Diabetic Nephropathy and COVID-19: The Potential Role of Immune Actors

Abstract

Nowadays, type II diabetes mellitus, more specifically ensuing diabetic nephropathy, and severe COVID-19 disease are known to be closely associated. The exact mechanisms behind this association are less known. An implication for the angiotensin-converting enzyme 2 remains controversial. Some researchers have started looking into other potential actors, such as neuropilin-1, mitochondrial glutathione, vitamin D, and DPP4. In particular, neuropilin-1 seems to play an important role in the underlying mechanism linking COVID-19 and diabetic nephropathy. We suggest, based on the findings in this review, that its up-regulation in the diabetic kidney facilitates viral entry in this tissue, and that the engagement of both processes leads to a depletion of neuropilin-1, which was demonstrated to be strongly associated with the pathogenesis of DN. More studies are needed to confirm this hypothesis, and research should be directed towards elucidating the potential roles of all these suggested actors and eventually discovering new therapeutic strategies that could reduce the burden of COVID-19 in patients with diabetic nephropathy.

Keywords: ACE-2; COVID-19; DPP4; Neuropilin-1; diabetic nephropathy; immune actors; mitochondrial glutathione; vitamin D.

Figure 1

Mechanism of Cellular Entry of SARS-CoV-2 through NRP1. After binding of the spike protein to ACE-2 receptor, Furin-mediated cleavage of S protein at S1/S2 site leads to the exposure of the CendR motif of S1 which easily binds to the b1 subdomain of NRP1 receptor. This allows it to undergo membrane fusion and endocytosis. Abbreviations: ACE2, angiotensin-converting enzyme 2; CendR, C-end rule; NRP1, neuropilin 1.