Scientific publications

A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells

Jun 7, 2022 | Magazine: Cell Metabolism

Elena Garreta  1 , Patricia Prado  1 , Megan L Stanifer  2 , Vanessa Monteil  3 , Andrés Marco  1 , Asier Ullate-Agote  4 , Daniel Moya-Rull  1 , Amaia Vilas-Zornoza  4 , Carolina Tarantino  1 , Juan Pablo Romero  5 , Gustav Jonsson  6 , Roger Oria  7 , Alexandra Leopoldi  6 , Astrid Hagelkruys  6 , Maria Gallo  1 , Federico González  1 , Pere Domingo-Pedrol  8 , Aleix Gavaldà  9 , Carmen Hurtado Del Pozo  1 , Omar Hasan Ali  10 , Pedro Ventura-Aguiar  11 , Josep María Campistol  11 , Felipe Prosper  4 , Ali Mirazimi  12 , Steeve Boulant  13 , Josef M Penninger  14 , Nuria Montserrat  15


Abstract

It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development.

Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection.

Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections.

Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism.

CITATION  Cell Metab. 2022 Jun 7;34(6):857-873.e9. doi: 10.1016/j.cmet.2022.04.009. Epub 2022 May 12

Our authors

Asier Ullate Agote
Investigador postdoctoral del Grupo de Patología Mieloide del Cima Universidad de Navarra
Juan Pablo Romero Riojas