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Cytokine Storm – An Overview

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Cytokine storm is a physiological response to an infection or disease, in which your inherent immune system releases large quantities of cytokines into the blood. All this happens  quickly, and therefore, it is a catastrophic health concern. This immune response is also known as hypercytokinemia, Cytokine storm syndrome [ CSS ].

What is Cytokine Storm?

The word cytokine is a mix of two Greek words – Cyto and Kinos. Cyto refers to cell and kinos mean movement. So cytokines refer to cell-signaling molecules that promote communication between cells during an immune reaction. These molecules drive cell movement towards the points of infection, inflammation, or injury in your body.

Cytokines are crucial and a part of your natural immune response to various health conditions. However, the out of control and abrupt release of cytokine into the blood can be dangerous. It can even lead to multiple organ failure and death.

Lately, cytokine storm has gained more attention in the context of the global pandemic, COVID-19, because it seems to play a pivotal role in deaths related to the coronavirus infection.

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Symptoms of Cytokine Storm

The primary symptoms of the cytokine storm include the following:

  • High fever
  • Chills
  • Nausea
  • Vomiting
  • Swelling of legs and ankles
  • Headache
  • Muscle pain
  • Joint pain
  • Allergies
  • Shortness of breath
  • Cough
  • Seizures
  • Fast breathing
  • Confusions
  • Poor concentration and responsiveness

Besides, if you have respiratory symptoms, those can turn to ARDS (Acute Respiratory Distress Syndrome) requiring ventilation.

What causes a Cytokine Storm?

Although scientists are still working on deciphering the factors that trigger the cytokine storm, some of the commonly known causes include the following:

Autoimmune disorders

Episodes of hypercytokinemia commonly occur in cases of autoimmune ailments, such as juvenile idiopathic arthritis (JIA) and lupus.

Infections

Some types of infections caused by bacteria, viruses, and other causative organisms can also initiate CSS, for example, influenza. According to a study on deceased patients of H1N1 flu or swine flu, 81% of them had the cytokine storm’s clinical and laboratory features.

Although the SARS-CoV-2 or the coronavirus has been around only for a couple of months, various studies show that COVID-19 can also produce this flaring and uncontrolled immune response, like other infections. Therefore, it has become a global pandemic.

Genetic conditions

Like the HLH (familial hemophagocytic lymphohistiocytosis), people with genetic disorders are susceptible to developing CSS.

Other causes

People undergoing cancer treatments or any specific therapy are also predisposed to experiencing CSS

COVID-19

The COVID-19 infection is mild in some people while life-threatening in others. The majority of the fatal cases have an uncontrolled and deranged immune response to the virus in the form of the cytokine storm.

When cytokines overflow, they tend to attack the lungs (the organ they were supposed to protect). As a result, blood vessels rupture, leading to blood clot formation followed by a drop in the blood pressure and eventually multiple organ failure.

The cytokine storm can be catastrophic because it destroys  cells instead of fighting it.

Initially, coronavirus infection was in the category of respiratory disorders. However, with the rapid spread of the disease affecting many people, it has become quite evident to doctors and scientists that COVID-19 has many physical manifestations other than the respiratory features. This disease goes way ahead of being just a pulmonary infection. It involves your heart, kidneys, brain, and other organs too.

How is Cytokine Storm diagnosed?

The diagnosis of CSS depends on  underlying health conditions. Depending on what underlying medical condition you are suffering from, your doctor will suggest further medical examinations, including blood tests and other diagnostic procedures.

Blood tests

The lab tests of people who are experiencing cytokine storm might show the following abnormalities –

  • Reduced immune cells
  • Elevated liver and kidney damage markers
  • Elevated inflammatory markers
  • Increased ferritin level

Chest X-ray and CT scan

These imaging tests can help your doctor understand your lung condition and assess extent of damage

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What is the treatment for Cytokine Storm?

Supportive treatment is r one of the crucial aspects of CSS treatment. If a patient shows severe signs and symptoms, for example – difficulty breathing, the doctor is more likely to shift him or her to an ICU (Intensive Care Unit). The range of support he or she might need include the following –

  • Stringent monitoring of his/her vital signs
  • Hemodialysis
  • Electrolyte (Sodium, Potassium, Calcium, Chloride, Magnesium, and Phosphate) management
  • Intravenous fluid supply
  • Ventilatory support

In some cases, it might be possible for your doctor to treat and manage the cytokine storm’s underlying cause. For instance, if a bacterial infection is a source of CSS, your doctor can prescribe antibiotics to make the symptoms subside.

However, there are many scenarios in which no associated treatment is available to cure a particular health condition’s principal cause. In such cases, medical professionals try different approaches to minimize the immune response. As there are many aspects of the immune system, it might get complicated for the clinicians to manage it all at once.

Although doctors and scientists have tried and tested various therapies, they are yet to agree upon the best and most effective treatment for managing CSS in all the scenarios. For example, in people with autoimmune disease-induced cytokine storm, corticosteroids can be helpful. However, if it isor not  the best option for COVID-19 induced CSS is still not clear.

Timing also plays a critical role in light of the effectiveness of any given therapy in such cases. A treatment that has been helpful in the early stages of a health condition might not work later or vice-versa. Also, the response of different people to a given therapy might vary.

Previously, doctors have tried some therapies to manage CSS, and they have got mixed responses. It includes the following –

  • Corticosteroids
  • Aspirin
  • Plasma therapy
  • Statin drugs
  • Biological therapies to block cytokines

Cytokine Storm due to COVID-19 – Treatment Options

Researchers from all across the world are actively working on exploring different types of treatments to suppress CSS due to COVID-19. Some studies focus on examining the existing therapies to determine if any of them can help people experiencing CSS due to COVID-19.

For example – Anakinra or Kineret is a  biopharmaceutical drug to treat people who have rheumatoid arthritis. It checks the action of interleukin (a specific cytokine). This treatment option has worked well for many people with autoimmune condition-induced CSS.

Another similar therapy is Actemra (tocilizumab).

Researchers are studying these and many other potential therapies to control the cytokine storm’s effects because of COVID-19.

Conclusion

Cytokine storm is a condition that arises when your immune system goes erratic and produces too many of these cell-signaling molecules into the blood. It can also lead to life-threatening situations. Medical professionals, researchers, and scientists are doing whatever possible to ensure the best possible care.

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Verified By Dr Chennamchetty Vijay Kumar
MD (Pulmonology), IDCC (Critical Care), FSM (Sleep Medicine), FCCP, Consultant Interventional Pulmonologist & Sleep Disorder Specialist, Apollo Hospitals, Jubilee Hills, Hyderabad
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