In severe viral pneumonias , including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by a hyperinflammatory reaction ('cytokine storm syndrome') that leads to acute respiratory distress syndrome and death, despite maximal supportive care. Preventing hyperinflammation is key to avoiding these outcomes. We previously demonstrated that alpha-1 adrenergic receptor antagonists (\alpha-blockers) can prevent cytokine storm syndrome and death in mice. Here, we conduct a retrospective analysis of patients with acute respiratory distress or pneumonia ( n= 13,125 and n= 108,956, respectively)from all causes; patients who were incidentally taking \alpha-blockers had a reduced risk of requiring ventilation (by 35\% and 16\%, respectively), and a reduced risk of being ventilated and dying (by 56\% and 20\%, respectively), compared to non-users. Beta-adrenergic receptor antagonists had no significant effects .  These results highlight the urgent need for prospective trials testing whether prophylactic \alpha-blockers improve outcomes in diseases with a prominent hyperinflammatory component such as COVID-19.
In severe viral pneumonia , including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation ('cytokine storm syndrome') , which can lead to acute respiratory distress syndrome , URLan failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (\alpha_1-AR) antagonists can prevent cytokine storm syndrome in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n= 19,659) and three cohorts with pneumonia ( n= 423,897). Federated across two ARD cohorts, our main result shows that patients using \alpha_1-AR antagonists, as compared to nonusers, had a 40\% relative risk reduction for ventilation and dying (p=0.014) . We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to various sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of \alpha_1-AR antagonists ameliorates diseases associated with cytokine storm syndrome, such as COVID-19.
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pneumonias
pneumonia
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a hyperinflammatory reaction
hyperinflammation
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that leads
, which can lead
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and death, despite maximal supportive care. Preventing hyperinflammation is key to avoiding these outcomes.
, URLan failure, and death.
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antagonists (\alpha-blockers)
(\alpha_1-AR) antagonists
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and death
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conduct a retrospective analysis
conducted retrospective analyses in two cohorts
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or pneumonia (
(ARD,
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13,125 and
19,659) and three cohorts with pneumonia (
R
108,956, respectively)from all causes; patients who were incidentally taking \alpha-blockers had a reduced risk of requiring ventilation (by 35\% and 16\%, respectively), and a reduced risk of being ventilated and dying (by 56\% and 20\%, respectively), compared to non-users. Beta-adrenergic receptor antagonists had no significant effects
423,897). Federated across two ARD cohorts, our main result shows that patients using \alpha_1-AR antagonists, as compared to nonusers, had a 40\% relative risk reduction for ventilation and dying (p=0.014)
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We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to various sensitivity analyses.
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\alpha-blockers improve outcomes in diseases with a prominent hyperinflammatory component
use of \alpha_1-AR antagonists ameliorates diseases associated with cytokine storm syndrome,