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

  1. Shilong Li
  2. Tomi Jun
  3. Jonathan Tyler
  4. Emilio Schadt
  5. Yu-Han Kao
  6. Zichen Wang
  7. Maximilian F. Konig
  8. Chetan Bettegowda
  9. Joshua T. Vogelstein
  10. Nickolas Papadopoulos
  11. Ramon E. Parsons
  12. Rong Chen
  13. Eric E. Schadt
  14. Li Li
  15. William K. Oh

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Abstract

Apha-1-adrenergic receptor antagonists (α 1 -blockers) can suppress pro-inflammatory cytokines, thereby potentially improving outcomes among patients with COVID-19. Accordingly, we evaluated the association between α 1 -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 α 1 -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 α 1 -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 α 1 -blockers was stronger among patients with documented inpatient exposure to α 1 -blockers (OR 0.624; 95% CI 0.431-0.903; P = 0.012). Finally, age-stratified analyses suggested variable benefit from inpatient α 1 -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 α 1 -blockers for COVID-19 complications are warranted.

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  1. Version published to 10.3389/fmed.2022.849222
  2. ScreenIT

    SciScore for 10.1101/2021.04.08.21255148: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Mount Sinai institutional review board (IRB): IRB-17-01245.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We utilized Python and R, and their open-source libraries to conduct our analysis tailored to MSH data.
    Python
    suggested: (IPython, RRID:SCR_001658)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations: Our study has several limitations. The cohort did not include women since most α1-blockers were prescribed to men, most likely for benign prostatic hyperplasia. Male sex is a recognized risk factor for adverse COVID-19 outcomes, possibly due to sex-specific differences in immunity.19 Thus, these results may not extrapolate to women. We did not account for different types of α1-blockers, which differentially target the three α1-adrenergic receptor subtypes. Importantly, a causal relationship cannot be definitively established between α1-blockers and improved COVID-19 outcomes in this retrospective study. Several confounders, such as older age and comorbidities were more common in the α1-blocker group. However, these adverse risk factors would be expected to bias the study result towards the null rather than inflate a protective association. Furthermore, our findings are consistent with prior data, and were robust to different methods of adjustment for confounding and sensitivity analysis. The ongoing randomized clinical trial of prazosin against placebo among hospitalized COVID-19 patients (NCT04365257) will include women and provide more definitive data on the therapeutic value of α1-blockers. Finally, our study is based on a single center EMR and medication via outpatient use cannot be tracked for adherence. Therefore, analyzing in-hospital medication administration is more robust. Furthermore, EMR in MSHS is the one of the largest and most comprehensive EMR sys...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04365257RecruitingPrazosin to Prevent COVID-19 (PREVENT-COVID Trial)

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2021.04.08.21255148 on medRxiv