Nature Sub-journal: Treatment of new crowns requires anti-diabetes, anti-inflammation, anti-viral “three-pronged”

In patients with new coronavirus pneumonia (COVID-19), type 2 diabetes and hypertension are often the most common combinations in the clinic, and researchers believe that the link between coronary virus infection and some endocrine and metabolic pathways will have a significant impact on the treatment of severe COVID-19.

On April 2nd, local time, Nature Reviews, a sub-journal of nature, published an online commentary article from researchers from Germany, the United Kingdom, Singapore and other countries, pointing to growing evidence of evidence

There is an important direct link between metabolic and endocrine mechanisms and the development of viral diseases, and clinicians need to ensure early and thorough metabolic control of all COVID-19 patients.

The authors are from the Department of Diabetes affiliated with the University of Dresden, the Department of Diabetes at King’s College London, Nanyang Technological University in Singapore, and The Chen Dusheng Hospital in Singapore, and are the authors of the report by Stefan R. Bornstein, Director of the Department of Internal Medicine and Outpatient Clinics at The University of Dresden and the Third Medical Clinic and Outpatient Department of The Third Phase of Medical Clinic, king’s college in London.

Although COVID-19 is not a major metabolic disease, it is essential for the metabolic control of blood sugar, lipid levels and blood pressure in patients, which will help control metabolic and cardiovascular complications, the paper notes.

In addition, effective control of these metabolic parameters may represent a special treatment mechanism that prevents and improves the acute effects of the virus by reducing local inflammatory responses and blocking the entry of new coronaviruses into human cells.

People say type 2 diabetes (T2DM) appears to be one of the risk factors for infection with the new coronavirus. In fact, T2DM and hypertension have been identified as the most common comorbidities of other coronavirus infections, such as Severe Acute Respiratory Syndrome (SARS) and Mers(MERS) coronaviruses.

According to a previous report by the U.S. Centers for Disease Control and Prevention (CDC), patients with T2DM and metabolic syndrome are ten times more likely to die from COVID-19 infection. A team from Wuhan University and others also published a study recently published on the preprintplatform SSRN, saying that the new coronaof diabetes in the sample had higher mortality rates and were more likely to have a potential combination.

In SARS virus infection, the diagnosis of hyperglycemia and T2DM is an independent predictor of mortality and morbidity in patients. This may be due to the fact that these patients are in a state of metabolic inflammation and tend to increase the release of cytokines.

Cytokines are a class of small molecular proteins with wide biological activity that are stimulated by immune cells (e.g. mononucleosis, macrophages, T cells, etc.) and certain non-immune cells (endothelial cells, epidermal cells, fibroblasts, etc.) that are stimulated and secreted, regulating the immune response by regulating cell growth, differentiation and effect by binding corresponding receptors.

In patients with COVID-19, cytokine storms, i.e. “inflammatory storms” brought about by significant increases in inflammatory cytokine levels, result in multi-organ failure.

Metabolic inflammation also damages the immune system, reduces the body’s ability to fight infection, and prolongs recovery. Previous animal models have shown that a combined t2DM can lead to immune dysfunction and lead to more severe symptoms of MERS infection.

Based on the above data, the researchers hypothesized that patients with both T2DM and coronavirus infection were prone to immune reflexes, leading to increased lung lesions and longer recovery times.

The researchers went on to point out that in the clinical treatment of new coronary virus infection, the use of angiotensin II receptor blockers (such as chloratan or temetan), or more direct recombinant ACE2 in early treatment, will combine anti-diabetic, anti-inflammatory and antiviral to help patients recover.

Direct link between new coronavirus and high blood pressure and type 2 diabetes

The new coronavirus (SARS-CoV-2) enters human cells through a encapsulation proglycin, which in turn spreads from person to person. This glycoprotein is present on the surface of the virus and binds to angiotensin-changeenzyme 2 (ACE2) and enters the cells.

