Why do people with diabetes develop severe COVID-19?

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Through the COVID-19 pandemic, clinicians have found that certain patients are at particular risk of developing serious illness or dying from a coronavirus infection. Type 2 diabetes, which affects more than 10% of the US population, is one of the major risk factors for severe COVID-19 disease. A new study from UM reveals why this is and provides hope for potential treatments.

The culprit seems to be an enzyme called SETDB2. This same enzyme Diabetes mellitus.. Researcher W. James Melvin, a researcher working in the laboratory of Dr. Catherine Gallagher, MD, Department of Microbiology and Immunology, Michigan Medical Surgery, and his colleagues found that enzymes could be associated with the runaway inflammation they witnessed directly. I decided to investigate sex. In ICU COVID patients.

Starting with a mouse model of coronavirus infection, they found that SETDB2 was reduced. Immune cells It is involved in an inflammatory response called macrophages in diabetic-infected mice. They later saw the same with blood monocyte macrophages from people with diabetes and severe COVID-19.

“I think there’s a reason these patients have cytokine storms,” ​​Melvin said.

Melvin and Gallagher state that lowering SETDB2 increased inflammation in mouse and human models.In addition, they revealed that a pathway known as JAK1 / STAT3 regulates macrophage SETDB2. Coronavirus infection..

In summary, the results show potential treatment routes. Previous findings from the laboratory have shown that interferon, a cytokine important for viral immunity, increases SETDB2 in response to wound healing. Their new study found sera in patients with ICU with diabetes, and severe COVID-19 had lower levels of interferon beta compared to patients without diabetes.

“Interferon is being studied throughout the pandemic as a potential treatment, going back and forth between attempts to raise and lower interferon levels,” said Gallagher. “In my sense, its effectiveness as a treatment will be unique to both the patient and the timing.”

To test this, the researchers found that coronavirus-infected diabetic mice could be given interferon beta to increase SETDB2 and decrease inflammatory cytokines.

“We are trying to focus on what controls SETDB2, which is one of many of these master regulators. Inflammatory cytokine I’ve heard that it is increasing with COVID-19 such as IL-1B, TNFalpha and IL-6, “Gallagher explains.

“If you look upstream at what controls SETDB2, interferon is at the top end and JaK1 and STAT3 are in the center. Interferon increases both and increases SETDB2 in a kind of cascade.”

She added that this is important because identifying the pathway presents other potential ways to target the enzyme.

Melvin and Gallagher hope that the results of this study will help in ongoing clinical trials of other downstream components of the pathway, including interferon or epigenetic targets for COVID-19. Their study also understands the timing and cell specificity of treatment and highlights the need to adjust its application to patients with underlying diseases, especially diabetics.

“Our study shows that if you can target diabetics, interferonIt can actually make a big difference, especially in the early stages of infection. ”

New discoveries point towards possible treatments for diabetic non-healing wounds

For more information:
Coronavirus induces inflammation via diabetic macrophages via SETDB2. PNAS, DOI: 10.1073 / pnas.2101071118 ,

Quote: Why do people with diabetes develop severe COVID-19? (September 7, 2021) Obtained September 7, 2021 from https: //

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Why do people with diabetes develop severe COVID-19?

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