Late onset infectious complications and safety of tocilizumab in the management of COVID-19

J Med Virol. 2021 Mar;93(3):1459-1464. doi: 10.1002/jmv.26429. Epub 2020 Aug 21.

Abstract

Background: Tocilizumab (TCZ) has been used in the management of COVID-19-related cytokine release syndrome (CRS). Concerns exist regarding the risk of infections and drug-related toxicities. We sought to evaluate the incidence of these TCZ complications among COVID-19 patients.

Methods: All adult inpatients with COVID-19 between 1 March and 25 April 2020 that received TCZ were included. We compared the rate of late-onset infections (>48 hours following admission) to a control group matched according to intensive care unit admission and mechanical ventilation requirement. Post-TCZ toxicities evaluated included: elevated liver function tests (LFTs), GI perforation, diverticulitis, neutropenia, hypertension, allergic reactions, and infusion-related reactions.

Results: Seventy-four patients were included in each group. Seventeen infections in the TCZ group (23%) and 6 (8%) infections in the control group occurred >48 hours after admission (P = .013). Most infections were bacterial with pneumonia being the most common manifestation. Among patients receiving TCZ, LFT elevations were observed in 51%, neutropenia in 1.4%, and hypertension in 8%. The mortality rate among those that received TCZ was greater than the control (39% versus 23%, P = .03).

Conclusion: Late onset infections were significantly more common among those receiving TCZ. Combining infections and TCZ-related toxicities, 61% of patients had a possible post-TCZ complication. While awaiting clinical trial results to establish the efficacy of TCZ for COVID-19 related CRS, the potential for infections and TCZ related toxicities should be carefully weighed when considering use.

Keywords: Il-6 inhibition; SARS coronavirus; coronavirus; cytokine/chemokine; immune responses; tocilizumab.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use
  • Bacterial Infections / complications*
  • Biomarkers, Pharmacological / blood
  • COVID-19 / complications*
  • COVID-19 / mortality
  • COVID-19 Drug Treatment*
  • Cytokine Release Syndrome / drug therapy*
  • Cytokine Release Syndrome / virology
  • Female
  • Humans
  • Inpatients
  • Male
  • Middle Aged
  • Mycoses / complications*
  • Retrospective Studies

Substances

  • Antibodies, Monoclonal, Humanized
  • Antiviral Agents
  • Biomarkers, Pharmacological
  • tocilizumab