Circulating extracellular vesicles from patients with severe COVID-19 upregulate Cathepsin B and activate STAT3 in normal human mesangial cells

Abstract

Abstract Severe COVID-19 disease is associated with acute kidney injury in up to 57% of infected patients. The etiology of this is likely multifactorial. Extracellular vesicles (EVs) contain unique molecular cargo that contributes to health and disease in many different organ systems and can contain useful surrogate biomarkers. To gain insight into SARS-CoV2’s impact on the human kidney, we prospectively collected blood and urine from individuals hospitalized with severe COVID-19 infection and isolated EVs. Using these EVs, we investigated the impact of circulating EVs released during COVID-19 infection on healthy human glomerular mesangial cells. Nanoparticle tracking analysis and electron microscopy showed that EVs isolated from the plasma of COVID-19 patients were larger in size compared to those isolated from the plasma of non-COVID-19 patients, suggesting the presence of unique cargo within circulating EVs in the setting of COVID-19. The plasma derived EV’s from COVID-19 patients also increased glomerular cell proliferation, STAT3 activation, and cathepsin B protein expression in normal human glomerular cells when compared to EVs isolated from the plasma of non-COVID-19 patients. These data suggest systemic EVs during COVID-19 infection alter normal human mesangial cell function. and provide insight into the effects of SARS-CoV2 on the kidney. This work was supported by the University of Florida College of Medicine and the University of Mississippi Medical Center.