Strikingly, patients from all three groups had elevated levels of proinflammatory cytokines IL-6, IL-8, IL-10, and MCP-10, as well as a protein called PAI-1, which causes small blood clots in vessels throughout the body, including the lungs.
Importantly, increased PAI-1 levels are associated with more severe cases of pneumonia, a common cause of death among COVID-19 patients.
Because IL-6 was positively associated with the levels of the other cytokines and PAI-1, the researchers concluded that IL-6 signaling is crucial for the development of Cytokine Release Syndrome (CRS) following infection or trauma, and may play a role in the pathogenesis of COVID-19.
"Examination of cytokine profiles in severe COVID-19 patients revealed an increase in IL-6 early in the disease process, causing release of PAI-1 from blood vessels," says study senior author Tadamitsu Kishimoto. "Interestingly, PAI-1 levels were significantly higher in COVID-19 patients with severe respiratory impediment."
Most significantly though, when severe COVID-19 patients were treated with a human monoclonal antibody-based drug called Actemra, which blocks IL-6 signaling, PAI-1 levels rapidly declined and severe disease symptoms were alleviated.
