Immunologists have discovered possible treatments for COVID-19 using existing therapies.
Scientists at St. Jude Children’s Research Hospital have ascertained the process which drives the life-threatening inflammation damage and organ failure which plagues coronavirus disease 2019 (COVID-19) patients. The research suggests that a potential strategy for treatment could be possible using drugs that already exist.
The study, published in the online journal Cell, discovered that the hyperinflammatory immune response connected with COVID-19, lead to multi-organ failure and tissue damage in mice. This was found to be caused by a triggering of the inflammatory cell death pathways. The research determined how this process works, which eventually led to the discovery of potential therapies to disrupt it.
"Understanding the pathways and mechanism driving this inflammation is critical to develop effective treatment strategies," corresponding author Thirumala-Devi Kanneganti, PhD, said. "This research provides that understanding. We also identified the specific cytokines that activate inflammatory cell death pathways and have considerable potential for treatment of COVID-19.”
Cytokines are small proteins that are secreted by immune cells and help ensure a rapid response to restrict a virus. Some cytokines have been found to trigger inflammation, which explains the high cytokine levels in COVID-19 patients. However, the exact pathways that initiate the cytokines and the molecular mechanisms behind them was unknown. The study found that the cytokine PANoptosis was the main source fueling the inflammation through cell death and inflammatory molecules.
The research concludes that the cytokine-mediated inflammatory cell death process caused by PANoptosis is at the center of the inflammation damage. The cytokine storm releases more cytokines, intensifying systemic inflammation and resulting in more inflammatory molecules. Many cytokine inhibitors are already on the market and can be used for potential treatment of inflammation, making these findings a crucial next step in the fight against COVID-19.
"We have solved a major piece of the cytokine storm mystery by characterizing critical factors responsible for initiating this process, and thereby identifying a unique combination therapy using existing drugs that can be applied in the clinic to save lives," Kanneganti said.