Researchers at Yale University have identified ways to determine which patients have the greatest risk of developing severe COVID-19 based on their immune activity. The research shows that the body’s immune system provides early indications of whether an infection will become life-threatening.
The findings may help doctors recognize which patients will likely require critical care, and could also help pinpoint which drugs will be most effective.
The researchers examined 113 patients admitted to Yale New Haven Hospital, analyzing their immune system responses from the time of admittance until discharge or death.
In the early stages of infection, the experts found that all of the patients shared a common COVID-19 “signature” in immune activity.
Over time, those who experienced only moderate symptoms exhibited diminishing immune system responses and viral load. Patients who developed severe COVID-19 infections showed no decrease in their immune activity or viral load, and many of the immune signals accelerated.
However, there were indicators early on that predicted which patients were at greatest risk of severe infection.“We were able to pull out signatures of disease risk,” said study senior author Professor Akiko Iwasaki.
While it was known that the immune system unleashes a massive “cytokine storm” in the worst cases of COVID-19, it was not known which specific components of the immune system are responsible. The Yale team has found some new clues as to the cause of this damaging immune response.
Curiously, said researchers, one risk factor was the presence of alpha interferon, a cytokine mobilized to combat viral pathogens such as the flu virus. However, high levels of alpha interferon were associated with the worst COVID-19 outcomes.
“This virus just doesn’t seem to care about alpha interferon,” said Professor Iwasaki. “The cytokine appears to be hurting, not helping.”
Another early indicator of severe disease is activation of the inflammasome, a network of proteins triggers an inflammatory response when pathogens are detected.
The researchers found that individuals who had the best outcomes expressed high levels of a type of cytokine that repairs tissue damage to the linings of blood vessels and lungs.
Taken together, the data can help predict patients at high risk of poor outcomes, said the study authors. They added that drugs which target specific causes of inflammation identified in the study could help treat patients at risk of developing severe cases of COVID-19.
The study is published in the journal Nature.