تقرير
Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection
| العنوان: | Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection |
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| المؤلفون: | Koenecke, Allison, Powell, Michael, Xiong, Ruoxuan, Shen, Zhu, Fischer, Nicole, Huq, Sakibul, Khalafallah, Adham M., Trevisan, Marco, Sparen, Pär, Carrero, Juan J, Nishimura, Akihiko, Caffo, Brian, Stuart, Elizabeth A., Bai, Renyuan, Staedtke, Verena, Thomas, David L., Papadopoulos, Nickolas, Kinzler, Kenneth W., Vogelstein, Bert, Zhou, Shibin, Bettegowda, Chetan, Konig, Maximilian F., Mensh, Brett, Vogelstein, Joshua T., Athey, Susan |
| المصدر: | Elife 10 (2021): e61700 |
| سنة النشر: | 2020 |
| المجموعة: | Quantitative Biology |
| مصطلحات موضوعية: | Quantitative Biology - Tissues and Organs, Quantitative Biology - Quantitative Methods |
| الوصف: | 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. Comment: 31 pages, 10 figures |
| نوع الوثيقة: | Working Paper |
| DOI: | 10.7554/eLife.61700 |
| الوصول الحر: | http://arxiv.org/abs/2004.10117Test |
| رقم الانضمام: | edsarx.2004.10117 |
| قاعدة البيانات: | arXiv |
| DOI: | 10.7554/eLife.61700 |
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