SARS-CoV-2 disease severity and diabetes: why the connection and what is to be done?

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus responsible for the current coronavirus disease 2019 (COVID-19) pandemic, has infected over 3.5 million people all over the world since the first case was reported from Wuhan, China 5 months ago. As more epidemiological data regarding COVID-19 patients is acquired, factors that increase the severity of the infection are being identified and reported. One of the most consistent co-morbidities associated with worse outcome in COVID-19 patients is diabetes, along with age and cardiovascular disease. Studies on the association of diabetes with other acute respiratory infections, namely SARS, MERS, and Influenza, outline what seems to be an underlying factor in diabetic patients that makes them more susceptible to complications. In this review we summarize what we think may be the factors driving this pattern between diabetes, aging and poor outcomes in respiratory infections. We also review therapeutic considerations and strategies for treatment of COVID-19 in diabetic patients, and how the additional challenge of this co-morbidity requires attention to glucose homeostasis so as to achieve the best outcomes possible for patients.

Keywords: ACE2; COVID-19; Diabetes mellitus (DM); SARS-CoV-2.

Fig. 1

SARS-CoV-2 sites of infection and complications in diabetic patients. As is the case for SARS-CoV, SARS-CoV-2 uses the ectopeptidase ACE2 as an entry site in human host cells. ACE2 is part of the renin-angiotensin system, responsible for the termination of the angiotensin signal, promoting conversion of angiotensin II (Ang II) into angiotensin 1–7 (Ang 1–7). Ang II acts through the angiotensin receptor 1 (AT1), which results in vasoconstriction and sympathetic nervous stimulation. Ang 1–7, on the other hand, acts on angiotensin receptor 2 (AT2), and has opposite effects, inducing vasodilation. ACE2 is expressed throughout the respiratory epithelium, from the nasal and oral mucosa to the epithelium in alveoli. Diabetic patients are at higher risk of infection and complications from COVID-19 as a result of several factors. Dampened anti-viral response with reduced interferon production is a common feature seen in persons with diabetes. Additionally, diabetic patients may be more vulnerable to SARS-CoV-2 infection due to elevated ACE2 expression. Finally, diabetes-related subclinical pulmonary dysfunction and microvascular disease may be aggravating factors that contribute to the severity of the respiratory symptoms associated with COVID-19