Biochimica et biophysica acta. Molecular cell researchJul 24, 2026

IL-6 Family Proteins Linked to Acute COVID-19 and Long COVID: How They Work, Markers to Detect Them, and Possible Treatments

Updated Jul 25, 2026

Abstract

Altered regulation and signaling of the IL-6 family of cytokines may explain the variability in clinical outcomes observed in COVID-19.

The IL-6 family of cytokines is involved in a complex network that integrates antiviral defense, tissue repair, and inflammation.
Evidence suggests that the actions of these cytokines contribute to the immune changes associated with COVID-19 and its long-term effects.
Clinical outcomes of COVID-19 can range from acute respiratory failure to persistent symptoms, potentially linked to cytokine signaling variations.
Recent developments include multispecific fusion proteins that may block viral entry and modulate IL-6-related inflammatory pathways.
Understanding the timing of cytokine expression is critical to ensure that beneficial immune responses are not disrupted.

Simplified

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.

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PubMed

IL-6 Family Proteins Linked to Acute COVID-19 and Long COVID: How They Work, Markers to Detect Them, and Possible Treatments

Abstract

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Funding

Competing interests

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