DOM COVID-19 Journal Club: Effective Treatment of Severe COVID-19 Patients with Tocilizumab

Background: The “cytokine storm” or hyper-inflammatory state of some patients with COVID-19 has been reported since the early days of the pandemic. Mediators of this inflammatory state include IL-2, IL-6, IL-7, IL-12, TNF-α, and IL-1β, among others. Pharmacologic blockade of these inflammatory pathways has been postulated as a possible treatment for severe COVID-19 illness. Tocilizumab is a recombinant humanized anti-IL-6 receptor monoclonal antibody.

Methods: Case series of 21 patients treated with tocilizumab at 2 hospitals in Anhui Province, China. All patients were confirmed SARS-CoV-2 positive and met criteria for severe infection (respiratory +/- other organ failure). All patients received the standard of care at the time (lopinavir-ritonavir, INF-α, ribavirin, glucocorticoids) and tocilizumab in 1 or 2 doses. Median time from symptom onset to treatment was 5.6 ± 2.8 d.

Results: Treatment with tocilizumab was associated with resolution of fever within the first day in all patients, as well as subjective improvement in clinical symptoms, and reduction in oxygen requirement in 75% of the treated patients. CRP decreased dramatically, and chest CT scans showed improvement in infiltrates in 91% of the patients. All of the patients were discharged from the hospital after mean hospitalization of 15.1 ± 5.8 d after the treatment with tocilizumab.

Limitations: This is a case series with no control group. There are a small number of treated patients, and long-term outcomes after discharge are not provided. Other treatments the patients received were not strictly controlled.

Conclusions: As a case series, this study establishes that tocilizumab is a potent anti-inflammatory that can be given to severe COVID-19 patients without apparent immediate adverse events. Claims of efficacy are overstated, given the absence of a control group and very small number of treated patients. This study certainly does not provide rationale for broad adoption of off-label use of IL-6 inhibitors for COVID-19, but does support the rationale behind currently enrolling randomized controlled trials.

Reference:

  1. Xu et al. Effective treatment of severe COVID-19 patients with tocilizumab. PNAS. 2020 Apr 29.

 

The Department of Medicine COVID-19 Journal Club is dedicated to understand and applying data on COVID-19 to inform prevention and management efforts for healthcare workers and patients.

This article by Stephen Halliday, MD, MSCI, assistant professor, Allergy, Pulmonary, and Critical Care Medicine. Reviewed by Nasia Safdar, MD, PhD, professor, Infectious Disease, vice chair for research, Department of Medicine.

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