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WHAT IS A CYTOKINE STORM?

Hector Osorio 02 Apr 2020
WHAT IS A  CYTOKINE STORM?

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Recent global events have forced us to think more about health and risk factors at a large scale. COVID-19 has certainly become the main focus of many health professionals and researcher’s work because of its high infectivity and the difficult management of very severe cases that often lead to death in the elderly (2-3% of cases) [1].

Most COVID-19 fatalities are due to a respiratory failure caused by an acute respiratory distress syndrome which is characterized by the inner space of the lungs being filled by fluid and preventing the proper oxygenation of the body. In these cases, this syndrome is attributed to a “viral hyperinflammation” or “cytokine storm” [2].

A “cytokine storm” is a somewhat complex concept that is not often explained in simple terms but is a critical element in severe cases of respiratory virus infections such as the one caused by SARS-CoV-2. In this article we’ll provide some basic information to help you understand this phenomenon better.

Inflammation is a clinical manifestation of many processes mediated by the immune system and is characterized by 4 main features: heat, pain, blushing and swelling. To put it simply, when some non-self agent (foreign body, virus, bacteria, etc) is detected by the body, a complex network of cells, tissues and organs need to organize to guide and facilitate the entry of “protector” cells and fluids into the affected area to eliminate the agent. These events cause the area to swell by the facilitated entry of new cells and fluids, also, the increased activity and structural changes of the area translates into localized heat and pain [3].

Cytokines are a diverse group of small proteins secreted by different kinds of cells. These have a great number of functions mostly related to local (and sometimes distant) communication inside the body. Each cytokine function will vary according to a number of factors, but the important thing is that they are essentially a chemical language used by the immune system to organize its components and produce an effective inflammatory process [3,4]. Some examples of cytokines include: IL-2 (interleukin 2), INF-γ (interferon gamma), SCF (stem cell factor), etc [2].

Inflammation is an intense process that costs a lot of energy and can even damage perfectly healthy tissues and organs over time.  In general, localized acute inflammation tends to be helpful while systemic chronic inflammatory processes are harmful [4].

Knowing these basic concepts, we can now talk about cytokine storms. This phenomenon is well known in the context of respiratory infections such as the ones caused by SARS and MERS and makes sense for it to be the main cause of death in COVID-19 patients. Out of all infected individuals, most of them will develop a mild and localized inflammation at some level of their respiratory system, however some people are susceptible to develop a severe and uncontrolled inflammation with high levels of pro-inflammatory cytokines overflowing and affecting the lungs and neighboring organs, this excessive amount of cells and fluid make respiration difficult and gradually cause an acute respiratory syndrome [5].

Data suggests that around 20% of COVID-19 cases require hospitalization and are frequently checked for some of the common features of a cytokine storm: excessive blood levels of ferritin, low levels of lymphocytes, longer blood coagulation times, high levels of lactate dehydrogenase, elevated IL-6 (a pro-inflammatory cytokine), elevated C protein (inflammatory marker) and elevated CD25 (an important cell receptor often overexpressed during inflammation) [6].

Determining who is more susceptible to experiencing a cytokine storm as a result of infection is not simple. This seems to mostly depend on how your immune system reacts to new threats. So far, the elderly (over 65 years old) remain the most affected group and the most likely to develop an acute respiratory syndrome while juvenile individuals (children) rarely experience any severe symptoms. Researchers are still finding new explanations for this trend, so far, there are 2 factors that could be relevant: 1) some people might just have genes associated to their immune system that equip them with “overactive” receptors with a tendency to promote excessive inflammation and 2) Children tend to have less developed immune systems which are less capable of such intense forms of inflammation [4,5].           

Since the body’s reaction to this virus seems to be more associated with mortality than the infection itself, is no wonder that some treatment therapies are focusing on inhibiting inflammation. This approach is not new, several different diseases behave in this way and plenty of pharmaceutical treatments already exist, however, it will take some time until we find the right options to prevent cytokine storms in COVID-19 patients [4,5]

The global healthcare industry is very active right now treating patients and looking for the right treatments, eventually effective methods to save more people’s lives will be found, but for now, preventing infection by practicing social distancing and keeping basic precautions in potentially contaminated spaces is the best way to not only help yourself, but also help your community and healthcare system.

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About the Author:
Hector Osorio is a cell biologist, research assistant and science/health content writer. He loves complex topics related to life sciences like cancer, viral infections and aging. He graduated from Central University of Venezuela Faculty of Sciences and worked as a research assistant for the Center of Experimental Medicine of the Venezuelan Center for Scientific Research (IVIC) for 5 years.

References:

  • [1] Cron, R. Q., & Chatham, W. W. (2020, March 16). Don’t Forget the Host: COVID-19 Cytokine Storm. Retrieved from https://www.the-rheumatologist.org/article/dont-forget-the-host-covid-19-cytokine-storm/10.1016….8-0
  • [2] Murphy, K., Travers, P., Walport, M., & Janeway, C. (2008). Janeway's immunobiology. New York: Garland Science.
  • [3] Tisoncik, J. R., Korth, M. J., Simmons, C. P., Farrar, J., Martin, T. R., & Katze, M. G. (2012). Into the eye of the cytokine storm. Microbiology and molecular biology reviews : MMBR, 76(1), 16–32. https://doi.org/10.1128/MMBR.05015-11
  • [4] George, A. (n.d.). Cytokine storm. Retrieved from https://www.newscientist.com/term/cytokine-storm/
  • [5] Zhang, J. M., & An, J. (2007). Cytokines, inflammation, and pain. International anesthesiology clinics, 45(2), 27–37. https://doi.org/10.1097/AIA.0b013e318034194e
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