When Viruses Talk through Extracellular Vesicles: a New Perspective on Sars-Cov-2-Induced Neurodegeneration.

SARS-CoV-2 infection is linked to persistent neurological symptoms Post-Acute Sequelae SARS-CoV-2 (neuro-PASC) and elevated risk of neurodegenerative disease, but molecular events connecting acute viral injury to long-term CNS dysfunction remain unclear. Here, we advance a perspective that Extracellular Vesicles (EVs) act as active mediators bridging SARS-CoV-2 infection and neurodegenerative processes. As nanoscale messengers capable of crossing the blood-brain barrier, EVs can transmit post-viral signals and orchestrate multi-target gene regulation in recipient cells through their microRNA (EV-miRNA) cargo. Our integrative analysis suggests that EV-miRNAs dysregulated in acute COVID-19, Alzheimer's Disease (AD), and Parkinson's Disease (PD) converge on pathways governing neurovascular integrity, redox and metabolic homeostasis, and neuronal proteostasis. We propose that sustained dysregulation of these interconnected modules-driven by EV-mediated signalling-may underlie the perpetuation of neuro-PASC and accelerate neurodegeneration in susceptible individuals. Viewing EVs as mechanistic agents that both transmit and amplify pathogenic cues reframes them as actionable targets for intervention and risk stratification. This perspective calls for translational frameworks that leverage EVs to illuminate, predict, and modify the trajectory of post-viral neurodegeneration.