Study Lends Insight into COVID-19 Cytokine Storm

Group is first to demonstrate the activation of inflammasome in response to infection by SARS-CoV-2.

For the first time, a team of researchers at the University of São Paulo have shown the immune mechanism, known as inflammasome, leads to the activation of an inflammatory process which damages lungs and may potentially lead to death in patients with the coronavirus disease 2019 (COVID-19).

The study, published in the Journal of Experimental Medicine, found that the use of inflammasome activation as a marker of disease prognosis can help physicians identify patients who may be high risk at an early stage and as a potential therapeutic target in severe COVID-19. The team also suggests that the findings support the idea that inflammasome could potentially be used as a therapeutic target in cases of severe COVID-19.

Inflammasome is an innate, multiprotein, intracellular complex that helps to detect pathogenic microorganisms and activates pro-inflammatory cytokines. Most immune cells have the complex and when one senses a viral or bacterial particle, it activates defense machinery.

Almost all immune cells are equipped with the protein complex that constitutes the inflammasome. When one of these proteins identifies a sign of danger, such as a viral or bacterial particle, the defense machinery is activated. Once this occurs, the cell enters the process of pyroptosis, which is a type of programmed death. This releases the cell into the bloodstream and signals the cytokines and begins the inflammatory response which helps to fight the potential threat.

"When this kind of inflammasome is activated, the proteins that form the complex, and are normally distributed throughout the cytoplasm, cluster together in what are called puncta, or specks, which can be observed under a microscope," Dario Zamboni, principal investigator behind the study said. "This, in turn, activates caspase-1, the enzyme that 'processes' the precursors of pro-inflammatory cytokines such as IL-18 and IL-1β so that they become 'mature' and active."

The study led by the Ribeirão Preto group was not the first to study this immune mechanism, but they were the first to demonstrate the activation of the specific type of inflammasome which responds to an infection of COVID-19. The research has led to other studies which are looking into existing therapies that may help to reduce the inflammatory process.