Beta-blockers, which are commonly used to control heart problems and anxiety, have an anti-inflammatory effect that could be used to target the extreme inflammation seen in severe cases of COVID-19.
A research team based in Naples in Italy and Adelaide in Australia has suggested in a paper published in the journal Frontiers in Immunology that non-selective beta blockers such as propranolol should be tested for treating patients with severe COVID-19. This is because these drugs can reduce levels of the inflammatory cytokines that cause the severe, life threatening symptoms in severe COVID-19 patients such as acute respiratory distress syndrome.
“Patients with COVID-19 suffer from many abnormalities, including inflammation, because the SARS-CoV-2 virus disrupts the body’s immune system. Beta-2 blockers could potentially reduce this inflammation and help rebalance the immune system,” says Nirmal Robinson, Ph.D., a senior researcher at the Centre for Cancer Biology at the University of South Australia who is a co-author on the paper.
Although most people infected with the SARS-CoV-2 virus experience mild-moderate symptoms, around 15% are admitted to hospital with more severe disease. There is still some uncertainty about predicting who will fall into this group, but certain factors are known to increase a person’s risk.
Older age, male gender and the presence of other conditions such as diabetes are known to increase the risk for severe disease. Having high levels of certain inflammatory biomarkers – notably interleukin (IL)-6 and tumor necrosis factor (TNF)- α — in the blood at an early stage can also increase risk for more severe symptoms.
Beta-blockers block beta-2-adrenergic receptors, which are present on lung and airway cells and are also present on the surface of many types of immune cell. Although beta-blockers have traditionally been used to lower heart rate, they have recently been observed to have anti-inflammatory properties. More specifically, they reduce the Th-17 immune response – known to be a key driver of the cytokine storm reaction seen in severe COVID-19 cases.
In recent years, the immune system has been shown to play an important role in fighting and driving cancer as well as in infectious disease. Reports from breast cancer patients show that propranolol treatment has the potential to lower both IL-6 and TNF-α, as well as other inflammatory proteins and seems to have a beneficial effect both on recurrence and survival.
Although beta blockers have shown beneficial anti-inflammatory effects in cancer patients, they have not yet been tested in COVID-19 patients.
“We believe the beta-2-adrenergic pathway should be more deeply investigated as a possible target to reduce the inflammatory symptoms related to COVID-19. The next step is to perform clinical trials to explore an alternative therapy to treat COVID-19, based on the lessons we have learned from cancer,” says Robinson.
If effective beta-blockers such as propranolol, which has a well established safety profile, could provide an additional tool for doctors fighting the effects of COVID-19. It would not be the first treatment targeting the Th17 response, as the immune modulating drugs tocilizumab and ruxolitinib have already been use to treat COVID-19 patients with some success.