New Criteria Helps Predict Which COVID-19 Patients Experience Cytokine Storm

Researchers at Temple University have identified criteria to help identify which COVID-19 patients are at a high risk of developing a cytokine storm, a severe immune reaction that can turn deadly. Until now, there were no predictive criteria established for at-risk patients that could be used in clinical practice.

The criteria, which is preliminary, was published in the Annals of the Rheumatic Diseases in September. For the report, researchers analyzed data on more than 60 different laboratory variables collected from 513 hospitalized patients who were positive for COVID-19— 64 of which developed a cytokine storm. Those variables included factors like white blood cell count, metabolic enzyme activity, and markers of inflammation and respiratory function.

Based on the data, the researchers developed a genetic algorithm to identify cut-off values for each laboratory variable to determine levels that may predict a cytokine storm.

The analyses found predictive criteria that could be lumped into three clusters:

• Inflammation
• Cell death and tissue damage
• Electrolyte imbalance

The researchers found that patients in a cytokine storm had a pro-inflammatory status and elevated levels of enzymes that suggested they had significant, widespread tissue damage. Patients who met the criteria also had longer hospital stays and were at an increased risk of death from COVID-19. Almost half of the patients who had a cytokine storm met all the criteria within the first day they were hospitalized.

“We hope that by applying the criteria and by identifying early patients that are most at risk of this complication, they might guide more appropriate therapy and also help the design of clinical trials, which are very much in need,” lead study author Roberto Caricchio, MD, chief of the section of rheumatology and director of the Temple Lupus Program, tells Verywell. 

Cytokine Storm Basics

Cytokines are proteins produced by cells that serve as messengers between cells, helping regulate the activity of your immune system. When your body releases cytokines, it signals to your immune system that it’s time to go to work, the American Cancer Society (ACS) says.

But during a cytokine storm, your body releases too many cytokines into your blood too quickly, according to the National Cancer Institute (NCI). That can cause a harmful reaction in your body.

“In general, cytokine storm syndromes lead to multi-organ system failure and are highly fatal,” Randy Q. Cron, MD, PhD, director of the division of pediatric rheumatology at Children’s of Alabama, tells Verywell.

Cytokine storm isn’t unique to COVID-19. It can also happen as a result of other infections, certain diseases, autoimmune conditions, and some forms of cancer treatment, the NCI says.

Why Predicting Which Patients May Experience Cytokine Storm Matters

“The ability to predict early on during the hospitalization which
patient will develop the cytokine storm could help prevent both the
cytokine storm and in turn, the poor outcome,” Caricchio says.

Timing matters. “Early diagnosis and treatment of cytokine storm syndromes improves survival,” Cron says.

The criteria Caricchio and his team developed are based on routine laboratory tests available to most hospitals and “could be readily used in clinical practice,” he says. The hope, Caricchio says, is that “doctors can be better informed and decide [when] to be more aggressive with the available therapies.”

While the predictive criteria are preliminary at this point, Caricchio says he hopes other medical professionals and hospital centers will use his criteria to help validate it and, ultimately, to help save lives.

How Cytokine Storm Is Treated

When someone experiences a cytokine storm, they typically have the following symptoms, according to the NCI:

• High fever
• Redness and swelling
• Severe fatigue
• Nausea

When that happens, doctors will try to identify a trigger, such as an infection, and treat it, Cron says. But, he says, more importantly, medical staff will try to “dampen the cytokine storm” with medications to suppress or modulate the immune system.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.