ArticleCell metabolism2022
A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells.
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Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57 citing papers in PubMed, 109 citations in OpenAlex.
- Construction, evaluation, and applications of renal barrier-on-a-chip system.Bioactive materials · 2026Review
- Advances and continuing challenges in differentiation of stem cells to human kidney tissue.Nature reviews. Nephrology · 2026Review
- Technological Innovations and the Translational Path of Kidney Organoids.Biomedicines · 2026Review
- Analysis of high glucose injury using human induced pluripotent stem cell-derived kidney organoids.BMC nephrology · 2026Article
- New Dimensions in Diabetic Kidney Disease Research: Advanced Organoids and Organs-on-a-Chip.BME frontiers · 2026Review
- Integrative Single-Cell RNA Sequencing and Machine Learning Reveals Candidate Plasma Protein-Associated Gene Signatures for Osteoporosis: A Preliminary Exploratory in Silico Study.International journal of general medicine · 2026Article
- FLOT1 and EEF1D: ac4C-related genes bridging Alzheimer's disease and sleep deprivation.Frontiers in aging neuroscience · 2026Article
- Decoding the interplay between COVID-19 and diabetic nephropathy through bioinformatics and systems biology techniques.Biochemistry and biophysics reports · 2025Article
- Systematic production of human kidney organoids for transplantation in porcine kidneys during ex vivo machine perfusion.Nature biomedical engineering · 2025Article
- Kidney Organoids: Current Advances and Applications.Life (Basel, Switzerland) · 2025Review
- Human Small Airway Epithelia Reveal Dichloroacetate as a Broad-Spectrum Antiviral Against Respiratory Viruses.International journal of molecular sciences · 2025Article
- Human iPSC-derived salivary gland organoids model diabetic salivary gland dysfunction.bioRxiv : the preprint server for biology · 2025Article
- A Vascularized Human Organ Chip Reveals SARS-CoV-2 Susceptibility in Developmentally Guided Tissue Maturation.Cellular and molecular bioengineering · 2025Article
- A survey of SARS-CoV-2 tropism.Infectious diseases & immunity · 2025Review
- Organoids: physiologically relevantJournal of virology · 2025Review
- Molecular dissection of the role of ACE2 in glucose homeostasis.Physiological reviews · 2025Review
- The Intersection of SARS-CoV-2 and Diabetes.Microorganisms · 2025Review
- Evaluating the impact of COVID-19 on cancer care: a comprehensive analysis of treatment modifications, risk factors, and patient outcomes.BMC infectious diseases · 2025Article
- Characterization of a SARS-CoV-2 infection model in golden hamsters with diabetes mellitus.Virologica Sinica · 2025Article
- Pathological Glucose Levels Enhance Entry Factor Expression and Hepatic SARS-CoV-2 Infection.Journal of cellular and molecular medicine · 2025Article
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Authors and funding
27 authors at 12 institutions in 7 countries.
Elena GarretaPluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Patricia PradoPluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Megan L StaniferDepartment of Infectious Diseases, Molecular Virology, Heidelberg University Hospital, Heidelberg, Germany; Research Group "Cellular Polarity and Viral Infection," German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA.
Vanessa MonteilKarolinska Institute and Karolinska University Hospital, Unit of Clinical Microbiology, 17182 Stockholm, Sweden.
Andrés MarcoPluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Asier Ullate-AgoteÁrea de Hemato-Oncología, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra (IDISNA), Universidad de Navarra, 31008 Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain; Departamento de Hematología, Clínica Universidad de Navarra, Universidad de Navarra, 31008 Pamplona, Spain.
Daniel Moya-RullPluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Amaia Vilas-ZornozaÁrea de Hemato-Oncología, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra (IDISNA), Universidad de Navarra, 31008 Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain; Departamento de Hematología, Clínica Universidad de Navarra, Universidad de Navarra, 31008 Pamplona, Spain.
Carolina TarantinoPluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Juan Pablo RomeroÁrea de Hemato-Oncología, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra (IDISNA), Universidad de Navarra, 31008 Pamplona, Spain.
Gustav JonssonIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
Roger OriaCenter for Bioengineering and Tissue Regeneration, UCSF, San Francisco, CA, USA.
Alexandra LeopoldiIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
Astrid HagelkruysIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
Maria GalloPluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Federico GonzálezPluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Pere Domingo-PedrolInternal Medicine Department, Hospital Universitario de la Santa Creu i Sant Pau, Barcelona, Spain.
Aleix GavaldàDepartament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina (IBUB), Universitat de Barcelona and CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain.
Carmen Hurtado Del PozoPluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Omar Hasan AliDepartment of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada; Department of Dermatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
Pedro Ventura-AguiarNephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Barcelona, Spain; Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain.
Josep María CampistolNephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Barcelona, Spain; Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain.
Felipe ProsperÁrea de Hemato-Oncología, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra (IDISNA), Universidad de Navarra, 31008 Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain; Departamento de Hematología, Clínica Universidad de Navarra, Universidad de Navarra, 31008 Pamplona, Spain.
Ali MirazimiKarolinska Institute and Karolinska University Hospital, Unit of Clinical Microbiology, 17182 Stockholm, Sweden; National Veterinary Institute, Uppsala, Sweden. Electronic address: ali.mirazimi@ki.se.
Steeve BoulantResearch Group "Cellular Polarity and Viral Infection," German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA; Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: s.boulant@ufl.edu.
Josef M PenningerIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada. Electronic address: josef.penninger@ubc.ca.
Nuria MontserratPluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain; Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Madrid, Spain. Electronic address: nmontserrat@ibecbarcelona.eu.
Institute for Bioengineering of Catalonia · ESInstitute of Molecular Biotechnology · ATNavarre Institute of Health Research · ESGerman Cancer Research Center · DEHospital Clínic de Barcelona · ESCalifornia Institute for Regenerative Medicine · USCentro de Investigación Biomédica en Red · ESHospital de Sant Pau · ESInstitució Catalana de Recerca i Estudis Avançats · ESKarolinska University Hospital · SESwedish Veterinary Agency · SEUniversity of British Columbia · CA
Funding
Austrian Science Fund FWF Z 271CIHR F20-02015CIHR F20-02343
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.
Indexed as
COVID-19Diabetes MellitusDiabetic NephropathiesAngiotensin-Converting Enzyme 2HumansKidneyOrganoidsPeptidyl-Dipeptidase ASARS-CoV-2ACE2 protein, humanAngiotensin-Converting Enzyme 2Peptidyl-Dipeptidase AACE2angiotensin-converting enzyme 2COVID-19diabetes 2human kidney organoidsSARS-CoV-2
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