IL-6 family cytokines behind acute COVID-19 and Long COVID syndrome: Mechanisms, biomarkers, and intervention strategies

IL-6 family of cytokines is increasingly recognized as a potential contributor to the immune alterations observed in COVID-19 and its long-term sequelae. Beyond the well-established pro-inflammatory actions of IL-6 itself, members of this family collectively orchestrate a complex network integrating antiviral defence, tissue repair, and maladaptive inflammation. Evidence accumulated over the past five years suggests altered regulation and signalling of those cytokines may help explain the heterogeneity of clinical outcomes, ranging from acute respiratory failure to persistent post-COVID symptoms. Recent advances -including the development of multispecific fusion proteins capable of simultaneously blocking viral entry and selectively modulating IL-6-related inflammatory pathways- highlight the expanding therapeutic potential of targeting this cytokine axis. Effective intervention requires precise knowledge of the cytokines temporal expression patterns to avoid interfering with beneficial immune responses. This review examines the molecular mechanisms involving IL-6 family cytokines, their promise as biomarkers of disease progression, and the current or emerging therapeutic strategies aimed at modulating their signalling pathways.