世界上目前正使用这些方法治疗COVID-19

宾夕法尼亚大学佩雷尔曼医学院的研究团队在PubMed,BioRxiv,MedRxiv和ChinaXiv中搜索了2019年12月1日至2020年3月27日期间发表的COVID-19患者治疗方法的文章,对记载的每种方法进行了分类,发现目前已经报告了100多种不同的非处方或实验性疗法的使用。这项研究结果目前发表在MedRxiv上。


研究小组审阅了来自世界各地的约2706篇发表的论文,从中选择了155项符合纳入标准的研究,包括来自14个不同国家和地区(阿富汗、中国、法国、德国、意大利、日本、韩国、苏格兰、新加坡、西班牙、台湾、英国、美国和越南)的9152名患者,其中女性占45.4%,住院患者占98.3%,平均年龄为44.4岁(SD 21.0)。纳入研究文献标准:所有报告COVID-19患者使用任何治疗方法的研究。排除标准:没有基于参与者、治疗、结果、研究设计或研究时间的研究。在这些治疗中,涉及到了115种不同的药物的使用。使用频率最高的药物类别是抗病毒药物(N=6547,71.5%)、其次是抗生素(N=4263,46.6%)和皮质类固醇(N=2392,26.1%)。在115种已报告的药物中,使用频率最高的是洛比那韦/利托那韦联合用药(N=2 0 0 0,21.9%),临床有意义反应(症状完全缓解或出院)时间为11.7天(1.09天)。其次是干扰素α/β(N=1767,19.3%)和免疫球蛋白(N=1049,11.5%)。


由于SARS-CoV-2与纤毛支气管上皮细胞上的ACE2受体结合,进入这些细胞进行病毒复制和在气道和全身传播。免疫反应减弱的患者可能难以控制COVID-19,而具有高免疫反应的患者会出现急性呼吸窘迫综合征、感染性休克和由细胞因子风暴引起的多器官系统衰竭。这项研究中确定的治疗方法具有如下几种潜在的作用机制。1,限制进入纤毛支气管上皮细胞(N-乙酰半胱氨酸、肝素、甲普拉珠单抗、乌米诺韦、羟氯喹);2,抑制病毒复制(干扰素-α/β、利托那韦/洛吡那韦、奥司他韦、更昔洛韦、利巴韦林、法维匹拉韦、瑞德西韦、达诺普利);3,通过增加SARS-CoV-2特异性抗体(恢复期血浆)或非特异性抗体(IVIg、胸腺五肽),通过抗体介导的中和来防止病毒传播;4,用免疫刺激剂(干扰素-α/β、胸腺肽-α-1)增强减弱的免疫反应;5,用免疫抑制剂(皮质类固醇、羟氯喹、静脉注射免疫球蛋白)预防高免疫反应;6,控制高免疫反应(皮质类固醇、托西珠单抗)。这些药物可能通过预防继发感染、控制炎症、调节微生物群或直接起到抗病毒作用。到这项研究截止为止,最受关注的治疗方法包括羟氯喹、阿奇霉素、有效对抗类似病毒(SARS、MERS、流感)的抗病毒药物、恢复期血浆和细胞因子风暴导向疗法。


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Figure 1. 最常使用的治疗类药物。(A)最常使用的治疗药物类别。(B)报告在9,152名患者中使用最频繁的药物。

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Figure 2. 用于治疗COVID19的潜在机制


这项研究发现目前正在使用的药物比出现在头条新闻的药物要多很多。但所有药物都仍然需要在临床试验中进行严格测试,以了解是否它是有效和安全的。这项工作的目的不是指向最有效的治疗方法,而是为可能的进一步研究提供资源。


原文阅读



Background 


The emergence of SARS-CoV-2/2019 novel coronavirus (COVID19) has created a global pandemic with no approved treatments or vaccines. Repurposing existing drugs and rapidly launching clinical trials present the greatest near-term opportunities for mitigating COVID19s impact. Many treatments have already been administered to COVID19 patients but have not been systematically evaluated. We performed a systematic literature review to identify and assess all treatments reported to be administered to COVID19 patients. Methods We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID19 patients published between Dec 1, 2019 and Mar 27, 2020. All studies reporting treatments were included. Data for each paper were manually extracted by two independent extractors. Outcomes included the duration from drug administration to clinically-meaningful response (complete symptom resolution or hospital discharge). Data were analysed descriptively. Results We identified 2,706 articles from single patient case reports to single-centre interventional studies. Of these, 155 studies met inclusion criteria, comprising 9,152 patients from 14 different countries. The cohort was 45.4% female and 98.3% hospitalised, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a response time of 11.7 (1.09) days. Discussion A large number of treatments have been administered to the first 9,152 reported cases of COVID19. Further work is needed to prioritise drugs for investigation in well-controlled clinical trials and treatment protocols.


Treatments 


used to date have been proposed to work by: 1) limiting entry into ciliated bronchial epithelial cells (N-acetylcysteine, heparin, meplazumab, umifenovir, hydroxychloroquine), 2) inhibiting viral replication (interferon-α/β, ritonavir/lopinavir, oseltamivir, ganciclovir, ribavirin, favipiravir, remdesivir, danoprevir), 3) preventing viral dissemination via antibody-mediated neutralization by increasing SARS-CoV-2-specific antibodies (convalescent plasma) or non-specific antibodies (IVIg, thymopentin), 4) strengthening a weakened immune response with immunostimulants (interferon-α/β, thymosin-α-1), 5) preventing a hyper-immune response with immunosuppressants (corticosteroids, hydroxychloroquine, IVIg), or 6) controlling a hyper-immune response (corticosteroids, tocilizumab). A number of antibiotics were also given to COVID19 patients. These drugs may be acting by preventing secondary infections, controlling inflammation, modulating the microbiome, or directly having an anti-viral effect; they may also have had no effect.


参考文献


Fajgenbaum DC, Khor JS, Gorzewski A, Tamakloe M, Powers V, Kakkis J, Repasky M, Taylor A, Beschloss A and Hernandez-Miyares L, et al: Treatments administered to the first 9,152 reported cases of COVID19: a systematic review. medRxiv: 2020-2025, 2020.




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