"PNAS" why diabetes is closely related to severe COVID-19

Throughout the COVID-19 pandemic, clinicians have noticed that certain patients have a particularly high risk of serious illness or death from coronavirus infection

The culprit seems to be an enzyme called SETDB2

Starting with a mouse model of coronavirus infection, they found that SETDB2 was reduced in immune cells called macrophages in the inflammatory response of diabetic mice

Gallagher said: "We think we have reasons to explain why these patients have a cytokine storm

Melvin and Gallagher pointed out that in mouse and human models, when SETDB2 decreases, inflammation increases

In summary, these results point to a potential therapeutic approach

Gallagher said: "Interferon has been studied as a potential treatment throughout the pandemic, trying to switch back and forth between trying to increase or decrease interferon levels

To verify this, the research team injected interferon into diabetic mice infected with coronavirus and found that they can increase SETDB2 and reduce inflammatory cytokines

Gallagher explained: "We are trying to figure out what controls SETDB2, which is the main regulator of many inflammatory cytokines that you have heard of increased in COVID-19, such as IL-1B, TNFalpha and IL-6

"Upstream of controlling SETDB2, interferon is at the top, JaK1 and STAT3 are in the middle

This is important, she adds, because recognition pathways provide other potential ways to target enzymes

Melvin and Gallagher hope that the findings of this study will inform ongoing clinical trials of COVID-19 interferon or other downstream components of the pathway, including epigenetic targets

Melvin said: "Our research shows that if we can treat diabetic patients with interferon, especially in the early stages of their infection, it may be very different

DOI

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