Towards treatment for diabetics with Covid-19? Since the start of the pandemic, it has been noticed that the risk of developing severe forms is closely linked to certain factors, such as age, hypertension, obesity and diabetes. The latter, for example, considerably increases the risk of death following infection: according to the French study Coronado, which looked at the fate of diabetic patients hospitalized with Covid-19, the mortality in this population is 11.2% within seven days of infection and 20.6% within 28 days. But while this increased risk had already been highlighted in April 2020, experts were still unsure how to explain it. This has just changed thanks to a study from the University of Michigan (United States) published on September 21, 2021 in PNAS.
A cytokine storm out of control
One of the main mechanisms by which Covid causes severe forms is the famous cytokine storm, which causes hyperinflammation of blood vessels and organs. This storm occurs when the body tries to control the virus, but fails to do so, starting an escalation where immune cells release too many pro-inflammatory cytokines, which instead of neutralizing the virus will cause damage in the body. This inflammatory excess is particularly present in diabetics, leading to greater mortality.
By studying human cells from infected diabetic patients and diabetic mice infected with another coronavirus (causing hepatitis in rodents), the researchers found that this storm is worsened in diabetics because of a decrease in blood pressure. expression of an enzyme involved in epigenetic modifications, SETDB2. Normally, this enzyme modifies histone 3 by adding three methyl groups (CH3) to lysine in position 9, which results in the repression of the expression of several inflammatory genes. In diabetics, the underexpression of SETDB2 results in uncontrolled expression of these inflammatory genes, worsening the inflammation caused by the virus. “Coronavirus infection and type 2 diabetes are a double blow… allowing deregulated inflammation ”, summarize the authors.
Treatment with interferons could be the solution
The authors also noted that the levels of interferon beta (IFNβ), a cytokine released by the immune system during infection, were lower in infected diabetic patients, compared to those infected but without diabetes. It has already been proposed that a low level of this type 1 interferon could be a marker indicating people at high risk of developing severe forms, which, on the other hand, would produce more pro-inflammatory cytokines such as interleukins. And the treatment of Covid-19 with interferon has already been tried in the WHO Solidarity trial, without success.
But the verdict might be different for diabetic patients. This is because the authors observed that the expression of SETDB2 increased in the cells of infected diabetics after treatment with beta interferon. Thus decreasing the expression of inflammatory genes and, consequently, the inflammation caused by this cytokine storm.
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