New trial will try to stop the “cytokine storms” that make COVID-19 cases deadly

Our own immune systems may be to blame for producing some of the worst symptoms of COVID-19, through a process known as a “cytokine storm”. Now, new research plans to fix this.

image credits Engin Akyurt.

The prolonged, high fevers, severe respiratory distress, and lung damage seen in some critically ill patients are actually caused by our immune systems trying (way too hard) to fight off the infection, not by the virus itself. New research at the Johns Hopkins University School of Medicine plans to test the efficiency of a prescription drug called an alpha-blocker as a protection against this process.

A cure for storms

“The approach we’re advocating involves treating people who are at high risk early in the course of the disease, when you know they’re infected but before they have severe symptoms,” says Bert Vogelstein, chief investigator on this project.

The team is setting up a clinical trial with patients ages 45 to 85 who have COVID-19 but who aren’t on a ventilator or in the ICU. These participants will help establish whether alpha blocker prazosin can be used to stop macrophage activation syndrome, or “cytokine storms“, by preventing hyper-inflammation in response to the infection.

Such an effect has been documented in mouse studies, the team explains. If alpha blockers are found efficient in humans as well, they could help keep more people safe at home where they can recover without taking up hospital resources, which are already spread thin.

Exaggerated immune responses aren’t unique to COVID-19, as people with autoimmune diseases and cancer patients receiving immunotherapy can attest.

Cytokines are chemical messengers used by our immune systems to organize against a threat. In moderation, they help immune cells converge to where they’re needed and fight off the infection. However, our bodies also use signaling molecules called catecholamines when a more heavy-handed response is needed, and they trigger the release of more cytokines — this process can form a feedback loop that drives our immune cells berserk.

“It seems that once this process starts, there’s this inability to properly switch it off,” says Maximilian Konig, a rheumatologist at Hopkins who is helping to coordinate the trial.

Alpha blockers interfere with the signaling pathways of cytokines, and Vogelstein’s past research on mice has found that they can be used to lessen cytokine storms and decrease mortality rate without having adverse effects on our immune response.

Giving mice with bacterial infections an alpha-blocker lessened cytokine storms and decreased deaths, Vogelstein’s team reported in the journal Nature in 2018. And, the researchers found, the treatment didn’t seem to harm other aspects of the immune response.

The patients in this trial will be given gradually-increasing doses of prazosin over six days, and will then be monitored to see if they have a lower ICU admission rate or ventilator use than patients who received the standard treatment. The trials will last for 60 days but preliminary data could be available within a few weeks, according to the team.

The paper “Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists” has been published in the Journal of Clinical Investigation.

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