Dual-histamine receptor blockade with cetirizine - famotidine reduces pulmonary symptoms in COVID-19 patients
Dual-histamine receptor blockade with cetirizine - famotidine reduces pulmonary symptoms in COVID-19 patients
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DOI：
10.1016/j.pupt.2020.101942
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发表时间：
2020-08-01
影响因子：
3.2
通讯作者：
Dooley, Thomas P.
中科院分区：
文献类型：
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作者：
Hogan, Reed B., II;Hogan, Reed B., III;Dooley, Thomas P.
背景资料：由SARS-CoV-2感染引起的COVID-19大流行可因肺部细胞因子风暴而产生急性呼吸窘迫综合征。抗组胺药是减少炎症和细胞因子释放的安全有效的治疗方法。组胺-1和组胺-2受体拮抗剂的组合在荨麻疹中有效，并且可能减少COVID-19中组胺介导的肺细胞因子风暴。组胺-1和组胺-2受体阻滞剂的组合可以改善COVID-19住院患者的结局吗？研究方法：在重度至危重肺部症状住院患者中进行了一项由医生申办的西替利嗪和法莫替丁队列研究。肺病学家在一个医疗中心领导了110例接受西替利嗪10 mg b.i.d.治疗的高急性期患者的住院治疗。和法莫替丁20 mg b.i.d.加上标准治疗。结果：在接受双重组胺受体阻滞剂至少48小时的所有患者中，包括有“不要复苏”指令的患者，联合药物治疗导致插管率为16.4%，治疗至少48小时后插管率为7.3%，住院死亡率为15.5%，住院时间为11.0天。与已发表的COVID-19住院患者报告相比，该药物组合显示出有益的住院死亡率和症状进展降低。伴随用药进行了评估，羟氯喹与更差的outcomes.Conclusions：这医生赞助的队列研究西替利嗪和法莫替丁提供了一个安全有效的方法来减少症状严重程度的进展，大概是通过最大限度地减少组胺介导的细胞因子风暴的概念验证。对COVID-19的进一步临床研究需要重新使用两种历史上安全的组胺受体阻滞剂的标签外组合。
Background: The COVID-19 pandemic due to SARS-CoV-2 infection can produce Acute Respiratory Distress Syndrome as a result of a pulmonary cytokine storm. Antihistamines are safe and effective treatments for reducing inflammation and cytokine release. Combinations of Histamine-1 and Histamine-2 receptor antagonists have been effective in urticaria, and might reduce the histamine-mediated pulmonary cytokine storm in COVID-19. Can a combination of Histamine-1 and Histamine-2 receptor blockers improve COVID-19 inpatient outcomes?Methods: A physician-sponsored cohort study of cetirizine and famotidine was performed in hospitalized patients with severe to critical pulmonary symptoms. Pulmonologists led the inpatient care in a single medical center of 110 high-acuity patients that were treated with cetirizine 10 mg b.i.d. and famotidine 20 mg b.i.d. plus standard-of-care.Results: Of all patients, including those with Do Not Resuscitate directives, receiving the dual-histamine receptor blockade for at least 48 h, the combination drug treatment resulted in a 16.4% rate of intubation, a 7.3% rate of intubation after a minimum of 48 h of treatment, a 15.5% rate of inpatient mortality, and 11.0 days duration of hospitalization. The drug combination exhibited beneficial reductions in inpatient mortality and symptom progression when compared to published reports of COVID-19 inpatients. Concomitant medications were assessed and hydroxychloroquine was correlated with worse outcomes.Conclusions: This physician-sponsored cohort study of cetirizine and famotidine provides proof-of-concept of a safe and effective method to reduce the progression in symptom severity, presumably by minimizing the histamine-mediated cytokine storm. Further clinical studies in COVID-19 are warranted of the repurposed offlabel combination of two historically-safe histamine receptor blockers.