Fig. 3

Cell death in cytokine storm. Robust release of cytokines has been suggested to correlate with lung injury and multiple organ failure. This state can activate a variety of cell death pathways, including but not limited to PANoptosis, necroptosis, apoptosis, and pyroptosis. Macrophages infected in conditions such as sepsis and HLH can trigger cytokine storm, during which the synergistic stimulation by inflammatory factors TNF and IFN-γ induces PANoptosis in macrophages. Multiple inflammatory cytokines are produced during β-coronavirus infection, HLH, and sepsis. ZBP1, AIM2, and RIPK1 are common triggers of PANoptosome. Cytokines and caspases, including caspase-8, were involved in the immunoregulation stage of sepsis. The coronavirus infection triggered caspase-8-dependent apoptosis and lead to lung damage. SARS-CoV-2-encoded coronavirus products could modulate various key components in the pyroptosis pathways and leading to cytokine storm syndrome. Abbreviations: HLH hemophagocytic lymphohistiocytosis, NK cell natural killer cell, DC dendritic cell, TNFR tumor necrosis factor receptor, ISGs interferon-stimulated genes, IFN interferon, FADD Fas-associated death domain, NLR NOD-like receptor, ASC apoptosis related spot like protein, GSDMD gasdermin D, RIPK receptor interacting protein kinases, MLKL mixed-lineage kinase domain-like pseudokinase, ZBP1 Z-DNA binding protein 1, AMI2 Absent in Melanoma 2, CASP caspase, BCL-2 B-cell lymphoma-2. The figure was created with the assistance of FIGDRAW