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  • Writer's pictureMed Insider

Covid-19 billows a cytokine storm

By Aleena Kuriakose


  • Severe virus cases have been associated with neurological complications.

  • Many Covid-19 complications are suggested to be stimulated by a condition known as cytokine release syndrome or an intracranial cytokine storm.

  • A cytokine storm is when an infection causes the immune system to flood the bloodstream with cytokines, killing tissues, and damaging the organs.

Covid-19, being a respiratory disease, has served as a stark reminder of the importance of an effective immune system and the grave consequences of immune dysregulation.


What are Cytokine Storms?

Though a clear definition of a cytokine storm remains controversial, it is essentially an umbrella term consisting of many immune dysregulation disorders distinguished by constitutional symptoms, systemic inflammation, and multiorgan dysfunction that can result in multiorgan failure if inadequately treated. In other words, a cytokine storm is an over-catalyzed and life threatening reaction of the immune system that results in the bloodstream being flooded with proteins called cytokines, killing tissues and damaging organs. Almost all patients with cytokine storm are feverish and in severe cases, fever can be of high grade. Symptoms that patients may experience include fatigue, anorexia, headache, rash, diarrhea, arthralgia, myalgia, and neuropsychiatric findings. These symptoms could be directly linked to cytokine-induced tissue damage, acute-phase physiological changes, or from immune-cell-mediated responses.

It is with no surprise that cases with cytokine storms are of concern and can be severe. They can develop rapidly to spread intravascular coagulation with devastating hemorrhages, dyspnea, hypoxemia, hypotension, hemostatic imbalance, vasodilatory shock, and death. Many cytokine storm patients have respiratory symptoms, such as coughs that can progress to acute respiratory distress syndrome that may require mechanical ventilation. As a result, cytokine storms pose an increased risk for spontaneous hemorrhage.

Clinical Presentation of a Cytokine Storm. (Longo et al., 2021).


Pathophysiological Features of Cytokine Storm

Normally, the role of the immune system serves to recognize foreign invaders, respond to pathological infection, and then return to homeostasis. For this to be accomplished, there must be an equilibrium between sufficient cytokine production to remove the pathogen and evasion of a hyperinflammatory response, in which an overflow of cytokines can produce significant collateral damage. Albeit the cytokines’ pathological characteristics, at a sustained level, cytokines coordinate antimicrobial effector cells and provide regulatory signals that direct, amplify, and resolve the immune response. Furthermore, cytokines have brief half-lives, preventing them from having effects outside sites of inflammation. It is at heightened levels in which cytokines can produce damaging effects to crucial organ systems.

Immune hyperactivation, or when the immune system reacts to substances that are normally harmless, can occur as a result of inappropriate triggering/danger sensing. Having an allergic reaction is the most common form of immune hyperactivation. In all the cases ranging from inappropriate inflammasome activation to failure to resolve the immune response, negative feedback mechanisms fail to prevent hyperinflammation and thus lead to the overabundance of inflammatory cytokines.

Pathological Features of Cytokine Storm. (Longo et al., 2021).


Covid-19 Associated Cytokine Storms

Covid-19 is indicated by diverse symptoms ranging from mild exhaustion to life-threatening respiratory illnesses, cytokine storm, and multiorgan failure. Although researchers are still investigating the mechanisms of lung and multiorgan failure in Covid-19, reports of increased cytokine levels suggest that cytokine storm may contribute to the pathogenesis of the virus.

For instance, elevated serum cytokine levels in Covid-19 patients encompass interleukin-1β, interleukin-6, IP-10, TNF, interferon-γ, macrophage inflammatory protein (MIP) 1α and 1β, and VEGF. Specifically, increased levels of interleukin-6 levels are strongly correlated with shorter survival. Moreover, many laboratory test results indicate that hyperinflammation and tissue damage aggravate outcomes in Covid-19.



In summary, although severe cases of Covid-19 have shown immune dysregulation, it is still unknown whether it is immune hyperactivity or an inability to resolve the inflammatory response due to continuous viral replication that underlies severe cases. Consequently, research should be focused on further developing therapeutic strategies for cytokine storms.



Fajgenbaum, D. C., & June, C. H. (2021, April 22). Cytokine Storm: NEJM. New England Journal of Medicine.


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