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New Treatments for Diabetes, Inflammation, and COVID-19

Promising trials using a common and affordable steroid have been shown to reduce deaths from Coronavirus-related inflammation by a third

With Roger Clemens DrPH

A cell is protected from the invasive virus.

The novel Coronavirus, COVID-19, affects individuals differently and seems to be more serious for those with certain underlying conditions. As scientists work to better understand the virus, there is increasing focus on the link between COVID-19 and inflammation.

Our bodies love to be in equilibrium and work for something called redox homeostasis, a balance between free radicals and the systems that scavenge them. Our cells want an equal amount of oxidants and antioxidants (positives and negatives). When this balance is disrupted, our cells become more reactive and more susceptible to outside invaders.

The damage done by COVID-19 seems to be propagated by our bodies’ exaggerated immune response. In Coronavirus patients who suffer severe respiratory failure, the immune system overreacts, leading to something called a “cytokine storm” triggered by extreme oxidative stress. Researchers at USC believe that pre-existing, oxidative stress could affect the infectivity and severity of the COVID-19 virus.

COVID-19 and inflammation

All viruses must first attach to certain docking stations on cells, called cell surface receptors (SCR). COVID-19 attaches to the enzyme ACE 2, and its entry into the cell is facilitated by a secondary enzyme (TMPRSS2). Because ACE 2 is a common enzyme throughout our bodies, the Coronavirus can affect several systems. And because this enzyme is also controlled by redox, it is affected by an imbalanced system.

Certain factors increase the density of ACE 2, meaning there are more docking stations for the virus and possibly a higher chance of infection. Males tend to have more ACE 2 enzymes than women, which may be why they are more susceptible to the virus and tend to get sicker and take longer to recover. We also tend to develop more ACE 2 enzymes as we age, due to oxidative stress.

ACE 2 is an important enzyme within the body, playing an anti-inflammatory role in the angiotensin system. When the Coronavirus uses ACE 2 to invade the host cell, there is a down-regulation of ACE 2 enzymes, disrupting the balance of the angiotensin system and potentially increasing inflammatory markers.

People who already have down-regulated ACE 2 enzymes due to underlying conditions, such as diabetes and obesity, may be more susceptible to severe inflammation once infected with COVID-19.

The Coronavirus is still relatively new, and much of the research is still preliminary, but scientists have tagged the important role of inflammation in the body’s response to this virus.

Inflammatory endocrine conditions that can put you at an increased risk include:

  • Type 1 Diabetes
  • Type 2 Diabetes
  • Metabolic Syndrome
  • Obesity

Across various studies of the novel Coronavirus, diabetes is the second most common co-morbidity for patients presenting with severe respiratory failure. Type 1 diabetes often presents with decreased ACE 2, and some researchers believe this may be what makes type 1 diabetes a risk factor for a severe inflammatory response.

Type 2 diabetes is often a symptom of metabolic syndrome, in which there is a cascade of pro-inflammatory markers that throws the body into a cycle of imbalance and oxidative stress.

In a recent paper, Roger Clemens, a doctor of public health at the USC School of Pharmacy writes, “Metabolic syndrome is a chronic imbalance in redox homeostasis associated with conditions such as type 2 diabetes and chronic heart dysfunction.”

The clinical characteristics of metabolic syndrome are linked to dysregulated ACE 2-dependant metabolic pathways. Dr. Clemens believes that any adverse outcomes of metabolic syndrome could be serious risk factors for clinical onset and expression of COVID-19.

What’s behind the increased risk?

The imbalance marked by chronic inflammation and oxidative stress and the imbalance of the angiotensin system could potentially explain why certain populations are at an increased risk for a severe response to COVID-19.

A recent study evaluated how chronic systematic inflammation puts patients with diabetes at a higher risk for severe infection from COVID-19. According to the study, “Several reports for COVID-19 show a clear correlation between the severity of the disease and the level of dysregulated biomarkers for systemic inflammation.” Correlation is not fact, but it can point us in the right direction.

Another new study by Glamarellos-Bourboulis et al. found that all patients who experienced severe respiratory failure had immune dysregulation, and specifically identified interleukin-6 (acting as a cytokine) as a mediating factor in this severe inflammatory response. This interleukin is also common in persons with chronic inflammatory conditions.

New developments in the management of COVID-19 

In the fight against COVID-19, much research has turned to the study of already existing medications used to treat chronic inflammatory disorders. It is believed that treating the inflammation may be a key factor in increasing survival rates. 

Dexamethasone, a common and inexpensive steroid used to reduce inflammation in patients with arthritis, has recently been found to reduce inflammation in patients with the Coronavirus. Preliminary trials have shown that it may reduce deaths in patients who are severely ill by up to one third. 

Managing inflammation can not only decrease the symptoms of chronic diseases such as those instigated by diabetes and metabolic syndrome, it may also improve your body’s own immune response.

Clemens and colleagues believe that the management of chronic oxidative stress may present a novel approach in the clinical management of COVID-19.

The researchers focused on possible nutrient intervention, with an emphasis on the down-regulation of reactive pro-oxidant pathways. Several nutrients may play a role in this down-regulation.

  • Zinc may help to prevent the virus from replicating within the host cell.
  • Selenium, a mineral associated with the antioxidant enzyme glutathione peroxidase, exhibits anti-inflammatory and antiviral activities (selenium deficiency can increase the risk of viral infections).
  • Vitamin D plays a crucial role in the body’s immunity and inflammatory pathways and may reduce the risk of contracting COVID-19. One study recommends a dosage of 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D levels, followed by 5000 IU/d.8.
  • Epigallocatechin gallate (EGCG), a polyphenol from green tea, is shown to have broad antiviral effects and has been previously used in complementary therapy of SARS and MERS.
  • Melatonin may play a role in the regulation of the immune system, inflammation, and oxidative stress.

Additional interventions such as exercise, weight loss (for overweight individuals), and sufficient sleep (quality and quantity) may also play a protective role in your body’s defense system.

The exaggerated immune response in COVID-19 is not the same as the inflammatory response of chronic diseases, but a dysregulated immune system marked by oxidative stress could put you at greater risk for a severe reaction. We cannot control everything, including this virus, but we can change our habits in an effort to safeguard our health.

If you are part of an at-risk population, talk with your doctor. Discuss healthy habits that you can begin implementing now to help you stay healthy in the future.

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Diabetes and COVID-19