Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection

Allison Koenecke, Michael Powell, Ruoxuan Xiong, Zhu Shen, Nicole Fischer, Sakibul Huq, Adham M. Khalafallah, Marco Trevisan, Pär Sparen, Juan J. Carrero, Akihiko Nishimura, Brian Caffo, Elizabeth A. Stuart, Renyuan Bai, Verena Staedtke, David L. Thomas, Nickolas Papadopoulos, Ken W. Kinzler, Bert Vogelstein, Shibin ZhouChetan Bettegowda, Maximilian F. Konig, Brett D. Mensh, Joshua T. Vogelstein, Susan Athey

Research output: Contribution to journalArticlepeer-review


In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replica-tion 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 (⍺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 ⍺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 ⍺1-AR antagonists ameliorates lower respiratory tract infection-associated hyper-inflammation and death, as observed in COVID-19.

Original languageEnglish (US)
Article numbere61700
StatePublished - Jun 2021

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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