IL6 and COVID-19: As regards signaling modalities, trans-signaling and trans-presentation are suggested to be the main pathogenic pathways in severe progressive COVID-19, accounting for disseminated inflammation up to shock, secondary to cytokine-mediated dysfunction [50], whereas IL-6 cis-signaling, exerting negative feedback mechanisms on pro-inflammatory cytokines, appears as predominant in the advanced stages of disease in which the IL-6 peak is accompanied by elevated IL-10 concentrations, endeavoring to restore homeostatic conditions [51].