Title : Cytokine storm control in severe fever with thrombocytopenia syndrome: Tocilizumab’s potential role in reducing IL-6 and mortality
Abstract:
Background: Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic infectious disease prevalent in East Asia, with a mortality rate of 5–30%. Despite trials with therapeutic plasma exchange (TPE) and antiviral treatments, no established treatment strategy exists for severe cases. Recent evidence suggests cytokine storms, particularly elevated levels of interleukin (IL)-6, contribute to severe disease progression in SFTS. Tocilizumab, an anti-IL-6 receptor monoclonal antibody, may help manage cytokine storms in SFTS patients, similar to its use in severe COVID-19. This study aimed to investigate the therapeutic potential of tocilizumab in patients with severe SFTS, focusing on IL-6 dynamics and clinical outcomes, and comparing its efficacy to TPE and conservative treatment.
Methods: A prospective, longitudinal study was conducted involving 97 adult patients diagnosed with SFTS at a single hospital in Korea between 2013 and 2023. Tocilizumab was administered to patients with IL-6 levels ≥30 ng/mL from 2022 onwards. Patient outcomes in the tocilizumab (TCZ) group were compared to those in the TPE and conservative treatment groups. Data on demographics, viral load, IL-6 levels, and multiple organ dysfunction scores (MODS) were collected. Kaplan-Meier curves and log-rank tests were used for survival analysis.
Results: Of the 40 patients, 30 underwent TPE and 10 received tocilizumab. In the TCZ group, the median initial SFTS viral load was higher compared to the TPE group (578,664 copies RNA/mL vs. 58,747 copies RNA/mL, p=0.08). The 14-day mortality rate was 10.0% in the TCZ group versus 16.7% in the TPE group (p=0.608), and the 28-day mortality rate was 10.0% versus 20.0%, respectively (p=0.480). While both treatments significantly reduced IL-6 levels and SFTS viral loads over time, IL-6 levels were significantly higher in the TPE and TCZ groups compared to the conservative treatment group at the 0–5 days interval (p=0.005). Kaplan-Meier survival analysis showed no significant difference in 14-day mortality between the TCZ and TPE groups (log-rank p=0.505), though a trend towards lower mortality was observed in the TCZ group.
Conclusion: Tocilizumab significantly reduced IL-6 levels and showed potential in improving survival in patients with SFTS, although the results were not statistically significant. Both TPE and TCZ effectively managed viral load and IL-6 dynamics, highlighting their potential in controlling SFTS progression. Larger clinical trials are needed to establish the efficacy and safety of tocilizumab as a standard treatment for SFTS.
