Prognostic significance of serum interleukin-6 in severe/critical COVID-19 patients treated with tocilizumab: a detailed observational study analysis

Abstract

Baseline IL-6 levels have been found to be non-predictive of subsequent outcomes following tocilizumab treatment, highlighting the need for more reliable predictive markers. To address this, a retrospective analysis was conducted on the clinical profiles, diagnostic tests, and follow-up prognoses of 60 patients with severe or critical COVID-19, all of whom were identified as experiencing a cytokine storm and subsequently received tocilizumab treatment. Among the patients, the overall survival rate during follow-up was 80%, with further analysis revealing that advanced age was an independent risk factor for adverse outcomes. Following tocilizumab administration, a statistically significant increase in IL-6 and D-dimer levels was observed, while markers such as C-reactive protein (CRP), procalcitonin (PCT), and fibrinogen demonstrated reductions compared to pre-treatment values. Specifically, IL-6 levels initially surged briefly after tocilizumab intervention before gradually diminishing. To assess the prognostic utility of IL-6, the Receiver Operating Characteristic (ROC) curve was employed, which yielded an area under the curve (AUC) of 0.812, indicating strong predictive capability, with a sensitivity of 100% and a specificity of 53.49%. The optimal cut-off value for IL-6 was identified at 147.79 pg/mL. In conclusion, IL-6 levels tend to rise transiently following tocilizumab therapy, before gradually declining. These post-treatment IL-6 measurements may serve as a valuable biomarker for assessing prognosis in patients undergoing this treatment.

Keywords: COVID-19; IL6; Prognosis; Tocilizumab.

Fig. 1

Temporal changes in Interleukin-6 after tocilizumab administration. Panel A shows the changes in interleukin-6 over time; Panel B shows the changes in interleukin-6 levels over time between survivors and non-survivors.

Fig. 2

The receiver operating characteristic curve of Interleukin-6 level and prognosis.

Fig. 3

The analysis of Interleukin-6 level and prognosis after receiving tocilizumab treatment.

Fig. 4

Temporal changes in C-reactive protein after tocilizumab administration. Panel A shows the changes of C-reactive protein over time; Panel B shows the changes in C-reactive protein over time between survivors and non-survivors.

Fig. 5

Interleukin-6 in patients treated with 3 or 4 doses of tocilizumab.

Fig. 6

Response of laboratory parameters to tocilizumab treatment. (A) Interleukin-6; (B) C-reactive protein; (C) Ferritin; (D) Procalcitonin; (E) Fibrinogen; (F) D-dimer.

Fig. 7

The changes in fibrinogen and D-dimer in patients treated with 4 doses of tocilizumab.