Covid-19 and Diabetes: A Complex Bidirectional Relationship

Abstract

Covid-19 is a recently-emerged infectious disease caused by the novel severe acute respiratory syndrome coronavirus SARS-CoV2. SARS-CoV2 differs from previous coronavirus infections (SARS and MERS) due to its high infectivity (reproduction value, R₀, typically 2-4) and pre- or asymptomatic transmission, properties that have contributed to the current global Covid-19 pandemic. Identified risk factors for disease severity and death from SARS-Cov2 infection include older age, male sex, diabetes, obesity and hypertension. The reasons for these associations are still largely obscure. Evidence is also emerging that SARS-CoV2 infection exacerbates the underlying pathophysiology of hyperglycemia in people with diabetes. Here, we discuss potential mechanisms through which diabetes may affect the risk of more severe outcomes in Covid-19 and, additionally, how diabetic emergencies and longer term pathology may be aggravated by infection with the virus. We consider roles for the immune system, the observed phenomenon of microangiopathy in severe Covid-19 infection and the potential for direct viral toxicity on metabolically-relevant tissues including pancreatic beta cells and targets of insulin action.

Keywords: Covid-19; diabetes; ketoacidosis; management; microangiopathy.

Figure 1

Cellular pathogenesis of coronavirus infection. The lipid envelope (viral) includes spike glycoprotein binding to receptors (ACE2) on the surface of the host. The, entry of cell by endocytosis followed by membrane fusion and release of the virion into the cytosol. Entry of viral RNA into the nucleus and production of new strands of viral RNA and viral proteins. Viral RNA output from the nucleus. Assembly, budding and release of new viruses, impact on organs.

Figure 2

SARS-CoV-2 infection worsens diabetes. Recognition by SAR-CoV-2 of receptors present on immune cells (macrophages, monocytes.) and ACE2 receptors, expressed in several tissues (brain, muscle, adipose tissue, liver, pancreas). Infection causes lowered insulin production and insulin resistance by presently undefined mechanisms.

Figure 3

Type 2 diabetes management therapeutics in Covid-19. The six main classes of glucose-lowering drugs summarized according to their reported effect on inflammation, cardiovascular disease, respiratory disease and critically ill patient safety.