Extracellular Vesicle Protein Cargo Reveals Potential Long-Term Biological Impact of Long COVID
5 affiliations
- 1Henry M Jackson Foundation for Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA
- 2Agile Vaccines and Therapeutics Department, Infectious Diseases Directorate, Navy Medicine Research and Development Command, Silver Spring, MD 20910, USA
- 3Translational and Clinical Research Department, Infectious Diseases Directorate, Navy Medicine Research and Development Command, Silver Spring, MD 20910, USA
- 4Division of Infectious Diseases, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA
- 5U.S. Naval Medical Research Unit SOUTH, U.S. Embassy Lima, Centro Medico Naval, Av. Venezuela cuadra 36 s/n, Callao 15088, Peru
Abstract
Extracellular vesicles (EVs) carry status quo messages across the body that can help decode the long-term impact of Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Here, we analyzed paired peripheral blood mononuclear cell (PBMC)-EVs (pre- and 6–8 months post-infection) collected from a subset of young United States (US) Marines with and without a history of PASC symptoms lasting >30 days post-infection, who participated in the COVID-19 Health Action and Response for Marines (CHARM) studies. Integrated nanospray LC-MS/MS, STRING and Reactome analysis of PBMC-EVs identified distinct proteomic signatures and biological pathways associated with different PASC symptoms. An individual who reported PASC headache and drowsiness (n = 1) had elevated histones, prelamin A/C, lysozyme C and S100-A9, among other proteins enriched with cellular stress pathways, including DNA damage, oxidative/metabolic/cytoskeletal stress, senescence, neutrophil degranulation and neurodegenerative-like diseases. Conversely, some participants who reported pulmonary PASC (n = 5, pooled) had elevated histones but decreased fibrinogen, integrin β-3 and S100-A9, mapped to senescence, platelet dysfunction, and immune exhaustion pathways. Non-PASC individuals (n = 9) exhibited active inflammation resolution, without returning to the pre-infection homeostasis even after 6–8 months post-infection. These distinct PBMC-EV proteomic signatures suggest potential long-term impact of long COVID with implications for the public health and mission readiness of US service members.
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BibTeX
@article{oda2026extracellular,
title = {{Extracellular Vesicle Protein Cargo Reveals Potential Long-Term Biological Impact of Long COVID}},
author = {Kyosuke Oda and Arnel Belmonte and David Boulifard and Silvia Jakubski and Lindsey White and Charmagne Beckett and Andrew Letizia and Chad Porter and Eileen Villasante and Yuliya S. Johnson and Wathsala Wijayalath},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211969},
url = {https://www.mdpi.com/2073-4409/15/21/1969},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Extracellular Vesicle Protein Cargo Reveals Potential Long-Term Biological Impact of Long COVID
AU - Kyosuke Oda
AU - Arnel Belmonte
AU - David Boulifard
AU - Silvia Jakubski
AU - Lindsey White
AU - Charmagne Beckett
AU - Andrew Letizia
AU - Chad Porter
AU - Eileen Villasante
AU - Yuliya S. Johnson
AU - Wathsala Wijayalath
PY - 2026
DA - 2026/10/29
JO - Cells
DO - 10.3390/cells15211969
UR - https://www.mdpi.com/2073-4409/15/21/1969
AB - Extracellular vesicles (EVs) carry status quo messages across the body that can help decode the long-term impact of Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Here, we analyzed paired peripheral blood mononuclear cell (PBMC)-EVs (pre- and 6–8 months post-infection) collected from a subset of young United States (US) Marines with and without a history of PASC symptoms lasting >30 days post-infection, who participated in the COVID-19 Health Action and Response for Marines (CHARM) studies. Integrated nanospray LC-MS/MS, STRING and Reactome analysis of PBMC-EVs identified distinct proteomic signatures and biological pathways associated with different PASC symptoms. An individual who reported PASC headache and drowsiness (n = 1) had elevated histones, prelamin A/C, lysozyme C and S100-A9, among other proteins enriched with cellular stress pathways, including DNA damage, oxidative/metabolic/cytoskeletal stress, senescence, neutrophil degranulation and neurodegenerative-like diseases. Conversely, some participants who reported pulmonary PASC (n = 5, pooled) had elevated histones but decreased fibrinogen, integrin β-3 and S100-A9, mapped to senescence, platelet dysfunction, and immune exhaustion pathways. Non-PASC individuals (n = 9) exhibited active inflammation resolution, without returning to the pre-infection homeostasis even after 6–8 months post-infection. These distinct PBMC-EV proteomic signatures suggest potential long-term impact of long COVID with implications for the public health and mission readiness of US service members.
SN - 2073-4409
ER -