Preventing "cytokine storms" may relieve severe COVID-19 symptoms

, June 6, 2020 /PRNewswire/-- For some patients with COVID-19, the body's immune response may be as devastating as the virus that causes the diseasePersistent high fever, severe respiratory distress and lung damage in some critically ill patients are all signs of an overworked immune systemNow, a newclinical trialwill test a treatment for this overactive immune response, said Bert Vogelstein, a medical researcher at howard Hughes in theHe and his team at Johns Hopkins University School of Medicine are currently recruiting trial participants, including patients aged 45 to 85 at Johns Hopkins Hospital who have COVID-19 but do not use a ventilator or live in the ICUtheir treatment is a common prescription drug called alpha-receptor blockers, and their findings and a recent medical statement data analysis suggest that this approach may break the cycle of excessive inflammation before inflammation increases"The way we're advocating is to treat high-risk people in the early stages of the disease, that you know they're infected, but before they develop severe symptoms," saidVogelsteinIf tests show that the drug is safe and effective for COVID-19, it may help many people recover safely at home and relieve pressure on hospital resourcesPicture Source: NIHout-of-control response
overactive immune response is not unique to COVID-19patients with autoimmunediseases and cancer patients who receive immunotherapy may experience similar symptomsThese reactions are called macrophage activation syndrome, cytokine release syndrome, or "cytokine storms" when macrophages (and some other types of immune cells) detect viral particles, they alert by releasing a variety of proteins called cytokines These cytokines attract other immune cells to this area, producing a moderate inflammatory response that helps the body fight the virus But macrophages can also release other signaling molecules, called catecholamines, further amplifying this reaction and triggering the release of more cytokines The result is an out-of-control feedback loop, like a snowball rolling down the hill Maximilian Konig, a rheumatologist at Johns Hopkins University in who is helping to coordinate the trial, said: "It seems that once the process begins, it cannot be properly shut down "
before the COVID-19 outbreak, Vogelstein's team was already exploring ways to reduce the inflammatory immune response of cancer patients treated with immunotherapy Researchers are interested in a drug called alpha receptor blocker, which is widely used to treat prostate disease and high blood pressure , and also interferes with cellular signals, triggering cytokine storms In theory, alpha blockers may block cytokine before a storm begins Vogelstein's team reported in the 2018 issue of Nature that the use of alpha-receptor blockers to bacteria infected mice can reduce cytokine storms and reduce deaths Moreover, the researchers found that the treatment did not appear to harm other aspects of the immune response avoid storms
Vogelstein's team recently suggested in the journal of Clinical Investigation that the idea of testing alpha receptor blockers in humans has become more urgent as the COVID-19 pandemic in the United States has escalated over the past few months and severe patients develop cytokine storm symptoms in order to obtain approval for the clinical trial
sander of alpha receptor blockers, Vogelstein's team first looked at medical claims data They combed the records of patients hospitalized for pneumonia and acute respiratory distress and analyzed whether the prognosis was better if patients were given alpha blockers in unrelated situations The team's preliminary conclusion is that taking alpha-receptor blockers reduces the risk of death due to respiratory distress Susan Ahe, an economist at Stanford University in , says that alone is not enough to prescribe the drug for a whole new disease such as COVID-19 Athey has worked with Vogelstein's team to conduct claims analysis But this helps support the team's clinical trials the source of the picture; In the trial, patients with COVID-19 will be treated with an alpha receptor blocker called prazosin within six days and gradually increase the dose, said Chetan Bettegowda, a neurosurgeon at Johns Hopkins University in Nature The team will then assess whether patients receiving the treatment have lower ICU admission rates or ventilator use than those receiving standard treatment Each patient will be followed up for 60 days, but preliminary data for the first patients may be available within weeks to months if the results show that alpha receptor blockers are safe and effective, the team hopes to conduct a second trial in patients diagnosed with COVID-19 who have not yet been hospitalized They also encouraged colleagues at other hospitals to join their clinical trials to collect patient data more quickly If the treatment works, it will be a second form of prevention that relieves symptoms before they become severe, rather than stopping infection in the first place, Vogelstein said "Ultimately, hopefully, we can develop a vaccine that will be the essence of prevention," he said But until the vaccine is available, secondary prevention makes sense References: 1
Preventing 'cytokine storm' mayease severe COVID-19 symptoms 2 Maximilian F Konig et al, -preventing cytokinesyndrome in COVID-19 using alpha-
1 DOI: 10.1172/JCI139642
3Staedtke, V., Bai, R., Kim, K et al.
Disruption of a self-amprifying catecholamine loop reduces cytokine release syndrome.
Nature 564, 273-277 (2018) https://doi.org/10.1038/s41586-018-0774-y