Extracellular vesicles in COVID-19 and long COVID: Structural mediators of viral persistence and immune dysfunction

Extracellular vesicles (EVs) have emerged as pivotal structural mediators of immune dysregulation and viral antigen persistence in long COVID. Rather than passive biological carriers, EVs released during SARS-CoV-2 infection function as highly organized lipid nanostructures that preserve the native conformational integrity of viral proteins, including the spike glycoprotein, thereby facilitating chronic signaling and systemic inflammation. Recent advancements in single-particle analytical techniques, such as cryo-electron tomography and atomic force microscopy, are now overcoming the limitations of bulk analysis, enabling the visualization of EV heterogeneity and the quantitative profiling of their nanomechanical properties. This review synthesizes current insights into how EV-associated viral remnants and host-derived inflammatory cargo propagate neuro-immune crosstalk and vascular injury. We conclude by evaluating the potential of EVs as precision biomarkers and bioengineered therapeutic platforms, emphasizing the need for standardized structural characterization to transition these nanovesicles from physiological mediators to clinical diagnostic and regenerative tools.