Path of diabetic risk for severe COVID-19

Sept. 9, 2021

Type 2 diabetes is thought to be a risk factor for developing severe illness or dying from a coronavirus infection. Researchers at University of Michigan sought to uncover why and offer hope for a potential therapy.

Michigan researchers have found a link between an enzyme, called SETDB2, and the runaway inflammation they witnessed first-hand in COVID patients in the ICU. The enzyme has been implicated in the non-healing, inflammatory wounds found in diabetics.

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

In the mouse and human models, noted the researchers, as SETDB2 went down, inflammation went up. In addition, they revealed that a pathway known as JAK1/STAT3 regulates SETDB2 in macrophages during coronavirus infection.

Previously, the researchers demonstrated that interferon, a cytokine important for viral immunity, increased SETDB2 in response to wound healing. In the new study, they found ICU patients with diabetes and severe COVID-19 had blood serum with reduced levels of interferon-beta compared to patients without diabetes.

“Interferon has been studied throughout the pandemic as a potential therapy, with efforts going back and forth between trying to increase or decrease interferon levels,” said Katherine Gallagher, MD, of the Michigan Medicine Departments of Surgery and Microbiology and Immunology.

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