What is cytokine release syndrome?

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CRS is a collection of symptoms that can vary from fever to vomiting. These symptoms are the result of abnormally high cytokine levels.

Cytokines are small proteins that help cells around the body communicate. When the immune system detects a threat, cells release cytokines to coordinate the body’s response.

In CRS, the immune system is overactive. The elevated cytokines cause harmful levels of inflammation throughout the body, which disrupts normal bodily functions. The inflammation may interfere with organ function and cause severe symptoms.

CRS can occur due to infection or as a result of certain medical treatments.

CRS can affect many different organs throughout the body, and the symptoms vary widely depending on the severity of the inflammation. They can range from mild to severe.

Some general symptoms of CRS include:

• fever
• tiredness
• appetite loss
• nausea and vomiting
• diarrhea
• head and body aches
• rashes

A person may also experience other symptoms, which will vary according to the organ systems that CRS affects.

Heart and blood vessels

When CRS affects this system, additional symptoms may include:

• increased heart rate
• irregular heartbeat
• drop in blood pressure
• reduced heart function
• edema

Brain and nervous system

Symptoms relating to the central nervous system may include:

• confusion
• dizziness
• coordination and movement problems
• difficulty swallowing
• seizures
• hallucinations

Lungs

If CRS affects a person’s lungs, they may have:

• a cough
• reduced lung functioning
• shortness of breath
• difficulty breathing

CRS can also cause problems with kidney and liver function.

CRS can occur as a result of immunotherapy. Immunotherapy is a type of treatment that helps the immune system attack pathogens or, in the case of some cancers, a tumor. Occasionally, doctors also use immunotherapy to treat health conditions, such as rheumatoid arthritis and Crohn’s disease.

Several types of immunotherapy may cause CRS. These include T-cell transfer therapy, which takes immune cells from a tumor and repurposes them to attack the cancerous cells, and monoclonal antibody therapy. Monoclonal antibody therapy involves creating proteins in the lab that latch onto cancer cells. These proteins help the immune system target and destroy cancer cells.

Both types of immunotherapy can cause a large and rapid release of cytokines. The rise in cytokines may lead to CRS.

CRS can also occur as a result of an infection. For example, a virus will trigger the body’s immune system. The immune system may overreact and release excess cytokines, causing CRS.

Timely and effective treatment is essential for CRS, as the symptoms can rapidly worsen and become severe.

Doctors will use medication to reduce inflammation safely in people with CRS. Some drugs will target specific cytokines. For example, tocilizumab (Actemra) and siltuximab (Sylvant) reduce the action of the cytokine interleukin-6.

Another option is corticosteroids. These drugs reduce inflammation without targeting a specific cytokine. However, they suppress the immune system and can interfere with cancer treatment.

Depending on the severity of CRS, other treatments may be necessary to support organs and prevent further damage. These treatments may include:

• intravenous fluids
• oxygen or ventilator support
• medicines to support heart function
• blood product transfusions
• medicine or dialysis for the kidneys

COVID-19 is the disease that the SARS-CoV-2 virus causes. When a person gets the virus, their immune system will respond by causing some inflammation. If a person’s immune system responds too aggressively, it may result in CRS.

CRS can cause severe illness and death in some people with COVID-19. However, scientists are learning how to treat CRS in these individuals. Researchers in China found that tocilizumab helped treat CRS in 21 people with SARS-CoV-2, reducing their fever in 24 hours.

Corticosteroids, which doctors sometimes use to treat CRS, did not appear to work effectively for people with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which are other illnesses resulting from coronaviruses. Therefore, scientists will need to perform more studies to get a better understanding of how to approach CRS in people with COVID-19.

People who are in at-risk groups should follow the Centers for Disease Control and Prevention (CDC) guidelines on how to prevent the spread of SARS-CoV-2. People at increased risk include those who:

• are undergoing immunotherapy
• are over 65 years old
• live in a nursing home or care facility
• have a chronic underlying condition, such as heart disease, diabetes, or kidney disease
• have a body mass index (BMI) of 40 or more

People can help stop SARS-CoV-2 from spreading by:

• washing the hands regularly, particularly after being outside
• avoiding close contact with other people, keeping at least 6 feet away
• wearing a mask to cover the nose and mouth while in public
• covering coughs and sneezes
• cleaning frequently touched surfaces and objects regularly

The symptoms of CRS, which include fever, headaches, and diarrhea, can worsen quickly. It is important to call a doctor if these symptoms suddenly get worse or have lasted more than a few days.

Severe symptoms require immediate medical attention. These might include difficulty breathing, confusion, or changes in heart rate or function.

CRS is a collection of symptoms that result from abnormally high cytokine levels. CRS can cause systemic symptoms, such as a fever, but it can also affect organs and cause specific related symptoms, such as heart problems.

People receiving immunotherapy are at risk of developing CRS. Viral infections can also cause CRS. The symptoms of CRS can become severe, and timely treatment is critical.