The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 320 000 deaths as of May 19, 2020. COVID-19 deaths are primarily caused by acute respiratory distress syndrome (ARDS) and by a cytokine storm syndrome—ie, a state of hyperinflammation leading to multiorgan failure. 1 A recent Lancet letter2 suggested that screening patients with COVID-19 for hyperinflammation and treating them with immunosuppressive drugs could improve mortality. Cytokine storm complicating macrophage activation syndrome associated with rheu matic disease shares considerable biochemical overlap with the hyperinflammation observed in patients with COVID-19. 1, 3 At the time of writing, there are ten ongoing clinical trials in COVID-19 with the drug anakinra (table). Anakinra inhibits the proinflammatory cytokines interleukin (IL)-1α and IL-1β and has been used with some success to treat macrophage activation syndrome caused by various inflammatory conditions, 4, 5 and in several small studies in patients with COVID-19. 6, 7 Here we support the rationale for targeting hyperinflammation in COVID-19 with anakinra and comment on different aspects of its use, patient selection, dosing, and outcome measures. Anakinra is an immunosuppressive drug that carries the theoretical risk of harm in the wrong patient group by potentially targeting beneficial inflammation; however, positive effects might also be missed if the correct patient group is not ascertained. It is important, therefore, to target treatment to individuals considered to have hyperinflammation. Diagnostic criteria in this patient group are poorly developed and there is no consensus, as seen from the inclusion criteria listed for the ongoing anakinra trials (table). Although serum ferritin and IL-6 concentrations are highly specific to hyperinflammation and have been shown to be associated with a need for ventilation in patients with COVID-19, 8 they are not routinely measured in the clinical setting, a short coming that is highly relevant given the requirement to identify as many patients as possible that might benefit. We suggest a pragmatic approach to patient selection based on identifying patients with progressive disease and evidence of increasing inflammation. Therefore, we pro pose using worsening lymphopenia, a marker of disease progression and severity in COVID-19, and increas ing C-reactive proteinas evidence of worsening inflammation. The dose and route of administration of anakinra is especially relevant given its short plasma half-life, with both intravenous and subcutaneous routes being considered. 6, 7

While a short half-life is beneficial in limiting the drug’s duration of action in case of adverse events, it also leads to large peak–trough fluctuations with an intravenous formulation. Variation in dosing needs to be minimised to ensure constant and adequate bioavailability, and to avoid a detrimental rebound