论文标题
α-1肾上腺素能受体拮抗剂可防止下呼吸道感染过度炎症和死亡
Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection
论文作者
论文摘要
在包括2019年冠状病毒病（COVID-19）在内的严重病毒性肺炎中，病毒复制阶段通常紧随其后，会导致急性呼吸窘迫综合征，多器官衰竭和死亡。我们先前证明了α-1肾上腺素能受体（$α_1$ -AR）拮抗剂可以防止小鼠的过度炎症和死亡。在这里，我们对两名急性呼吸窘迫患者（ARD，n = 18,547）的患者进行了回顾性分析，并进行了三个与肺炎的队列（n = 400,907）。在两个ARD队列中联合会，我们发现与未暴露的患者相比，暴露于$α_1$ -AR拮抗剂的患者的机械通气和死亡相对风险降低了34％（OR = 0.70，p = 0.021）。我们在三个肺炎同类中复制了这些方法，所有这些方法都对这两个结果都有相似的影响。所有结果对敏感性分析都是可靠的。这些结果突出了对前瞻性试验的迫切需求，以预防$α_1$ -AR拮抗剂是否可以改善下呼吸道感染相关的过度炎症和死亡，如COVID-19所示。
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 ($α_1$-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 $α_1$-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 $α_1$-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.
