Researchers Identify a Possible Solution to COVID-19 Cytokine Storm

Researchers from Johns Hopkins University have discovered a key factor in how SARS-CoV-2, the virus that causes COVID-19, attacks the body. These findings unlock a potential method of stopping the virus from turning deadly.

The September study, which was published in the journal Blood, analyzed animal models and found that a particular protein enables SARS-CoV-2 to prompt the body’s immune system to attack healthy cells. The researchers theorize that tamping down on the protein, which is called factor D, can help stop or dampen inflammatory reactions in the body people can experience in reaction to the virus. 

People who contract COVID-19 are at risk of developing what’s known as a cytokine storm, a severe immune reaction that can turn deadly. During a cytokine storm, the body releases too many cytokines—proteins that help regulate the activity of your immune system—into your blood too quickly, according to the National Cancer Institute (NCI).^ This can cause a harmful, and sometimes deadly, reaction in your body. Lowering the inflammation experienced with the virus could, in theory, help lead to better outcomes, the researchers say.

How Does Factor D Work?

Factor D is a protein in a portion of the immune system called the complement system, Jamie Alan, RPH, PharmD, PhD, an assistant professor of pharmacology and toxicology at Michigan State University, tells Verywell.

“Complement is involved in activating the immune system and inflammatory processes in order for the body to fight infections,” she says. “Normally, this is a very good thing. However, as we know, with COVID-19, the immune system activation can actually become quite strong, which causes damage to the body.” This process can then lead to a cytokine storm.

Factor D works immediately upstream in the pathway from another protein, called factor H. And, when researchers in this particular study were able to block factor D, they were able to stop the chain of negative events often caused by SARS-CoV-2.

Why Blocking Factor D May Inhibit Deadly Inflammation

SARS-CoV-2 contains spike proteins on its surface, which help the virus attach to cells and infect them. In order to attach to cells, those spikes first latch onto heparan sulfate—a large sugar molecule found on the surface of cells in the lungs—blood vessels, and smooth muscles. SARS-CoV-2 then uses another component, a protein known as angiotensin-converting enzyme 2 (ACE2), to get into the attacked cell.

Researchers in this particular study found that, when SARS-CoV-2 attaches to heparan sulfate, it keeps factor H—which normally regulates the chemical signals that trigger inflammation and keeps the immune system from harming healthy cells—from using the heparan sulfate to bind with cells. As a result, the cells in the lungs, heart, kidneys, and other organs can be destroyed.

In a series of experiments, the research team found that by blocking factor D, which, again is on the same pathway as factor H, they were able to stop the destructive chain of events triggered by SARS-CoV-2.

By blocking factor D, “you will block a part of the inflammatory reaction,” Alan says.

“The goal of our study was to discover how the virus activates this pathway and to find a way to inhibit it before the damage happens,” study senior author Robert Brodsky, MD, director of the hematology division at the Johns Hopkins University School of Medicine in Maryland, said in a press release.

Brodsky likens the whole process to a car in motion. “If the brakes are disabled, the gas pedal can be floored without restraint, very likely leading to a crash and destruction,” he said in the press release. “The viral spike proteins disable the biological brakes—factor H—enabling the gas pedal—factor D—to accelerate the immune system and cause cell, tissue, and organ devastation. Inhibit factor D, and the brakes can be reapplied and the immune system reset.”

Treatments to Target Factor D

Currently, there are some drugs in development targeting factor D. “There are some in the pipeline, but none on the market yet,” Alan says. It’s hard to say how long it will be until they’re available for public use, Alan says, but, she adds, “it seems that they are years away.”

One drug, called BCX9930 from BioCryst, is in a phase one clinical trial, while another, called Danicopan, is in a phase two clinical trial. “The process may be accelerated in light of the pandemic, but there are certainly no guarantees,” Alan says.

However, Brodsky seems hopeful that a treatment will be available sooner. “There are a number of these drugs that will be FDA-approved and in clinical practice within the next two years,” he says. “Perhaps one or more of these could be teamed with vaccines to help control the spread of COVID-19 and avoid future viral pandemics.”

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