NEW IDENTIFICATION OF GENETIC BASIS OF COVID-19 SUSCEPTIBILITY
Italian researchers are reporting that they have been able to identify the genetic basis of susceptibility to COVID-19 infection. This has important implications for treatment and drug development. The clinical presentation of COVID-19 varies from patient to patient, and understanding individual genetic susceptibility to the disease is therefore vital to prognosis, prevention and the development of new treatments. Scientists have been able to identify the genetic and molecular basis of this susceptibility to infection as well as to the possibility of contracting a more severe form of the disease. Professor Alessandra Renieri, who is director of the Medical Genetics Unit at the University Hospital of Siena in Italy, is part of a team that collected genomic samples from COVID-19 patients across the whole of Italy in order to try to identify the genetic bases of the high level of clinical variability they showed. Using whole exome sequencing (WES) to study the first data from 130 COVID-19 patients from Siena and other Tuscan institutions, they were able to uncover a number of common susceptibility genes that were linked to a favourable or unfavourable outcome. “We believe that variations in these genes may determine disease progression,” said Renieri. These results will have significant implications for health and healthcare policy. Understanding the genetic profile of patients may allow the repurposing of existing medicines for specific therapeutic approaches against COVID-19 as well as speeding the development of new antiviral drugs. Being able to identify patients’ susceptible to severe pneumonia and their responsiveness to specific drugs will allow rapid public health treatment interventions.
RE-PURPOSED CANCER DRUG FOR INDIVIDUALS WITH SEVERE COVID-19
Early data from a clinical study is suggesting that blocking the Bruton tyrosine kinase (BTK) protein with the cancer drug acalabrutinib may provide clinical benefits to some patients with severe COVID-19. Researchers observed that the off-label use of acalabrutinib, a BTK inhibitor that is respiratory distress and a reduction in the overactive immune response in most of the treated patients. Researchers conducted a prospective off-label clinical study that included 19 patients with a confirmed COVID-19 diagnosis that required hospitalisation. Of these patients, 11 had been receiving supplemental oxygen for a median of two days, and eight others had been on ventilators for a median of 1.5 days (range 1-22 days). Within one to three days after they began receiving acalabrutinib, the majority of patients in the supplemental oxygen group experienced a substantial drop in inflammation and their breathing improved. In this study, eight of these 11 patients were able to come off supplemental oxygen and were discharged from the hospital. Although the benefit of acalabrutinib was less dramatic in patients on ventilators, four of the eight patients were able to come off the ventilator, two of whom were eventually discharged. The authors note that the ventilator patient group was extremely clinically diverse and included patients who had been on a ventilator for prolonged periods of time and had major organ dysfunction. Two of the patients in this group died. Blood samples from patients in the study showed that levels of interleukin-
6 (IL-6), a major cytokine associated with hyper inflammation in severe COVID-19, decreased after treatment with acalabrutinib. Counts of lymphocytes (a type of white blood cell) also rapidly improved in most patients. A low lymphocyte count has been associated with worse outcome for patients with severe COVID-19. The researchers also tested blood cells from patients with severe COVID- 19 who were not in the study. In comparison with samples from healthy volunteers, they found that the patients with severe COVID-19 had higher activity of the BTK protein and greater production of IL-6. These findings suggest that acalabrutinib may have been effective because its target (BTK) is hyperactive in severe COVID-19 immune cells. The authors of the study caution that this strategy now must be tested in a randomised, controlled clinical trial in order to understand the best and safest treatment options for patients with severe COVID-19.
John Schieszer is an award-winning national journalist and radio and podcast broadcaster of The Medical Minute. He can be reached at firstname.lastname@example.org.