The drug acalabrutinib, FDA-approved for the treatment of several types of B cell cancers, improved the oxygenation levels and decreased molecular markers of inflammation in a majority of 19 patients hospitalized for the treatment of severe COVID-19, according to a new study by Mark Roschewski and colleagues. The drug was administered to 11 patients on supplemental oxygen and 8 patients on mechanical ventilation over a 10-to-14-day course of treatment. At the end of treatment, 8 of 11 patients on supplemental oxygen were breathing room air, and 4 of 8 patients on ventilation were extubated, with 2 of the 8 breathing room air. Measurements of two proteins related to inflammation decreased in the majority of patients, with no signs of toxicity from the drug. The study is not a clinical trial, but rather an off-label observational study to see if acalabrutinib could help dampen the massive immune response - sometimes called a "cytokine storm" - that is associated with the most severe cases of COVID-19. Acalabrutinib inhibits the Bruton tyrosine kinase (BTK) protein, which aids immune cells called macrophages in activating a variety of other proteins in the body's innate immune response. Patients with severe COVID-19 have a hyperinflammatory immune response that appears to be driven by macrophage activation, leading to acute respiratory distress syndrome (ARDS) and often death. Roschewski et al. also studied BTK activation and immune markers in whole blood from 4 COVID-19 patients and 5 healthy individuals. BTK activation levels and the presence of the inflammatory protein IL-6 were higher in the COVID-19 patients, further suggesting that BTK may play a critical role in the disease's progression. An international prospective randomized controlled clinical trial is now underway to confirm the safety and efficacy of this BTK inhibitor as a therapeutic strategy against COVID-19, the authors note.