Anakinra for severe forms of COVID-19

There is an urgent need to seek new therapeutic approaches to combat the infective and post-infective stages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The Article by Thomas Huet and colleagues¹ on the clinical use of the interleukin-1 (IL-1) receptor antagonist, anakinra, to treat patients with COVID-19 is very interesting. The main hypothesis of the study was based on hyperinflammation caused by an increase in proinflammatory cytokines, such as IL-1β, IL-6, and tumour necrosis factor (TNF), triggered by SARS-CoV-2 infection. The recruited participants in this study did not have any other infection, but what if the patients did have another proinflammatory condition, such as obesity, rheumatoid arthritis, or other autoimmune disease?

The strategy to block peripheral inflammation as a treatment is not new. Humanised antibodies raised against TNF have been very promising for the treatment of inflammation-associated pathologies, such as rheumatoid arthritis.² Tocilizumab, another humanised antibody which blocks the action of circulating IL-6, has been shown to increase survival in patients with COVID-19.³ At the start of the COVID-19 pandemic, there was controversy regarding the use of classic anti-inflammatory drugs, such as glucocorticoids, because these drugs might exacerbate the pathogenesis. However, corticosteroid therapy along with tocilizumab is associated with improved clinical outcome of patients with COVID-19.⁴

Can anakinra and tocilizumab be used as a combination therapy with corticosteroids in the treatment of severe SARS-CoV-2 infection, in the presence of inflammation-associated pathologies? A subgroup of patients with COVID-19 have a cytokine storm, characterised by a large increase in proinflammatory cytokines.⁵ Therefore, the use of combination therapy might be justified for improved protection and treatment of patients with severe COVID-19 associated with systemic hyperinflammation. However, one should be careful; corticosteroids exert not only an anti-inflammatory effect but also immunosuppression, and the aforementioned cytokine storm is also followed by an immunosuppression. SARS-CoV-2 infection in patients with obesity is associated with an increased rate of pneumonia, artificial ventilation, and respiratory tract illness. The pathology of obesity is also marked with a cytokine storm, with high concentrations of IL-6 and TNF, largely from inflamed adipocytes. Inflamed adipocytes provide a favourable habitat for infiltrated macrophages and can cause some of the adipocytes to be transformed into macrophage-like cells, which can result in immunosuppression. Obesity with known increased viral shedding and hyperinflammation might lead to life-threatening outcomes in case of SARS-CoV-2 infection. The question regarding the use of anti-inflammatory drugs in patients with COVID-19 patients remains open.