In the respiratory system, ACE2 has the function of degrading angiotensin II to angiotensin 1-7, and plays the role of diastocaander and cardiovascular protection, which is the key regulatory point of the angiotensin system. Angiotensin 1-7 acts on the Mas receptor pathway, which causes the body to produce anti-inflammatory and antififistosis reactions, which is beneficial to the rehabilitation of COVID-19 patients.

When the virus invades, ACE1 activity increases and ACE2 is inhibited, the complete angiotensin II (angII) reacts with pro-inflammatory through the angiotensin 1 receptor (AT1R) or AT2R and stimulates the secretion of aldosterone. These effects not only increase blood pressure and may lead to hypothermia, but also partially increase vascular permeability and increase the risk of respiratory distress syndrome.

It can be assumed that patients with severe COVID-19 were reduced in the activation of angiotensin 1-7, while the activation of AT1R and AT2R increased, which can also be observed in type 2 diabetes, hypertension and insulin resistance.

In addition to the link between neo-coronavirus and high blood pressure, it also appears to be directly linked to T2DM (type 2 diabetes).

For example, in the pancreas, the combination of SARS coronavirus and its receptor ACE2 damages the islet and reduces insulin release. A previous study tracked SARS patients with no t2DM history and was not treated with steroids for 3 years after the virus infection and found that more than 50 percent of the patients in the sample had diabetes as a result of SARS coronavirus infection during their stay. But three years after the virus was cured, only 5% of patients still had diabetes.

When the pancreas in the human endocrine system expresses ACE2, coronaviruses can enter the islet and cause acute beta cell dysfunction, leading to acute hyperglycemia and transient T2DM.

What’s more, the researchers noted that ace2 activity levels in the pancreas in mice with diabetes increased. This suggests that patients with T2DM may be particularly vulnerable to coronavirus infection.

In addition, T2DM induces the expression of angiotensin-transformation enzymes in other tissues of the body, including the lungs, liver, and heart, which explains why having T2DM causes multi-organ failure in SARS coronavirus infection.

Anti-diabetes, anti-inflammatory and antiviral combination, glucocorticoid effect is not obvious

The researchers say it is clear that optimal T2DM treatment and associated metabolic parameter control are necessary for COVID-19 patients. This is not only because T2DM and metabolic problems pose a higher risk of complications in patients with severe infections, but also because this approach may contribute to the treatment of all COVID-19 patients.

In clinical treatment, the researchers recommend the use of anti-diabetic drugs, such as GLP1 agonists, that improve metabolic function and induce the activity of the protective pathways of ACE2 and Mas receptors. They may have the advantage of improving glucose metabolism and blood pressure, and may also help prevent coronaviruses from entering cells due to competitive binding ace2, which may help protect and restore lung function.

Similarly, the authors suggest that the use of angiotensin II receptor blockers (such as chloratan or temetan), or recombinant ACE2 more directly in early treatment, may enhance ace2 and Mas systems by giving priority to angiotensin receptor-mediated pathways. This approach will combine anti-diabetic, anti-inflammatory and anti-viral to help patients recover.

In addition, synthetic protease inhibitor camustat can block ace2-mediated coronary viruses from entering the cell as needed by serine protease TMPRS2, which can also improve blood lipid abnormalities and hyperglycemia.

Notably, the researchers also noted that glucocorticoids, which are useful in clinical treatment for acute respiratory distress syndrome, were less effective in “resisting” the new coronavirus. This is because glucocorticoids not only increase metabolic control, but also weaken the expression of angiotensin 1-7 and Mas receptors.

In contrast, the anti-rheumatic drug hydroxychloroquine is now widely used in the treatment of COVID-19 worldwide, and its potential treatment as a T2DM has also attracted the interest of health care workers. At this point, it is not clear whether hydroxychloroquine, in addition to anti-inflammatory and anti-diabetic drugs, will directly interfere with the route of coronavirus binding ace2 invasion.