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

tetano

Editor, Senior Moderator
Front Immunol


. 2025 Apr 16:16:1501666.
doi: 10.3389/fimmu.2025.1501666. eCollection 2025. SARS-CoV-2 post-acute sequelae linked to inflammation via extracellular vesicles

Sara Bachiller[SUP] 1 2 [/SUP], Joana Vitallé[SUP] 1 [/SUP], Lluís Camprubí-Ferrer[SUP] 3 [/SUP], Manuel García[SUP] 1 [/SUP], Isabel Gallego[SUP] 1 2 [/SUP], Marina López-García[SUP] 4 [/SUP], María Isabel Galvá[SUP] 5 [/SUP], Julio Cañizares[SUP] 5 [/SUP], Inmaculada Rivas-Jeremías[SUP] 1 [/SUP], María Díaz-Mateos[SUP] 6 [/SUP], Carmen Gasca-Capote[SUP] 1 [/SUP], Cristina Moral-Turón[SUP] 1 [/SUP], Lourdes Galán-Villamor[SUP] 7 [/SUP], María Fontillón[SUP] 7 [/SUP], Salvador Sobrino[SUP] 8 [/SUP], José Miguel Cisneros[SUP] 1 [/SUP], Luis Fernando López-Cortés[SUP] 1 [/SUP], Tomas Deierborg[SUP] 3 [/SUP], Ezequiel Ruiz-Mateos[SUP] 1 [/SUP]



Affiliations
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 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.

Keywords: SARS-CoV-2; colon tissue; extracellular vesicles; immune system; post-acute sequelae.

 
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