First, Do No Harm: Caution Against Use of Tocilizumab in COVID-19.

To the Editor:

I read with great interest the case report by Radbel et al in CHEST (July 2020) on their use of tocilizumab in severe coronavirus disease 2019 (COVID-19) and two adverse outcomes. Their call for caution regarding the use of IL-6 inhibitors is justified. The “hyperinflammatory state” as a major driver of morbidity and mortality in severe COVID-19 is still a hypothesis. C-reactive protein levels in COVID-19 are no different from other etiologies of pneumonia and ARDS.2, 3, 4 Although it has been posited that reducing IL-6 may be beneficial because high IL-6 levels are associated with poor outcomes in COVID-19 and other diseases, this question is far from settled. The assumption that IL-6 in this disease is pathologic and not an appropriate response to the infection has not been proven, and in fact, the opposite has been shown in other viral infections. I question the uncontrolled use of tocilizumab in severe cases of COVID-19 given the possible protective effect of IL-6 in this disease. Its off-label use should only be carefully considered in the setting of a clinical trial.

The proliferation of unreviewed manuscripts on preprint servers, study results released via press release, and large number of uncontrolled retrospective studies should give us all pause. As this pandemic worsens in the Americas, Africa, and the Indian subcontinent, those suffering from COVID-19 would benefit from well-controlled trials capable of providing high-quality, actionable treatment and diagnostic interventions. Small, uncontrolled trials are vulnerable to well-known biases that affect the direction and magnitude of treatment effects. With so many critically ill patients, there is a temptation to do something, but our first commitment should be to do no harm.

Radbel et al should be commended for publishing this result.