COVID-19
Hypertension Drug May Help Treat Severe COVID-19
Sep
Approximately 14–33% of individuals with a SARS-CoV-2 infection develop severe illness, and about two-thirds of those with severe illness develop ARDS.
ARDS involves injury to the lung tissue due to inflammation and the accumulation of fluid in the alveoli, the air sacs in the lungs where the exchange of gases occurs with blood vessels.
The accumulation of fluids in the alveoli due to leaking blood vessels limits the lungs’ ability to supply oxygen to the rest of the body. ARDS thus requires admission to the intensive care unit (ICU) and invasive mechanical ventilation to compensate for limited lung function.
ARDS is a major cause of mortality in COVID-19, and there is a lack of effective treatments for severe COVID-19 associated SARS.
Beta-adrenergic receptor antagonists (β-blockers) have been used for many decades to treat cardiovascular conditions such as hypertension, arrhythmias and myocardial infarction. Observational retrospective studies have established a link between β-blocker therapy and increased survival in critically ill patients caused by different conditions such as sepsis, acute respiratory failure, severe traumatic brain injury and others.
Recent findings show that the β1-selective blocker metoprolol has a direct effect on neutrophils, dampening their deleterious effects during exacerbated inflammation.
A group of researchers published their study at the Journal of the American College of Cardiology reporting that metoprolol (a β1-selective blocker) can reduce lung inflammation and improve respiratory function in people with COVID-19 induced ARDS. Metoprolol is a commonly used beta-blocker designed to treat hypertension, and it may provide an inexpensive treatment for severe COVID-19.
The infection by SARS-CoV-2 activates an immune response that aims to block the progression of the disease.
However, in some cases of severe COVID-19, uncontrolled and excessive activation of the immune system can occur in response to the rapidly replicating virus, causing ARDS and other complications such as organ failure.
The initial damage to the tissues due to SARS-CoV-2 infection results in the production of molecules called cytokines. These and other molecules released from damaged tissue recruit immune cells, such as neutrophils and macrophages to the lungs and result in the activation of these cells. This excessive production of cytokines, called cytokine storm, and the overactivation of neutrophils are hallmarks of ARDS associated with severe COVID-19.
These data suggest that neutrophils could be a promising target for reducing lung inflammation in people with severe COVID-19.
The team led by researchers at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) has now shown that the beta-blocker metoprolol can reduce lung inflammation and improve blood oxygen levels. The results come from a small pilot study involving COVID-19 patients with ARDS.
Specifically, the team found that metoprolol reduced neutrophil count in the lungs and resulted in lower levels of neutrophil activation.
The study included 20 COVID-19 patients with ARDS who had been on mechanical ventilation for less than 3 days. They were randomized to receive either intravenous (IV) metoprolol or standard care in the control group.
They concluded that IV administration of metoprolol to patients with severe COVID-19 associated ARDS is safe and abrogates the exacerbated lung inflammation associated with the disease. This reduced lung inflammation was associated with a significant improvement in oxygenation and with a trend toward fewer days on mechanical ventilation and ICU admission.
The study has the limitation of being a small sample of patients, but researchers consider that the good results of the study could be enough to consider the use of metoprolol in some patients, such as young patients admitted to the ICU with severe COVID-19 and that a larger trial could be conducted to confirm their results.
Source:
Agustin Clemente-Moragon, et al. Metoprolol in Critically Ill Patients With COVID-19. J Am Coll Cardiol. 2021 Sep, 78 (10) 1001-1011.
