In a letter published in the Journal of Clinical Investigation in April, a team of researchers led by Chetan Bettegowda and Maximilian Konig from Ludwig Johns Hopkins presented a rationale for a trial employing a hypertension drug named prazosin to prevent cytokine storm syndrome—a leading cause of COVID-19 mortality. Induced by a cascading immune response that causes runaway, systemic inflammation, the cytokine storm is the main reason COVID-19 patients wind up in the ICU on ventilators with acute respiratory distress (ARD). In 2018, Ludwig Johns Hopkins researchers led by Bert Vogelstein, Verena Staedtke and Shibin Zhou had detailed in Nature the molecular mechanisms, mediated by immune cells, that precipitate cytokine storms. That study showed that hypertension drugs known as alpha-1 adrenergic receptor antagonists (alpha-blockers) could impede self-amplifying cycles of cytokine release in mice. In a recent analysis on arXiv, an extended team including Susan Athey and Joshua Vogelstein retrospectively examined clinical data on 13,125 men who had ARD from multiple causes and had been taking alpha-blockers for other reasons and compared their outcomes to men who hadn’t. They found patients who had ARD and were taking alpha-blockers had a 35% lower risk of requiring ventilation and 56% lower risk of dying while on ventilators. In May, the researchers received approval from the U.S. Food and Drug Administration for a clinical trial led by Chetan to test the alpha-blocker prazosin as an early, preventive intervention against cytokine storms in hospitalized patients with COVID-19. With case numbers rising, the team is currently focused on extending clinical trials to non- hospitalized COVID-19 patients in the earliest disease stages to prevent hospital admission.
This article appeared in the August 2020 issue of Ludwig Link. Click here to download a PDF (2 MB).