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Ann Arbor, Michigan – A deficiency in an enzyme that has already been linked to impaired wound healing could explain why infection with SARS-CoV-2 often triggers a fatal cytokine storm in type 2 diabetics.

The ones in the Proceedings of the National Academy of Sciences (PNAS 2021; 118: e2101071118) would explain a good effect of interferons in the disease, which, however, has not yet been proven.

Obesity and type 2 diabetes are among the most important and in Western countries most common risk factors for a severe course of COVID-19. A cytokine storm is blamed for the death of the patient. The initiators are the macrophages, which, as a central actor in the innate immune system, release the cytokines.

A team led by Katherine Gallagher from the University of Michigan at Ann Arbor has investigated the role of macrophages in mice. An infection with the murine hepatitis virus A59 (MHV-A59), which belongs to the coronaviruses, can trigger a cytokine storm in the mice.

The viruses achieve this by lowering the production of the enzyme SETDB2. SETDB2 belongs to the group of histone methyltransferases that prevent certain genes from being read by attaching methyl groups.

Interestingly, the activity of SETDB2 is already reduced in people with type 2 diabetes. In an earlier study, Gallagher had shown this in wounds that are difficult to heal and are one of the common complications of type 2 diabetes.

The researcher is convinced that the reduced production of SETDB2 in the macrophages is responsible for the wound healing disorders (Immunity 2019; 51: 258-271). An infection with SARS-CoV-2 could further reduce SETDB2 production, which is reduced by type 2 diabetes. Gallagher speaks of a “double hit”.

Their current results suggest that the production of SETDB2 is activated by the JAK-STAT signaling pathway. If so, interferons could be an effective tool in preventing a cytokine storm in COVID-19.

The JAK-STAT signal path is started in the cells by interferons. Interferons belong to the signaling substances of the innate immune response. Clinical trials are currently being investigated for its benefit in the treatment of COVID-19.

However, the results published so far, for example in the Solidarity Study of the World Health Organization, were not convincing, so that interferons are currently not among the recommended active ingredients.

However, this does not rule out that the treatment could be effective in the right patient (such as type 2 diabetes) at the right time (such as the onset of the cytokine storm), although this still has to be proven in clinical studies. © rme / aerzteblatt.de

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