The effect of tocilizumab on procalcitonin and other biochemical and clinical markers in severe COVID-19 infection : time to rethink our interpretation of results?

Abstract

BACKGROUND: Tocilizumab is an interleukin-6 inhibitor approved for use in patients severely affected by COVID-19. It has reduced mortality and duration of mechanical ventilation but the effects of tocilizumab on routinely monitored biochemical parameters in the critically ill COVID-19 population are unclear.

In Malta, tocilizumab started being administered to acutely deteriorating COVID-19 patients in January 2021. This study aims to assess the effect of tocilizumab on procalcitonin primarily, and white cell count, lymphocyte and neutrophil counts, neutrophil to lymphocyte ratio, C-reactive protein and PaO2/FiO2 ratio as secondary measures.

METHODS: 50 patients who received tocilizumab were recruited to the treatment group along with a matched control group of 50 patients who did not receive the drug. Serum procalcitonin and other biochemical markers were recorded daily for both groups along with results of blood cultures for 20 days or until discharge or death. Non-parametric univariate analysis and linear mixed model analysis was used to check for differences between the two groups. Outcome measures included differences between the biomarkers at 5, 10 and 15 days, and differences in the trajectories of the biomarkers between the two groups.

RESULTS: Procalcitonin and C-reactive protein are significantly lowered by administration of tocilizumab on Day 5. White cell count, lymphocyte and neutrophil counts and PaO2/FiO2 ratios were not affected. There was no difference in positive blood culture results between the two groups.

CONCLUSION: Procalcitonin and C-reactive protein may not be reliable indicators of bacterial superinfection in severe COVID-19 pneumonia patients who have been given tocilizumab.