Extracellular vesicles containing SARS-CoV-2 proteins are associated with multi-organ dysfunction and worse outcomes in patients with severe COVID-19.

Autor: de Miguel-Perez D; Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Division of Medical Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA., Arroyo-Hernandez M; Thoracic Oncology Unit, Instituto Nacional de Cancerologia (INCan), Mexico City, Mexico., La Salvia S; Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Gunasekaran M; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.; Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Pickering EM; Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.; Division of Pulmonary, Critical Care and Sleep Medicine, Rush University Medical Center, Chicago, Illinois, USA., Avila S; Transplant and Cellular Therapy Program, Department of Medicine, University of Maryland School of Medicine and Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA., Gebru E; Transplant and Cellular Therapy Program, Department of Medicine, University of Maryland School of Medicine and Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA., Becerril-Vargas E; National Institute of Respiratory Diseases, Mexico City, Mexico., Monraz-Perez S; National Institute of Respiratory Diseases, Mexico City, Mexico., Saharia K; Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA., Grazioli A; Department of Medicine, Program in Trauma, University of Maryland School of Medicine, Baltimore, Maryland, USA., McCurdy MT; Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA., Frieman M; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA., Miorin L; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Russo A; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA., Cardona AF; Institute for Research and Education, Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center (CTIC), Bogotá, Colombia., García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; The Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Kaushal S; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.; Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Hirsch FR; Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Atanackovic D; Transplant and Cellular Therapy Program, Department of Medicine, University of Maryland School of Medicine and Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA., Sahoo S; Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Arrieta O; Thoracic Oncology Unit, Instituto Nacional de Cancerologia (INCan), Mexico City, Mexico., Rolfo C; Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Division of Medical Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Jazyk: angličtina
Zdroj: Journal of extracellular vesicles [J Extracell Vesicles] 2024 Nov; Vol. 13 (11), pp. e70001.
DOI: 10.1002/jev2.70001
Abstrakt: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and has been related to more than 7 million deaths globally since 2019. The association of high levels of IL-6 with severe cases led to the early evaluation of the anti-IL6 inhibitor tocilizumab as a potential treatment, which unfortunately failed to improve survival in many trials. Moreover, little is known about the development of COVID-19 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-19, 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-up, 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-cytometry, 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-19 and possible long COVID.
(© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)
Databáze: MEDLINE
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