Higher levels of IL-6 early after tocilizumab distinguish survivors from nonsurvivors in COVID-19 pneumonia: A possible indication for deeper targeting of IL-6

Abstract

Introduction: The most serious COVID-19 deriving from severe acute respiratory syndrome coronavirus 2 causes a cytokine release storm and it is associated with worse outcomes. In COVID-19 patients, interleukin-6 (IL-6) levels are significantly elevated. Blocking IL-6 preliminarily resulted in the improvement of this hyperinflammatory state. It is unknown which patients could require higher doses of tocilizumab to get out of the cytokine storm.

Materials and methods: Twenty-four patients affected by COVID-19 pneumonia were included. All the patients underwent tocilizumab 8 mg/kg intravenously and were tested for serum IL-6 24 to 48 hours before and 12 to 48 hours after tocilizumab infusion. Comparisons between survivors and nonsurvivors were performed.

Results: Eighteen patients were discharged, while six patients died, with no clinical or laboratory differences between the two groups at baseline. IL-6 was not different at baseline (P = .41), while 24 to 48 hours post-tocilizumab IL-6 serum levels were significantly higher in nonsurvivors than in survivors (2398.5 [430.5-9372] vs 290.5 [58.5-1305.5] pg/mL, P = .022). Serum IL-6 post-tocilizumab showed a good predictive ability to discriminate survivors from nonsurvivors (area under the curve, 0.815; 95% confidence interval, 0.63-0.99, P = .02).

Conclusion: Repeated measurement of the serum level of IL-6 early after tocilizumab may distinguish nonsurvivors from survivors and support the choice of deeper targeting IL-6 in COVID-19 pneumonia.

Keywords: COVID-19; coronavirus; cytokine; interleukin-6; tocilizumab.

Figure 1

On a logarithmic scale, this figure reports the value of interleukin‐6 (IL‐6), C‐reactive protein (CRP), and procalcitonin (PCT) over time in survivors (A) and nonsurvivors (B) as median. Below the graphs, the median and the number of available observations at each time are indicated. For completeness, the interquartile ranges [25%‐75% IQR], which have been omitted in the figure, are as follows: for survivors (A), baseline IL‐6 (pg/mL): 63.5 [52.2‐136], IL‐6 24 to 48 hours: 290.5 [76.7‐1119.7], IL‐6 week 2: 76.5 [47‐198.75], IL‐6 week 4: 116 [66‐124]; baseline CRP (mg/L): 150.6 [66.5‐210], CRP 24 to 48 hours: 41.3 [26.9‐63.8], CRP week 2: 4.4 [1.5‐6.4], CRP week 4: 1.6 [0.2‐5.1]; baseline PCT (ng/mL): 0.14 [0.08‐0.28], PCT 24 to 48 hours: 0.06 [0.04‐0.09], PCT week 2: 0 [0‐0.04], PCT week 4: 0.03 [0‐0.04]. For nonsurvivors (B), baseline IL‐6 (pg/mL): 171 [51‐523.5], IL‐6 24 to 48 hours: 2398.5 [594‐6819.7], IL‐6 week 2: 579 [338‐820], IL‐6 week 4: 146 [80‐212]; baseline CRP (mg/L): 158 [116‐255.5], CRP 24 to 48 hours: 91.7 [54.5‐116.5], CRP week 2: 6.8 [3.9‐160.6], CRP week 4: 68.9 [60.9‐77]; baseline PCT (ng/mL): 0.28 [0.09‐0.46], PCT 24 to 48 hours: 0.37 [0.36‐1.01], PCT week 2: 0.15 [0.09‐0.63], PCT week 4: 0.22 [0.14‐0.29]