Inpatient Administration of Alpha-1-Adrenergic Receptor Blocking Agents Reduces Mortality in Male COVID-19 Patients

Shilong Li; Tomi Jun; Jonathan Tyler; Emilio Schadt; Yu-Han Kao; Zichen Wang; Maximilian F Konig; Chetan Bettegowda; Joshua T Vogelstein; Nickolas Papadopoulos; Ramon E Parsons; Rong Chen; Eric E Schadt; Li Li; William K Oh

doi:10.3389/fmed.2022.849222

Inpatient Administration of Alpha-1-Adrenergic Receptor Blocking Agents Reduces Mortality in Male COVID-19 Patients

Front Med (Lausanne). 2022 Feb 28:9:849222. doi: 10.3389/fmed.2022.849222. eCollection 2022.

Authors

Shilong Li¹, Tomi Jun¹, Jonathan Tyler¹, Emilio Schadt¹, Yu-Han Kao¹, Zichen Wang¹, Maximilian F Konig^{2

3}, Chetan Bettegowda^{2

4}, Joshua T Vogelstein^{5

6}, Nickolas Papadopoulos^{2

7}, Ramon E Parsons^{8

9}, Rong Chen^{1

10}, Eric E Schadt^{1

10}, Li Li¹, William K Oh^{1

8}

Affiliations

¹ Sema4, Stamford, CT, United States.
² Lustgarten Laboratory, Ludwig Center, The Howard Hughes Medical Institute, The Johns Hopkins Kimmel Cancer Center, Baltimore, MD, United States.
³ Division of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁴ Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁵ Department of Biomedical Engineering, Institute for Computational Medicine, The Johns Hopkins University, Baltimore, MD, United States.
⁶ Department of Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, United States.
⁷ Department of Oncology and Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁸ Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
⁹ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
¹⁰ Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Abstract

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.

Keywords: COVID-19; alpha-1-adrenergic receptor antagonist; coronavirus disease; electronic medical record; infectious disease; multivariate logistic analysis; off-label drug use; real-world evidence.

Abstract

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