托珠单抗在新型冠状病毒治疗中的临床药学指引

2019年12月末国在内外相继出现新型冠状病毒肺炎（corona virus disease-19,COVID-19）病例。有专家指出COVID-19感染者病情的突然加重可能和"细胞因子风暴"（炎症风暴）有关,目前并无针对于此的特效药。托珠单抗为IL-6拮抗剂,很可能阻断细胞因子风暴进而阻止COVID-19患者向重症转变。但因证据有限,临床工作者在实践中面临着许多问题,如缺乏托珠单抗在一般和特殊人群中的详细用药指导,推荐方案的依据不明确等。本文就该药物的基本信息、国内外研究现状、相互作用、不良反应等方面进行概述,以期为临床用药提供参考。     

托珠单抗的临床应用概述及治疗新型冠状病毒肺炎的可行性探索

摘要：托珠单抗是免疫球蛋白Ig G1亚型的重组人源化抗人白细胞介素6(IL-6)受体单克隆抗体,临床用于治疗类风湿关节炎、血管炎等疾病。现有研究证明IL-6等细胞因子与新型冠状病毒肺炎(COVID-19)病情恶化相关。本文系统介绍托珠单抗的临床治疗特点、安全性、药物相互作用以及在COVID-19治疗中的应用。     

新型冠状病毒肺炎相关儿童多系统炎症综合征临床诊治研究进展

虽然目前儿童总体新型冠状病毒肺炎(corona virus disease 2019,COVID-19)感染率较低,病情相对轻微,罕见重症病例,病死率显著低于成人,但部分COVID-19可能诱发患儿细胞因子风暴,导致儿童多系统炎症综合征(multisystem inflammatory syndrome in children,MIS-C)。MIS-C病情危重,进展迅速,但若早期明确诊断,及时正确干预,预后则良好。本文归纳了近期有关MIS-C性质、发病机制、流行病学、临床特征及诊治要点的文献,以供临床参考。     

新型冠状病毒肺炎（COVID-19）合并糖尿病患者的药学服务和监护策略

新型冠状病毒肺炎（COVID-19）来势汹汹,而合并其他基础疾病的COVID-19患者更属于高危人群。血糖控制水平直接影响身体免疫应答和状态,其导致的免疫力低下状态极易增加患病几率,已感染的患者则更易加重感染,进一步继发细胞因子风暴。因此COVID-19合并2型糖尿病患者在疫情期间需要在治疗新型冠状病毒感染的同时做好血糖控制和管理。结合糖尿病合理用药相关研究,对COVID-19现有临床数据特征进行分析,探讨COVID-19合并糖尿病患者的药学实践模式和用药监护策略,以期对这类患者提供更为优化合理的用药方案,改善临床用药水平。     

抗新型冠状病毒肺炎药物靶点的研究进展

自2019年12月以来,新型冠状病毒(SARS-CoV-2)在国内爆发,并且目前已在日本和韩国等地进入高发态势,该病毒导致的新型冠状病毒肺炎(COVID-19)已造成多人感染并有2500余人死亡,世界卫生组织于2020年1月31日宣布疫情为"国际关注的突发公共卫生事件"。抗新型冠状病毒药物是阻止病毒传播以及在宿主体内复制从而引起肺炎的有力武器。综述了抗COVID-19药物靶点以及相应的药物和候选物的研究进展。     

浅谈儿童新型冠状病毒感染的核酸检测

2019年12月首发于湖北省武汉市的新型冠状病毒肺炎(corona virus disease 2019,COVID-19)疫情火速蔓延,并迅速扩散,2020年2月11日国际病毒学分类委员会正式将新型冠状病毒命名为严重急性呼吸综合征冠状病毒2型(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)[1]。2020年2月2日,国家卫生健康委员会发布的《关于做好儿童和孕产妇新型冠状病毒感染的肺炎疫情防控工作的通知》中明确指出,儿童和孕产妇是COVID-19的易感人群。为了更好地指导和规范全国COVID-19的诊治工作,国家卫生健康委员会发布的《新型冠状病毒肺炎诊疗方案(试行第六版)》将核酸检测和基因测序作为COVID-19的确诊依据。     

