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。     

新型冠状病毒肺炎疫苗研究进展概述

摘要：新型冠状病毒（SARS-CoV-2）自发现以来就引起了人们的广泛关注,其感染引发的肺炎（COVID-19）疫情在多国发生,SARS-CoV-2对全球公共卫生安全造成了巨大威胁。目前COVID-19病理机制尚不明确,尚未有治疗COVID-19的特效药物,科学认识SARS-CoV-2和尽快研制针对该病毒的有效疫苗成为近期的研究热点,部分疫苗已进入Ⅲ临床试验阶段。本文主要从SARS-CoV-2的病原学特性、感染机制及其疫苗研究现状等方面进行综述,以便为其后续研究及防治提供参考。     

ACE2与新型冠状病毒肺炎的心肾损伤

由新型冠状病毒(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染引起的新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19)不仅可以诱发典型的呼吸系统疾病,也能导致心肾系统等相关疾病。SARS-CoV-2的受体为血管紧张素转换酶2(Angiotensin-converting enzyme 2,ACE2)。本文通过阐述ACE2在心脏和肾脏中的作用,分析SARS-CoV-2感染引起患者心肾损伤的可能机制,为临床治疗COVID-19及研发抗SARS-CoV-2药物提供参考依据。     

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。     

氯喹抗冠状病毒的作用及其安全性研究进展

冠状病毒作为一种人畜共患病毒,可引起肺部感染,严重的会引起死亡甚至肆虐传播。2019年12月底陆续出现了新型冠状病毒——严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染引起的新型冠状病毒肺炎(COVID-19)患者。针对冠状病毒,目前并无特效药。氯喹作为一种经典抗疟药,可通过改变内吞体pH值、自噬反应以及改变病毒包膜的糖基化模式等途径发挥抗病毒效应。在细胞水平上,氯喹对SARS-CoV、中东呼吸综合征冠状病毒(MERS-CoV)和SARS-CoV-2均有抑制作用。近期临床研究初步表明,氯喹可以提高COVID-19患者成功救治率,改善预后。由于氯喹副作用较多,近些年已经较少用于临床,氯喹用于治疗COVID-19的安全性需要深入评估。本文结合氯喹的药理学特点,针对氯喹抗冠状病毒感染的作用及其安全性作一概述,以期为其临床合理应用提供参考。     

新型冠状病毒肺炎相关心血管疾病风险及其治疗中的药学监护

新型冠状病毒肺炎(COVID-19)是一种由新型冠状病毒(SARS-CoV-2)引起的传染性疾病。多项研究显示,SARS-CoV-2感染除了导致病毒性肺炎,还可能产生潜在的心血管危害,增加已有心血管疾病患者潜在的并发症和死亡风险。其发生机制尚不清楚,可能由于SARS-CoV-2通过血管紧张素转化酶2(ACE2)途径侵入人体,ACE2在心血管系统高表达相关,也可能与炎症风暴、病毒性心肌炎、COVID-19治疗药物有关。COVID-19治疗药物也存在潜在的心脏毒性,可导致房室传导阻滞、心肌梗死、PR间期延长、QT间期延长、尖端扭转型室性心动过速、结构性心脏疾病、心脏传导异常等心脏毒性,故缺血性心脏病、房室传导阻滞、心律失常、未纠正的低血钾患者慎用。COVID-19治疗药物与心血管疾病药物也具有潜在的药物相互作用。笔者通过收集近期国内外的相关文献作简要综述,为一线临床工作者开展药学监护提供参考。     

从1例儿童新型冠状病毒普通型肺炎浅析抗病毒药物临床应用

摘要：儿童是呼吸道病毒的易感人群,儿童新型冠状病毒肺炎（COVID-19）会存在新型冠状病毒（SARS-CoV-2）与其他常见呼吸道病毒混合感染的复杂情况。目前尚无确认有效的抗SARS-CoV-2药物,因此国家诊疗方案中推荐的药物用于儿童仍需谨慎。为提高抗病毒药物在COVID-19儿童患者中应用的安全性,本文结合1例儿童COVID-19普通型病例的诊治过程,剖析该病例的抗病毒药物治疗方案,建议抗病毒药物在非重型儿童COVID-19病例的应用中需要特别关注用法用量、给药途径、疗程,以及药品不良反应的密切监测和及时处理,供儿科临床参考。     

