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In the Sickest COVID-19 Patients, an Overactive Immune System May Be the Problem

Prevention logo Prevention 6/22/2020 Korin Miller
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Perhaps one of the most confusing (and terrifying) things about COVID-19 is how suddenly the illness goes from mild to severe. While researchers are still studying and learning new things about the novel coronavirus virus every day, they still haven’t pieced together why, exactly, some people get so sick while others present no symptoms at all.

Many experts believe that the rapid decline in certain COVID-19 patients, including those who need support from a ventilator, comes down to an individual’s immune system and how it reacts—or overreacts—to the virus.

You already know that your immune system is your body’s first line of defense against any infection. Specialized cells are able to recognize foreign substances, like bacteria and viruses, and mount a quick response to wipe them out. But for some people, the immune system goes a bit haywire and produces a severe response by releasing too many cytokines—small proteins that control the growth and activity of other immune system cells—at a destructively rapid pace.

This is known as a cytokine storm, and in certain patients, it could actually be even more harmful to the body than the novel coronavirus itself. Below, what you should know about cytokine storms and the role they play in the progression of COVID-19.

What is a cytokine storm, exactly?

When cytokines are released, they signal to your immune system that it’s time to do its job. “Cytokines are molecules that regulate the activity of the immune system,” says infectious disease expert Amesh A. Adalja, M.D., senior scholar at the Johns Hopkins Center for Health Security. “When you get a fever or chills, it’s all the result of cytokines in your bloodstream.”

But during a cytokine storm, your body releases too many of these proteins into your blood too quickly, according to the National Cancer Institute (NCI). While a moderate release of cytokines is a healthy and normal part of your body’s immune response, a flood of them can cause high levels of inflammation, which can be very damaging and even lead to multi-organ failure, Dr. Adalja says. Basically, your immune cells starts attacking healthy tissues and cells instead, spreading beyond the zones they were first deployed to protect.

Other viral infections, including influenza, can cause a cytokine storm in some people, says William Schaffner, M.D., an infectious disease specialist and professor at the Vanderbilt University School of Medicine. “Even in young, healthy people, they can get enormously sick very rapidly because their immune system is so strong,” he says.

In the case of COVID-19, it’s a completely new illness that your body hasn’t detected before, explains Reynold Panettieri, M.D., a lung specialist and vice chancellor for translational medicine and science at Rutgers University. Essentially, your body may not know how to handle the presence of the virus and overreact.

In addition to infections, certain diseases, autoimmune conditions, and some forms of cancer treatment like immunotherapy can also induce a cytokine storm, the NCI says.

What are the symptoms of a cytokine storm?

At first, most people will have a general feeling of being unwell, but “it can happen suddenly, or you can have a precipitous worsening of the infection,” Dr. Panettieri says. This can lead to symptoms like a high fever, redness and swelling caused by bodily inflammation, severe fatigue, and nausea.

Most people who experience a cytokine storm are already “profoundly ill,” Dr. Panettieri explains. “Typically, they would have gone to the ER because they’re not feeling well.”

Then, they may experience shock and dangerously low blood pressure, and “that’s when the cytokine storm really kicks in,” he says. Blood vessels will start to leak, and clots can form. Eventually, organ failure can occur.

How is a cytokine storm treated in COVID-19 patients?

While some research has found an elevated presence of cytokines in coronavirus patients (and other research calls it very common) there isn’t enough data to say all rapidly-declining cases of COVID-19 are a result of an immune system gone rogue.

However, if patients are presenting with the symptoms of a cytokine storm and a test confirms it, doctors have been turning to various treatments case by case until more science-backed data is available.

One is a medication called an interleukin-6 inhibitor, which can calm the immune system, says Jamie Alan, Pharm.D., Ph.D., an assistant professor of pharmacology and toxicology at Michigan State University. Dr. Adalja adds that corticosteroids, like the drug dexamethasone, can also quell a hyperactive immune response.

“Many people who experience a cytokine storm can recover but it’s usually a big struggle,” Dr. Schaffner says, especially for patients who already face a high risk of complications. “By that time, they are seriously ill. With COVID-19, they are invariably on a ventilator or will soon be put on one.”

The trickiest part for doctors is understanding how to treat patients as early as possible in hopes of avoiding the ventilator altogether—a lofty task, as those who wind up in the ER with severe symptoms may already be in a storm phase.

Still, some experts have expressed concern in tamping down the immune system completely “given the viral nature” of COVID-19, per one review of research published in May. “It is critical to balance the risk and benefits” before going all in with anti-inflammation therapies, the authors write. “A timely anti-inflammation treatment initiated at the right window time is of pivotal importance” and should be uniquely tailored to the patient to achieve the best outcomes—but only the results of ongoing clinical trials can help answer what that should look like.

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