Impact of SARS-CoV-2 Infection on Diabetes Pathophysiology

The interaction between SARS-CoV-2 and glucose metabolism has become a focal point in understanding both acute and long-term complications of COVID-19. Evidence now indicates that the virus can infiltrate pancreatic tissues, perturbing endocrine and exocrine cell function. Direct infection of β-cells may provoke cell stress, impaired insulin secretion and even transdifferentiation towards non-insulin-producing phenotypes. Concomitant inflammatory responses, characterised by elevated chemokines and cytokines, further exacerbate insulin resistance in peripheral tissues while promoting β-cell dysfunction. In older or metabolically vulnerable individuals, these effects are compounded by pre-existing adipose tissue inflammation and dysregulated energy homeostasis, yielding sustained hyperglycaemia. Epidemiological reports document an increased incidence of both type 1 and type 2 diabetes following SARS-CoV-2 infection, with risk peaking in the first months post-infection. Together, mechanistic and population studies underscore a bidirectional relationship in which diabetes predisposes to severe COVID-19 and conversely, SARS-CoV-2 infection accelerates glycaemic deterioration. These insights carry global significance for patient monitoring, blood-glucose management and the development of targeted interventions to mitigate long-term metabolic sequelae.

Research from Nature Portfolio

Recent studies using non-human primate models have recapitulated key features of post-acute metabolic sequelae. Infected African green monkeys developed persistent hyperglycaemia correlated with a dysregulated chemokine signature during acute illness. Despite minimal long-term viral replication in liver or pancreas, altered liver glycogen storage and sustained impairment of glucose tolerance were observed, mirroring human post-COVID metabolic decline. Moreover, administration of an mRNA vaccine early after infection appeared to ameliorate glycaemic disruption, suggesting potential benefits of timely immunomodulation.

Autopsy investigations of pancreatic tissue from COVID-19 patients have confirmed direct viral infiltration of β-cells. These analyses revealed variable expression of ACE2 and alternative entry factors in islet and microvascular compartments. Infiltration coincided with necroptotic cell death, immune cell recruitment and reduced β-cell mass, even in the absence of overt new-onset diabetes. Such findings highlight a mechanistic link between viral entry, local inflammation and subsequent metabolic dysregulation.

Impact of SARS-CoV-2 Infection on Diabetes Pathophysiology publication trend

The graph below shows the total number of articles in impact of sars-cov-2 infection on diabetes pathophysiology across all publications each year (not limited to Nature Index journals).

Technical terms

β-cell: A specialised pancreatic cell that synthesises and secretes insulin in response to elevated blood glucose.

ACE2 (Angiotensin-converting enzyme 2): A membrane receptor facilitating SARS-CoV-2 entry into host cells, expressed in pancreatic islets and microvasculature.

Hyperglycaemia: A condition characterised by elevated levels of glucose in the bloodstream, often resulting from impaired insulin action or secretion.

Transdifferentiation: The process by which a differentiated cell type converts into another mature cell phenotype without reverting to a stem cell state.

Chemokine: A small secreted protein that directs migration of immune cells to sites of inflammation or tissue injury.

References

1. Infection with SARS-CoV-2 can cause pancreatic impairment. Signal Transduction and Targeted Therapy (2024).
2. Diabetes Mellitus, Energy Metabolism, and COVID-19. Endocrine Reviews (2023).
3. Non-human primate model of long-COVID identifies immune associates of hyperglycemia. Nature Communications (2024).
4. SARS-CoV-2 Receptor Angiotensin I-Converting Enzyme Type 2 (ACE2) Is Expressed in Human Pancreatic β-Cells and in the Human Pancreas Microvasculature. Frontiers in Endocrinology (2020).
5. SARS-CoV-2 infection induces beta cell transdifferentiation. Cell Metabolism (2021).
6. Viral infiltration of pancreatic islets in patients with COVID-19. Nature Communications (2021).
7. Incidence of type 2 diabetes before and during the COVID-19 pandemic in Naples, Italy: a longitudinal cohort study. EClinicalMedicine (2023).
8. Risk for newly diagnosed diabetes after COVID-19: a systematic review and meta-analysis. BMC Medicine (2022).