Efficacy of Tocilizumab Therapy in Different Subtypes of COVID-19 Cytokine Storm Syndrome

Viruses. 2021 Jun 3;13(6):1067. doi: 10.3390/v13061067.

Abstract

Background: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis.

Methods: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In the MAS and CRS groups, treatment results were assessed depending on whether or not tocilizumab was used.

Results: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/mL, p < 0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p = 0.043), RR = 2.1 (95% CI 1.0-4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p = 0.013), RR = 0.50 (95% CI 0.25-0.99).

Conclusions: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients, it contributed to reduced mortality.

Keywords: ARDS; cytokine storm syndrome; inflammation; monoclonal antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • COVID-19 / classification
  • COVID-19 / immunology
  • COVID-19 / mortality
  • COVID-19 Drug Treatment*
  • Cytokine Release Syndrome / classification*
  • Cytokine Release Syndrome / drug therapy*
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / mortality
  • Female
  • Ferritins / blood
  • Humans
  • Macrophage Activation Syndrome / drug therapy
  • Macrophage Activation Syndrome / mortality
  • Macrophage Activation Syndrome / virology
  • Male
  • Retrospective Studies
  • Sepsis / drug therapy
  • Sepsis / virology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Ferritins
  • tocilizumab