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SARS-CoV-2 post-acute sequelae linked to inflammation via extracellular vesicles

Bachiller, Sara LU ; Vitallé, Joana ; Camprubí-Ferrer, Lluís LU ; García, Manuel ; Gallego, Isabel ; López-García, Marina ; Galvá, María Isabel ; Cañizares, Julio ; Rivas-Jeremías, Inmaculada and Díaz-Mateos, María , et al. (2025) In Frontiers in Immunology 16.
Abstract

Background: Despite the efficacy of SARS-CoV-2 vaccines in reducing mortality and severe cases of COVID-19, a proportion of survivors experience long-term symptoms, known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study investigates the long-term immunological and neurodegenerative effects associated with extracellular vesicles (EVs) in COVID-19 survivors, 15 months after SARS-CoV-2 infection. Methods: 13 Controls and 20 COVID-19 survivors, 15 months after SARS-CoV-2 infection, were recruited. Pro-inflammatory cytokines were analyzed in both plasma and EVs. A deep-immunophenotyping of monocytes, T-cells and dendritic cells (DCs) was performed, along with immunostainings of SARS-CoV-2 in the colon. Results: Higher... (More)

Background: Despite the efficacy of SARS-CoV-2 vaccines in reducing mortality and severe cases of COVID-19, a proportion of survivors experience long-term symptoms, known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study investigates the long-term immunological and neurodegenerative effects associated with extracellular vesicles (EVs) in COVID-19 survivors, 15 months after SARS-CoV-2 infection. Methods: 13 Controls and 20 COVID-19 survivors, 15 months after SARS-CoV-2 infection, were recruited. Pro-inflammatory cytokines were analyzed in both plasma and EVs. A deep-immunophenotyping of monocytes, T-cells and dendritic cells (DCs) was performed, along with immunostainings of SARS-CoV-2 in the colon. Results: Higher concentrations of pro-inflammatory cytokines and neurofilaments were found in EVs but not in plasma from COVID-19 survivors. Additionally, COVID-19 participants exhibited altered monocyte activation markers and elevated cytokine production upon lipopolysaccharide stimulation. Increased activation markers in CD4+ T-cells and decreased indoleamine 2,3-dioxygenase expression in DCs were observed in COVID-19 participants. Furthermore, the amount of plasmacytoid DCs expressing β7-integrin were higher in COVID-19, potentially associated with the viral persistence observed in the colon. Conclusions: COVID-19 survivors exhibit long-term immune dysregulation and neurodegeneration, emphasizing the need for ongoing monitoring of PASC. The cargo of EVs can be a promising tool for early detection of virus-induced neurological disorders.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
colon tissue, extracellular vesicles, immune system, post-acute sequelae, SARS-CoV-2
in
Frontiers in Immunology
volume
16
article number
1501666
publisher
Frontiers Media S. A.
external identifiers
  • pmid:40330474
  • scopus:105004456864
ISSN
1664-3224
DOI
10.3389/fimmu.2025.1501666
language
English
LU publication?
yes
id
a3cc9cc3-a05f-4a6a-80a8-711bdd13b3b6
date added to LUP
2025-09-19 15:25:17
date last changed
2025-10-03 17:23:19
@article{a3cc9cc3-a05f-4a6a-80a8-711bdd13b3b6,
  abstract     = {{<p>Background: Despite the efficacy of SARS-CoV-2 vaccines in reducing mortality and severe cases of COVID-19, a proportion of survivors experience long-term symptoms, known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study investigates the long-term immunological and neurodegenerative effects associated with extracellular vesicles (EVs) in COVID-19 survivors, 15 months after SARS-CoV-2 infection. Methods: 13 Controls and 20 COVID-19 survivors, 15 months after SARS-CoV-2 infection, were recruited. Pro-inflammatory cytokines were analyzed in both plasma and EVs. A deep-immunophenotyping of monocytes, T-cells and dendritic cells (DCs) was performed, along with immunostainings of SARS-CoV-2 in the colon. Results: Higher concentrations of pro-inflammatory cytokines and neurofilaments were found in EVs but not in plasma from COVID-19 survivors. Additionally, COVID-19 participants exhibited altered monocyte activation markers and elevated cytokine production upon lipopolysaccharide stimulation. Increased activation markers in CD4+ T-cells and decreased indoleamine 2,3-dioxygenase expression in DCs were observed in COVID-19 participants. Furthermore, the amount of plasmacytoid DCs expressing β7-integrin were higher in COVID-19, potentially associated with the viral persistence observed in the colon. Conclusions: COVID-19 survivors exhibit long-term immune dysregulation and neurodegeneration, emphasizing the need for ongoing monitoring of PASC. The cargo of EVs can be a promising tool for early detection of virus-induced neurological disorders.</p>}},
  author       = {{Bachiller, Sara and Vitallé, Joana and Camprubí-Ferrer, Lluís and García, Manuel and Gallego, Isabel and López-García, Marina and Galvá, María Isabel and Cañizares, Julio and Rivas-Jeremías, Inmaculada and Díaz-Mateos, María and Gasca-Capote, Carmen and Moral-Turón, Cristina and Galán-Villamor, Lourdes and Fontillón, María and Sobrino, Salvador and Cisneros, José Miguel and López-Cortés, Luis Fernando and Deierborg, Tomas and Ruiz-Mateos, Ezequiel}},
  issn         = {{1664-3224}},
  keywords     = {{colon tissue; extracellular vesicles; immune system; post-acute sequelae; SARS-CoV-2}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{SARS-CoV-2 post-acute sequelae linked to inflammation via extracellular vesicles}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2025.1501666}},
  doi          = {{10.3389/fimmu.2025.1501666}},
  volume       = {{16}},
  year         = {{2025}},
}