新型冠状病毒肺炎潜在的发病机制及间充质干细胞治疗作用的研究进展

摘要：新型冠状病毒肺炎（COVID-19）传染性强,重型患者病死率高,其发病机制尚不明确,缺乏特异性治疗方法。细胞因子风暴、免疫应答失衡可能是新型冠状病毒感染导致急性呼吸窘迫综合征（ARDS）及多脏器功能衰竭（MOF）甚至死亡的病生理基础。间充质干细胞（MSC）凭借其免疫调节、组织修复及抗纤维化等特性在COVID-19重症患者的救治中初显疗效,具有良好的临床应用前景。本文就COVID-19潜在的致病机制、MSC对COVID-19治疗的可能机制及在治疗中的应用进行综述,以期为临床治疗提供参考。     

新型冠状病毒肺炎患者肝损伤的原因及保肝药物治疗

新型冠状病毒（SARS-CoV-2）感染引起的新型冠状病毒肺炎（COVID-19）患者临床表现出不同程度的肝损伤。一系列研究表明细胞因子风暴、SARS-CoV-2病毒所致的胆管细胞损伤以及药物性肝毒性可以诱导继发性肝损伤,对不同因素所致的肝损伤的机制以及保肝药物治疗进行综述,以期为后续深入揭示该方面的研究提供参考支持。     

逍遥散治疗糖尿病的网络药理学分析

新型冠状病毒肺炎（COVID-19）已成为全球性的重大疫情,中医药在重大疫情防控过程中发挥了重要作用。基于对COVID-19的认识以及中医药防控路径,以疏风解毒胶囊为例,概述了中医药针对早期干预、阻断病情进展、改善症状、抗炎免疫、抑制“细胞因子风暴”以及辨证分型、发挥配伍优势等方面的思路和研究实践,并提出中药新药研发科学模式建立的设想。     

新型冠状病毒肺炎抗病毒药物的治疗现状

目的:探究新型冠状病毒肺炎抗病毒药物的治疗现状。方法:2019年12月开始,新型冠状病毒(以下简称2019-nCoV)感染引起的新型冠状病毒肺炎(COVID-19)病例在国内陆续被发现,并呈暴发趋势;2020年3月3日,国家卫生健康委员会发布的《新型冠状病毒肺炎诊疗方案(试行第7版)》中,治疗COVID-19患者的抗病毒药物主要有干扰素-α2b、洛匹那韦/利托那韦、利巴韦林、磷酸氯喹和阿比多尔。结果与结论:通过检索相关文献并结合现有临床治疗证据,评价与分析了抗病毒药物的治疗现状和优缺点,以及药学监护。     

Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality

Since December 2019, a viral pneumonia, named coronavirus disease 2019 (COVID-19), from Wuhan, China, has swept the world. Although the case fatality rate is not high, the number of people infected is large and there is still a large number of patients dying. With the collation and publication of more and more clinical data, a large number of data suggest that there are mild or severe cytokine storms in severe patients, which is an important cause of death. Therefore, treatment of the cytokine storm has become an important part of rescuing severe COVID-19 patients. Interleukin-6 (IL-6) plays an important role in cytokine release syndrome. If it is possible to block the signal transduction pathway of IL-6, it is expected to become a new method for the treatment of severe COVID-19 patients. Tocilizumab is an IL-6 receptor (IL-6R) blocker that can effectively block the IL-6 signal transduction pathway and thus is likely to become an effective drug for patients with severe COVID-19.     

Baricitinib,a drug with potential effect to prevent SARS-COV-2 from entering target cells and control cytokine storm induced by COVID-19

In December 2019, a novel coronavirus pneumonia (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suddenly broke out in China and rapidly spread all over the world. Recently, a cell surface protein, known as angiotensin-converting enzyme II (ACE2), has been identified to be involved in receptor-mediated endocytosis for SARS-CoV-2 entry to the cells. Many studies have reported the clinical characteristics of COVID-19: sudden deterioration of disease around 1–2 weeks after onset; much lower level of lymphocytes, especially natural killer (NK) cells in peripheral blood; extremely high pro-inflammatory cytokines and C reactive protein (CRP). About 15.7% of patients develop severe pneumonia, and cytokine storm is an important factor leading to rapid disease progression. Currently, there are no specific drugs for COVID-19 and the cytokine storm it causes. Baricitinib intracellularly inhibits the proinflammatory signal of several cytokines by suppressing Janus kinase (JAK) JAK1/JAK2. It has been demonstrated clinical benefits for the patients with rheumatoid arthritis (RA), active systemic lupus erythematosus and atopic dermatitis with good efficacy and safety records. Baricitinib is expected to interrupt the passage and intracellular assembly of SARS-CoV-2 into the target cells mediated by ACE2 receptor, and treat cytokine storm caused by COVID-19. Several clinical trials are currently investigating the drug, and one of which has been completed with encouraging results. In this paper, we will elaborate the role of cytokine storm mediated by JAK-STAT pathway in severe COVID-19, the possible mechanisms of baricitinib on reducing the viral entry into the target cells and cytokine storm, the key points of pharmaceutical care based on the latest research reports, clinical trials progress and drug instruction from the US FDA, so as to provide reference for the treatment of severe COVID-19.     

