Coronavirus disease 2019 (COVID-19) has left an indelible mark on 21st century history, but in the ancient saga of humans and the viruses we encounter, what makes this chapter so special? For one, it's the story of inflammation in severe COVID-19. Clinical features and biomarker measurements in patients with COVID-19 have generated buzz around the term cytokine storm and fostered comparisons to canonical syndromes such as haemophagocytic lymphohistocytosis and macrophage activation syndrome. But are these comparisons warranted?

Although the degree and extent of systemic inflammation seen in patients with COVID-19 is typically less than in haemophagocytic lymphohistocytosis and macrophage activation syndrome, many observational studies have identified associations between inflammatory biomarkers (eg, C-reactive protein, ferritin, lactate dehydrogenase, D-dimer, interleukin [IL]-2 receptor, and IL-6) and development of acute respiratory distress syndrome (ARDS) and death. ^,  It is also true in other postviral hyperinflammatory states that seemingly modest elevations of C-reactive protein and ferritin have been associated with increased mortality. ^,  But the association between severe infections and increased inflammation does not mean targeting the latter will fix the former. Thus, dozens of clinical trials are ongoing in patients with COVID-19 targeting the host inflammatory response.

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