Jennifer R. Tisoncik et al. Microbiiol. Mol. Biol. Rev.2012; doi 10.1128/MMBR.05015-11
During this COVID-19 pandemic, a lot has been mentioned in popular media about a cytokine storm. It is said that most mortalities due to COVID-19 are attributed to this biological phenomenon, where the body’s immune response is overwhelmed by an infectious agent. Though mounting an immune response is the body’s normal reaction when bacteria or viruses enter the system, too much reactivity may result in organ damage and eventually death. Thus, one of the therapeutic measures undertaken to combat the cytokine storm is to slow down its progression.
The first use of the term “cytokine storm” appears to be in an article published in 1993 on graft-versus-host disease after a transplant operation. Its subsequent use in infectious disease began in early 2000, most especially when SARS-CoV 1 became a pandemic. Normally, when the human body encounters a germ, the immune system attacks the invader and tries to neutralize it. Sometimes, the army of defenders behave out of control, transforming in a “stormy” aftermath. Variants of this hyperactive immune reaction occur in an array of conditions, triggered by infection, faulty genes, or autoimmune disorders (where the body thinks its own tissues are enemies).
The term "cytokine" is derived from a combination of two Greek words - "cyto" meaning cell and "kinos" meaning movement. Cytokines are cell signaling molecules that aid cell-to-cell communication in immune responses and stimulate the movement of cells towards sites of inflammation, infection and trauma. Most are produced by T-helper lymphocytes, but other cells can also produce them.
During an innate immune response to a viral infection, pattern recognition receptors (PRRs) recognize different molecular structures that are characteristic to the invading virus. These molecular structures are referred to as pathogen associated molecular patterns (PAMPs). The binding of PAMPs to PRRs triggers an inflammatory response against the invading virus resulting in the activation of several signaling pathways that trigger gene expression. Once the gene is expressed, cytokines are generated.
When the cytokines that raise immune activity become too abundant, the immune system may not be able to apply the brakes. Immune cells spread beyond infected body parts and start attacking healthy organs, destroying red and white blood cells, and damaging the liver. Blood vessel walls open up to let immune cells into surrounding tissues, but the vessels get porous. The lungs start to swell with fluid, and blood pressure drops. Blood clots may form throughout the body, further compromising the circulation. This is the reason why we hear a lot of those who perish from COVID-19 report signs such as bleeding, pallor, lowered blood pressure, and of course, breathlessness. Most patients experiencing a storm will have a fever, and about half will have some sort of nervous system symptoms, such as headache, seizures or even coma.
The solution to a storm is to quiet the destructive immune response. Steroids are often the first choice of treatment, so a lot of these drugs are given. There are also medications that interfere with specific cytokines, and because of their specificity, they may produce less side effects. None of these are guaranteed cures. Factors such as genetics and other medical conditions such as Diabetes Mellitus and heart disease can complicate matters. The biggest trick in a cytokine storm is to recognize it, and treat it early. However, you have to balance the benefits of a drug with the risks. Thus, these treatments are only given in advanced disease states.
SOURCES:
Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76(1):16-32.
Sherwani S, Khan MWA. Cytokine Response in SARS-CoV-2 Infection in the Elderly. J Inflamm Res. 2020;13:737-747.
Zhang W, Zhao Y, Zhang F, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clin Immunol. 2020;214:108393.