Diabetes is linked to enhanced susceptibility to severe COVID-19, but the underlying reasons are not well understood. Here, Garetta et al. report the development of diabetic-like kidney organoids, induced by an oscillatory glucose regimen. Expression of the cell surface receptor ACE2 was shown to be essential for infection with SARS-CoV-2. Diabetic conditions both enhanced cellular expression of ACE2 and induced a switch from oxidative phosphorylation to aerobic glycolysis, which increased viral loads upon infection of the organoids. Similar observations were made in kidney proximal tubular cells isolated from patients with diabetes, where altered mitochondrial respiration and enhanced glycolysis correlated with higher viral loads after SARS-CoV-2 infection. Conversely, treatment of patient kidney cells with an inhibitor of aerobic glycolysis resulted in reduced viral loads upon viral exposure. This demonstrates that diabetes-associated metabolic reprogramming increases susceptibility of kidney cells to SARS-CoV-2 infection, providing a possible explanation why diabetes can worsen outcome in patients with COVID-19.
Garreta, E. et al. A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells. Cell Metab. https://doi.org/10.1016/j.cmet.2022.04.009 (2022)
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Flemming, A. Diabetes enhances viral loads in COVID-19. Nat Rev Immunol 22, 410 (2022). https://doi.org/10.1038/s41577-022-00748-7