We also acknowledge the significant amount of time and effort Maggie Y. Chen, a second-year medical student, has devoted to maintaining the clinical data and registry for this study. We would also like to thank medical student, Hien Tran, for his assistance with bio-specimen collection. We thank Luigi?Boccardi, Department of Internal Medicine, KUMC, for his assistance in the preparation of IRB protocols, consent forms and other regulatory documents for COVID-19 biorepository. We acknowledge Electron Microscope Research Laboratory (NIH/NIGMS COBRE grant P20GM104936 and NIH grant 1S10RR027564) for the TEM analysis. We also acknowledge the Flow Cytometry Core Laboratory, which is sponsored, in part, by the NIH/NIGMS COBRE grant P30GM103326 and the NIH/ NCI Cancer Center grant P30 CA168524. The funds to carry out the study were supported by National Institute of Health (NIH) grants R01 DA042715 and R01 HL129875 awarded to Navneet K. Dhillon and intramural R&D funds to Leslie Spikes. Publisher Copyright: {\textcopyright} 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles",
year = "2021",
month = jul,
doi = "10.1002/jev2.12117",
language = "English (US)",
volume = "10",
journal = "Journal of Extracellular Vesicles",
issn = "2001-3078",
publisher = "Taylor and Francis Ltd.",
number = "9",
}