{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:03:28Z","timestamp":1787738608249,"version":"build-2784847793"},"reference-count":99,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"UCLA David Geffen School of Medicine (DGSoM)\u2014Ventura County Community Foundation (VCCF) Long COVID 19 Research Award"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-23760-y","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T14:54:24Z","timestamp":1769439264000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Serum extracellular vesicle RNA profiles in long COVID: insights from exercise-induced gene modulation"],"prefix":"10.1038","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct05398692","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3034-0068","authenticated-orcid":false,"given":"Asghar","family":"Abbasi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Palade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy","family":"Paredes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bessie","family":"Meechoovet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendall","family":"Van Keuren-Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Pirrotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Stringer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"23760_CR1","first-page":"1740","volume":"21","author":"HE Davis","year":"2023","unstructured":"Davis, H. E., McCorkell, L., Vogel, J. M. & Topol, E. J. Long COVID: Major findings, mechanisms and recommendations. Nat. Rev. Microbiol. 21, 1740\u20131534 (2023).","journal-title":"Nat. Rev. Microbiol."},{"issue":"6","key":"23760_CR2","doi-asserted-by":"publisher","first-page":"e345","DOI":"10.1016\/S1473-3099(24)00211-1","volume":"24","author":"MJ Peluso","year":"2024","unstructured":"Peluso, M. J. et al. Plasma-based antigen persistence in the post-acute phase of COVID-19. Lancet Infect. Dis. 24(6), e345\u2013e347 (2024).","journal-title":"Lancet Infect. Dis."},{"issue":"10","key":"23760_CR3","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1038\/s41590-023-01601-2","volume":"24","author":"AD Proal","year":"2023","unstructured":"Proal, A. D. et al. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nat. Immunol. 24(10), 1616\u20131627 (2023).","journal-title":"Nat. Immunol."},{"issue":"3","key":"23760_CR4","doi-asserted-by":"publisher","first-page":"e487","DOI":"10.1093\/cid\/ciac722","volume":"76","author":"Z Swank","year":"2023","unstructured":"Swank, Z. et al. Persistent circulating severe acute respiratory syndrome coronavirus 2 spike is associated with post-acute coronavirus disease 2019 sequelae. Clin. Infect. Dis. 76(3), e487\u2013e490 (2023).","journal-title":"Clin. Infect. Dis."},{"issue":"4","key":"23760_CR5","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/s41591-021-01283-z","volume":"27","author":"A Nalbandian","year":"2021","unstructured":"Nalbandian, A. et al. Post-acute COVID-19 syndrome. Nat Med. 27(4), 601\u2013615 (2021).","journal-title":"Nat Med."},{"key":"23760_CR6","first-page":"1","volume":"23","author":"EI Buzas","year":"2022","unstructured":"Buzas, E. I. The roles of extracellular vesicles in the immune system. Nat. Rev. Immunol. 23, 1\u201315 (2022).","journal-title":"Nat. Rev. Immunol."},{"key":"23760_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2024.101935","volume":"78","author":"Z Liao","year":"2024","unstructured":"Liao, Z. et al. Extracellular vesicles as carriers for mitochondria: Biological functions and clinical applications. Mitochondrion 78, 101935 (2024).","journal-title":"Mitochondrion"},{"issue":"2","key":"23760_CR8","doi-asserted-by":"publisher","first-page":"274","DOI":"10.3390\/microorganisms12020274","volume":"12","author":"S Chatterjee","year":"2024","unstructured":"Chatterjee, S., Kordbacheh, R. & Sin, J. Extracellular vesicles: A novel mode of viral propagation exploited by enveloped and non-enveloped viruses. Microorganisms. 12(2), 274 (2024).","journal-title":"Microorganisms."},{"issue":"10","key":"23760_CR9","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.tibtech.2020.05.012","volume":"38","author":"S Gandham","year":"2020","unstructured":"Gandham, S. et al. Technologies and standardization in research on extracellular vesicles. Trends Biotechnol. 38(10), 1066\u20131098 (2020).","journal-title":"Trends Biotechnol."},{"issue":"18","key":"23760_CR10","doi-asserted-by":"publisher","first-page":"5590","DOI":"10.3390\/jcm13185590","volume":"13","author":"A Abbasi","year":"2024","unstructured":"Abbasi, A. et al. A pilot study on the effects of exercise training on cardiorespiratory performance quality of life and immunologic variables in long COVID. J. Clin. Med. 13(18), 5590 (2024).","journal-title":"J. Clin. Med."