Figure 4. PANoptosis and cytokine storm during SARS-CoV-2 infection.
The induction of innate immune signaling during SARS-CoV-2 infection leads to the production of pro-inflammatory cytokines. TNF and IFN-γ induce a form of inflammatory cell death called PANoptosis, which is mediated through the formation of a multiprotein complex called the PANoptosome. TNF and IFN-γ–mediated PANoptosis can lead to a cytokine storm loop, featuring further pathogenic cytokine release that can perpetuate PANoptosis as well as systemic inflammation, multi-organ failure and lethality.