Ortolani Claudio, Pastorello Elide A
Istituto Allergologico Lombardo. Casa Di Cura Ambrosiana, Cesano Boscone, Milano, Italy.
Unit of Allergy and Immunology, Università Degli Studi Di Milano, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy.
Clin Mol Allergy. 2020 Sep 9;18:17. doi: 10.1186/s12948-020-00132-7. eCollection 2020.
On June 30, 2020, the WHO reported over 10 millions of COVID-19 cases worldwide with over half a million deaths. In severe cases the disease progresses into an Acute Respiratory Distress Syndrome (ARDS), which in turn depends on an overproduction of cytokines (IL-6, TNFα, IL-12, IL-8, CCL-2 and IL1) that causes alveolar and vascular lung damage. Clearly, it is essential to find an immunological treatment that controls the "cytokine storm". In the meantime, however, it is essential to have effective antiviral and anti-inflammatory drugs available immediately.
PHARMACOLOGIC THERAPY FOR COVID-19: Hydroxychloroquine or chloroquine have been widely adopted worldwide for the treatment of SARS-CoV-2 pneumonia. However, the choice of this treatment was based on low quality of evidence, i.e. retrospective, non-randomized controlled studies. Recently, four large Randomized Controlled Trials (RCTs) have been performed in record time delivering reliable data: (1) the National Institutes of Health (NIH) RCT included 60 hospitals participating all over the world and showed the efficacy of remdesivir in reducing the recovery time in hospitalized adults with COVID-19 pneumonia; (2) three large RCTs already completed, for hydroxychloroquine, dexamethasone and Lopinavir and Ritonavir respectively. These trials were done under the umbrella of the 'Recovery' project, headed by the University of Oxford. The project includes 176 participating hospitals in the UK and was set up to verify the efficacy of some of the treatments used for COVID-19. These three 'Recovery' RCTs concluded definitely: (a) that treatment with hydroxychloroquine provides no benefits in patients hospitalized with COVID-19; (b) that treatment with dexamethasone reduced deaths by one-third in COVID-19 patients that were mechanically ventilated, and by one-fifth in patients receiving oxygen only; (c) that the combination of Lopinavir and Ritonavir is not effective in reducing mortality in COVID-19 hospitalized patients.
The results of these four large RCTs have provided sound indications to doctors for the treatment of patients with COVID-19 and prompted the correction of many institutional provisions and guidelines on COVID-19 treatments (i.e. FDA, NIH, UK Health Service, etc.). Even though a definitive treatment for COVID-19 has not yet been found, large RCTs stand as the Gold Standards for COVID-19 therapy and offer a solid scientific base on which to base treatment decisions.
2020年6月30日，世界卫生组织报告全球新冠肺炎病例超过1000万例，死亡人数超过50万。在重症病例中，该疾病会发展为急性呼吸窘迫综合征（ARDS），而这又取决于细胞因子（白细胞介素-6、肿瘤坏死因子α、白细胞介素-12、白细胞介素-8、趋化因子配体-2和白细胞介素-1）的过度产生，这些细胞因子会导致肺泡和肺部血管损伤。显然，找到一种控制“细胞因子风暴”的免疫疗法至关重要。然而，与此同时，立即提供有效的抗病毒和抗炎药物也至关重要。
羟氯喹或氯喹已在全球广泛用于治疗新型冠状病毒肺炎。然而，这种治疗方法的选择基于低质量的证据，即回顾性、非随机对照研究。最近，四项大型随机对照试验（RCT）在创纪录的时间内完成并提供了可靠数据：（1）美国国立卫生研究院（NIH）进行的随机对照试验有60家来自世界各地的医院参与，结果显示瑞德西韦对缩短新冠肺炎住院成人患者的康复时间有效；（2）三项大型随机对照试验已分别完成，分别针对羟氯喹、地塞米松以及洛匹那韦和利托那韦。这些试验是在牛津大学牵头的“康复”项目框架下进行的。该项目包括英国176家参与医院，旨在验证一些用于新冠肺炎的治疗方法的疗效。这三项“康复”随机对照试验得出明确结论：（a）羟氯喹治疗对新冠肺炎住院患者没有益处；（b）地塞米松治疗使接受机械通气的新冠肺炎患者死亡率降低三分之一，仅接受吸氧治疗的患者死亡率降低五分之一；（c）洛匹那韦和利托那韦联合使用对降低新冠肺炎住院患者的死亡率无效。
这四项大型随机对照试验的结果为医生治疗新冠肺炎患者提供了可靠依据，并促使许多机构对新冠肺炎治疗的规定和指南（如美国食品药品监督管理局、美国国立卫生研究院、英国国民医疗服务体系等）进行了修正。尽管尚未找到针对新冠肺炎的确定性治疗方法，但大型随机对照试验是新冠肺炎治疗的金标准，为治疗决策提供了坚实的科学基础。