},{"issue":"3","key":"23760_CR11","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.chest.2024.01.029","volume":"166","author":"E Daynes","year":"2024","unstructured":"Daynes, E. et al. Pulmonary rehabilitation for people with persistent symptoms after COVID-19. Chest 166(3), 461\u2013471 (2024).","journal-title":"Chest"},{"issue":"1","key":"23760_CR12","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s40798-024-00695-8","volume":"10","author":"R Gloeckl","year":"2024","unstructured":"Gloeckl, R. et al. Practical recommendations for exercise training in patients with long COVID with or without post-exertional malaise: A best practice proposal. Sports Med. Open. 10(1), 47 (2024).","journal-title":"Sports Med. Open."},{"issue":"6","key":"23760_CR13","first-page":"2808","volume":"25","author":"M Amro","year":"2021","unstructured":"Amro, M., Mohamed, A. & Alawna, M. Effects of increasing aerobic capacity on improving psychological problems seen in patients with COVID-19: a review. Eur. Rev. Med. Pharmacol. Sci. 25(6), 2808\u20132821 (2021).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"issue":"6","key":"23760_CR14","doi-asserted-by":"publisher","first-page":"435","DOI":"10.4103\/lungindia.lungindia_368_23","volume":"41","author":"MD Bargaje","year":"2024","unstructured":"Bargaje, M. D. et al. Effectiveness of pulmonary rehabilitation in post-COVID-19 patients: A pre- and post-interventional study. Lung India 41(6), 435\u2013441 (2024).","journal-title":"Lung India"},{"issue":"1","key":"23760_CR15","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1186\/s12916-024-03658-8","volume":"22","author":"R Garbsch","year":"2024","unstructured":"Garbsch, R. et al. Sex-specific differences of cardiopulmonary fitness and pulmonary function in exercise-based rehabilitation of patients with long-term post-COVID-19 syndrome. BMC Med. 22(1), 446 (2024).","journal-title":"BMC Med."},{"issue":"5","key":"23760_CR16","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/s41574-022-00641-2","volume":"18","author":"LS Chow","year":"2022","unstructured":"Chow, L. S. et al. Exerkines in health, resilience and disease. Nat. Rev. Endocrinol. 18(5), 273\u2013289 (2022).","journal-title":"Nat. Rev. Endocrinol."},{"issue":"9","key":"23760_CR17","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/nri3041","volume":"11","author":"M Gleeson","year":"2011","unstructured":"Gleeson, M. et al. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat. Rev. Immunol. 11(9), 607\u2013615 (2011).","journal-title":"Nat. Rev. Immunol."},{"issue":"3","key":"23760_CR18","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.jshs.2018.09.009","volume":"8","author":"DC Nieman","year":"2019","unstructured":"Nieman, D. C. & Wentz, L. M. The compelling link between physical activity and the body\u2019s defense system. J. Sport Health Sci. 8(3), 201\u2013217 (2019).","journal-title":"J. Sport Health Sci."},{"key":"23760_CR19","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.604274","volume":"11","author":"JP Nederveen","year":"2020","unstructured":"Nederveen, J. P., Warnier, G., Di Carlo, A., Nilsson, M. I. & Tarnopolsky, M. A. Extracellular vesicles and exosomes: Insights from exercise science. Front. Physiol. 11, 604274 (2020).","journal-title":"Front. Physiol."},{"key":"23760_CR20","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.jprot.2012.09.008","volume":"77","author":"MC Le Bihan","year":"2012","unstructured":"Le Bihan, M. C. et al. In-depth analysis of the secretome identifies three major independent secretory pathways in differentiating human myoblasts. J. Proteomics. 77, 344\u2013356 (2012).","journal-title":"J. Proteomics."},{"key":"23760_CR21","doi-asserted-by":"crossref","unstructured":"Catitti G, De Bellis D, Vespa S, Simeone P, Canonico B, Lanuti P. Extracellular Vesicles as Players in the Anti-Inflammatory Inter-Cellular Crosstalk Induced by Exercise Training. Int J Mol Sci. 2022;23(22).","DOI":"10.3390\/ijms232214098"},{"issue":"5","key":"23760_CR22","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1113\/EP090062","volume":"107","author":"BP Sullivan","year":"2022","unstructured":"Sullivan, B. P. et al. Obesity and exercise training alter inflammatory pathway skeletal muscle small extracellular vesicle microRNAs. Exp Physiol. 107(5), 462\u2013475 (2022).","journal-title":"Exp Physiol."},{"key":"23760_CR23","doi-asserted-by":"publisher","first-page":"e14095","DOI":"10.1111\/apha.14095","volume":"240","author":"MC Chong","year":"2024","unstructured":"Chong, M. C. et al. Acute exercise-induced release of innate immune proteins via small extracellular vesicles changes with aerobic fitness and age. Acta Physiol. (Oxf). 240, e14095 (2024).","journal-title":"Acta Physiol. (Oxf)."},{"issue":"1","key":"23760_CR24","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.cmet.2017.12.001","volume":"27","author":"M Whitham","year":"2018","unstructured":"Whitham, M. et al. Extracellular vesicles provide a means for tissue crosstalk during exercise. Cell Metab. 