In a new study, researchers found that preventing ‘cytokine storm’ may ease severe COVID-19 symptoms.
Their treatment, a common type of prescription drug called an alpha-blocker, might break a cycle of hyper-inflammation before it ramps up.
The research was conducted by a team at Howard Hughes Medical Institute and elsewhere.
For some COVID-19 patients, the body’s immune response may be as destructive as the virus that causes the disease.
The persistent high fevers, severe respiratory distress, and lung damage seen in some critically ill patients are all signs of an immune system in overdrive.
A hyperactive immune response isn’t unique to COVID-19. People with autoimmune diseases and cancer patients receiving immunotherapy can experience similar symptoms.
These responses are referred to as macrophage activation syndrome, cytokine release syndrome—or simply “cytokine storms.”
When macrophages (and some other kinds of immune cells) detect virus particles, they send out alert messages by releasing various proteins known as cytokines.
Those cytokines recruit other immune cells to the scene—an inflammatory response that, in moderation, helps the body fight off a virus.
But macrophages can also release other signaling molecules, called catecholamines, that amplify this response further, triggering the release of more cytokines.
The result is a runaway feedback loop, like a snowball getting bigger as it barrels down a hill.
Before COVID-19 hit, the team was already exploring ways to ease the hyperinflammatory immune response in cancer patients treated with immunotherapy.
The researchers were interested in drugs called alpha-blockers, which are widely prescribed for prostate conditions and high blood pressure—and also interfere with the cell signaling that triggers cytokine storms.
In theory, alpha-blockers might stop a cytokine storm before it starts.
Giving mice with bacterial infections an alpha-blocker lessened cytokine storms and decreased deaths, the 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.
As the COVID-19 pandemic escalated in the United States over the past few months and severely ill patients presented with cytokine storm symptoms, the idea of testing alpha-blockers in humans has become more urgent, researchers say.
To obtain approval for an alpha-blocker clinical trial, Vogelstein’s team first surveyed medical claims data.
They combed through records from people hospitalized for pneumonia and acute respiratory distress and analyzed whether patients’ outcomes were better if they had been taking alpha-blockers for unrelated conditions.
The team’s tentative conclusion: taking alpha-blocker drugs correlated to a lower risk of death from respiratory distress.
On its own, that’s not strong enough evidence to prescribe the drug for a wholly new disease like COVID-19. But it helps bolster the case for the team’s clinical trial.
The team is currently recruiting individuals for a new clinical trial, which includes patients ages 45 to 85 at the Johns Hopkins Hospital who have COVID-19 but who aren’t on a ventilator or in the ICU.
In the trial, COVID-19 patients will take gradually increasing doses of an alpha-blocker called prazosin, sold under the brand name Minipress, over six days.
Then, the team will evaluate whether people who received this treatment had a lower ICU admission rate or ventilator use than patients who received the standard treatment.
They’ll follow each patient for 60 days, but preliminary data from the first patients could be available within weeks to months.
If the trial’s results suggest the drug is safe and effective against COVID-19, it could potentially help many people recover safely at home and lessen the strain on hospital resources.
This treatment, if it works, would be a secondary form of prevention, mitigating symptoms before they become severe, rather than stopping infection in the first place.
The lead author of the study is Howard Hughes Medical Investigator Bert Vogelstein.
The study is published in the Journal of Clinical Investigation.
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