Beta‐Adrenergic Blockers as a Potential Treatment for COVID‐19 Patients

Abstract

More than 15 million people have been affected by coronavirus disease 2019 (COVID-19) and it has caused 640 016 deaths as of July 26, 2020. Currently, no effective treatment option is available for COVID-19 patients. Though many drugs have been proposed, none of them has shown particular efficacy in clinical trials. In this article, the relationship between the Adrenergic system and the renin-angiotensin-aldosterone system (RAAS) is focused in COVID-19 and a vicious circle consisting of the Adrenergic system-RAAS-Angiotensin converting enzyme 2 (ACE2)-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (which is referred to as the "ARAS loop") is proposed. Hyperactivation of the ARAS loop may be the underlying pathophysiological mechanism in COVID-19, and beta-adrenergic blockers are proposed as a potential treatment option. Beta-adrenergic blockers may decrease the SARS-CoV-2 cellular entry by decreasing ACE2 receptors expression and cluster of differentiation 147 (CD147) in various cells in the body. Beta-adrenergic blockers may decrease the morbidity and mortality in COVID-19 patients by preventing or reducing acute respiratory distress syndrome (ARDS) and other complications. Retrospective and prospective clinical trials should be conducted to check the validity of the hypothesis. Also see the video abstract here https://youtu.be/uLoy7do5ROo.

Combinatorial analysis of phenotypic and clinical risk factors associated with hospitalized COVID-19 patients

“…This correlates with our previous genomic analysis on the UK Biobank COVID-19 cohort, which identified genes associated with some of these complications, including host pathogenic responses, inflammatory cytokine production, modulation of cardiac function and endothelial cell function 20. Use of medications such as proton pump inhibitors, dihydropyridines and beta-adrenergic blockers were observed in seven disease signatures in Cohort 1 and 80 signatures in Cohort 2. Dihydropyridines 33,34 and beta-adrenergic blockers 35,36 have been associated with improved outcomes for COVID-19 patients and suggested as potential treatments, while proton pump inhibitors have been associated with adverse outcomes in several studies 37,38 . The incidence of the medications in the disease signatures could be either due to adverse effects cause by the medication resulting in more severe COVID-19 response or it could reflect the comorbidities in patients for which they are generally prescribed.…”

Cardiovascular Disease and COVID-19: Insight From Cases With Heart Failure

“…A previous metaanalysis also showed that ACEIs/ARBs may have a protective effect in patients with community-acquired pneumonia and may reduce pneumonia-related mortality compared with that observed for the control group (30). Of note, losartan has been shown to ameliorate lung injury caused by SARS-CoV in an experimental study (40,41). Therefore, losartan may be a possible treatment method for reducing acute cardiopulmonary injury that can be applied in the clinic immediately (40,41).…”

“…Of note, losartan has been shown to ameliorate lung injury caused by SARS-CoV in an experimental study (40,41). Therefore, losartan may be a possible treatment method for reducing acute cardiopulmonary injury that can be applied in the clinic immediately (40,41). Unfortunately, the effects of ACEIs/ARBs in the treatment of patients with heart failure during COVID-19 have yet to be established.…”

“…Moreover, betablockers, as another major class of drugs used in heart failure treatment, may have beneficial effects in COVID-19 patients through several functions, ranging from reducing adrenergic activation (like their pivotal role in Takotsubo cardiomyopathy), inhibiting NLRP3 inflammasome, and decreasing SARS-CoV-2 entry into the cell by downregulating ACE2 receptors (still only a hypothesis) ( 42 ). Spironolactone may also provide protection through concurrent actions in the modulation of ACE2 expression and increasing angiotensin 1–7 levels ( 43 ).…”

Adrenergic Storm Induced Warburg Effect in COVID-19

“…The author had recently proposed that adrenergic hyperactivation may explain all the complications occurring in the COVID-19 condition. [23] Recently alpha1 adrenergic blockers and beta-adrenergic blockers have been proposed to treat COVID-19 patients. [24,25] This evidence supports the claim that alpha1 and betaadrenergic blockers can be used in the COVID-19 patients to prevent adrenergic storm and thereby reverse the Warburg effect.…”