Post Acute Infection Of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Leads To Systemic Inflammation And Podocyte Injury.

Introduction: COVID-19 attributed to SARS-CoV2 infection is a world-wide pandemic. SARS-CoV2 has been associated with cardiovascular disease and diabetes. At a cellular level, the infection causes endothelial cell dysfunction (ECD), which is manifested by entities such as microvascular thrombosis. ECD is quite common in type 2 diabetes mellitus (T2DM) where the renal podocyte dysfunction is often an early manifestation of microvascular complication. In this study we explored whether presence of hyperglycemia predisposes to increased SARS-CoV2 infection and whether co-morbid presence of COVID-19 and hyperglycemia predisposes to cardio-metabolic complications such as diabetic kidney disease (DKD). To estimate kidney damage we evaluated albuminuria and podocyte markers in urine exosomes from SARS-CoV2 patients at 10 days, 6 months and 12 months post COVID-19 infection. Methods: Blood and Urine samples from SARS-CoV2 patients post acute phase of infection were procured from the core facility. Peripheral blood mononuclear cells (PBMNCs) and urine exosomes were isolated and podocyte protein markers such as Nephrin (Nep), Podocalyxin (PODXL) and Wilm’s Tumour-1 (WT-1) were identified by western blot analysis. Results: Our results showed that human kidney cells on exposure to hyperglycemia (5 vs 25mM) upregulates expression of TMPRSS2 gene, a key receptor for SARS-CoV2, by 5 fold. Next we examined blood and urine samples from COVID-19, subjects (n=16). As all examined subjects had blood glucose levels above 400mg%, we used samples from T2DM subjects with no COVID-19 infection, as a comparator. COVID-MNCs showed persistent over-expression of IL-6 and TNFa (4-fold) even at 12 months post infection. Urine-exosomal-Nephrin protein band expression was 10-fold higher than T2DM-No-COVID urine-exosomal-Nephrin protein band Similar trend was noted on estimating PODXL and WT-1. Conclusions: A persistent inflammatory marker over-expression at 12 months in COVID samples indicate possible long standing renal damage. Increased podocyte specific protein loss at 12 months compared to samples from T2DM subjects with similar GFR also indicates persistent kidney damage which may lead to renal failure and hypertension.