Is a “Cytokine Storm” Relevant to COVID-19?

In its most severe form, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), leads to a life-threatening pneumonia and acute respiratory distress syndrome (ARDS). The mortality rate from COVID-19 ARDS can approach 40% to 50%. Although the mechanisms of COVID-19–induced lung injury are still being elucidated, the term cytokine storm has become synonymous with its pathophysiology, both in scientific publications and the media. Absent convincing data of their effectiveness in COVID-19, drugs such as tocilizumab and sarilumab, which are monoclonal antibodies targeting interleukin (IL)-6 activity, are being used to treat patients; trials of these agents typically cite the cytokine storm as their rationale (NCT04306705, NCT04322773). A critical evaluation of the term cytokine storm and its relevance to COVID-19 is warranted.