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2020, May 01

Are people with diabetes, cardiovascular problems or hypertension at higher risk of more severe form of COVID-19 infection?

According to a scientific review by Borstein and colleagues in Nature Reviews Endocrinology (2020), Type 2 diabetes (T2D), hypertension and cardiovascular diseases have all been highlighted as risk factors for infection with COVID-19.

However, it should be pointed out that generally, people with such diseases are more prone to illnesses such as the common cold, flu and other coronavirus infections, namely severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS-CoV).

Reports from the Centre for Disease Control and Prevention (CDC) have indicated that T2D and the metabolic syndrome may increase the risk of death from COVID-19 by about ten-times (CDC coronavirus reports). Similar to other infectious diseases, the presence of co-morbidities is well known to enhance the risk of more severe symptoms as well as mortality.

It is thought that patients who suffer from these underlying conditions are in a constant state of inflammation, which triggers an excess release of inflammatory factors called cytokines. In cases of COVID-19, exaggerated amounts of inflammatory cytokines, also known as a cytokine storm, is believed to be the cause of multi-organ failure in patients suffering from severe form of the disease.

The COVID-19 virus enters inside human cells via its spike-like proteins known as glycoproteins found on its surface. The glycoprotein binds to the ACE2 receptor located on the cells to form a lock & key mechanism which enables the virus to gain entry inside the cells. ACE2 receptors are present in abundant amounts throughout organs and tissues, which means that the virus can easily penetrate the blood system and cause harm.

In addition to a link between coronavirus infection and hypertension, there seems to be a direct link to T2D. The pancreas which secretes the hormone insulin (which plays an important role in breaking down sugar in the body) has abundant amounts of ACE2 receptors, and it is thought that binding of the SARS coronavirus to these receptors damages the insulin-producing beta-cells within the pancreas, resulting in reduced secretion of insulin.
It is important that diabetes and associated metabolic factors are well-controlled in patients with COVID-19. Blood sugar-lowering medications, such as GLP-1 analogues, which are known to improve blood pressure are expected to have a beneficial effect. This effect might help to protect and restore lung function. Likewise, early treatment with angiotensin II receptor blockers (such as losartan or telmisartan) to regulate blood pressure may be useful.

The link between coronavirus infections and hormonal and metabolic pathways may have an important effect on the general medical management of severe COVID-19. The anti-rheumatic drug hydroxychloroquine, which is being widely used in many centres around the world as an experimental treatment for COVID-19, has also attracted interest as a potential therapeutic intervention for patients with T2D. Currently, it is unclear whether hydroxychloroquine in addition to anti-inflammatory and antidiabetic drugs will also directly interfere with the coronavirus–ACE2 pathways. In conclusion, COVID-19 itself is not primarily a metabolic disease, but metabolic control of glucose, lipid levels and blood pressure are key in patients afflicted with COVID-19. This approach is important to address the well-established metabolic and cardiovascular complications of this primary comorbidity. Moreover, effective control of these metabolic parameters might represent a crucial approach to prevent and ameliorate the acute effects of this virus by reducing the local inflammatory response and blocking its entry into cells.


Prepared by:
Dr Reshma Ramracheya
Research Scientist & University Research Lecturer at the University of Oxford
Senior Research Fellow at Wolfson College, University of Oxford
Reshma.ramracheya@ocdem.ox.ac.uk


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