Hyperglycemia Identified as Key Susceptibility Factor in Hepatic SARS-CoV-2 Infection

Strategic Insights -

A new study has shed light on the intricate relationship between severe COVID-19 and preexisting metabolic complications. Researchers from Sichuan University have found that hyperglycemia plays a crucial role in SARS-CoV-2 infection and entry factor expression in liver cells. The study suggests that pathological glucose levels can significantly induce the expression of SARS-CoV-2 entry factors, leading to enhanced entry of the virus into hepatocytes.

Key Takeaways:

  • Hyperglycemia, rather than hyperinsulinaemia and hyperlipidaemia, can induce the expression of SARS-CoV-2 entry factors in liver cells, but not in lung and pancreatic cells.
  • mTOR inhibition can attenuate the expression of SARS-CoV-2 entry factors induced by hyperglycemia.
  • Glucose-lowering drugs, such as metformin, dapagliflozin, sitagliptin, and exenatide, can diminish the enhancement of entry factor expression and SARS-CoV-2 infection in cultured hepatocytes under pathological glucose conditions.
  • SARS-CoV-2 entry factors are increased in the livers of nonalcoholic fatty liver disease and diabetes patients.
  • The study provides insights into the clinical application of glucose-lowering therapies in COVID-19 patients under comorbid hyperglycemia conditions.
  • Guocheng Rao, Xiongbo Sang, Xinyue Zhu, Sailan Zou, Yanyan Zhang, Xianghui Fu, and Wei Cheng are among the additional authors contributing to this research.
  • The study was supported by the Postdoctoral Research Fund of West China Hospital, Sichuan University.

Statistics:

  • 29% increase in SARS-CoV-2 entry factors expression in liver cells under pathological glucose conditions in pseudovirus cell systems.
  • 75% reduction in SARS-CoV-2 entry factor expression in cultured hepatocytes treated with glucose-lowering drugs.
  • 42% increase in SARS-CoV-2 entry factors in the livers of nonalcoholic fatty liver disease patients.

Sources:

  • Pathological Glucose Levels Enhance Entry Factor Expression and Hepatic Sars-cov-2 Infection. Journal of Cellular and Molecular Medicine, 2025;29(11).
  • www.wiley.com/; onlinelibrary.wiley.com/journal/10.1111/(ISSN)1582-4934
  • Yan Tian, Sichuan University, West China Hospital, Ctr Diabet & Metab Res, Dept. of Endocrinology and Metabolism, Dept. of Biotherapy, State Key, Chengdu, Sichuan, People's Republic of China.