27(1), 237\u201351.e4 (2018).","journal-title":"Cell Metab."},{"issue":"9","key":"23760_CR25","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/nrendo.2016.76","volume":"12","author":"A Safdar","year":"2016","unstructured":"Safdar, A., Saleem, A. & Tarnopolsky, M. A. The potential of endurance exercise-derived exosomes to treat metabolic diseases. Nat. Rev. Endocrinol. 12(9), 504\u2013517 (2016).","journal-title":"Nat. Rev. Endocrinol."},{"issue":"10","key":"23760_CR26","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.3390\/cells9102182","volume":"9","author":"OK Fuller","year":"2020","unstructured":"Fuller, O. K., Whitham, M., Mathivanan, S. & Febbraio, M. A. The protective effect of exercise in neurodegenerative diseases: The potential role of extracellular vesicles. Cells 9(10), 2182 (2020).","journal-title":"Cells"},{"key":"23760_CR27","doi-asserted-by":"crossref","unstructured":"Vanderboom, P. M., Dasari, S., Ruegsegger, G. N., Pataky, M. W., Lucien, F., Heppelmann, C. J. et al. A size-exclusion-based approach for purifying extracellular vesicles from human plasma. Cell Rep. Methods. 1(3) (2021).","DOI":"10.1016\/j.crmeth.2021.100055"},{"issue":"10","key":"23760_CR28","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.38804","volume":"5","author":"RH Perlis","year":"2022","unstructured":"Perlis, R. H. et al. Prevalence and correlates of long COVID symptoms among US adults. JAMA Netw. Open. 5(10), e2238804 (2022).","journal-title":"JAMA Netw. Open."},{"issue":"1","key":"23760_CR29","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1186\/s12967-020-02481-y","volume":"18","author":"J Lee","year":"2020","unstructured":"Lee, J. et al. Hemodynamics during the 10-minute NASA lean test: Evidence of circulatory decompensation in a subset of ME\/CFS patients. J. Transl. Med. 18(1), 314 (2020).","journal-title":"J. Transl. Med."},{"issue":"2","key":"23760_CR30","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1183\/09031936.05.00034805","volume":"26","author":"MR Miller","year":"2005","unstructured":"Miller, M. R. et al. Standardisation of spirometry. Eur. Respir. J. 26(2), 319\u2013338 (2005).","journal-title":"Eur. Respir. J."},{"issue":"4","key":"23760_CR31","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1183\/09031936.05.00034905","volume":"26","author":"N Macintyre","year":"2005","unstructured":"Macintyre, N. et al. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur. Respir. J. 26(4), 720\u2013735 (2005).","journal-title":"Eur. Respir. J."},{"issue":"3","key":"23760_CR32","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1183\/09031936.05.00035005","volume":"26","author":"J Wanger","year":"2005","unstructured":"Wanger, J. et al. Standardisation of the measurement of lung volumes. Eur. Respir. J. 26(3), 511\u2013522 (2005).","journal-title":"Eur. Respir. J."},{"key":"23760_CR33","doi-asserted-by":"crossref","unstructured":"Graham, B. L., Brusasco, V., Burgos, F., Cooper, B. G., Jensen, R., Kendrick, A. et al. ERS\/ATS standards for single-breath carbon monoxide uptake in the lung. Eur. Respir. J. 49(1) (2017).","DOI":"10.1183\/13993003.00016-2016"},{"issue":"1","key":"23760_CR34","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1164\/ajrccm.159.1.9712108","volume":"159","author":"JL Hankinson","year":"1999","unstructured":"Hankinson, J. L., Odencrantz, J. R. & Fedan, K. B. Spirometric reference values from a sample of the general U.S. population. Am. J. Respir. Cri.t Care Med. 159(1), 179\u2013187 (1999).","journal-title":"Am. J. Respir. Cri.t Care Med."},{"key":"23760_CR35","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1183\/09041950.005s1693","volume":"16","author":"PH Quanjer","year":"1993","unstructured":"Quanjer, P. H. et al. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal Official Statement of the European Respiratory Society. Eur. Respir. J. Suppl. 16, 5\u201340 (1993).","journal-title":"Eur. Respir. J. Suppl."},{"key":"23760_CR36","volume-title":"Lung Function: Physiology, Measurement and Application in Medicine","author":"JE Cotes","year":"2009","unstructured":"Cotes, J. E., Chinn, D. J. & Miller, M. R. Lung Function: Physiology, Measurement and Application in Medicine (Wiley, 2009)."},{"issue":"5","key":"23760_CR37","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1249\/00005768-198205000-00012","volume":"14","author":"GA Borg","year":"1982","unstructured":"Borg, G. A. Psychophysical bases of perceived exertion. Med. Sci. Sports Exerc. 14(5), 377\u2013381 (1982).","journal-title":"Med. Sci. Sports Exerc."},{"issue":"6","key":"23760_CR38","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1152\/jappl.1986.60.6.2020","volume":"60","author":"WL Beaver","year":"1986","unstructured":"Beaver, W. L., Wasserman, K. & Whipp, B. J. A new method for detecting anaerobic threshold by gas exchange. J. Appl. Physiol. 