IntroductionĮach year, approximately 300 million people develop pneumonia ( GBD 2016 Lower Respiratory Infections Collaborators, 2018), which usually results in appropriate, self-limiting immune responses and clearance of the bacterial or viral pathogen. 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. All results were robust to sensitivity analyses. We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. 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). 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). We previously demonstrated that alpha-1 adrenergic receptor (⍺ 1-AR) antagonists can prevent hyperinflammation and death in mice. 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. Stanford Graduate School of Business, Stanford University, United States.
Janelia Research Campus, Howard Hughes Medical Institute, United States.Division of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, United States.Ludwig Center, Lustgarten Laboratory, and the Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, United States.Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health at Johns Hopkins University, United States.Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden, Sweden.Department of Neurosurgery and Neurology, The Johns Hopkins University School of Medicine, United States.The Johns Hopkins University School of Medicine, United States.Department of Statistics, Stanford University, United States.Management Science & Engineering, Stanford University, United States.Department of Biomedical Engineering, Institute for Computational Medicine, The Johns Hopkins University, United States.Institute for Computational & Mathematical Engineering, Stanford University, United States.
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