新型冠状病毒肺炎与血管紧张素转化酶2的研究现状

自2019年底起，新型冠状病毒肺炎（Coronavirus disease 2019，COVID-19）病例席卷全球。该病毒为β属冠状病毒，基因特征与严重急性呼吸综合征冠状病毒（Severe Acute Respiratory Syndrome Coronavirus，SARS-CoV）有较高相似性，被命名为2019新型冠状病毒（2019 Novel Coronavirus，2019-nCoV）或严重急性呼吸综合征冠状病毒-2（SARS-CoV-2），主要通过棘突蛋白介导与宿主血管紧张素转化酶2（angiotensin-converting enzyme 2，ACE2）受体结合侵犯人体。ACE2与COVID-19感染密切相关，既是SARS-CoV-2感染人体的关键靶点，ACE2表达多寡也是影响COVID-19患者疾病严重程度和死亡率的重要因素。因此靶向ACE2和肾素-血管紧张素系统（renin-angiotensin system，RAS）的诸多上市药物和在研药物，如血管紧张素转化酶抑制剂（angiotensin-converting enzyme inhibitor，ACEI）、血管紧张素受体拮抗剂（angiotensin receptor blocker，ARB）、重组人ACE2、Ⅱ型跨膜丝氨酸蛋白酶（type II transmembrane serine proteases，TMSPSS2）抑制剂、特异性中和抗体等都有可能成为治疗COVID-19的可行策略。此外，依据现有证据并不建议合并高血压的轻症COVID-19确诊病例或疑似病例轻易停用ACEI/ARB，以免造成血压波动。     

儿童新型冠状病毒肺炎药物治疗研究进展

新型冠状病毒(severe acute respiratory syndrome corona virus,SARS-CoV)-2感染在全球暴发,目前尚无明确有效的抗病毒药物治疗SARS-CoV-2感染。结合以往临床一线治疗新型冠状病毒肺炎(corona virus disease 2019,COVID-19)的经验,从核苷类似物、蛋白酶抑制剂等抗病毒药物、免疫相关药物及恢复期血浆治疗等方面,本文就儿童COVID-19药物治疗研究进展作一综述。     

新型冠状病毒感染治疗药物研究进展

新型冠状病毒（SARS-CoV-2）疫情自发生以来,给全球公共卫生安全和经济带来了巨大冲击。如今,全球抗疫已取得阶段性成果,SARS-CoV-2疫情也不再构成“国际关注的突发公共卫生事件”,但并不意味着SARS-Co V-2流行的结束。SARS-CoV-2感染（COVID-19）治疗药物的研发不仅不应停止,还需要更进一步的探索。简介SARS-Co V-2的感染机制,并对基于病毒和宿主细胞的靶标的COVID-19治疗药物研究进展进行综述。     

Coronavirus disease 2019 (COVID-19): current status and future perspectives

Coronavirus disease 2019 (COVID-19) originated in the city of Wuhan, Hubei Province, Central China, and has spread quickly to 72 countries to date. COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [previously provisionally known as 2019 novel coronavirus (2019-nCoV)]. At present, the newly identified SARS-CoV-2 has caused a large number of deaths with tens of thousands of confirmed cases worldwide, posing a serious threat to public health. However, there are no clinically approved vaccines or specific therapeutic drugs available for COVID-19. Intensive research on the newly emerged SARS-CoV-2 is urgently needed to elucidate the pathogenic mechanisms and epidemiological characteristics and to identify potential drug targets, which will contribute to the development of effective prevention and treatment strategies. Hence, this review will focus on recent progress regarding the structure of SARS-CoV-2 and the characteristics of COVID-19, such as the aetiology, pathogenesis and epidemiological characteristics.     

