Alpha-1 Adrenergic Receptor Antagonists to Prevent Acute Respiratory Distress Syndrome and Death from Cytokine Storm Syndrome

Allison Koenecke, Michael Powell, Ruoxuan Xiong, Zhu Shen, Nicole Fischer, Sakibul Huq and Adham M. Khalafallah, et al.
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Allison Koenecke: Institute for Computational and Mathematical Engineering, Stanford U
Michael Powell: Johns Hopkins U
Ruoxuan Xiong: Stanford U
Zhu Shen: Stanford U
Nicole Fischer: Johns Hopkins U School of Medicine
Sakibul Huq: Johns Hopkins U School of Medicine
Adham M. Khalafallah, et al.: Johns Hopkins U School of Medicine

Research Papers from Stanford University, Graduate School of Business

Abstract: 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, multi-organ 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 non-users, 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.

Date: 2020-08
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