Hydroxychloroquine and COVID-19: a Rheumatologist's Take on the Lessons Learned.
Hydroxychloroquine and COVID-19: a Rheumatologist's Take on the Lessons Learned.
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DOI：
10.1007/s11882-020-00983-9
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发表时间：
2021-01-21
影响因子：
5.5
通讯作者：
Rogers JL
中科院分区：
文献类型：
--
作者：
Udupa A;Leverenz D;Balevic SJ;Sadun RE;Tarrant TK;Rogers JL
这篇综述从风湿学家的角度讲述了羟氯喹及其作为对抗新型SARS-CoV-2病毒的治疗策略迅速成为家喻户晓的名称的故事。本文综述了羟氯喹作为免疫调节剂和抗病毒药物的历史、作用机制、药代动力学、治疗应用和安全性概况。它还总结了开展和评估羟氯喹用于抗新冠肺炎感染的主要研究。最近的文献质疑了长期以来的教条，即内溶酶体碱化是羟氯喹的主要作用方式。目前对羟基氯喹在风湿和病毒疾病中的疗效的多个潜在机制的持续不确定性导致了在治疗新冠肺炎方面的天然探索途径。总的来说，文献不支持使用羟氯喹来治疗或预防SARS-CoV-2病毒的感染。这至少在一定程度上是由于患者之间的羟氯喹药代动力学差异很大，而且在不遇到不可接受的毒性的情况下很难达到足够的羟氯喹目标组织浓度。羟基氯喹仍然是风湿病的常规处方、耐受性好、有效和低成本的治疗方法。它的治疗多功能性导致了它经常被用于其他疾病，最近的一次是作为对SARS-CoV-2病毒的研究性治疗。尽管总体上是负面的发现，但羟基氯喹抗新冠肺炎感染的密集研究提高了我们对羟基氯喹在自身免疫性疾病和其他疾病中如何发挥作用的总体理解。
Told from the viewpoint of rheumatologists, this review tells the story of hydroxychloroquine and its swift ascent to become a household name as a therapeutic strategy against the novel SARS-CoV-2 virus. This review describes the history, mechanisms, pharmacokinetics, therapeutic applications, and safety profile of hydroxychloroquine as an immunomodulatory and antiviral agent. It also summarizes the major studies that launched and assessed the use of hydroxychloroquine against COVID-19 infection. More recent literature calls into question the long-held dogma that endolysosomal alkalinization is the primary mode of action of hydroxychloroquine. Ongoing uncertainty about the multiple potential mechanisms contributing to the therapeutic effect of hydroxychloroquine in rheumatic and viral disease led to a natural avenue for exploration in the treatment of COVID-19. Taken as a whole, the literature does not support utilizing hydroxychloroquine to treat or prevent infection from the SARS-CoV-2 virus. This is, at least in part, due to the wide variability in hydroxychloroquine pharmacokinetics between patients and difficulty achieving adequate target tissue concentrations of hydroxychloroquine without encountering unacceptable toxicities. Hydroxychloroquine continues to be a routinely prescribed, well-tolerated, effective, and low-cost treatment for rheumatic disease. Its therapeutic versatility has led to frequent repurposing for other conditions, most recently as an investigative treatment against the SARS-CoV-2 virus. Despite overall negative findings, the intense study of hydroxychloroquine against COVID-19 infection has enhanced our overall understanding of how hydroxychloroquine operates in autoimmune disease and beyond.
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DOI：
10.1111/tra.12617
发表时间：
2019-01
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Lamming DW;Bar-Peled L
通讯作者：
Bar-Peled L
影响因子：
3.9
作者：
Balevic, Stephen J.;Hornik, Christoph P.;Cohen-Wolkowiez, Michael
通讯作者：
Cohen-Wolkowiez, Michael
影响因子：
158.5
作者：
Boulware, David R.;Pullen, Matthew F.;Hullsiek, Kathy H.
通讯作者：
Hullsiek, Kathy H.
影响因子：
158.5
作者：
Cavalcanti, A. B.;Zampieri, F. G.;Berwanger, O.
通讯作者：
Berwanger, O.
DOI：
10.1016/j.ijantimicag.2020.105949
发表时间：
2020-07-01
影响因子：
10.8
作者：
Gautret, Philippe;Lagier, Jean-Christophe;Raoult, Didier
通讯作者：
Raoult, Didier