Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection
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) ant...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:27cc1efbc7b74373ace05076206c199b2021-11-23T12:54:36ZAlpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection10.7554/eLife.617002050-084Xe61700https://doaj.org/article/27cc1efbc7b74373ace05076206c199b2021-06-01T00:00:00Zhttps://elifesciences.org/articles/61700https://doaj.org/toc/2050-084XIn 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.Allison KoeneckeMichael PowellRuoxuan XiongZhu ShenNicole FischerSakibul HuqAdham M KhalafallahMarco TrevisanPär SparenJuan J CarreroAkihiko NishimuraBrian CaffoElizabeth A StuartRenyuan BaiVerena StaedtkeDavid L ThomasNickolas PapadopoulosKen W KinzlerBert VogelsteinShibin ZhouChetan BettegowdaMaximilian F KonigBrett D MenshJoshua T VogelsteinSusan AtheyeLife Sciences Publications Ltdarticleobservational studycausal inferencerespiratory diseaseinfectious diseaseMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
observational study causal inference respiratory disease infectious disease Medicine R Science Q Biology (General) QH301-705.5 |
| spellingShingle |
observational study causal inference respiratory disease infectious disease Medicine R Science Q Biology (General) QH301-705.5 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 Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Allison Koenecke |
| title |
Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection |
| title_short |
Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection |
| title_full |
Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection |
| title_fullStr |
Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection |
| title_full_unstemmed |
Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection |
| title_sort |
alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/27cc1efbc7b74373ace05076206c199b |
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1718416692479000576 |