In what can be considered a positive step in the formulation of an effective treatment strategy for severe cases of COVID-19, a new study has found that a cancer drug can provide relief to patients with severe forms of the coronavirus infection.
Acalabrutinib, is a drug is used to treat several types of blood cancer. It is also an inhibitor of a protein known as Bruton tyrosine kinase(BTK) that plays a crucial role in the immune system of the body. The study led by the Center for Cancer Research at the National Cancer Institute (NCI), found that the cancer drug was linked to diminished respiratory distress and reduced hyperactive immune response in COVID-19 patients treated with it.
BTK's Role In Immune System
The protein plays a crucial role in the normal functioning of the immune system. These include macrophages, a form of innate immune cell that lead to inflammation through the production of proteins known as cytokines.
Cytokines are signaling proteins that regulate the immune system by drawing immune cells to the site of infection. In patients with severe COVID-19, this signaling process is impaired and a haywire response of the immune system or a "cytokine storm", damages healthy tissues. This causes lung damage and organ failure. Currently, there are no prescribed treatment options to tackle this condition in COVID-19 patients.
The prospective off-label clinical study was designed to ascertain whether the blocking of BTK using acalabrutinib could reduce inflammation in patients hospitalized with severe COVID-19 and improve clinical outcomes in them.
It consisted of 19 patients confirmed to have COVID-19. They were hospitalized with as with low blood-oxygen levels and exhibited inflammation. Supplemental oxygen had been provided to 11 of these patients for a median of two days. The remaining eight patients had been on ventilator support for a median of 1.5 (range 1-22) days.
Visible Benefits of Acalabrutinib
Most patients belonging to the group that received supplemental oxygen experienced a significant drop in inflammation levels within one to three days after receiving acalabrutinib. Of the 11 patients, eight were taken off supplemental oxygen and discharged later.
While the effect of acalabrutinib was less profound in the group of patients receiving ventilator support, four were able to come of it. Two of them were discharged eventually. In the paper, the authors stress that the ventilator group consisted of a clinically diverse range of patients, some of whom had vital organ failure. It also involved those who had been on a ventilator for extended periods of time. The mortality among this group was two.
Decrease In Hyperinflammation
An analysis of the blood samples from the patients involved in the study showed that the levels of an important cytokine — interleukin-6 (IL-6) — which is linked to hyperinflammation in extreme cases of COVID-19, reduced after being treated with the cancer drug.
Along with the fall in cytokine levels, the count of lymphocytes — a variety of white blood cells that play an important role in the body's immune response — was also found to improve rapidly. This is of special significance as a low lymphocyte count has been found to lead to negative outcomes severe cases of COVID-19.
Comparison of Blood Samples
In order to understand the expression of BTK protein better, the scientists tested blood cells from COVID-19 patients who were not involved in the study. Through the comparison of blood samples from healthy volunteers, the authors discovered that there was increased activity of the BTK protein and the production of IL-6 in patients with severe COVID-19.
Therefore, the results suggest that acalabrutinib could have had a positive effect as it targeted BTK, which is hyperactive in the immune cells of severe COVID-19 patients. The authors reiterate that the findings are not clinical advice but rather the sharing of information to enable the public health response to the disease. They also add that BTK inhibitors are not an approved treatment for COVID-19 and a controlled clinical trial is required in this regard.