SARS-CoV-2 post-acute sequelae linked to inflammation via extracellular vesicles, 2025, Bachiller et al

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

Sara Bachiller, Joana Vitalle, Lluís Camprubí-Ferrer, Manuel García, Isabel Gallego, Marina López-García, María Isabel Galvá, Julio Cañizares, Inmaculada Rivas-Jeremías, María Díaz-Mateos, Carmen Gasca-Capote, Cristina Moral-Turón, Lourdes Galán- Villamor, María Fontillón, Salvador Sobrino, José Miguel Cisneros, Luis F. Lopez-Cortes, Tomas Deierborg, Ezequiel Ruiz-Mateos

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Background
Despite the efficacy of SARS-CoV-2 vaccines in reducing mortality and severe cases of COVID-19, a significant proportion of survivors experience long-term symptoms, known as postacute 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 healthy donors (HD)Controls and 20 COVID-19 survivors, 15 months after SARS-CoV-2 infection, were recruited. Proinflammatory 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 proinflammatory 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 (LPS) stimulation.

Increased activation markers in CD4+ T-cells and decreased indoleamine 2,3-dioxygenaseIDO expression in DCs were observed in COVID-19 participants.

Furthermore, the levels amount of plasmacytoid DCs (pDCs) 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 seems tocan be a promising tool for early detection of virus-induced neurological disorders.

Link (Frontiers in Immunology) [Provisionally accepted, currently only abstract]
 
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I’m very curious how they confirmed COVID-negative status for their controls.
eighteen Controls (without any documented SARS-CoV-2 infection) from Heliopolis nursing home (Seville, Spain). The Control population included a highly monitored group of elderly individuals, with regulated visits and routine analytical assessments. In fact, due to this rigorous monitoring, five active cases of SARS-CoV-2 were detected during the sample collection and were therefore excluded from the analysis.
thirteen aged- and sex-matched Controls were enrolled.
 
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