CLEVELAND, Ohio — Weathering the “cytokine storm” could be one of the keys in saving severely ill coronavirus patients, but doctors still don’t know all the facts about the extreme inflammatory response.
Cytokines play a major role in regulating the human immune system, generally helping the body fight off infection and alerting to any problems.
But in more severe coronavirus cases, doctors are seeing that these proteins aren’t prepared for the SARS-CoV-2 virus, and may be causing a long list of problems by prompting the immune system to overreact to the threat.
Cleveland.com reached out to Ohio experts to explain the threat cytokine storms and resulting inflammation pose to the battle against the COVID-19 pandemic.
Q: What is a cytokine storm?
A: What’s referred to as a “cytokine storm” is a severe immune response to an infection. Cytokines are proteins produced by the body that sound the alarm when there’s an infection. This is generally helpful to ward off illness.
Cytokines are also responsible for some of the pro-inflammatory symptoms we feel when sick, like fever, according to Mark Cameron, an associate professor at Case Western Reserve University.
When the body encounters a new virus and doesn’t know how to react, the immune system can go haywire, produce higher levels of cytokines and cause intense inflammation.
“(SARS-CoV-2) takes advantage of our naive immune systems to evade detection and set up a strong battleground within our bodies,” Cameron wrote. “In COVID-19’s case, this battleground is set within our lungs. When our immune system does detect COVID-19, the response is often a cytokine storm, or an immune over-reaction to the otherwise entrenched and novel invader.”
Q: What problems do cytokine storms cause?
A: Hyper-inflammation can cause severe damage to the lungs, where the body is primarily fighting the virus. However, the virus infects cells all over the body. Inflammation can also cause hyper-coagulation, leading to troublesome blood clots.
The vast majority of coronavirus patients do not have a harmful cytokine response, but it’s often seen in those in severe condition.
“What we are learning is that the patients that do poorly, who require intubation, are not dying or doing poorly because of the viral infection, but rather from collateral damage,” said Dr. Cassandra Calabrese, who specializes in infectious disease and rheumatology at the Cleveland Clinic.
Q: Is it just COVID-19 that prompts a severe inflammatory response?
A: It’s more of a ripple effect. COVID-19 also causes secondary infections, like pneumonia or sepsis, that can heighten the inflammatory response even more, said Kelly McCall, a professor for Ohio University’s Heritage College of Osteopathic Medicine.
So, theoretically, COVID-19 would cause a first wave of inflammation from the body fighting off the virus. It would then cause another wave because of the secondary infections.
Q: Is anyone more at risk for cytokine storms prompted by COVID-19?
A: That’s something researchers and doctors are trying to figure out.
People who are immunocompromised also seem to be more susceptible to an overzealous immune system response and are listed on the Centers for Disease Control and Prevention website as vulnerable to more severe outcomes. Diabetes patients, for example, are prone to inflammation and immune system dysregulation.
“The question is does those pre-dispose people to have more of a cytokine storm, because their immune system is on a hair-trigger,” said Ohio University Russ College of Engineering and Technology professor Douglas Goetz.
Q: Can doctors see this coming?
A: Though cytokine storms have occurred in response to other illnesses, further research is needed before gaining a deeper understanding of who is more vulnerable to the extreme immune response.
“The complete reason why some do well and others do not has not been elucidated,” Calabrese said. “We have a lot to learn.”
Calabrese said the Cleveland Clinic is researching how markers in the blood could indicate whether a patient is going to have a severe inflammatory response, which could prepare the health-care workers to take steps to protect the patient.
Q: How do we treat the inflammation from cytokine storms?
A: Dr. Frank Jacono, a pulmonologist with University Hospitals and the Louis Stokes Cleveland VA Medical Center, said the medical community as a whole is trying to figure out the best path forward on how to treat patients suffering severe complications.
There is no approved anti-viral treatment or vaccine yet for COVID-19. Right now, intensive care unit workers can offer supportive care as the body fights off the virus and intervene in an emergency.
Hospital systems are working on developing and testing more options. The Cleveland Clinic is exploring the use of rheumatology drugs to treat inflammation in COVID-19 patients. University Hospitals is hosting a clinical trial of a stem cell treatment for acute respiratory distress syndrome, linked to inflammation.
Q: What about preventing the cytokine storms?
A: Goetz is partnering with McCall on research testing the effectiveness of different chemicals to prevent cytokine storms.
The team received a $100,000 grant from a fellowship and grant program at the Mercatus Center of George Mason University in Virginia for the study. Research will test five compounds that limit the activity of GSK-3 enzymes, which play a role in immune regulation.