Towards the treatment of diabetics with Covid-19? Since the beginning of the pandemic, it has been noted 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 after an infection: according to the French Coronado study, which analyzed the fate of diabetic patients hospitalized with Covid-19, mortality in this population is 11.2% at seven days after infection. and 20.6% in 28 days. But while this increased risk had already been highlighted in April 2020, experts were still not sure how to explain it. This has just changed thanks to a study by 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, initiating an escalation in which the immune cells release too many pro-inflammatory cytokines, which instead of neutralizing the virus will cause damage to the body. This inflammatory excess is particularly present in diabetics, causing higher mortality.
By studying human cells from infected diabetic patients and diabetic mice infected with another coronavirus (which causes hepatitis in rodents), the researchers found that this storm is exacerbated in diabetics due to a drop in blood pressure. Expression of an enzyme involved in epigenetic modifications, SETDB2. Normally, this enzyme modifies histone 3 adding three methyl groups (CH3) to lysine at position 9, resulting in the repression of the expression of several inflammatory genes. In diabetics, underexpression of SETDB2 results in uncontrolled expression of these inflammatory genes, exacerbating the inflammation caused by the virus. “Coronavirus infection and type 2 diabetes represent a double whammy … allowing for dysregulated inflammation,” the authors summarize.
Interferon treatment could be the solution
The authors also noted that 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 of 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 tested in the WHO Solidarity trial, without success.
But the verdict could be different for diabetic patients. Because the authors observed that SETDB2 expression increased in infected diabetic cells after treatment with interferon beta. Thus decreasing the expression of inflammatory genes and, consequently, the inflammation caused by this cytokine storm.