Podocyte specific protein expression in urine exosome acts as a marker for renal injury in Long-COVID

Abstract Introduction: SARS-CoV2 has been associated with cardiometabolic diseases. At a cellular level, the infection may cause cellular inflammation and endothelial cell dysfunction (ECD). ECD is common in cardiometabolic diseases and is often associated with renal podocyte defect and proteinuria which has been recognized as an early manifestation of microvascular complication. In this study we explored whether presence of hyperglycemia predisposes to increased SARS-CoV2 infection at a cellular level. We also wanted to determine whether SARS-CoV2 infection puts an individual at a higher risk of developing cardio-metabolic complications such as kidney disease (DKD), associated with podocytopathy, in months to come following acute COVID infection. To estimate kidney damage, we evaluated albuminuria and podocyte specific protein in urine derived exosomes in urine obtained from SARS-CoV2 patients at 10 days, 6 months and 12 months post-acute SARS-CoV2 infection. Methods: Blood and Urine samples from SARS-CoV2 patients’ post-acute phase of infection were procured from George Washington University core facility. Peripheral blood mononuclear cells (PBMNCs) and urine exosomes were isolated and podocyte protein markers Podocalyxin (PODXL) and Nephrin (NEPH) were identified by western blot analysis. Results: Podocalyxin levels were significantly high at 10wk (n=18; p=0.001), 6month (n=25; p=0.003) and 12month(n=14; 0.0001) time points and Nephrin levels were noted to be high at 10week (n=18; p=0.001) and 12Months (n=14; p=0.007) time points. Interestingly, there were no significant differences noted on urine albumin: creatinine ratios (UACR) between the two groups at any of the time-points. Conclusion: A persistent high levels of podocyte specific proteins were noted in urinary exosomes even as far out as 12 months post Covid which may indicate long-standing podocyte inflammation leading to chronic kidney disease (CKD)The study also indicates that urine exosome based protein estimation specific for podocyte inflammation may be more sensitive biomarker for early CKD detection compared to UACR.