COVID-19 Vaccines and Hyperglycemia-Is There a Need for Postvaccination Surveillance?

Abstract

The COVID-19 vaccines currently in use have undoubtedly played the most significant role in combating the SARS-CoV-2 virus and reducing disease severity and the risk of death among those affected, especially among those with pre-existing conditions, such as diabetes. The management of blood glucose levels has become critical in the context of the COVID-19 pandemic, where data show two- to threefold higher intensive care hospital admissions and more than twice the mortality rate among diabetic COVID-19 patients when compared with their nondiabetic counterparts. Furthermore, new-onset diabetes and severe hyperglycemia-related complications, such as hyperosmolar hyperglycemic syndrome (HHS) and diabetic ketoacidosis (DKA), were reported in COVID-19 patients. However, irrespective of the kind of vaccine and dosage number, possible vaccination-induced hyperglycemia and associated complications were reported among vaccinated individuals. The current article summarizes the available case reports on COVID-19 vaccination-induced hyperglycemia, the possible molecular mechanism responsible for this phenomenon, and the outstanding questions that need to be addressed and discusses the need to identify at-risk individuals and promote postvaccination monitoring/surveillance among at-risk individuals.

Keywords: COVID-19; COVID-19 vaccine; SARS-CoV-2; diabetes; diabetic ketoacidosis; hyperglycemia; hyperosmolar hyperglycemic syndrome.

Figure 1

Possible mechanism of COVID-19 vaccination-associated pancreatic injury and hyperglycemia/hyperglycemic complications (figure adapted and modified from [7]). The angiotensin-converting enzyme 2 (ACE2) receptor, the key binding site for the SARS-CoV-2 virus, is a key regulator of the renin–angiotensin–aldosterone system (RAAS) and an endogenous inhibitor of the angiotensin II/angiotensin II type 1 receptor (AngII/AT1R) axis. SARS-CoV-2 binding to the pancreatic cells that express the ACE2 receptor and subsequent ACE2 downregulation diminish the inhibitory effect of ACE2 on the AngII/AT1R axis, which in turn leads to macrophage activation, upregulation of proinflammatory pathways, and hypercytokinemia (cytokine storm), culminating in pancreatic injury. It may be possible that vaccine excipients, vectors (adenoviral vectors), and the COVID-19 vaccine SARS-CoV-2 spike protein immunogen trigger similar mechanisms that cause pancreatic injury and subsequent hyperglycemia and hyperglycemic complications, such as hyperglycemic hyperosmolar syndrome (HHS) and diabetic ketoacidosis (DKA). Studies are warranted to address the outstanding questions in this area. Created with BioRender.com. * indicates potential postvaccination hyperglycemic scenarios.