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.
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, URLan failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (\alpha_1-AR) antagonists can prevent hyperinflammation ( cytokine storm syndrome ) 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 \alpha_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 \alpha_1-AR antagonists ameliorates lower respiratory tract infection-associated cytokine storm syndrome, as observed in COVID-19.
D
('cytokine storm syndrome')
A
hyperinflammation (
A
)
R
19,659
18,547
R
423,897
400,907
R
our main result shows that patients using
we find that patients exposed to
R
nonusers
unexposed patients
R
40
34
R
ventilation and dying (
mechanical ventilation and death (OR=0.70,
R
0.014
0.021
D
various
R
diseases associated with
lower respiratory tract infection-associated
R
such as
as observed in