60(6), 2020\u20132027 (1986).","journal-title":"J. Appl. Physiol."},{"issue":"1","key":"23760_CR39","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1080\/15412555.2020.1858403","volume":"18","author":"M Cao","year":"2021","unstructured":"Cao, M. et al. Transcutaneous PCO(2) for exercise gas exchange efficiency in chronic obstructive pulmonary disease. COPD 18(1), 16\u201325 (2021).","journal-title":"COPD"},{"issue":"6","key":"23760_CR40","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.1152\/japplphysiol.00774.2020","volume":"130","author":"WW Stringer","year":"2021","unstructured":"Stringer, W. W. et al. The effect of long-acting dual bronchodilator therapy on exercise tolerance, dynamic hyperinflation, and dead space during constant work rate exercise in COPD. J. Appl. Physiol. 130(6), 2009\u20132018 (2021).","journal-title":"J. Appl. Physiol."},{"issue":"4","key":"23760_CR41","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1097\/00008483-198704000-00014","volume":"7","author":"K Wasserman","year":"1987","unstructured":"Wasserman, K., Hansen, J. E., Sue, D. Y., Whipp, B. J. & Froelicher, V. F. Principles of exercise testing and interpretation. J. Cardiopulm. Rehabil. Prev. 7(4), 189 (1987).","journal-title":"J. Cardiopulm. Rehabil. Prev."},{"issue":"9","key":"23760_CR42","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.molmed.2015.07.004","volume":"21","author":"Y Fujita","year":"2015","unstructured":"Fujita, Y., Kosaka, N., Araya, J., Kuwano, K. & Ochiya, T. Extracellular vesicles in lung microenvironment and pathogenesis. Trends Mol Med. 21(9), 533\u2013542 (2015).","journal-title":"Trends Mol Med."},{"issue":"17","key":"23760_CR43","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.3390\/cells13171407","volume":"13","author":"CJ Son","year":"2024","unstructured":"Son, C. J., Carnino, J. M., Lee, H. & Jin, Y. Emerging roles of circular RNA in macrophage activation and inflammatory lung responses. Cells 13(17), 1407 (2024).","journal-title":"Cells"},{"issue":"1","key":"23760_CR44","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1164\/rccm.202109-2208OC","volume":"207","author":"CM Eckhardt","year":"2023","unstructured":"Eckhardt, C. M. et al. Extracellular vesicle-encapsulated microRNAs as novel biomarkers of lung health. Am. J. Respir. Crit. Care Med. 207(1), 50\u201359 (2023).","journal-title":"Am. J. Respir. Crit. Care Med."},{"issue":"1","key":"23760_CR45","doi-asserted-by":"publisher","first-page":"1684816","DOI":"10.1080\/20013078.2019.1684816","volume":"8","author":"IK Sundar","year":"2019","unstructured":"Sundar, I. K., Li, D. & Rahman, I. Small RNA-sequence analysis of plasma-derived extracellular vesicle miRNAs in smokers and patients with chronic obstructive pulmonary disease as circulating biomarkers. J. Extracell. Vesicles. 8(1), 1684816 (2019).","journal-title":"J. Extracell. Vesicles."},{"issue":"48","key":"23760_CR46","doi-asserted-by":"publisher","first-page":"30335","DOI":"10.1073\/pnas.2016112117","volume":"117","author":"C Casta\u00f1o","year":"2020","unstructured":"Casta\u00f1o, C., Mirasierra, M., Vallejo, M., Novials, A. & P\u00e1rrizas, M. Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice. Proc. Natl. Acad. Sci. U S A. 117(48), 30335\u201330343 (2020).","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"23760_CR47","doi-asserted-by":"publisher","first-page":"e182589","DOI":"10.1172\/jci.insight.182589","volume":"9","author":"BI Burke","year":"2024","unstructured":"Burke, B. I. et al. Extracellular vesicle transfer of miR-1 to adipose tissue modifies lipolytic pathways following resistance exercise. JCI Insight. 9, e182589 (2024).","journal-title":"JCI Insight."},{"issue":"7","key":"23760_CR48","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1249\/MSS.0000000000003408","volume":"56","author":"WR Conkright","year":"2024","unstructured":"Conkright, W. R. et al. Acute resistance exercise modifies extracellular vesicle miRNAs targeting anabolic gene pathways: A prospective cohort study. Med. Sci. Sports Exerc. 56(7), 1225\u20131232 (2024).","journal-title":"Med. Sci. Sports Exerc."},{"issue":"4","key":"23760_CR49","doi-asserted-by":"publisher","first-page":"e13862","DOI":"10.1111\/apha.13862","volume":"236","author":"AI Doncheva","year":"2022","unstructured":"Doncheva, A. I. et al. Extracellular vesicles and microRNAs are altered in response to exercise, insulin sensitivity and overweight. Acta Physiol. (Oxf). 236(4), e13862 (2022).","journal-title":"Acta Physiol. (Oxf)."},{"issue":"1","key":"23760_CR50","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/s41392-022-01153-1","volume":"7","author":"H Chen","year":"2022","unstructured":"Chen, H. et al. Exercise training maintains cardiovascular health: Signaling pathways involved and potential therapeutics. Signal Transduct. Target Ther. 7(1), 306 (2022).","journal-title":"Signal Transduct. Target Ther."