Efficacy of Therapeutic Plasma Exchange Alone or in Combination with Ruxolitinib for the Treatment of Penn Class 3 and 4 Cytokine Release Syndrome Complicating COVID-19

Abstract

Observations early in the viral pandemic of 2020 noted the resemblance between severe coronavirus disease 2019 (COVID-19) infection and the hypercytokinemic state of secondary hemophagocytic lymphohistiocytosis (sHLH) [1]. Conti and colleagues [2] have outlined the binding of COVID-19 to the Toll-like receptor with subsequent cytokine driven fever and pneumonitis, while in Kenderian’s [3] murine model of CRS, ruxolitinib abrogated the development of cytokine excess. Cao [4] reported faster clinical recovery with JAK inhibition and Capochiani’s RESPIRE trial reported an 89% overall response rate (ORR) with ruxolitinib therapy [5]. Discordant findings regarding JAK inhibition have been reported on the superiority of baricitinib plus remdesivir over remdesivir alone in shortening recovery times in hospitalized patients [6] while the randomized RUXCOVID trial failed to impact severe complications of the disease by adding ruxolitinib to standard of care [7]. Other groups [8,9] have reported inflammatory cytokine profiles along with evidence that elevated IL-6 and TNFα are strong predictors of disease severity and survival. While cytokine excess could be an epiphenomenal surrogate for another process, therapeutic strategies have evolved around addressing the excessive cytokine levels complicating a significant fraction of COVID-19 patients.