The Association Between Alpha-1 Adrenergic Receptor Antagonists and In-Hospital Mortality from COVID-19

Rose, Liam; Graham, Laura A.; Koenecke, Allison; Powell, Michael; Xiong, Ruoxuan; Shen, Zhu; Kinzler, Kenneth W.; Bettegowda, Chetan; Vogelstein, Bert; Konig, Maximilian F.; Athey, Susan; Vogelstein, Joshua T.

doi:10.1101/2020.12.18.20248346

Cited by 11 publications

(12 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1,2,11 These pre-clinical findings have been bolstered by recent retrospective clinical analyses linking α1blockers with improved outcomes in hospitalized patients with both COVID-19 and non-COVID-19 respiratory infections. 12,13 In a large COVID-19 cohort drawn from the US Veterans Health Administration hospital system, outpatient α1-blocker exposure was associated with a relative risk reduction of 18% for in-hospital mortality compared to matched controls. 13 Interestingly, the nonselective α1-blocker doxazosin, which inhibits all three α1-adrenergic receptor subtypes (α1A, α1B, α1D), was associated with a greater relative risk reduction (74%) than the uroselective (α1A, α1D) α1-blocker tamsulosin (18%).…”

Section: Discussionmentioning

confidence: 99%

COVID-19 outcomes among hospitalized men with or without exposure to alpha-1-adrenergic receptor blocking agents

Jun

Wang

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Importance: Alpha-1-adrenergic receptor antagonists (α1-blockers) can abrogate pro-inflammatory cytokines and may improve outcomes among patients with respiratory infections. Repurposing readily available drugs such as α1-blockers could augment the medical response to the COVID-19 pandemic. Objective: To evaluate the association between α1-blocker exposure and COVID-19 mortality Design: Real-world evidence study Setting: Patient level data with 32,355 records tested for SARS-CoV-2 at the Mount Sinai Health System including 8,442 laboratory-confirmed cases extracted from five member hospitals in the New York City metropolitan area. Participants: 2,627 men aged 45 or older admitted with COVID-19 between February 24 and May 31, 2020 Exposures: α1-blocker use as an outpatient or while admitted for COVID-19 Main Outcomes and Measures: In-hospital mortality Results: Men exposed to α1-blockers (N=436) were older (median age 73 vs. 64 years, P<0.001) and more likely to have comorbidities than unexposed men (N=2,191). Overall, 758 (28.9%) patients died in hospital, 1,589 (60.5%) were discharged, and 280 (10.7%) were still hospitalized as of May 31, 2020. Outpatient exposure to α1-blockers was not associated with COVID-19 hospital outcomes, though there was a trend towards significance (OR 0.749, 95% CI 0.527-1.064; P=0.106). Conversely, inpatient use of α1-blockers was independently associated with improved in-hospital mortality in both multivariable logistic (OR 0.633, 95% CI 0.434-0.921; P=0.017) and Cox regression analyses (HR 0.721, 95% CI 0.572-0.908; P=0.006) adjusting for patient demographics, comorbidities, and baseline vitals and labs. Age-stratified analyses suggested greater benefit from inpatient α1-blocker use among younger age groups: Age 45-65 OR 0.384, 95% CI 0.164-0.896 (P=0.027); Age 55-75 OR 0.511, 95% CI 0.297-0.880 (P=0.015); Age 65-89 OR 0.810, 95% CI 0.509-1.289 (P=0.374). Conclusions and Relevance: Inpatient α1-blocker use was independently associated with improved COVID-19 mortality among hospitalized men. Clinical trials to assess the therapeutic value of α1-blockers in COVID-19 are warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

COVID-19 outcomes among hospitalized men with or without exposure to alpha-1-adrenergic receptor blocking agents

Jun

Wang

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Prospective learning thus crucially benefits from causal models: they are more likely to be useful as they encode real invariances that persist across environments. For example, different variants of COVID will continue to emerge, but certain treatments are likely to be effective for each of them insofar as they act on the mechanism of disease which remains constant [141]. Such scenarios pose a problem for traditional AI algorithms.…”

Section: Causality Causal Estimation Is the Ability To Identify How O...mentioning

confidence: 99%

Prospective Learning: Back to the Future

Vogelstein¹,

Verstynen²,

Kording³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Research on both natural intelligence (NI) and artificial intelligence (AI) generally assumes that the future resembles the past: intelligent agents or systems (what we call 'intelligence') observe and act on the world, then use this experience to act on future experiences of the same kind. We call this 'retrospective learning'. For example, an intelligence may see a set of pictures of objects, along with their names, and learn to name them. A retrospective learning intelligence would merely be able to name more pictures of the same objects. We argue that this is not what true intelligence is about. In many real world problems, both NIs and AIs will have to learn for an uncertain future. Both must update their internal models to be useful for future tasks, such as naming fundamentally new objects and using these objects effectively in a new context or to achieve previously unencountered goals. This ability to learn for the future we call 'prospective learning'. We articulate four relevant factors that jointly define prospective learning. Continual learning enables intelligences to remember those aspects of the past which it believes will be most useful in the future. Prospective constraints (including biases and priors) facilitate the intelligence finding general solutions that will be applicable to future problems. Curiosity motivates taking actions that inform future decision making, including in previously unmet situations. Causal estimation enables learning the structure of relations that guide choosing actions for specific outcomes, even when the specific action-outcome contingencies have never been observed before. We argue that a paradigm shift from retrospective to prospective learning will enable the communities that study intelligence to unite and overcome existing bottlenecks to more effectively explain, augment, and engineer intelligences."No man ever steps in the same river twice. For it's not the same river and he's not the same man." -Heraclitus

show abstract

“…However, these therapeutics, as are all α 1 -AR antagonists, are contraindicated in people with heart problems ( O’Connell et al, 2013 ). Recent studies also suggest that α 1 -AR antagonists increase mortality rates in hospitalized patients with Covid-19 ( Rose et al, 2020 ).…”

Section: Pharmacological Interventionsmentioning

confidence: 99%

Current Developments on the Role of α1-Adrenergic Receptors in Cognition, Cardioprotection, and Metabolism

Perez

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The α1-adrenergic receptors (ARs) are G-protein coupled receptors that bind the endogenous catecholamines, norepinephrine, and epinephrine. They play a key role in the regulation of the sympathetic nervous system along with β and α2-AR family members. While all of the adrenergic receptors bind with similar affinity to the catecholamines, they can regulate different physiologies and pathophysiologies in the body because they couple to different G-proteins and signal transduction pathways, commonly in opposition to one another. While α1-AR subtypes (α1A, α1B, α1C) have long been known to be primary regulators of vascular smooth muscle contraction, blood pressure, and cardiac hypertrophy, their role in neurotransmission, improving cognition, protecting the heart during ischemia and failure, and regulating whole body and organ metabolism are not well known and are more recent developments. These advancements have been made possible through the development of transgenic and knockout mouse models and more selective ligands to advance their research. Here, we will review the recent literature to provide new insights into these physiological functions and possible use as a therapeutic target.

show abstract

The Association Between Alpha-1 Adrenergic Receptor Antagonists and In-Hospital Mortality from COVID-19

Cited by 11 publications

References 23 publications

COVID-19 outcomes among hospitalized men with or without exposure to alpha-1-adrenergic receptor blocking agents

COVID-19 outcomes among hospitalized men with or without exposure to alpha-1-adrenergic receptor blocking agents

Prospective Learning: Back to the Future

Current Developments on the Role of α1-Adrenergic Receptors in Cognition, Cardioprotection, and Metabolism

Contact Info

Product

Resources

About