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  ') that leads to acute respiratory distress syndrome (ARDS), URLan failure, and death  despite maximal supportive care. Preventing hyperinflammation is key to avoiding this progression to severe stages of COVID-19. We have previously demonstrated that alpha-1 adrenergic receptor ( %DIFDELCMD < \alpha1%%%  -AR) antagonists can prevent cytokine storms and resulting death in mice. Here  we present a retrospective study of outcomes in patients with ARDS (n = 13,125) or pneumonia (n = 108,956). Patients  who were taking %DIFDELCMD < \alpha1%%%  -AR antagonists for other conditions had lower probability of needing invasive mechanical ventilationand dying in the hospital compared to non-users , both in ARDS (adjusted OR = 0.59 , 95\% CI 0.34-0.95 , p = 0.021)and in pneumonia (adjusted OR = 0.77, 95\% CI 0.62-0.94, p = 0.007) . By contrast, no significant effect was observed for beta-adrenergic receptor (\beta-AR) antagonists. These results support the study of%DIFDELCMD < \alpha1%%%  -AR antagonists for  reducing mortality in pneumonia and ARDS and highlight the need for prospective trials of %DIFDELCMD < \alpha1%%%  -AR antagonists to assess their efficacy in preventing cytokine storm  and death in COVID-19.
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 ( %DIFDELCMD < \alpha1%%% \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 %DIFDELCMD < \alpha1%%% \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 %DIFDELCMD < \alpha1%%% 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 %DIFDELCMD < \alpha1%%% \alpha_1 -AR antagonists to assess their efficacy in preventing cytokine storm syndrome and death in COVID-19.
R
Disease
disease
R
viral-replication
viral replication
A
syndrome
A
-
D
this
A
\alpha_1
R
storms
storm syndrome
A
,
R
ARDS
acute respiratory distress
A
with acute respiratory distress
A
\alpha_1
R
lower probability of needing invasive mechanical ventilationand dying in the hospital
a 35\% reduced risk of requiring ventilation, and a 56\% reduced risk of ventilation and death,
D
, both in ARDS
R
0.59
0.41
R
0.34-0.95
0.17-0.81
R
0.021)and in pneumonia (adjusted OR = 0.77, 95\% CI 0.62-0.94, p = 0.007)
0.01)
D
the study of
A
studying \alpha_1
A
preventing ARDS and
R
ARDS and
acute respiratory distress, as well as
A
\alpha_1
A
syndrome