Learn more about our FREE COVID-19 Patient Support Program for chronic illness patients and their loved ones.

Cytokine Storm

Your immune system is your body’s army. When it is working properly, the immune system quickly detects invaders (such as viruses or bacteria), mounts an attack that is strong enough to kick them out, and promptly backs off when the job is done.

Of course, people with autoimmune disease — such as rheumatoid arthritis or lupus — don’t have perfect immune systems, because normal body tissue gets misidentified as “foreign” and is subsequently attacked.

Many people who are dying from COVID-19 don’t have perfect immune systems, either — even if they don’t have an autoimmune disease and aren’t taking any immunosuppressing medications. Yet they’re dying after enduring what’s known as a cytokine storm, which is an out-of-control immune system response that is too robust for the threat at hand.

What Is a Cytokine Storm?

A cytokine storm is often described as a hyperactive immune response. On a basic level, you can think of it like setting off a bomb in your house because you want to get rid of a few ants. But the real problem isn’t just that the response is too strong; it is that it keeps going when it shouldn’t.

“This is not a problem of ‘too good’ an immune response, but rather a subtle defect in the immune system that doesn’t let it ramp back down,” says Randy Cron, MD, PhD, director of the division of pediatric rheumatology at Children’s Hospital of Alabama/University of Alabama at Birmingham

Understanding Cytokines 101

Cytokines are small proteins that send out signals that allow different immune cells to talk to each other and tell each other what to do. Everyone has cytokines in their body, regardless of whether they have autoimmune disease or have been infected with COVID-19.

There are pro-inflammatory and anti-inflammatory cytokines. The pro-inflammatory ones call upon the soldiers of the immune system (natural killer cells and CD8+ T cells) when they are needed to combat an invader, says Micah Yu, MD, a rheumatology fellow in Southern California. They rush in when there is an infection or injury, bringing with them the heat and redness that’s characteristic of inflammation.

Tumor necrosis factor (TNF) and interleukin-6 (IL-6) are examples of pro-inflammatory cytokines. People with autoimmune conditions often have abnormally high levels of these cytokines. That’s why they often take TNF-inhibiting medications (such as etanercept, adalimumab, and infliximab) or IL-6 blockers (such as tocilizumab and sarilumab) that work to suppress them.

Anti-inflammatory cytokines, such as IL-4 and IL-10, are released when the body is almost done fighting an invader, says Dr. Yu. “Their job is to send out signals saying, ‘Let’s back off.'”

A Perfect Cytokine Storm

When everything is working as it should, pro-inflammatory cytokines and anti-inflammatory cytokines work together to kill off an invader and then settle down so the immune system isn’t perpetually in attack mode. When things go awry, however, your immune system stays on the attack and you can end up with a cytokine storm.

It’s important for autoimmune patients to know that s cytokine storm is not the same thing as a disease flare.

During a flare there is certainly too much pro-inflammatory immune activity, but it only goes so far. A cytokine storm, however, is like an out-of-control brush fire that picks up more power as it continues to spread.

Some autoimmune patients end up with cytokine storms (unrelated to COVID-19). This is most apt to occur in children with juvenile idiopathic arthritis (JIA). “About 10 percent of patients with JIA will experience it; in some cases, multiple times,” says Dr. Cron. Adults with lupus, Still disease, and other inflammatory/autoimmune conditions may also develop a cytokine storm.

In autoimmune disease patients, cytokine storms are believed to occur because of a genetic defect, though the presence of an infection often serves as a trigger.

When it comes to COVID-19, the coronavirus — likely coupled with a previously unknown defect in the immune system — is what leads the inflammatory cytokines to go haywire and essentially multiply. They “recruit and activate additional immune cells and amplify the immune response” so much so that the immune response starts killing off healthy cells in the body, says Dr. Cron. “If left untreated, this can result in multi-organ failure and eventual death.”

Symptoms of a Cytokine Storm

Generally speaking, people don’t go from feeling perfectly fine to battling a life-threatening cytokine storm in a flash.

“By the time you have a cytokine storm, you’re probably on your way to the ICU or you’re there already,” says Dr. Yu. In other words, someone is already pretty ill and in the hospital by the time this critical situation develops. It is not something you need to be monitoring for in yourself or a sick loved one at home.

Doctors know whether someone is in the midst of a cytokine storm thanks to a combination of symptoms and lab tests.

Symptoms tend to include:

  • Fever
  • Widespread pain
  • Shortness of breath

Dr. Cron says patients also have very low blood pressure and a very fast heart rate.

Lab work often indicates:

  • Abnormally high liver enzymes
  • Elevated inflammatory disease markers like C-reactive protein and TNF
  • High ferritin (iron storage) levels

“A cytokine storm produces a lot of inflammation everywhere, including in the lungs,” adds Dr. Yu. Excessive inflammation in the lungs is what is leading some people with COVID-19 to require a ventilator.

How to Treat a Cytokine Storm

There is more than one way to quiet the overactive immune response during a cytokine storm. When it occurs due to rheumatic disease, doctors may treat it with corticosteroids, immunosuppressive drugs like cyclosporine and tacromlimus, IL-1 inhibitors like anakinra, or IL-6 blockers like tocilizumab, says Dr. Cron.

Research on the efficacy of using such autoimmune drugs to treat COVID-19 patients (regardless of whether they have a pre-existing autoimmune disease) is ongoing. Doctors have already been experimenting with several and some are reporting that tocilizumab may be especially useful.

Get Free Coronavirus Support for Chronic Illness Patients

Join the Global Healthy Living Foundation’s free COVID-19 Support Program for chronic illness patients and their families. We will be providing updated information, community support, and other resources tailored specifically to your health and safety. Join now.

Interview with Micah Yu, MD, a rheumatology fellow in Southern California

Interview with Randy Cron, MD, PhD, director of the division of pediatric rheumatology at Children’s Hospital of Alabama/University of Alabama at Birmingham

Shaw, G. COVID-19 Brings Cytokine Storm. Infectious Disease Special Edition. April 21, 2020. https://www.idse.net/Covid-19/Article/03-20/COVID-19-Brings-Cytokine-Storm/58061.

Tisoncik JR, et al. Into the Eye of the Cytokine Storm. Microbiology and Molecular Biology Reviews. March 2012. doi: http://dx.doi.org/10.1128/MMBR.05015-11.