Inflammation across most or all of the body, so-called systemic inflammation, can be productive in fighting off a flu, for instance. Or, potentially, in combating the new coronavirus. (COVID-19 is the name of the disease caused by that virus.)
One of the mediators of inflammation in the body are proteins called cytokines. As the world well knows, COVID-19 in some patients devolves into a severe and deadly condition. Some doctors are now arguing that those severe infections require treatment for a patient’s increasingly desperate immune response to the coronavirus.
This is where medicine could make a possibly crucial intervention. Turning back the “storm” of cytokines in severe COVID-19 patients may seem like the opposite of what doctors should be doing. After all, it’s effectively telling the body to pull back a bit in its immune response to the viral invader.
“A life threatening infection can often result in a massive immune response,” Chan says. “It’s like a chaotic four alarm fire, when all semblance of organization is lost. The immune system goes into overdrive, churning out inflammatory mediators called cytokines at a very high rate, that then trigger even more cytokine production. Ultimately, this spiral, called a cytokine storm, can directly damage organs and cause such severe whole body inflammation that vital organs like the lungs, heart, and kidneys begin to fail.”
In other words, some of these severe COVID-19 cases, he says, may be creating a new and possibly treatable problem beyond the novel coronavirus infection. “Severe inflammation in the lungs causes the blood vessels in the lungs to become leaky, resulting in inflammatory cells, fluid, and chemicals to fill the air sacs of the lung, essentially drowning a patient from the inside out,” Chan says. “Physicians dealing with COVID-19 pneumonia call it the worst viral pneumonia they have ever seen, resulting in the need for weeks of mechanical ventilation while the lungs try to recover.”
Chan’s company manufactures a blood purification cartridge called CytoSorb that reduces the intensity of a patient’s cytokine storm by physically binding to and removing cytokines from the blood, in a process similar to dialysis. Chan says the goal of this “Brita filter for your blood,” as some call it, is to reduce the level of cytokines to a level where it no longer hurts the body—but still allows the body to fight the infection.
According to Chan, CytoSorb is approved in the European Union as a cytokine filter. He says it’s been used to date in some 80,000 treatments across 58 countries “to treat life-threatening complications such as sepsis, lung failure, and potentially fatal low blood pressure, often called shock.” (He points out many patients with severe COVID-19 have been dying from some of the same causes.)
He says CytoSorb has also been used in more than 70 critically-ill COVID-19 patients in Italy, China, Germany, and France. Clinical data is not yet available on these cases, though Chan describes what has been reported back to him is “preliminary positive results in terms of controlling cytokine storm, improving lung function that has helped patients get off of mechanical ventilation, and reversing shock.”
Not yet approved for use in the United States, CytoSorb had already been in line for consideration with the U.S. Food and Drug Administration (FDA) for cardiac surgeries prior to the coronavirus outbreak.
But COVID-19 has now dialed up global attention on cytokine storms—and any effective therapies that could treat the sometimes deadly coronavirus-induced condition.
“This is a fascinating idea,” said Jessica Manson, consultant rheumatologist and honorary senior lecturer at University College London Hospital. She is one of six co-authors of a 13 March letter to the journal The Lancet arguing that doctors need to be aware of so-called cytokine storm syndrome when treating critical COVID-19 patients.
Manson is careful to point out that fighting cytokine storms may only be relevant for a subgroup of critical COVID-19 patients. Her team’s letter to The Lancet argues that any patient with a severe case of COVID-19 should be lab tested for “hyperinflammation.” This test would be completely separate from a coronavirus test.
If a severe COVID-19 patient has markers for hyper-inflamed lungs, other organs, or similar conditions, her letter argues, cytokine storm therapies may need to be considered. She says one approved therapy is the drug tocilizumab, a.k.a. Actemra (which targets the cytokine IL-6). In fact, as of Monday, the FDA has launched Phase III trials of tocilizumab for treating COVID-19 pneumonia.
Chan says most pharmaceutical cytokine storm treatments target individual cytokines. Whereas CytoSorb, he says, targets some 100 different cytokines that normally help orchestrate the body’s immune response to infection and injury.
According to the CytoSorbents website, a patient’s blood is pumped out of their body using a standard blood dialysis machine and sent through the CytoSorb cartridge. Chan says the cartridge contains the company’s proprietary porous polymer beads that act like tiny sponges to extract cytokines from blood.
The purified blood then recirculates back into the patient’s body. During a 24-hour therapy period, a patient’s entire blood volume could be treated more than 70 times, the website says.
Manson says she recently talked with an official at University College London Hospital to see if they could set up a clinical trial to test a blood filtration idea for other cytokine storm-like conditions. Although this conversation was “pre-COVID.”
The evidence is still preliminary as to whether CytoSorb will be effective as an emergency COVID-19 intervention. That said, Manson says she’s at least convinced of the concept behind the therapy. “I think this is genius,” she says. “It’s something we should really work on.”
Chan says he’s already fielded a number of requests from hospitals in the United States to use CytoSorb for COVID-19 patients via the FDA’s “compassionate use” or “expanded access” programs for therapies already proven safe for other conditions. Since CytoSorb is not yet approved there, Chan’s company is in discussions with the FDA to help make the therapy temporarily available where needed during this crisis.