In  Coronavirus disease 2019 (COVID-19), the initial viral replication phase is often followed by a hyperinflammatory reaction in the lungs and URLan systems ('cytokine storm syndrome') that leads to acute respiratory distress syndrome (ARDS), URLan failure, and death- despite maximal supportive care. Preventing hyperinflammation is key to avoiding progression to severe stages of COVID-19. We have previously demonstrated that alpha-1 adrenergic receptor (\alpha_1-AR) antagonists can prevent cytokine storm syndrome and resulting death in mice. Here, we present a retrospective study of outcomes in patients with acute respiratory distress (n = 13,125) or pneumonia (n = 108,956) . Patients with acute respiratory distress who were taking \alpha_1-AR antagonists for other conditions had a 35\% reduced risk of requiring ventilation , and a 56\% reduced risk of ventilation and death, compared to non-users (adjusted OR = 0.41 , 95\% CI 0.17-0.81, p = 0.01). By contrast, no significant effect was observed for beta-adrenergic receptor (\beta-AR) antagonists .  These results support studying \alpha_1-AR antagonists for preventing ARDS and reducing mortality in pneumonia and acute respiratory distress, as well as highlight the need for prospective trials of \alpha_1-AR antagonists to assess their efficacy in preventing cytokine storm syndrome and death in COVID-19.
In severe 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 (n = 13,125) or pneumonia (n = 108,956) 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.
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95\% CI 0.17-0.81, p = 0.01). By contrast, no significant effect was observed for beta-adrenergic receptor (\beta-AR) antagonists
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support studying \alpha_1-AR antagonists for preventing ARDS and reducing mortality in pneumonia and acute respiratory distress, as well as highlight the
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of \alpha_1-AR antagonists to assess their efficacy in preventing cytokine storm syndrome and death in
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