RENAL DISEASE IN COVID-19: INSIGHTS FROM SARS-CoV-2 SPIKE PROTEIN

Severe COVID-19 involves multiple organ damage, including kidney damage. Some studies have reported a correlation between acute kidney injury and worse outcome in patients with COVID-19 with increased morbidity and mortality. This scenario could be worse because some patients with COVID-19 present subclinical acute kidney injury characterized by tubular damage without changes in the glomerular flow rate. Indeed, it has been shown that COVID-19 patients develop Fanconi-like syndrome characterized by proximal tubule epithelial cells (PTECs) injury associated with low-molecular-weight proteinuria and albuminuria. This syndrome encompasses changes in PTECs protein endocytic machinery. Protein reabsorption in PTECs occurs mainly via a canonical receptor-mediated endocytosis where the receptor is formed by the assembly of three proteins: megalin, cubilin and amnionless. Interestingly, changes in megalin expression have been correlated to a pro-inflammatory phenotype associated with development of tubule interstitial injury. Kidney biopsy samples from patients with COVID-19 revealed a specific decrease in megalin expression in PTECs. These observations suggest that megalin-mediated albumin reabsorption in PTECs could be involved in the albuminuria and tubule injury observed in COVID-19.

SARS-CoV-2 infection initially involves engagement of the SARS-CoV-2 spike protein (S protein) to angiotensin converting enzyme type 2 present at the cell surface of diverse cell types. However, the mechanism of COVID-19 pathogenesis could be more complex than has been imagined so far. One attractive hypothesis is the possible role of different proteins of SARS-CoV-2 in this process. Some authors have proposed that S protein, a structural glycoprotein, could also play an important role in the pathogenesis of COVID-19. It was observed that isolated S protein modulates cellular function in different cell types such as monocytes, endothelial cells and heart pericytes. In addition, S protein was found in the urine of patients with COVID-19, indicating its presence in the luminal side of PTECs and suggesting a possible effect on PTECs function.

In this symposium we will discuss results related to possible modulation of megalin-mediated albumin endocytosis by S protein and the molecular mechanisms underlying this process. We believe that this mechanism could be behind the albuminuria and tubular injury observed in COVID-19 patients.