Abstract
This study explores the concentration, size, and epitope profiles of extracellular vesicles (EVs) as biomarkers for COVID-19 outcomes. CD86 stood out as a key predictor of mortality, suggesting that EV profiling could help assess disease severity and guide treatment decisions. BACKGROUND: SARS-CoV-2 infection triggers a complex array of immune and vascular responses. Extracellular vesicles (EVs) have emerged as critical players in the disease's progression and potential biomarkers for assessing severity. AIM: To explore the concentration, size, and epitope profiles of EVs in COVID-19 patients and correlate these findings with clinical outcomes. METHODS: We analyzed EVs from 80 COVID-19 patients (critical or non-critical). EV concentration and size were measured using Nanoparticle Tracking Analysis (NTA) and Videodrop, while antigen expression was assessed via a 37-marker MACSPlex bead assay. RESULTS: Our findings reveal a significant elevation in circulating EV concentration in critical COVID-19 patients as measured by Videodrop (p = 0.007), though not by NTA (p = 0.063), highlighting method-specific sensitivities. Key EV surface markers, including CD86, CD8, CD326, CD209, and CD9, were significantly higher in critical patients, while CD19 was reduced. Kaplan-Meier survival analysis showed that higher expression levels of several EV markers, including CD86, were associated with decreased survival. Among these, CD86 emerged as the most potent independent predictor of in-hospital mortality, regardless of inflammatory status. CONCLUSION: This study highlights the importance of CD86-expressing EVs as biomarkers for COVID-19 severity and mortality, suggesting that EV profiling could inform personalized therapies for severe cases.