What is the rationale behind using Il-6 inhibitors to treat COVID-19 patients?
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?
Source:
www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
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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-? inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-?, and tumour necrosis factor-?.
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:
Sanofi and Regeneron Pharmaceuticals is evaluating sarilumab[3]
Genentech (of Roche Group) is evaluating tocilizumab in the COVACTA trial[4]
Source:
COVID-19: consider cytokine storm syndromes and immunosuppression
Effective Treatment of Severe COVID-19 Patients with Tocilizumab www.news.sanofi.us/2020-03-16-Sanofi-and-Regeneron-begin-global-Kevzara-R-sarilumab-clinical-trial-program-in-patients-with-severe-COVID-19 www.genengnews.com/virology/coronavirus/genentech-launches-phase-iii-trial-of-actemra-as-coronavirus-treatment/
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