细胞因子风暴及其治疗方法的研究进展

由致病因素激活人体先天性和适应性免疫反应所导致的炎症反应是人体的第一道防线。然而,某些病原体(如SARS-CoV-2、SARS-CoV、MERS-CoV和登革热病毒等)会在宿主内引发威胁生命的"细胞因子风暴",进而引起多器官功能衰竭并最终导致死亡。一些内源性消炎调控因子,如消退素、脂氧素、环氧不饱和脂肪酸等,可以调节组织损伤而不破坏有益的炎症应答,为炎性疾病的治疗提供了新途径。其中可溶性环氧化物水解酶(soluble epoxide hydrolase,sEH)抑制剂可以稳定环氧二十碳三烯酸(epoxyeicosatrienoic acids,EETs),通过多种机制调控细胞因子,重塑机体致炎/抗炎平衡,从而发挥消退炎症的作用,有望成为治疗细胞因子风暴的新靶点。本文综述了细胞因子风暴的病理机制以及目前潜在的治疗方法,希望为相关疾病的诊断和治疗提供新的思路。     

新冠肺炎患者救治及康复中的中药治疗思考

根据近期揭示的新型冠状病毒感染的肺炎的病理改变,基于国家医保政策及中药专业实践,建议临床救治中尽早使用活血化瘀类中药以保护呼吸膜及呼吸道,使用以百令片（胶囊）为代表的虫草菌发酵制剂来抑制细胞因子风暴,以减轻肺纤维化及肾损害。     

Exosomes: Emerging implementation of nanotechnology for detecting and managing novel corona virus- SARS-CoV-2

The spread of SARS-CoV-2 as an emerging novel coronavirus disease (COVID-19) had progressed as a worldwide pandemic since the end of 2019. COVID-19 affects firstly lungs tissues which are known for their very slow regeneration. Afterwards, enormous cytokine stimulation occurs in the infected cells immediately after a lung infection which necessitates good management to save patients. Exosomes are extracellular vesicles of nanometric size released by reticulocytes on maturation and are known to mediate intercellular communications. The exosomal cargo serves as biomarkers in diagnosing various diseases; moreover, exosomes could be employed as nanocarriers in drug delivery systems. Exosomes look promising to combat the current pandemic since they contribute to the immune response against several viral pathogens. Many studies have proved the potential of using exosomes either as viral elements or host systems that acquire immune-stimulatory effects and could be used as a vaccine or drug delivery tool. It is essential to stop viral replication, prevent and reverse the massive storm of cytokine that worsens the infected patients’ situations for the management of COVID-19. The main benefits of exosomes could be; no cells will be introduced, no chance of mutation, lack of immunogenicity and the damaged genetic material that could negatively affect the recipient is avoided. Additionally, it was found that exosomes are static with no ability for in vivo reproduction. The current review article discusses the possibilities of using exosomes for detecting novel coronavirus and summarizes state of the art concerning the clinical trials initiated for examining the use of COVID-19 specific T cells derived exosomes and mesenchymal stem cells derived exosomes in managing COVID-19.     

Calming the cytokine storm of COVID-19 through inhibition of JAK2/STAT3 signaling

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the unprecedented COVID-19 pandemic, which has infected over 178 million people worldwide. Even with new vaccines, global herd immunity will not be reached soon. New cases and viral variants are being reported at an alarming rate. Effective antiviral treatment is urgently needed. Patients with severe COVID-19 suffer from life-threatening respiratory failure due to acute respiratory distress syndrome in their lungs, a leading cause of COVID-19 mortality. This lung hyper-inflammation is induced by virus-caused massive tissue damage that is associated with uncontrolled cytokine release, known as a cytokine storm, through JAK/STAT signaling pathways. Here, we review the FDA-approved JAK inhibitors that are being clinically evaluated and repurposed for the treatment of patients with severe COVID-19 by calming SARS-CoV-2 infection.