COVID-19-ASSOCIATED CYTOKINE STORM IN MECHANICAL CIRCULATORY SUPPORT: AN IN-VITRO STUDY

Abstract

Catheter-based mechanical circulatory support (MCS) systems are increasingly utilized for therapy in advanced heart failure patients. The need for MCS has grown in parallel with COVID-19-associated heart dysfunction. Following COVID-19 infection, there is a rapid increase in levels of circulating pro-inflammatory cytokines referred to as a “cytokine storm”. This “cytokine storm” has been shown to disrupt the immune system drastically. Proteins (e.g. cytokines) are sensitive to their biochemical environment, undergoing conformational changes that can ultimately affect biological function. It is well recognized that MCS impart shear stress on the blood and circulating components. However, there remains a lack of understanding as to the impact of MCS devices on cytokines, particularly COVID-19-associated cytokines. Here, we utilized an Impella5.5 to circulate a cytokine mixture (IL-6, IL-8, TNF⍺, IL-1ꞵ) representative of the COVID-19 “cytokine storm”. We hypothesize that MCS-induced flow alterations - i.e. turbulence and shear stress, will alter cytokine structure and binding ability as indicated by gel electrophoresis and ELISA binding. We found a significant increase in cytokine-antibody binding via ELISA after 1 hour of shear exposure, compared to the resting sample. Gel electrophoresis of samples allowed for evaluation of molecular mass against protein standard (2-25 kDa). Notably, single bands of IL-6 and TNF⍺ were visible in the resting samples; however, sheared samples showed double bands at the same location, indicating influence of shear on a portion of IL-6 and TNF⍺ population size. Our findings suggest MCS play a role in cytokine function and ultimately inflammation in a wide range of diseases. With further translation and defining mechanisms involved, these findings could help to inform improved MCS therapy.