Trials of anti-tumour necrosis factor therapy for COVID-19 a
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Anti-tumour necrosis factor (TNF) antibodies have been used for more than 20 years in severe cases of autoimmune inflammatory disease such as rheumatoid arthritis, inflammatory bowel disease, or ankylosing spondylitis. There are ten USFDA approved and four off-label indications for anti-TNF therapy, indicating that TNF is a valid target in many inflammatory diseases. TNF is present in blood and disease tissues of patients with COVID-19 and TNF is important in nearly all acute inflammatory reactions, acting as an amplifier of inflammation. It is proposed that anti-TNF therapy should be evaluated in patients with COVID-19 on hospital admission to prevent progression to needing intensive care support.

There is evidence of an inflammatory excess in patients with COVID-19. Lung pathology in COVID-19 is characterised by capillary leakage of fluid and recruitment of immune-inflammatory lymphocytes, neutrophils, and macrophages, implying a role for adhesion molecules, chemokines, and cytokines targeting vascular endothelium.

Cytokine upregulation is documented in COVID-19. In patients with COVID-19, there is upregulation of pro-inflammatory cytokines in the blood, including interleukin (IL)-1, IL-6, TNF, and interferon γ, and patients in intensive care units have increased concentrations of many cytokines. Preliminary data from Salford Royal Hospital and the University of Manchester in the UK document the presence of proliferating excess monocytes expressing TNF by intracellular staining in patients with COVID-19 in intensive care.

We believe there is sufficient evidence to support clinical trials of anti-TNF therapy in patients with COVID-19. With an average of 2 days between hospital admission and ARDS,7 we propose anti-TNF therapy should be initiated as early as is practicable. If there is preliminary evidence of benefit and safety of anti-TNF therapy in hospitalised patients, we suggest consideration should be given to out of hospital treatment for patients with COVID-19 at high risk, such as older people and those with pre-existing conditions, and who can be monitored appropriately.

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