When patients develop disease, their bodies will release a slew of chemicals designed to alter the immune system’s response. This phenomenon is called a “cytokine storm,” cytokines being the chemicals released to interact with immune cells. Cytokine storms can be uniquely patterned depending on the disease, providing not only a signature for worsening disease, but also providing a map for what immune pathways are dysregulated in incredibly sick patients. We sought to characterize the cytokine storm in extremely sick COVID-19 patients hospitalized at the University of Utah Hospital.

Using a multiplex array, we measured the concentrations of cytokines in the patients’ plasma. Eight cytokines were found to be elevated in patient plasma, many of them known to recruit more immune cells to sites of injury. These cytokines are associated with a heightened innate immune response, which is the body’s first line of defense against any disease. Interestingly, we also found a couple of anti-inflammatory cytokines had risen in concentrations as well, most likely from the body attempting to counteract the deluge of pro-inflammatory signals.

Further analysis of patient plasma revealed an increase in growth factors that encourage changes in blood vessel growth. COVID-19 patients had more signals in their blood that encouraged blood vessel changes. However, when we examined the difference in cytokines between moderately and severely sick COVID patients, we found four cytokines that surprisingly decreased in severe disease. These cytokines, MDC22, FLT-3L, TNF-a, and IL-12, could be biomarkers to determine the difference between which patients are becoming severely diseased.  We also found cytokines relating to type 2 immune response (the branch of the immune system that combats parasitic worms) to also be increased in patients. We observed a slight increase in type 2 cytokines in males, which may explain the worse outcomes in male patients.

This study glimpsed into the immune responses involved in COVID-19 hospitalization, allowing for future studies to delve into which immune cells and interactions are driving or interacting with these cytokine changes.