{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:28:39Z","timestamp":1792772919162,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI135972"],"award-info":[{"award-number":["U19AI135972"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI168631"],"award-info":[{"award-number":["U19AI168631"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) causes coronavirus disease 2019 (COVID\u201019) and has been related to more than 7 million deaths globally since 2019. The association of high levels of IL\u20106 with severe cases led to the early evaluation of the anti\u2010IL6 inhibitor tocilizumab as a potential treatment, which unfortunately failed to improve survival in many trials. Moreover, little is known about the development of COVID\u201019 sequelae, and biomarkers are needed to understand and anticipate these processes. Because extracellular vesicles (EVs) play an important role in viral infection and immune response, they could potentially serve as predictive and prognostic biomarkers. We isolated EVs from 39 patients with severe COVID\u201019, from which 29 received tocilizumab and 10 were considered controls. Blood samples, which were collected at hospitalisation before treatment, at Day 7, and Day 15 during follow\u2010up, were assessed by immunoblot for longitudinal expression of spike (S) and nucleocapsid (N) proteins. Dynamic expression was calculated and compared with clinicopathological and experimental variables. Expression of EV S was validated by immunogold and imaging flow\u2010cytometry, revealing an enrichment in CD9+ EVs. As a result, decreasing expression of EV viral proteins was observed in patients treated with tocilizumab. Moreover, higher increase in EV S was observed in patients with lower antibody response, hyperfibrinogenemia, lower respiratory function, higher blood pressure and shorter outcomes. These findings lay the foundation for future studies characterizing the role of EVs in multiorgan assessment and identifying biomarkers in patients with severe COVID\u201019 and possible long COVID.<\/jats:p>","DOI":"10.1002\/jev2.70001","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T03:39:59Z","timestamp":1731987599000},"source":"Crossref","is-referenced-by-count":17,"title":["Extracellular vesicles containing SARS\u2010CoV\u20102 proteins are associated with multi\u2010organ dysfunction and worse outcomes in patients with severe COVID\u201019"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2822-4466","authenticated-orcid":false,"given":"Diego","family":"de Miguel\u2010Perez","sequence":"first","affiliation":[{"name":"Center for Thoracic Oncology, Tisch Cancer Institute Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Division of Medical Oncology, The James Comprehensive Cancer Center The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisol","family":"Arroyo\u2010Hernandez","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Unit Instituto Nacional de Cancerologia (INCan)  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"La Salvia","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthukumar","family":"Gunasekaran","sequence":"additional","affiliation":[{"name":"Marlene and Stewart Greenebaum Comprehensive Cancer Center University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M.","family":"Pickering","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"Division of Pulmonary, Critical Care and Sleep Medicine Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Avila","sequence":"additional","affiliation":[{"name":"Transplant and Cellular Therapy Program, Department of Medicine University of Maryland School of Medicine and Greenebaum Comprehensive Cancer Center  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etse","family":"Gebru","sequence":"additional","affiliation":[{"name":"Transplant and Cellular Therapy Program, Department of Medicine University of Maryland School of Medicine and Greenebaum Comprehensive Cancer Center  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Becerril\u2010Vargas","sequence":"additional","affiliation":[{"name":"National Institute of Respiratory Diseases  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Monraz\u2010Perez","sequence":"additional","affiliation":[{"name":"National Institute of Respiratory Diseases  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kapil","family":"Saharia","sequence":"additional","affiliation":[{"name":"Institute of Human Virology University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Grazioli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Program in Trauma University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5319-0475","authenticated-orcid":false,"given":"Michael T.","family":"McCurdy","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Frieman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Miorin","sequence":"additional","affiliation":[{"name":"Department of Microbiology Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Global Health and Emerging Pathogens Institute Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Russo","sequence":"additional","affiliation":[{"name":"Marlene and Stewart Greenebaum Comprehensive Cancer Center University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s F.","family":"Cardona","sequence":"additional","affiliation":[{"name":"Institute for Research and Education Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center (CTIC)  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"Garc\u00eda\u2010Sastre","sequence":"additional","affiliation":[{"name":"Department of Microbiology Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Global Health and Emerging Pathogens Institute Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"The Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Medicine, Division of Infectious Diseases Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunjay","family":"Kaushal","sequence":"additional","affiliation":[{"name":"Marlene and Stewart Greenebaum Comprehensive Cancer Center University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"Departments of Surgery and Pediatrics, Ann and Robert H. 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