COVID-19, Sepsis, and Cytokine Storms

The COVID-19 pandemic has brought new vocabulary to many people. Some of these words and phrases can be confusing without proper explanations. For example, many medically oriented news stories mention the term “cytokine storms”. What is a cytokine storm and why do some writers use the term in relation to COVID-19? And how is this connected to sepsis?

To understand what a cytokine storm is, we need to start at the beginning. How can an infection get out of control?

Fighting the infection

When you’re exposed to a bacterial, viral, fungal, or parasitic germ (called an antigen), your body’s immune system jumps into action to protect you from harm. The number of white blood cells circulating in your blood increases when your immune system detects the infection. The white blood cells either kill the invading antigens or keep them from replicating (copying and growing). If you get certain types of infections like chicken pox, these white blood cells can also make antibodies so your body remembers the invaders.

What are cytokines and cytokine storms?

Cytokines are a group of proteins. Through a process called cell signaling – communication between cells – cytokines control inflammation in your body. When you get an infection, your immune system releases more cytokines. Unfortunately, sometimes the body goes into overdrive and it releases more cytokines than it should. As the body loses control of cytokine production, it results in a “cytokine storm”. A cytokine storm is similar to a condition called cytokine release syndrome (CRS). But while CRS can be an immunotherapy side effect, cytokine storms are related to infections as they progress towards sepsis.

Researchers first used the term in 1993 to describe something they noticed among some patients who were rejecting transplants. “Cytokine storm” was used again when researchers noticed the same thing occurring among patients who had the avian H5N1 flu. In today’s news, a cytokine storm may describe the inflammation/inflammatory response in response to COVID-19.

“A deluge of chemicals can be released by white blood cells to attract additional white blood cells to fight infection or temper down the reaction if the infection appears to be under control,” explains Karin Molander, MD, an emergency room physician and chair of the Sepsis Alliance Board of Directors.  “These chemicals can also trigger the blood to clot or to become thinner. This cytokine storm, an important part of sepsis, can be triggered when we face an infection from a bacteria, virus, parasite or fungus. In typical years, bacteria are the most common cause of sepsis. But, alas, this is not a typical year.”

Viral sepsis is a challenge

While any form of sepsis can cause abnormal vital signs (blood pressure, pulse, and respirations), alerting care providers about worsening infection, typical tests that alert physicians to bacterial sepsis do not necessarily change in patients with viral sepsis. “This has been part of the challenge with COVID-19,” Dr. Molander adds.

You don’t necessarily have to have sepsis to have a cytokine storm. Non-infectious diseases, such as multiple sclerosis and pancreatitis, can also trigger this effect.

People at highest risk for sepsis are the elderly, the very young, and people who have chronic illnesses or weakened immune systems. But when a healthy person becomes severely ill with sepsis, it could be that their healthy immune system was so strong it triggered a cytokine storm.

Treating cytokine storms

Doctors can’t tell ahead of time which patients will develop sepsis from an infection. But they do know that the symptoms of cytokine storm (high fever, severe fatigue, nausea, organ failure) indicate severe illness. Knowing this allows them to be ready should there be a cytokine storm. Most of these severely ill patients receive treatment in an ICU or high acuity unit. There they may receive experimental medications like interleukin antibodies, such as anti-IL-1 or anti-IL-6 and high dose corticosteroids to try to get the cytokine storm under control.

Reading and hearing news about COVID-19 and its effects can be frightening. It can be more confusing if the writer is using terms you’ve never heard before. And when it comes to infections, this isn’t unusual. Until a few years ago, the majority of people in the United States had never heard the word sepsis. Now, 65% of adults say they have heard of it. To learn more about sepsis and how it affects the body, visit What Is Sepsis and download the fact sheet.