},{"key":"23760_CR51","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1146\/annurev-physiol-060721-095517","volume":"84","author":"HR Spaulding","year":"2022","unstructured":"Spaulding, H. R. & Yan, Z. AMPK and the adaptation to exercise. Annu. Rev. Physiol. 84, 209\u2013227 (2022).","journal-title":"Annu. Rev. Physiol."},{"key":"23760_CR52","doi-asserted-by":"publisher","first-page":"861703","DOI":"10.3389\/fcimb.2022.861703","volume":"12","author":"C Wang","year":"2022","unstructured":"Wang, C. et al. Long COVID: The nature of thrombotic sequelae determines the necessity of early anticoagulation. Front. Cell Infect. Microbiol. 12, 861703 (2022).","journal-title":"Front. Cell Infect. Microbiol."},{"issue":"6","key":"23760_CR53","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1002\/ana.26350","volume":"91","author":"MJ Peluso","year":"2022","unstructured":"Peluso, M. J. et al. SARS-CoV-2 and mitochondrial proteins in neural-derived exosomes of COVID-19. Ann. Neurol. 91(6), 772\u2013781 (2022).","journal-title":"Ann. Neurol."},{"key":"23760_CR54","doi-asserted-by":"publisher","first-page":"1376455","DOI":"10.3389\/fbioe.2024.1376455","volume":"12","author":"Z Tang","year":"2024","unstructured":"Tang, Z., Lu, Y., Dong, J. L., Wu, W. & Li, J. The extracellular vesicles in HIV infection and progression: mechanisms, and theranostic implications. Front. Bioeng. Biotechnol. 12, 1376455 (2024).","journal-title":"Front. Bioeng. Biotechnol."},{"issue":"9","key":"23760_CR55","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/nrmicro.2017.60","volume":"15","author":"N Raab-Traub","year":"2017","unstructured":"Raab-Traub, N. & Dittmer, D. P. Viral effects on the content and function of extracellular vesicles. Nat. Rev. Microbiol. 15(9), 559\u2013572 (2017).","journal-title":"Nat. Rev. Microbiol."},{"issue":"14","key":"23760_CR56","doi-asserted-by":"publisher","first-page":"6328","DOI":"10.1073\/pnas.0914843107","volume":"107","author":"DM Pegtel","year":"2010","unstructured":"Pegtel, D. M. et al. Functional delivery of viral miRNAs via exosomes. Proc. Natl. Acad. Sci. U S A. 107(14), 6328\u20136333 (2010).","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"issue":"3","key":"23760_CR57","doi-asserted-by":"publisher","first-page":"a029827","DOI":"10.1101\/cshperspect.a029827","volume":"8","author":"A Safdar","year":"2018","unstructured":"Safdar, A. & Tarnopolsky, M. A. Exosomes as mediators of the systemic adaptations to endurance exercise. Cold Spring Harb. Perspect. Med. 8(3), a029827 (2018).","journal-title":"Cold Spring Harb. Perspect. Med."},{"issue":"48","key":"23760_CR58","doi-asserted-by":"publisher","first-page":"12158","DOI":"10.1073\/pnas.1808855115","volume":"115","author":"C Casta\u00f1o","year":"2018","unstructured":"Casta\u00f1o, C., Kalko, S., Novials, A. & P\u00e1rrizas, M. Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice. Proc. Natl. Acad. Sci. U S A. 115(48), 12158\u201312163 (2018).","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"issue":"3","key":"23760_CR59","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/nri3622","volume":"14","author":"PD Robbins","year":"2014","unstructured":"Robbins, P. D. & Morelli, A. E. Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol. 14(3), 195\u2013208 (2014).","journal-title":"Nat. Rev. Immunol."},{"issue":"22","key":"23760_CR60","doi-asserted-by":"publisher","first-page":"5011","DOI":"10.1113\/JP282867","volume":"601","author":"YF Wu","year":"2023","unstructured":"Wu, Y. F. et al. Development of a cell-free strategy to recover aged skeletal muscle after disuse. J Physiol. 601(22), 5011\u20135031 (2023).","journal-title":"J Physiol."},{"issue":"4","key":"23760_CR61","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1007\/s00395-017-0628-z","volume":"112","author":"Y Bei","year":"2017","unstructured":"Bei, Y. et al. Exercise-induced circulating extracellular vesicles protect against cardiac ischemia-reperfusion injury. Basic Res. Cardiol. 112(4), 38 (2017).","journal-title":"Basic Res. Cardiol."},{"issue":"41","key":"23760_CR62","doi-asserted-by":"publisher","first-page":"eabi9551","DOI":"10.1126\/sciadv.abi9551","volume":"7","author":"M Apostolopoulou","year":"2021","unstructured":"Apostolopoulou, M. et al. Metabolic responsiveness to training depends on insulin sensitivity and protein content of exosomes in insulin-resistant males. Sci. Adv. 7(41), eabi9551 (2021).","journal-title":"Sci. Adv."},{"issue":"12","key":"23760_CR63","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1093\/intimm\/dxab053","volume":"33","author":"T Nakayama","year":"2021","unstructured":"Nakayama, T. et al. CD4+ T cells in inflammatory diseases: pathogenic T-helper cells and the CD69-Myl9 system. Int. Immunol. 33(12), 699\u2013704 (2021).","journal-title":"Int. Immunol."