A new study, published Friday in Science Immunology, has suggested that blocking a protein called Bruton tyrosine kinase (BTK) provided clinical benefit to a few patients with severe COVID-19, the infection caused by the novel coronavirus.
Researchers found that the off-label use of acalabrutinib, a BTK inhibitor that is advised to treat several blood cancers, reduced respiratory distress, and the overactive immune response in most of the COVID-10 patients.
Researchers from the Center for Cancer Research at the National Cancer Institute (NCI) and the National Institute of Allergy and Infectious Diseases (NIAID), conducted the study.
The researchers explained that these findings should not be considered medical advice, instead, they should be shared to assist the public health response to the coronavirus.
BTK inhibitors have been approved to treat certain blood cancers but they are not approved for the treatment of COVID-19. However, such drugs must be tested in a large clinical trial to understand whether they are safe and effective for patients with severe COVID-19.
The BTK protein has a key role in the normal immune system, including in macrophages, which can cause inflammation by producing cytokines. Cytokines are the proteins that act as chemical messengers to stimulate the immune response.
In severe cases of COVID-19, a large number of cytokines is released in the body, causing an intense immune response and leading to a dangerous inflammatory state called “cytokine storm.”
Currently, there are no clinically proven treatment strategies for this phase of the disease. The study was conducted to test whether the BTK inhibitors acalabrutinib would reduce the inflammatory response and improve the clinical outcome in patients with severe COVID-19.
The researchers conducted the study on 19 COVID-19 patients who required hospitalization and had low blood-oxygen levels with evidence of inflammation. Of these participants, 11 had been receiving supplemental oxygen for two days, while the remaining had been on ventilators.
Within three days of receiving acalabrutinib, most patients in the supplemental oxygen group had a substantial drop in the inflammation level, and their breathing improved. The majority of the patients came off supplemental oxygen and were discharged from the hospital.
The clinical benefit of acalabrutinib was not significant in patients who were on ventilators, with four of the eight patients came off the ventilator, while two of them were discharged.
The researchers analyzed the blood samples of all patients in the study and found that the levels of a major cytokine called interleukin-6, which is associated with increased inflammation in severe COVID-19, decreased after the treatment with acalabrutinib.
In addition, the count of lymphocytes, a type of white blood cell, also rapidly improved in the majority of the patients.
The researchers compared these blood samples with the samples collected from other COVID-19 patients who were not involved in the study. They found that patients with severe COVID-19 had “higher activity of the BTK protein and greater production of interleukin-6. The study findings suggest that acalabrutinib could be an effective drug because it targets BTK, the protein associated with an intense inflammatory response to the virus.
