COVID 19: in the eye of the cytokine storm

Abstract

This study focused on four cytokines known to contribute to pathogenic inflammation in CRS of patients receiving CAR-T cells, with clinically available or experimental blocking drugs. The clinical picture of the cytokine storm in COVID-19 was different from that of the coordinated increase during traditional CRS, showing different patterns of cytokine expression, and potentially distinct clinical presentations based on the relative profile of each cytokine. Accordingly, serum levels of IL-6 and TNF-a were lower in COVID-19 compared to classical CRS. The plasma cytokine cluster of COVID-19 recalls the cytokine pattern associated with acute coronary syndromes (ACS). In ACS, IL-6 levels are correlated with prognosis, and IL-6 blockade by tocilizumab quenches the acute inflammatory response of ACS patients undergoing percutaneous coronary intervention. In COVID-19, the cytokine storm might evoke and/or potentiate existing or new cardiac functional abnormalities, as well as trigger ACS through a thromboinflammatory response. Previous studies have demonstrated that higher serum concentrations of IL-6 are associated with higher levels of SARS-CoV-2 viraemia, prolonged viral RNA shedding, progression to mechanical ventilation, and death. Although IL-6-receptor blockade might theoretically interrupt the COVID-19 inflammatory cascade at an early stage, there has been a limited success so far with drugs blocking IL-6. Evidence from non-randomized trials and open-label studies has been contradictory, and recently published results from a randomized, double-blind, placebo-controlled trial failed to demonstrate the efficacy of IL-6 receptor blockade in the treatment of hospitalized patients with COVID-19. One potential explanation is that IL-6 and other inflammatory proteins elevated in patients with COVID-19 represent a physiological host response to the infection, rather than components of a selfamplifying, pathogenic inflammatory loop. In general, the higher risk of severe COVID-19 disease in diabetes mellitus, obesity, and heart disease might be attributable to synergistic activation of macroand micro-vascular thrombo-inflammatory pathways associated with both Key points