A cytokine storm is a severe, overreactive inflammatory response, which can lead to multi-organ failure and eventual death. This process occurs when a large number of white blood cells are activated, release inflammatory cytokines, and then create a vicious loop in which more white blood cells are activated. Cytokine storms are associated with a wide number of conditions such as infections, autoimmune diseases, CAR-T therapy, and graft-versus-host disease.
There is accumulating evidence that the progression of COVID-19 to acute respiratory distress syndrome or fulminant myocarditis is through a cytokine storm mechanism.
Coronavirus Infections Lead to Early Cytokine Storm
Human coronaviruses replicate to high viral loads very early after infection. This leads to rapid activation of inflammatory cytokines and recruitment of macrophages and neutrophils into damaged tissue. The result is increased cell death, breakdown of vasculature, and impaired virus clearance.
This leads to acute lung injury which can rapidly progress to acute respiratory distress syndrome. This mechanism is why we see reports of young patients quickly progressing to respiratory failure a couple days after they have their first symptom of coronavirus. More detail about the pathophysiology of cytokine storm in coronaviruses is available here: https://link.springer.com/article/10.1007%2Fs00281-017-0629-x
Cytokine Storm in Severe COVID-19
There are several reports that suggest now that patients with severe COVID-19 have an inflammatory cytokine storm. Ruan et al. showed that patients who died from COVID-19 have elevated C-reactive Protein and Interleukin-6 levels compared to those who recovered. https://link.springer.com/article/10.1007/s00134-020-05991-x
This was confirmed by Zhou et al, who showed that patients requiring ICU admission had increased levels of IL-6 and CM-CSF, which in turn create more pathogenic Th1 cells, a type of inflammatory white blood cell. Source: https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa041/5804736?searchresult=1
Repeated overactive, inflammatory cytokine activation eventually leads to T cell exhaustion, which decreases our ability to fight infection and may be the reason why some infected individuals take so long to recover.
In Zhou et al’s experience, the patients in the ICU with features suggestive of worsening cytokine storm had greater C-reactive protein, lower albumin, greater ALT/AST, and greater lactate dehydrogenase levels. These are relatively easy values we can track daily in patients.
Patients with COVID-19 infection are prone to early cytokine storm, leading to ARDS. We should be on the look out for patients that have elevated inflammatory markers or liver function enzymes.