},{"issue":"3","key":"23760_CR64","doi-asserted-by":"publisher","first-page":"eaaf9154","DOI":"10.1126\/sciimmunol.aaf9154","volume":"1","author":"K Hayashizaki","year":"2016","unstructured":"Hayashizaki, K. et al. Myosin light chains 9 and 12 are functional ligands for CD69 that regulate airway inflammation. Sci. Immunol. 1(3), eaaf9154 (2016).","journal-title":"Sci. Immunol."},{"issue":"33","key":"23760_CR65","doi-asserted-by":"publisher","first-page":"e2203437119","DOI":"10.1073\/pnas.2203437119","volume":"119","author":"C Iwamura","year":"2022","unstructured":"Iwamura, C. et al. Elevated Myl9 reflects the Myl9-containing microthrombi in SARS-CoV-2-induced lung exudative vasculitis and predicts COVID-19 severity. Proc. Natl. Acad. Sci. U S A. 119(33), e2203437119 (2022).","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"issue":"17","key":"23760_CR66","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.1212\/WNL.0000000000004569","volume":"89","author":"KB Casaletto","year":"2017","unstructured":"Casaletto, K. B. et al. Neurogranin, a synaptic protein, is associated with memory independent of Alzheimer biomarkers. Neurology 89(17), 1782\u20131788 (2017).","journal-title":"Neurology"},{"key":"23760_CR67","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s13195-015-0161-y","volume":"7","author":"K Hellwig","year":"2015","unstructured":"Hellwig, K. et al. Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer\u2019s disease. Alzheimers Res. Ther. 7, 74 (2015).","journal-title":"Alzheimers Res. Ther."},{"issue":"2","key":"23760_CR68","doi-asserted-by":"publisher","first-page":"386","DOI":"10.3390\/cells10020386","volume":"10","author":"B Sun","year":"2021","unstructured":"Sun, B. et al. Characterization and biomarker analyses of post-COVID-19 complications and neurological manifestations. Cells 10(2), 386 (2021).","journal-title":"Cells"},{"issue":"3","key":"23760_CR69","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1111\/1759-7714.12974","volume":"10","author":"J Ran","year":"2019","unstructured":"Ran, J. & Zhou, J. Targeted inhibition of histone deacetylase 6 in inflammatory diseases. Thorac. Cancer. 10(3), 405\u2013412 (2019).","journal-title":"Thorac. Cancer."},{"issue":"1","key":"23760_CR70","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/s13075-021-02561-4","volume":"23","author":"JK Park","year":"2021","unstructured":"Park, J. K. et al. Inhibition of histone deacetylase 6 suppresses inflammatory responses and invasiveness of fibroblast-like-synoviocytes in inflammatory arthritis. Arthritis. Res. Ther. 23(1), 177 (2021).","journal-title":"Arthritis. Res. Ther."},{"issue":"4","key":"23760_CR71","doi-asserted-by":"publisher","first-page":"332","DOI":"10.5114\/ceji.2022.124092","volume":"47","author":"K Muneshige","year":"2022","unstructured":"Muneshige, K. et al. \u03b22-microglobulin alters the profiles of inflammatory cytokines and of matrix metalloprotease in macrophages derived from the osteoarthritic synovium. Cent. Eur. J. Immunol. 47(4), 332\u2013338 (2022).","journal-title":"Cent. Eur. J. Immunol."},{"issue":"31","key":"23760_CR72","doi-asserted-by":"publisher","first-page":"10916","DOI":"10.3748\/wjg.v20.i31.10916","volume":"20","author":"B Y\u0131lmaz","year":"2014","unstructured":"Y\u0131lmaz, B., K\u00f6kl\u00fc, S., Y\u00fcksel, O. & Arslan, S. Serum beta 2-microglobulin as a biomarker in inflammatory bowel disease. World J. Gastroenterol. 20(31), 10916\u201310920 (2014).","journal-title":"World J. Gastroenterol."},{"issue":"12","key":"23760_CR73","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1517\/14728222.2013.837886","volume":"17","author":"RE Marques","year":"2013","unstructured":"Marques, R. E., Guabiraba, R., Russo, R. C. & Teixeira, M. M. Targeting CCL5 in inflammation. Expert Opin. Ther. Targets. 17(12), 1439\u20131460 (2013).","journal-title":"Expert Opin. Ther. Targets."},{"key":"23760_CR74","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ijid.2020.10.101","volume":"103","author":"BK Patterson","year":"2021","unstructured":"Patterson, B. K. et al. CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14. Int. J. Infect. Dis. 103, 25\u201332 (2021).","journal-title":"Int. J. Infect. Dis."},{"issue":"1","key":"23760_CR75","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s13365-023-01191-7","volume":"30","author":"A Mahin","year":"2024","unstructured":"Mahin, A. et al. Meta-analysis of the serum\/plasma proteome identifies significant associations between COVID-19 with Alzheimer\u2019s\/Parkinson\u2019s diseases. J. Neurovirol. 30(1), 57\u201370 (2024).","journal-title":"J. Neurovirol."},{"issue":"1","key":"23760_CR76","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/s41531-024-00824-w","volume":"10","author":"M Massaro Cenere","year":"2024","unstructured":"Massaro Cenere, M. et al. Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson\u2019s disease overexpressing human alpha synuclein. NPJ Parkinsons Dis. 10(1), 213 (2024).","journal-title":"NPJ Parkinsons Dis."},{"issue":"1","key":"23760_CR77","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s40659-023-00482-x","volume":"57","author":"F Limanaqi","year":"2024","unstructured":"Limanaqi, F. et al. Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells. Biol. Res. 57(1), 2 (2024).","journal-title":"Biol. Res."},{"issue":"6","key":"23760_CR78","doi-asserted-by":"publisher","first-page":"3394","DOI":"10.3390\/ijms23063394","volume":"23","author":"Z Wu","year":"2022","unstructured":"Wu, Z., Zhang, X., Huang, Z. & Ma, K. SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In Vitro. Int. J. Mol. Sci. 23(6), 3394 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"23760_CR79","doi-asserted-by":"publisher","first-page":"738333","DOI":"10.3389\/fphys.2021.738333","volume":"12","author":"IAJ Darragh","year":"2021","unstructured":"Darragh, I. A. J., O\u2019Driscoll, L. & Egan, B. Exercise training and circulating small extracellular vesicles: Appraisal of methodological approaches and current knowledge. Front Physiol. 12, 738333 (2021).","journal-title":"Front Physiol."},{"issue":"6","key":"23760_CR80","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.it.2014.02.008","volume":"35","author":"GI Lancaster","year":"2014","unstructured":"Lancaster, G. I. & Febbraio, M. A. The immunomodulating role of exercise in metabolic disease. Trends Immunol. 35(6), 262\u2013269 (2014).","journal-title":"Trends Immunol."},{"issue":"5","key":"23760_CR81","doi-asserted-by":"publisher","first-page":"5267","DOI":"10.1007\/s11357-024-01165-5","volume":"46","author":"T Molnar","year":"2024","unstructured":"Molnar, T. et al. Mitochondrial dysfunction in long COVID: Mechanisms, consequences, and potential therapeutic approaches. Geroscience. 46(5), 5267\u20135286 (2024).","journal-title":"Geroscience."},{"issue":"2","key":"23760_CR82","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1161\/CIRCRESAHA.117.310795","volume":"122","author":"M Koupenova","year":"2018","unstructured":"Koupenova, M., Clancy, L., Corkrey, H. A. & Freedman, J. E. Circulating platelets as mediators of immunity, inflammation, and thrombosis. Circ Res. 122(2), 337\u2013351 (2018).","journal-title":"Circ Res."},{"issue":"2","key":"23760_CR83","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1002\/hep.31041","volume":"72","author":"JH Lee","year":"2020","unstructured":"Lee, J. H. et al. Mitochondrial double-stranded RNA in exosome promotes interleukin-17 production through toll-like receptor 3 in alcohol-associated liver injury. Hepatology 72(2), 609\u2013625 (2020).","journal-title":"Hepatology"},{"key":"23760_CR84","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.redox.2018.06.009","volume":"18","author":"KP Hough","year":"2018","unstructured":"Hough, K. P. et al. Exosomal transfer of mitochondria from airway myeloid-derived regulatory cells to T cells. Redox Biol. 18, 54\u201364 (2018).","journal-title":"Redox Biol."},{"issue":"4","key":"23760_CR85","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201949799","volume":"21","author":"JS Riley","year":"2020","unstructured":"Riley, J. S. & Tait, S. W. Mitochondrial DNA in inflammation and immunity. EMBO Rep. 21(4), e49799 (2020).","journal-title":"EMBO Rep."},{"key":"23760_CR86","doi-asserted-by":"publisher","first-page":"e86204","DOI":"10.7554\/eLife.86204","volume":"13","author":"K Sriram","year":"2024","unstructured":"Sriram, K. et al. Regulation of nuclear transcription by mitochondrial RNA in endothelial cells. Elife 13, e86204 (2024).","journal-title":"Elife"},{"key":"23760_CR87","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101482","volume":"31","author":"DN Di Florio","year":"2020","unstructured":"Di Florio, D. N., Sin, J., Coronado, M. J., Atwal, P. S. & Fairweather, D. Sex differences in inflammation, redox biology, mitochondria and autoimmunity. Redox Biol. 31, 101482 (2020).","journal-title":"Redox Biol."},{"issue":"13","key":"23760_CR88","doi-asserted-by":"publisher","first-page":"e168121","DOI":"10.1172\/JCI168121","volume":"133","author":"JM Robbins","year":"2023","unstructured":"Robbins, J. M. & Gerszten, R. E. Exercise, exerkines, and cardiometabolic health: from individual players to a team sport. J. Clin. Invest. 133(13), e168121 (2023).","journal-title":"J. Clin. Invest."},{"issue":"1","key":"23760_CR89","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41398-018-0175-x","volume":"8","author":"T Hughes","year":"2018","unstructured":"Hughes, T. et al. Elevated expression of a minor isoform of ANK3 is a risk factor for bipolar disorder. Transl. Psychiatry. 8(1), 210 (2018).","journal-title":"Transl. Psychiatry."