Endothelial exosomal mir-24 predicts cerebrovascular events in covid-19 patients

ABSTRACT

Introduction: Neuropilin-1 has been recently identified as a co-factor needed for the entry of SARSCoV-2 in host cells and has been linked to neurologic symptoms of COVID-19 (Science 2020). Emerging evidence indicates that exosomal microRNAs (miRNAs) are involved in a number of physiologic and pathologic processes. However, to our knowledge, exosomal miRNAs have not been hitherto investigated in COVID-19. Hypothesis: Since we have recently demonstrated that miR-24 targets the 3'UTR of the gene encoding for Neuropilin-1 and this miRNA is expressed in human brain endothelial cells, we hypothesized an association between plasma levels of CD31 extracellular vesicles (EVs) enriched in miR-24 and the risk of cerebrovascular manifestations in patients hospitalized for COVID-19. Methods and Results: We obtained plasma from >300 COVID-19 patients;as control COVID-19 negative populations, we obtained plasma from healthy donors and patients hospitalized for cerebrovascular disorders. CD31 EVs were isolated from plasma on hospital admission, and miR24 levels were quantified. When comparing patients with vs without cerebrovascular disorders, we found that plasma levels of CD31 EV miR-24 were significantly different between these populations. We did not find any significant difference among groups when assessing circulating free levels of miR-24. Using a multiple regression analysis, adjusting for age, hypertension, and diabetes, the association between EV miR-24 and cerebrovascular complications in COVID-19 patients was confirmed (P<0.05). Conclusions: This is the first study showing a significant association between EV non-coding RNAs and clinical outcome in COVID-19 patients. Our results are relevant for basic researchers, because we identified an unprecedented significant association between EV miR-24 and cerebrovascular disorders, which could be helpful to better understand the molecular mechanisms underlying the pathophysiology of cerebrovascular events in COVID-19, as well as for clinicians, inasmuch as this association may help healthcare professionals in identifying COVID-19 patients who are at high risk of developing cerebrovascular disease.