Combined with elevated levels of cfDNA from innate immune origin, cytokine analysis that showed elevated levels of myeloid-derived inflammatory cytokines such as IL-15, IL-16, IL-6, IL-8, TNF-α, MIP-1α, and MIP-1β in MIS-C implicates the innate immune system as a probable driver of MIS-C pathogenesis and suggests potential therapeutic targets. Here, CXCL8 is linked to COVID-19–associated multisystem inflammatory syndrome in children.