TY - JOUR
T1 - Inpatient Administration of Alpha-1-Adrenergic Receptor Blocking Agents Reduces Mortality in Male COVID-19 Patients
AU - Li, Shilong
AU - Jun, Tomi
AU - Tyler, Jonathan
AU - Schadt, Emilio
AU - Kao, Yu Han
AU - Wang, Zichen
AU - Konig, Maximilian F.
AU - Bettegowda, Chetan
AU - Vogelstein, Joshua T.
AU - Papadopoulos, Nickolas
AU - Parsons, Ramon E.
AU - Chen, Rong
AU - Schadt, Eric E.
AU - Li, Li
AU - Oh, William K.
N1 - Funding Information:
SL, TJ, JT, ES, Y-HK, ZW, RC, EES, LL, and WKO were all employees of Sema4 at the time this research was conducted. Sema4 is a publicly traded, for-profit company in which the Icahn School of Medicine at Mount Sinai (ISMMS) holds equity. RC, EES, LL, and WKO receive compensation from Sema4 that includes equity in the company. In addition to their roles with Sema4, RC, EES, and WKO remain affiliated with ISSMS as part-time employees and faculty members. WKO also has consulted for AAA, Astellas, AstraZeneca, Bayer, Conjupro, Foundry, Janssen, Merck, Sanofi and TeneoBio. The JHU filed a patent application on the use of various drugs to prevent cytokine release syndromes, on which NP is listed as an inventor. JHU will not assert patent rights from this filing for treatment related to COVID-19. NP is a founder of, consultant to and holds equity in Thrive an Exact company. NP is a founder of and holds equity in Personal Genome Diagnostics. NP is an advisor to and holds equity in Cage Pharma, ManaTbio, and NeoPhore. CB is a consultant to Depuy-Synthes and Bionaut Labs. CB, MFK, and NP are also inventors on technologies unrelated or indirectly related to the work described in this article. MFK is a consultant to argenx. Licenses to these technologies are or will be associated with equity or royalty payments to the inventors, as well as to JHU. The terms of all these arrangements are being managed by JHU in accordance with its conflict-of-interest policies. JV is supported by grants from Microsoft Research and Fast Grants. Microsoft Research and Fast Grants were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Funding Information:
MK was supported by grants from the Jerome L. Greene Foundation (Discovery and Scholar Award) and the Peter and Carmen Lucia Buck Foundation.
Publisher Copyright:
Copyright © 2022 Li, Jun, Tyler, Schadt, Kao, Wang, Konig, Bettegowda, Vogelstein, Papadopoulos, Parsons, Chen, Schadt, Li and Oh.
PY - 2022/2/28
Y1 - 2022/2/28
N2 - Apha-1-adrenergic receptor antagonists (α1-blockers) can suppress pro-inflammatory cytokines, thereby potentially improving outcomes among patients with COVID-19. Accordingly, we evaluated the association between α1-blocker exposure (before or during hospitalization) and COVID-19 in-hospital mortality. We identified 2,627 men aged 45 or older who were admitted to Mount Sinai hospitals with COVID-19 between February 24 and May 31, 2020, in New York. 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, 777 (29.6%) patients died in hospital, and 1,850 (70.4%) were discharged. Notably, we found that α1-blocker exposure was independently associated with improved in-hospital mortality in a multivariable logistic analysis (OR 0.699; 95% CI, 0.498-0.982; P = 0.039) after adjusting for patient demographics, comorbidities, and baseline vitals and labs. The protective effect of α1-blockers was stronger among patients with documented inpatient exposure to α1-blockers (OR 0.624; 95% CI 0.431-0.903; P = 0.012). Finally, age-stratified analyses suggested variable benefit from inpatient α1-blocker across age groups: Age 45-65 OR 0.483, 95% CI 0.216-1.081 (P = 0.077); Age 55-75 OR 0.535, 95% CI 0.323-0.885 (P = 0.015); Age 65-89 OR 0.727, 95% CI 0.484-1.092 (P = 0.124). Taken together, clinical trials to assess the therapeutic value of α1-blockers for COVID-19 complications are warranted.
AB - Apha-1-adrenergic receptor antagonists (α1-blockers) can suppress pro-inflammatory cytokines, thereby potentially improving outcomes among patients with COVID-19. Accordingly, we evaluated the association between α1-blocker exposure (before or during hospitalization) and COVID-19 in-hospital mortality. We identified 2,627 men aged 45 or older who were admitted to Mount Sinai hospitals with COVID-19 between February 24 and May 31, 2020, in New York. 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, 777 (29.6%) patients died in hospital, and 1,850 (70.4%) were discharged. Notably, we found that α1-blocker exposure was independently associated with improved in-hospital mortality in a multivariable logistic analysis (OR 0.699; 95% CI, 0.498-0.982; P = 0.039) after adjusting for patient demographics, comorbidities, and baseline vitals and labs. The protective effect of α1-blockers was stronger among patients with documented inpatient exposure to α1-blockers (OR 0.624; 95% CI 0.431-0.903; P = 0.012). Finally, age-stratified analyses suggested variable benefit from inpatient α1-blocker across age groups: Age 45-65 OR 0.483, 95% CI 0.216-1.081 (P = 0.077); Age 55-75 OR 0.535, 95% CI 0.323-0.885 (P = 0.015); Age 65-89 OR 0.727, 95% CI 0.484-1.092 (P = 0.124). Taken together, clinical trials to assess the therapeutic value of α1-blockers for COVID-19 complications are warranted.
KW - COVID-19
KW - alpha-1-adrenergic receptor antagonist
KW - coronavirus disease
KW - electronic medical record
KW - infectious disease
KW - multivariate logistic analysis
KW - off-label drug use
KW - real-world evidence
UR - http://www.scopus.com/inward/record.url?scp=85127351453&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85127351453&partnerID=8YFLogxK
U2 - 10.3389/fmed.2022.849222
DO - 10.3389/fmed.2022.849222
M3 - Article
C2 - 35295598
AN - SCOPUS:85127351453
SN - 2296-858X
VL - 9
JO - Frontiers in Medicine
JF - Frontiers in Medicine
M1 - 849222
ER -