Early in the COVID-19 pandemic, the role of ‘cytokine storm’ in patients with severe course was raised. Indeed, this triggered multiple investigations centred around calming excessive inflammation with pharmacotherapies such as corticosteroids and interleukin-6 inhibition, among others.

Not surprisingly, the editors of the Journal of the American Medical Association reported that over 9 months they received over 10,000 submissions on the topic of COVID-19 – many suggesting or observing novel therapies.

Even before the hydroxychloroquine debacle, intensivists were and are, appropriately, skeptical of sepsis immunomodulation.

This is probably rooted in the multitudinous therapeutic failures in this space – ranging from heparin to anti-thrombin III, anti-TNF alpha therapies to non-steroidal anti-inflammatories and, of course, activated protein C.

These flops seemingly, subconsciously, cemented themselves into the sepsis storage sulci of ICU practitioners – hardening clinicians to new tactics, pre-judging almost all new therapies as ‘doomed-to-fail.’

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