Some COVID-19 patients have a severe immune response (persistent high fever, lung distress, and lung damage) to the coronavirus, and this response can do as much damage as the virus itself. Now, a team of researchers from Johns Hopkins University School of Medicine in Baltimore, Maryland are going to start clinical trials to target the body’s immune response to the coronavirus. The researchers are currently recruiting patients, age 45-85 who have COVID-19 but are not in the ICU or on a ventilator.
The treatment uses an alpha-blocker to hopefully break the cycle of hyperinflammation before it really gets going. The team has studied this treatment in mice with promising results. According to Bert Vogelstein, a Howard Hughes Medical Investigator, notes: “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.”
A hyperactive immune response to disease is not unique to COVID-19; it can happen to cancer patients or people with autoimmune disorders. This hyper response is called macrophage activation syndrome, and it involves “cytokine storms.” When macrophages detect a virus, they send out an alert in the body by releasing cytokines, which in turn recruit other immune cells, which causes an inflammatory response. Like with most things, in moderation, cytokines help the human body fight off a virus, but the other part of the response is not. Macrophages also release catecholamines, which “amp up” the normal immune response.
"It seems that once this process starts, there's this inability to properly switch it off," says Maximilian Konig, a rheumatologist at Johns Hopkins who is helping to coordinate the trial.
As the COVID-19 pandemic ramped up in the United States, clinicians started seeing severely ill patients with cytokine storm symptoms. In the Journal of Clinical Investigation, Vogelstein and his team argued that this discovery made the new study using alpha-blockers of the utmost importance. In Vogelstein’s trial, COVID-19 patients will take slowly increasing doses of an alpha-blocker (prazosin) over the course of six days. Researchers follow the patients for 60 days, and evaluate them to see if they had a lower ICU admission or ventilator use rate than patients receiving the normal treatment.
If the trial is successful, it could allow doctors to mitigate a patient’s symptoms before their bodies become overwhelmed. This could save lives and work as a secondary form of prevention.