Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection.
In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (⍺1-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n = 18,547) and three cohorts with pneumonia (n = 400,907). Federated across two ARD cohorts, we find that patients exposed to ⍺1-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR = 0.70, p = 0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of ⍺1-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.
View details for DOI 10.7554/eLife.61700
View details for PubMedID 34114951
The Association Between Alpha-1 Adrenergic Receptor Antagonists and In-Hospital Mortality from COVID-19.
medRxiv : the preprint server for health sciences
Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed, and preclinical data suggest alpha-1 adrenergic receptor antagonists (α 1 -AR antagonists) may be effective in reducing mortality related to hyperinflammation. Using a retrospective cohort design with patients in the Department of Veterans Affairs healthcare system, we use doubly robust regression and matching to estimate the association between use of α 1 -AR antagonists at time of hospitalization and likelihood of death due to COVID-19 during an inpatient stay. Having an active prescription for an α 1 -AR antagonist (tamsulosin, silodosin, prazosin, terazosin, doxazosin, or alfuzosin) at the time of admission had a significant negative association with in-hospital mortality (relative risk reduction 14%; odds ratio 0.75; 95% CI 0.66 to 0.86; p ≤ 0.001). These effects were also found in an expanded cohort of suspected COVID-19 patients, supporting the need for clinical trials.
View details for DOI 10.1101/2020.12.18.20248346
View details for PubMedID 33398294
View details for PubMedCentralID PMC7781337