COVID-19 pandemic, coronaviruses, and diabetes mellitus

Abstract

The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.

Keywords: COVID-19; coronavirus; diabetes mellitus.

Fig. 1.

Cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The initial step in cellular entry of the virus is the binding of SARS-CoV-2 spike protein to cell surface angiotensin converting enzyme 2 (ACE2). Cellular proteases such as TMPRSS2 and furin are involved in priming of the S protein, which involves cleavage at the S1/S2 domains. This allows the fusion of the virus to the cell surface. Virions are taken up into endosomes, where SARS-CoV-2-S is cleaved and possibly activated by the pH-dependent cysteine protease cathepsin L. Once inside the cell, SARS-CoV-2 uses the endogenous cellular machinery to replicate itself. ACE catalyzes the conversion of angiotensin (Ang) I to the octapeptide AngII, whereas ACE2 converts AngII to Ang_1–7. AngII through the activation of Ang II type 1a receptors induces vasoconstriction and proliferation, whereas Ang_1–7 stimulates vasodilatation and suppresses cell growth.

Fig. 2.

Putative mechanisms contributing to increased susceptibility for coronavirus disease (COVID-19) in patients with diabetes mellitus (DM). Following aerosolized uptake of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), invasion of the respiratory epithelium and other target cells by SARS-CoV-2 involves binding to cell surface angiotensin converting enzyme 2 (ACE2). Increased expression of ACE2 may favor more efficient cell binding and entry into cells. Early recruitment and function of neutrophils and macrophages are impaired in DM. Delay in the initiation of adaptive immunity and dysregulation of the cytokine response in DM may lead to the initiation of cytokine storm.