T淋巴细胞亚群在新型冠状病毒肺炎诊疗中的临床意义

摘要：新型冠状病毒（SARS-CoV-2）以其强传染力通过呼吸道飞沫或密切接触广泛传播。新型冠状病毒肺炎 （COVID-19）患者以发热和（或）咳嗽为首发症状,部分患者迅速进展为重症,严重威胁患者生命。免疫紊乱是 COVID-19 重症化发展的重要因素,本文通过总结 COVID-19 与 T 淋巴细胞亚群的关系,阐述 T 淋巴细胞亚群对 COVID-19病情监测、治疗指导的临床意义,建议病程中动态监测T淋巴细胞亚群水平,预判病情并积极干预,以期为 临床防治免疫炎症级联反应、逆转重症进展提供指导     

Current approaches used in treating COVID-19 from a molecular mechanisms and immune response perspective

Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared by the World Health Organization (WHO) as a global pandemic on March 11, 2020. SARS-CoV-2 targets the respiratory system, resulting in symptoms such as fever, headache, dry cough, dyspnea, and dizziness. These symptoms vary from person to person, ranging from mild to hypoxia with acute respiratory distress syndrome (ARDS) and sometimes death. Although not confirmed, phylogenetic analysis suggests that SARS-CoV-2 may have originated from bats; the intermediary facilitating its transfer from bats to humans is unknown. Owing to the rapid spread of infection and high number of deaths caused by SARS-CoV-2, most countries have enacted strict curfews and the practice of social distancing while awaiting the availability of effective U.S. Food and Drug Administration (FDA)-approved medications and/or vaccines. This review offers an overview of the various types of coronaviruses (CoVs), their targeted hosts and cellular receptors, a timeline of their emergence, and the roles of key elements of the immune system in fighting pathogen attacks, while focusing on SARS-CoV-2 and its genomic structure and pathogenesis. Furthermore, we review drugs targeting COVID-19 that are under investigation and in clinical trials, in addition to progress using mesenchymal stem cells to treat COVID-19. We conclude by reviewing the latest updates on COVID-19 vaccine development. Understanding the molecular mechanisms of how SARS-CoV-2 interacts with host cells and stimulates the immune response is extremely important, especially as scientists look for new strategies to guide their development of specific COVID-19 therapies and vaccines.     

法匹拉韦治疗新冠肺炎临床研究进展

新型冠状病毒肺炎(COVID-19)疫情在全球大流行,临床上迫切需要特异性抗病毒治疗药物。对已批准上市或正在临床开发的药物开展重定位研究是针对突发疫情快速寻找潜在治疗药物最为快速和高效的策略。法匹拉韦是一种广谱抗RNA病毒药物,在日本和中国已批准上市用于治疗流感,其作为抗新型冠状病毒感染的潜在药物,全球多个国家正在开展相关临床试验,初步的结果令人鼓舞。本文主要综述在中国、日本、俄罗斯和印度等国家开展的法匹拉韦单用或联合其他药物治疗COVID-19的临床试验,考察用药剂量、试验设计、药物有效性和安全性等。研究结果显示,法匹拉韦在针对COVID-19轻症和中症患者的治疗中,能够有效提高患者病毒RNA清除率或改善临床恢复率,且表现出良好的安全性。本文对法匹拉韦治疗COVID-19临床研究进展进行总结,为其在抗COVID-19治疗中的应用提供参考。     

Remdesivir: Review of Pharmacology,Pre-clinical Data,and Emerging Clinical Experience for COVID-19

The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created an urgent need for effective antivirals. Remdesivir (formerly GS-5734) is a nucleoside analogue pro-drug currently being evaluated in COVID-19 clinical trials. Its unique structural features allow high concentrations of the active triphosphate metabolite to be delivered intracellularly and it evades proofreading to successfully inhibit viral RNA synthesis. In pre-clinical models, remdesivir has demonstrated potent antiviral activity against diverse human and zoonotic β-coronaviruses, including SARS-CoV-2. In this article, we critically review available data on remdesivir with an emphasis on biochemistry, pharmacology, pharmacokinetics, and in vitro activity against coronaviruses as well as clinical experience and current progress in COVID-19 clinical trials.     

Two important controversial risk factors in SARS-CoV-2 infection: Obesity and smoking

The effects of obesity and smoking in the coronavirus disease 2019 (COVID-19) pandemic remain controversial. Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system (RAS), is the human cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. ACE2 expression increases on lung alveolar epithelial cells and adipose tissue due to obesity, smoking and air pollution. A significant relationship exists between air pollution and SARS-CoV-2 infection, as more severe COVID-19 symptoms occur in smokers; comorbid conditions due to obesity or excess ectopic fat accumulation as underlying risk factors for severe COVID-19 strongly encourage the virus/ACE2 receptor-ligand interaction concept. Indeed, obesity, air pollution and smoking associated risk factors share underlying pathophysiologies that are related to the Renin-Angiotensin-System in SARS-CoV-2 infection. The aim of this review is to emphasize the mechanism of receptor-ligand interaction and its impact on the enhanced risk of death due to SARS-CoV-2 infection.     

