{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:21:41Z","timestamp":1785212501200,"version":"3.55.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Long COVID (LC) is characterized by symptoms persisting at least 3 months after SARS-CoV-2 infection and affecting multiple organ systems. Diagnosis relies on subjective criteria without established biomarkers. Immune dysregulation and mitochondrial dysfunction are implicated in LC pathophysiology. Given clinical overlap with myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS), we investigated whether plasma extracellular vesicles (EVs) capture shared molecular signatures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Plasma EVs from 125 individuals across pandemic-era and prepandemic cohorts were analyzed. The pandemic-era cohort included COVID-Recovered, LC with ME\/CFS phenotype (LC-ME\/CFS), and ME\/CFS without infection (pan-ME\/CFS). The prepandemic cohort included ME\/CFS and matched controls. Extracellular vesicles were isolated using size-exclusion chromatography. Concentration and size were assessed by nanoparticle tracking analysis, and surface markers and mitochondrial membrane potential were evaluated by flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both pan-ME\/CFS and LC-ME\/CFS exhibited elevated EV concentrations compared with COVID-recovered controls after false discovery rate (FDR) correction (q = 0.0042 and 0.0024). Leukocyte-, monocyte\/macrophage-, and platelet-derived EVs were increased, whereas B cell\u2013derived EVs were reduced in both groups. Compared with controls, pan-ME\/CFS demonstrated increased mitochondrial membrane potential in B cell\u2013, monocyte\/macrophage-, and NK cell\u2013derived subsets after FDR correction, whereas no significant differences were observed in LC-ME\/CFS. Prepandemic ME\/CFS showed a nominal increase in leukocyte-derived EVs that did not persist after correction, whereas elevated mitochondrial membrane potential in B cell\u2013derived EV subsets remained significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ME\/CFS and LC-ME\/CFS demonstrate partially overlapping immune cell\u2013associated EV alterations. Mitochondrial membrane potential alterations within selected immune-derived EV subsets, particularly B cell\u2013associated EVs, suggest immune-metabolic involvement. Plasma EV profiling may inform future biomarker development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofag209","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:46:34Z","timestamp":1778154394000},"source":"Crossref","is-referenced-by-count":1,"title":["Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell\u2013Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4019-8990","authenticated-orcid":false,"given":"Gentaro","family":"Ikeda","sequence":"first","affiliation":[{"name":"Stanford Cardiovascular Institute and Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Koike-Ieki","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute and Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute and Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arya V","family":"Dadhania","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-5424","authenticated-orcid":false,"given":"Vanessa","family":"El Kamari","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6305-758X","authenticated-orcid":false,"given":"Prasanna","family":"Jagannathan","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda N","family":"Geng","sequence":"additional","affiliation":[{"name":"Division of Primary Care Population Health, Department of Medicine, Stanford University School of Medicine , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell G","family":"Miglis","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Science, Stanford University School of Medicine , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W","family":"Shafer","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip C","family":"Yang","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute and Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector Fabio","family":"Bonilla","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"2026051213471084800_ofag209-B1","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1093\/infdis\/jiaf030","article-title":"The current and future burden of long COVID in the United States","volume":"231","author":"Bartsch","year":"2025","journal-title":"J Infect Dis"},{"key":"2026051213471084800_ofag209-B2","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1038\/s41591-024-03173-6","article-title":"Long COVID science, research and policy","volume":"30","author":"Al-Aly","year":"2024","journal-title":"Nat 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