Could anakinra outmatch dexamethasone/tocilizumab in COVID-19?

The hyperinflammatory state leading to an aberrant cytokine production, culminating in acute respiratory distress syndrome, sepsis and multi-organ dysfunction contribute much to the pathophysiologies of severe COVID-19. These severe patients have similar clinical manifestations with patients suffering from certain auto-inflammatory disorders and cytokine storm syndromes. Interestingly, anakinra (blocking both IL-1α and IL-1β) has shown promises in treating these patients with hyperinflammatory disorders, sepsis with multiorgan failures. Another inflammasome, AIM2, involved in production of IL-1 has also been found to be implicated in COVID-19. IL-1β, a known procoagulant, causes induction of tissue factor with increasing vascular endothelial permeability loss ensuing in hypercoagulability-one of the cardinal features of the disease. Hence, anakinra a 17kD recombinant human IL-1 receptor antagonist, used widely in Rheumatoid Arthritis treatments might prove efficacious in attenuating the hyperinflammatory state of the disease. Indeed, some of the controlled clinical trials have shown anakinra to effectively decrease mortality and hospital stay. Targeted cytokine blocking are always preferable in comparison with non-specific blocking (steroids) as it is more restrained with the chances of dampening of systemic immune system being much less. Early cell death and neutrophil migration have been one of the pivotal events in COVID-19 pathogenesis. Hence, suPAR levels which measures IL-1α (necroptosis) and S100A8/A9 (neutrophil migration) can perhaps be a good early biomarker predicting the disease progression. Lastly and importantly, as the vaccines are raised against spike protein and the different variants of concern are known to evade the neutralizing antibodies by varying degrees, it will be deserving to assess anakinra, against the variants of concern as an immunomodulatory drug.