US researchers have identified an enzyme that may explain the reason why people with diabetes are at especially high risk of developing severe illness or dying from coronavirus infection.
The culprit appears to be an enzyme called SETDB2. This same enzyme has been implicated in the non-healing, inflammatory wounds found in people with diabetes.
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.
The same thing was observed in monocyte-macrophages in the blood from people with diabetes and severe Covid-19.
“We think we have a reason for why these patients are developing a cytokine storm,” said researcher W. James Melvin from University of Michigan.
In the mouse and human models, the team found that as SETDB2 went down, inflammation went up. In addition, a pathway known as JAK1/STAT3 was found to regulate SETDB2 in macrophages during coronavirus infection.
Taken together, the results point to a potential therapeutic pathway.
Further, previous findings demonstrated that interferon — a cytokine important for viral immunity — increased SETDB2 in response to wound healing.
In the new study, the team found blood serum from patients in the ICU with diabetes and severe Covid-19 had reduced levels of interferon-beta compared to patients without diabetes.
To test this, the study team administered interferon beta to coronavirus-infected diabetic mice and saw that they were able to increase SETDB2 and decrease inflammatory cytokines.
“We’re trying to home in on what controls SETDB2, which is sort of the master regulator of a lot of these inflammatory cytokines that you hear about as being increased in Covid-19, such as IL-1B, TNFalpha, and IL-6,a explained Katherine Gallagher, from Michigan Medicine.
This is important, she added, because identifying the pathway presents other potential ways of targeting the enzyme.
“Our research is showing that maybe if we are able to target patients with diabetes with interferon, especially early in their infection, that may actually make a big difference,” Melvin said.
