eLife (Jun 2021)
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 Zhou,
- Chetan Bettegowda,
- Maximilian F Konig,
- Brett D Mensh,
- Joshua T Vogelstein,
- Susan Athey
Affiliations
- Allison Koenecke
- ORCiD
- Institute for Computational & Mathematical Engineering, Stanford University, Stanford, United States
- Michael Powell
- ORCiD
- Department of Biomedical Engineering, Institute for Computational Medicine, The Johns Hopkins University, Baltimore, United States
- Ruoxuan Xiong
- Management Science & Engineering, Stanford University, Stanford, United States
- Zhu Shen
- Department of Statistics, Stanford University, Stanford, United States
- Nicole Fischer
- The Johns Hopkins University School of Medicine, Baltimore, United States
- Sakibul Huq
- Department of Neurosurgery and Neurology, The Johns Hopkins University School of Medicine, Baltimore, United States
- Adham M Khalafallah
- Department of Neurosurgery and Neurology, The Johns Hopkins University School of Medicine, Baltimore, United States
- Marco Trevisan
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden, Solna, Sweden
- Pär Sparen
- ORCiD
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden, Solna, Sweden
- Juan J Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden, Solna, Sweden
- Akihiko Nishimura
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health at Johns Hopkins University, Baltimore, United States
- Brian Caffo
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health at Johns Hopkins University, Baltimore, United States
- Elizabeth A Stuart
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health at Johns Hopkins University, Baltimore, United States
- Renyuan Bai
- Department of Neurosurgery and Neurology, The Johns Hopkins University School of Medicine, Baltimore, United States
- Verena Staedtke
- Department of Neurosurgery and Neurology, The Johns Hopkins University School of Medicine, Baltimore, United States
- David L Thomas
- The Johns Hopkins University School of Medicine, Baltimore, United States
- Nickolas Papadopoulos
- Ludwig Center, Lustgarten Laboratory, and the Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, Baltimore, United States
- Ken W Kinzler
- Ludwig Center, Lustgarten Laboratory, and the Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, Baltimore, United States
- Bert Vogelstein
- Ludwig Center, Lustgarten Laboratory, and the Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, Baltimore, United States
- Shibin Zhou
- Ludwig Center, Lustgarten Laboratory, and the Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, Baltimore, United States
- Chetan Bettegowda
- The Johns Hopkins University School of Medicine, Baltimore, United States; Ludwig Center, Lustgarten Laboratory, and the Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, Baltimore, United States
- Maximilian F Konig
- ORCiD
- Division of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, United States
- Brett D Mensh
- Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
- Joshua T Vogelstein
- ORCiD
- Department of Biomedical Engineering, Institute for Computational Medicine, The Johns Hopkins University, Baltimore, United States; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health at Johns Hopkins University, Baltimore, United States
- Susan Athey
- Stanford Graduate School of Business, Stanford University, Stanford, United States
- DOI
- https://doi.org/10.7554/eLife.61700
- Journal volume & issue
-
Vol. 10
Abstract
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 (⍺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 hyperinflammation and death, as observed in COVID-19.
Keywords
