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Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection. 2021
Allison Koenecke, and
Michael Powell, and
Ruoxuan Xiong, and
Zhu Shen, and
Nicole Fischer, and
Sakibul Huq, and
Adham M Khalafallah, and
Marco Trevisan, and
Pär Sparen, and
Juan J Carrero, and
Akihiko Nishimura, and
Brian Caffo, and
Elizabeth A Stuart, and
Renyuan Bai, and
Verena Staedtke, and
David L Thomas, and
Nickolas Papadopoulos, and
Kenneth W Kinzler, and
Bert Vogelstein, and
Shibin Zhou, and
Chetan Bettegowda, and
Maximilian F Konig, and
Brett Mensh, and
Joshua T Vogelstein, and
Susan Athey
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, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor ($\alpha_1$-AR) antagonists can prevent hyperinflammation and death 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 hyperinflammation and death, as observed in COVID-19.
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