Thursday 09 September 2021
Type 2 diabetes is one of the main risk factors for severe COVID-19 disease.
New research from the University of Michigan reveals why this is happening and offers hope for a possible treatment.
The culprit appears to be an enzyme called SETDB2. This same enzyme is implicated in non-healing inflammatory wounds found in diabetic patients, according to what Russia Today reported.
Working in the lab of Catherine Gallagher, MD, in the Michigan Departments of Surgery, Microbiology, and Immunology, researcher W. James Melvin and colleagues decided to investigate the potential link between the enzyme and the rampant inflammation they saw for themselves in COVID-19 patients in the intensive care unit.
And in a mouse model infected with coronavirus, they found that SETDB2 was decreased in immune cells involved in the inflammatory response, called macrophages, in diabetic mice. They later saw the same thing in the blood of single-celled macrophages from patients with diabetes and severe Covid-19.
“We think we have a reason why these patients developed a cellular storm,” Melvin said.
In mouse and human models, Melvin and Gallagher note, with decreased SETDB2, inflammation increased. In addition, they revealed that a pathway known as JAK1/STAT3 regulates SETDB2 in macrophages during MERS infection.
Taken together, the results suggest a potential treatment pathway. Previous results from the laboratory showed that interferon, an important cytokine for viral immunity, increased SETDB2 in response to wound healing.
In their new study, they found that serum from patients in the intensive care unit with diabetes and severe “Covid-19” reduced interferon beta levels compared to patients without diabetes.
“Interferon has been studied throughout the pandemic as a potential treatment, with efforts between trying to increase or decrease interferon levels,” Gallagher said. “My sense is that its efficacy as a treatment will be specific to both the patient and the timing.”
To test this, the study team administered interferon-beta to mice infected with the coronavirus and saw that it was able to increase SETDB2 and reduce inflammatory cytokines.
Melvin and Gallagher hope that the results of this study will benefit the ongoing clinical trials of interferon or other components of the pathway, including epigenetic targets, for “Covid-19”. Their work also highlights the need to understand the timing and specificity of cells in therapy and to tailor its application to the underlying conditions of patients, particularly those with diabetes.
“Our research shows that it could actually make a big difference if we could target diabetic patients who have interferon, particularly early in the course of the infection,” Melvin said.