COVID‐19 and diabetes

Less than six months ago, no-one had heard of COVID-19 and few people knew what a coronavirus was, yet today it is on everyone’s lips. On 11 March 2020, the WHO declared the outbreak a global pandemic, and the disease has spread to multiple countries across the globe. COVID-19 is characterized by a fever, dry cough, fatigue and shortness of breath, and for the majority the symptoms will be minor; however, for a few, the illness can progress to pneumonia and multiorgan failure. While data are emerging, it seems that the mortality rate is of the order of 1–2% [1]. So, what does the epidemic mean for people with diabetes? People with diabetes have a higher overall risk of infection that results from multiple perturbations of innate immunity. While humoral immunity appears relatively unaffected, people with diabetes have impaired phagocytosis by neutrophils, macrophages and monocytes, impaired neutrophil chemotaxis and bactericidal activity, and impaired innate cell-mediated immunity. As overall mortality related to cardiovascular disease continues to decline among people with diabetes, pneumonia has become an increasingly important cause of death in diabetes, with different contributing pathogens [2]. Whether people with diabetes have a higher susceptibility to COVID-19 is currently unknown, but there is a perception that the risk is higher both of infection and severe disease. For example, the first three deaths related to COVID-19 in Hong Kong all occurred in people with diabetes. In a large series, 173 cases of 1099 laboratoryconfirmed COVID-19 cases (16%) in China were classified as severe [3]. Sixteen percent of those with severe disease had diabetes; in contrast only 5.7% of the remaining 926 cases with mild disease had diabetes. Likewise, 24% of those with severe disease had hypertension, compared to 13% among those with mild disease, highlighting the increased risk of adverse outcomes among those with chronic diseases like diabetes. It is currently unknown why people with diabetes, hypertension or other chronic diseases are more severely affected by COVID-19, but one possible explanation involves angiotensin-converting enzyme 2 (ACE2). ACE2 is present in cardiac, kidney, lung and intestinal tissue, and by converting angiotensin II to angiotensin 1–7, it counteracts the effects of angiotensin II and promotes vasodilation. In a similar manner to the coronavirus that caused Severe Acute Respiratory Syndrome (SARS-CoV), the novel coronavirus responsible for COVID-19 utilizes ACE2 on the surfaces of epithelial cells to bind and gain entry to infected cells [4,5]. Diabetes and conditions such as hypertension are associated with activation of the renin-angiotensin system in different tissues. Furthermore, people with diabetes and hypertension are often treated with ACE inhibitors and angiotensin receptor blockers (ARBs), which can lead to increased expression of ACE2, thereby facilitating viral uptake and increasing the risk of severe infection for people with diabetes [6]. Whilst these observations have led to suggestions that switching people on renin-angiotensin system blockers to other agents may modify disease risk [6], this would be premature and unwarranted in the absence of any experimental evidence to support this approach. On the contrary, treatment with ARBs has been proposed as a potential therapeutic strategy for COVID-19 [7], supported by observations that blocking the renin-angiotensin system in animal models attenuated the lung injury caused by the SARS-CoV, which also utilizes ACE2 [8]. A recent position statement from the European Society of Cardiology also strongly recommends that physicians and patients continue treatment with their usual anti-hypertensive treatment and that there is no clinical or scientific evidence to suggest that treatment with ACE inhibitors or ARBs should be discontinued because of the COVID-19 infection [9]. Credit: NIAID-RML / NATIONAL INSTITUTES OF HEALTH / SCIENCE PHOTO LIBRARY Caption: COVID-19 coronavirus particles, coloured transmission electron micrograph (tEM). Also called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this virus causes the disease COVID-19. This sample was isolated from a patient in the USA. SARSCoV-2 was first identified in Wuhan, China, in December 2019. It is an enveloped RNA (ribonucleic acid) virus. The coronaviruses take their name from their crown (corona) of surface proteins, which are used to attach and penetrate their host cells. As of mid-March 2020, over 230,000 people have been infected with over 9,500 deaths.