Anakinra for severe forms of COVID-19

We read the Article by Thomas Huet and colleagues¹ describing the effects of the interleukin-1 receptor antagonist anakinra in patients with severe COVID-19 with great interest. The authors compared a composite endpoint of death or admission to an intensive care unit for invasive ventilation between a group of patients with severe COVID-19 treated with anakinra plus standard of care (anakinra group) with a historical control group that received standard care alone.

Anakinra was found to significantly reduce the need for admission to an intensive care unit and mortality compared with standard care. Complementary analysis confirmed this benefit when adjusted for cofounding factors, including body-mass index and hydroxychloroquine intake. Furthermore, this clinical benefit was supported by a reduction of C-reactive protein in the anakinra group.

The analysis of the benefit of an innovative treatment using a historical cohort as control group has some methodological limitations that authors acknowledged. The presence of factors not included in the statistical analysis might compromise the relevance of the results. COVID-19 has been shown to be associated with a high rate of thrombotic complications, such as pulmonary embolism, in severe cases.² Anticoagulant treatment appears to be beneficial in this situation, which has led to changes in clinical practice in many centres that were managing patients with COVID-19.³ Of note, pulmonary embolism was not systematically investigated by Huet and colleagues.¹ Could the authors provide data on the proportion of patients receiving anticoagulant drugs in the two groups and analyse whether this parameter modifies the results observed on the primary endpoint when considered as a cofounding factor?

We would like to thank and congratulate the authors of this study for the important insight they provide into the treatment of this critical condition.