Alpha-1 adrenergic receptor antagonists prevent acute respiratory distress syndrome and death: implications for Coronavirus disease 2019

In Coronavirus disease 2019 (COVID-19), the initial viral replication phase is often followed by a hyperinflammatory reaction in the lungs and other organ systems (‘cytokine storm syndrome’) that leads to acute respiratory distress syndrome (ARDS), multi-organ 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 (​⍺​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 ​⍺​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 (β-AR) antagonists. These results support studying ​⍺​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 ​⍺​1​-AR antagonists to assess their efficacy in preventing cytokine storm syndrome and death in COVID-19.