二肽基肽酶4及其抑制剂在新型冠状病毒肺炎防治中的研究进展

新型冠状病毒肺炎(COVID-19)全球大流行给世界健康造成巨大威胁,然而到目前为止尚没有临床证实有效的治疗方法。最近研究显示二肽基肽酶4(DPP4)可能是新型冠状病毒的功能受体,然而DPP4是否直接参与新型冠状病毒与靶细胞的黏附与感染,抑制或者调节DPP4的表达与活性能否阻止COVID-19的发生发展尚需要进一步研究。以往研究显示DPP4抑制剂具有抗炎和抗纤维化作用,因此推测DPP4抑制剂可能具有抑制COVID-19患者高炎症反应状态、改善患者肺纤维化的作用,尚需临床试验加以证实。     

The absence of coronavirus in expressed prostatic secretion in COVID-19 patients in Wuhan city

Due to the cellular entry of the novel coronavirus (SARS-CoV-2) modulated by angiotensin converting enzyme 2 (ACE2), the ACE2 bearing prostate is therefore hypothesized as a susceptible organ to COVID-19. To delineate whether the pathogenic SARS-CoV-2 of the coronavirus disease (COVID-19) could be detected in the expressed prostatic secretion (EPS), a total of ten male patients with confirmed COVID-19 were recruited. All patients were stratified into two groups: one group with positive nasopharyngeal swabbing SARS-CoV-2 within 3 days of the EPS taken day (PNS group, n = 3) and the other group with previously positive nasopharyngeal swabbing SARS-CoV-2 but turned negative before the taken day (PNNS group, n = 7). The COVID-19 patients showed elevated inflammatory indictors, i.e. C-reaction protein (3.28 (1.14, 33.33) mg/L), erythrocyte sedimentation rate (22.50 (8.00, 78.50) mm/h), and interleukin-6 (6.49 (4.96, 21.09) pg/ml). Serum IgM against SARS-CoV-2 was only positive in the PNS group, whereas serum IgG was positive for all patients. Furthermore, our data showed for the first time that none of the COVID-19 patients had positive SARS-CoV-2 RNA in EPS. To this end, this study found the negativity of SARS-CoV-2 in EPS and possibly exclude the sexual transmission of COVID-19.     

Immune system response during viral Infections: Immunomodulators,cytokine storm (CS) and Immunotherapeutics in COVID-19

Coronaviruses are non-segmented and single stranded positive-sense RNA (+ssRNA) viruses. To date, 06 human coronaviruses (HCoVs) are reported; α-CoVs (HCoVs-NL63 and HCoVs-229E) and β-CoVs (HCoVs-OC43, HCoVs-HKU1, SARS-CoV, MERS-CoV). While, novel coronavirus (SARS-CoV-2) is the most recent member. The genome sequence of SARS-CoV-2 is 82% similar to SARS–COV-1. The compelling evidences link the progression of viral infection of SARS-CoV-2 with excessive inflammation as a result of the exaggerated immune response and elevated production of “immunocytokines” resulting in cytokine storm (CS); followed by a series of events, like acute organ damage, acute respiratory distress syndrome (ARDS) as well as death. Hence attempts to reduce cytokine storm are now being considered as a new paradigm shift in the clinical management of SARS-CoV-2. Tocilizumab (IL-6 blocker), Baricitinib (JAKs and AAK1 inhibitor), TNFα inhibitors (Infliximab, Adalimumab, Certolizumab) are currently being evaluated for possible block of the CS. Hence, rationalizing anti-inflammatory therapeutics would be the most judicious approach for significant reduction in COVID-19 mortality. In order to elucidate optimized and rationaled use of different therapeutics in COVID-19, we collated latest available information from emerging scientific evidences, integrated previous attempts as well as clinical successes, and various adopted approaches to mitigate past outbreaks with of SARS-CoV and MERS CoV.