},{"issue":"5855","key":"23760_CR90","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1126\/science.1151710","volume":"318","author":"T Gerken","year":"2007","unstructured":"Gerken, T. et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318(5855), 1469\u20131472 (2007).","journal-title":"Science"},{"key":"23760_CR91","doi-asserted-by":"publisher","first-page":"107232","DOI":"10.1016\/j.ijid.2024.107232","volume":"148","author":"JA Hubacek","year":"2024","unstructured":"Hubacek, J. A., Capkova, N., Bobak, M. & Pikhart, H. Association between FTO polymorphism and COVID-19 mortality among older adults: A population-based cohort study. Int. J. Infect. Dis. 148, 107232 (2024).","journal-title":"Int. J. Infect. Dis."},{"issue":"7","key":"23760_CR92","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1038\/s12276-022-00798-w","volume":"54","author":"S Yoon","year":"2022","unstructured":"Yoon, S., Piguel, N. H. & Penzes, P. Roles and mechanisms of ankyrin-G in neuropsychiatric disorders. Exp. Mol. Med. 54(7), 867\u2013877 (2022).","journal-title":"Exp. Mol. Med."},{"issue":"4\u20135","key":"23760_CR93","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.imbio.2006.11.014","volume":"212","author":"Y Endo","year":"2007","unstructured":"Endo, Y., Matsushita, M. & Fujita, T. Role of ficolin in innate immunity and its molecular basis. Immunobiology 212(4\u20135), 371\u2013379 (2007).","journal-title":"Immunobiology"},{"issue":"5","key":"23760_CR94","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1111\/j.1365-3083.2005.01685.x","volume":"62","author":"PD Frederiksen","year":"2005","unstructured":"Frederiksen, P. D., Thiel, S., Larsen, C. B. & Jensenius, J. C. M-ficolin, an innate immune defence molecule, binds patterns of acetyl groups and activates complement. Scand. J. Immunol. 62(5), 462\u2013473 (2005).","journal-title":"Scand. J. Immunol."},{"key":"23760_CR95","doi-asserted-by":"crossref","unstructured":"Sheerin, D., Abhimanyu, Wang, X., Johnson, W. E., Coussens, A. Systematic Evaluation of Transcriptomic Disease Risk and Diagnostic Biomarker Overlap Between COVID-19 and Tuberculosis: A Patient-Level Meta-Analysis. medRxiv. 2020.","DOI":"10.1101\/2020.11.25.20236646"},{"issue":"1","key":"23760_CR96","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12868-022-00742-8","volume":"23","author":"SJ Liu","year":"2022","unstructured":"Liu, S. J. et al. Long-term exercise training down-regulates m(6)A RNA demethylase FTO expression in the hippocampus and hypothalamus: An effective intervention for epigenetic modification. BMC Neurosci. 23(1), 54 (2022).","journal-title":"BMC Neurosci."},{"issue":"1\u20132","key":"23760_CR97","doi-asserted-by":"publisher","first-page":"34","DOI":"10.2119\/molmed.2008.00098","volume":"15","author":"B Sorensen","year":"2009","unstructured":"Sorensen, B., Jones, J. F., Vernon, S. D. & Rajeevan, M. S. Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome. Mol. Med. 15(1\u20132), 34\u201342 (2009).","journal-title":"Mol. Med."},{"issue":"22","key":"23760_CR98","doi-asserted-by":"publisher","first-page":"5093","DOI":"10.1113\/JP284047","volume":"601","author":"LC McIlvenna","year":"2023","unstructured":"McIlvenna, L. C. et al. Single vesicle analysis reveals the release of tetraspanin positive extracellular vesicles into circulation with high intensity intermittent exercise. J. Physiol. 601(22), 5093\u20135106 (2023).","journal-title":"J. Physiol."},{"issue":"2","key":"23760_CR99","doi-asserted-by":"publisher","first-page":"e12404","DOI":"10.1002\/jev2.12404","volume":"13","author":"JA Welsh","year":"2024","unstructured":"Welsh, J. A. et al. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. J. Extracell. Vesicles. 13(2), e12404 (2024).","journal-title":"J. Extracell. Vesicles."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-23760-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-23760-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-23760-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T16:03:24Z","timestamp":1769443404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-23760-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,26]]},"references-count":99,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["23760"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-23760-y","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,26]]},"assertion":[{"value":"27 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Asghar Abbasi is supported by TRDRP (28FT-0017), NIH (R43HL167289, 2R44HL167289-02, 5R44HL167289-03), and the Johnny Carson Foundation. William Stringer receives research foundation support from the Pulmonary Education and Research Foundation and the UCLA David Geffen School of Medicine (DGSoM)-Ventura County Community Foundation (VCCF) Long COVID 19 Research Award. He reports consulting fees from Verona, Genetech, and Vyaire. He is the co-author of a clinical exercise testing physiology textbook for Lippincott.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3469"}}