Potential Predictors of the Outcome of Tocilizumab Treatment in Patients with COVID-19-Associated Hyperinflammation.

Abstract

Objective: During the COVID-19 pandemic, a subset of patients developed COVID-19-associated hyperinflammation (HIC), which resulted in increased mortality. While early and effective anti-inflammatory therapies, such as glucocorticoids and tocilizumab, improved survival, tools to predict treatment response remained lacking. This study aimed to identify predictors of clinical outcomes in patients who received tocilizumab for HIC.

Materials and methods: We retrospectively analyzed the records of hospitalized adult patients with COVID-19 treated between March and December 2020. Patients who received tocilizumab for HIC constituted the study cohort. Dynamic changes in the laboratory parameters were analyzed, and the HIC scores (≥35) were calculated to assess disease severity and treatment response.

Results: Out of 961 hospitalized COVID-19 patients, 150 who received tocilizumab were identified. Among them, 124 were treated with only tocilizumab in the first phase of the pandemic (from March to September 2020). After this period, 26 patients also received glucocorticoids, typically initiated 2-3 days prior to tocilizumab administration. Anakinra treatment was given to 22 patients whose inflammatory parameters did not resolve with tocilizumab. Findings of HIC were treated in 122 patients (84%), with a significant reduction in C-reactive protein (CRP) levels (from 121.8 ± 8.2 to 9.8 ± 2.8 mg/L). Despite tocilizumab treatment, no effective resolution of the CRP response was observed (from 172 ± 22.8 to 53 ± 8 mg/L by Day 5) among non-survivors, alongside increasing trends in neutrophil count, D-dimer, lactate dehydrogenase (LDH), troponin, and creatine kinase. The composite HIC scores progressively decreased in survivors until the last day of hospitalization but increased in non-survivors (33.8 ± 0.14 vs. 72.3 ± 0.13).

Conclusion: Analysis of this cohort indicated that neutrophil count, CRP, D-dimer, LDH, troponin, and creatine kinase levels may serve as predictors of tocilizumab efficacy on Day 5. The score developed to diagnose HIC can also be used for monitoring treatment response.