According to the Infectious Disease Society of America (IDSA), one of the possible treatment options for COVID-19 patients is il-6 inhibitors (tocilizumab, sarilumab). What is the rationale behind this?



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Hemophagocytic lymphohistiocytosis (HLH) syndrome is a life-threatening condition commonly triggered by viral illness. It is caused by over-activated macrophages and low NK cell/cytotoxic T-cell activity, leading to increased cytokine release (cytokine storm) and organ failure. A non-exhaustive list of clinical features of this syndrome includes:

  • fever
  • splenomegaly
  • cytopenia
  • hypertriglyceridemia/hypofibrinogenemia
  • increased ferritin
  • macrophage phagocytosis of red blood cells in bone marrow, spleen, lymph node, or liver

COVID-19 infection seems to trigger a similar cytokine storm as HLH, as according to a Lancet paper[1]

A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α.

Cytokine storm is classically treated with IL-6 receptor inhibitors such as tocilizumab.

A preliminary study from China[2] has also shown that in a sample size 21 severe or critical COVID-19 patients treated with tocilizumab, 75% of patients needed oxygen therapy and there were no mortalities after 2 weeks of the study. Due to a low sample size and lack of control group, this is just an initial finding, but has prompted larger clinical trials on the efficacy of il-6 inhibitors for COVID-19.

Currently, two major U.S. clinical trials are being done on il-6 receptor inhibitors:

  1. Sanofi and Regeneron Pharmaceuticals is evaluating sarilumab[3]
  2. Genentech (of Roche Group) is evaluating tocilizumab in the COVACTA trial[4]


  1. COVID-19: consider cytokine storm syndromes and immunosuppression
  2. Effective Treatment of Severe COVID-19 Patients with Tocilizumab
  3. http://www.news.sanofi.us/2020-03-16-Sanofi-and-Regeneron-begin-global-Kevzara-R-sarilumab-clinical-trial-program-in-patients-with-severe-COVID-19
  4. https://www.genengnews.com/virology/coronavirus/genentech-launches-phase-iii-trial-of-actemra-as-coronavirus-treatment/

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