The cytokine IL-26 may be a biomarker of acute COVID-19 according to a preliminary study by researchers at Karolinska Institute. It may also be a good new target for drug discovery.
“We can show for the first time that blood levels of the cytokine IL-26 [interleukin-26] are much higher in patients with COVID-19 than in healthy controls,” says Eduardo Cardenas, postdoc researcher at the Institute of Environmental Medicine, Karolinska Institute, and principal author of the new pilot study, which appeared in Frontiers in Immunology today.
Researchers also observed that the increase was associated with the cytokine storm—an excessive and dangerous inflammatory response that signifies severe cases of COVID-19. A growing body of evidence suggests this reaction is associated with disease severity and death.
“Our discovery gives us a potential biomarker for severe COVID-19, but given the antiviral effects of IL-26, we may also have identified a new therapeutic target,” says Anders Lindén, senior author, consultant and professor at the Institute of Environmental Medicine, Karolinska Institute.
Vaccines for SARS-CoV-2 have effectively reduced the number of cases of severe COVID-19. However, there have been many breakout infections, some leading to death. In New York alone, over two million people have experienced breakthrough infections, resulting in almost 90,000 hospitalizations.
There are few approved treatments for COVID-19 so far, and the emergence of new viral variants, limited distribution of the vaccine, and declining immunity are additional problems driving the search for more efficacious treatments for the disease.
Also, although many people will suffer no symptoms or only mild disease, already over 6.6 people have died from the disease worldwide. Identifying those at risk of severe disease is thus a priority but so far, there is no reliable way to do this.
“We need to understand more about underlying immunological mechanisms in order to find better treatments. There is also a need for improved diagnostics in COVID 19-patients,” says Cardenas.
These researchers set out to ascertain whether immune signaling via IL-26 is involved in severe COVID-19.
“We already know that IL-26 is engaged in mobilizing immune cells that combat bacterial infections in the lungs and also in chronic respiratory disease in humans,” says Lindén. “What’s more, IL-26 has antiviral and antibacterial effects.”
In this study, the scientists recruited 49 patients who had been hospitalized with SARS-CoV-2-infection, 44 of whom had severe symptoms and needed oxygen therapy. The patients were recruited at a hospital in Stockholm from June 2020 to January 2021. A control group of 27 healthy individuals was also recruited during the same period. The researchers then measured levels of IL-26 protein and other inflammatory compounds in the blood. They found that the levels of the protein where much higher among patients with COVID-19 than the healthy controls.
In addition, they found that the blood concentration of IL-26 correlates with that of increased lactate dehydrogenase, an established marker of tissue damage, and decreased mean corpuscular hemoglobin (MCH), a previously verified hematological aberration in COVID-19. Both of these markers are associated with severe disease.
According to Cardenas, the results are promising but are preliminary and warrant further study with a larger patient cohort.
“Such a study is on the way and can give more information on the clinical value of measuring IL-26 in COVID-patients, such as whether the levels reflect the severity of the disease.