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。     

1 例轻症新型冠状病毒肺炎婴儿用药方案分析

新型冠状病毒肺炎(corona virus disease 2019,COVID-19)是由严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染导致的肺炎。潜伏期多为3~7 d,轻症主要表现为发热、乏力、干咳,重症多表现为呼吸困难/低氧血症,甚至危及生命[1]。据指南[2-3]报道,儿童COVID-19病例症状相对较轻,但考虑到儿童用药的特殊性,临床对治疗方案和用药的选择必须慎重。本研究对1例轻症COVID-19婴儿治愈病例的药物治疗过程进行分析,旨在为相似病例的药物治疗提供参考。     

中东呼吸综合征治疗药物研究进展

摘 要中东呼吸综合征（MERS）是由中东呼吸综合征冠状病毒（MERS-CoV）引起的急性呼吸道传染病。MERS-CoV是继SARS冠状病毒（SARS-CoV）之后发现的一种具有高致死率的新型病毒,可由单峰骆驼传染给人类。目前,临床尚无抗MERS-CoV的特效药物。抗MERS-CoV的药物开发策略主要是借鉴抗SARS-CoV药物的开发经验,包括疫苗,抗体,小分子化合物快速筛选等。本文结合临床治疗及动物模型对MERS治疗药物的研究进展进行综述,旨在为该病新型疫苗和抗病毒药物的研发提供借鉴。     

新型冠状病毒性肺炎临床特征及抗病毒药物治疗方案进展

2019年12月,湖北省武汉市出现多例新型冠状病毒肺炎病例。2020年2月,世界卫生组织(WHO)将该病毒正式命名为严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2),SARS-CoV-2所导致的感染被命名为新型冠状病毒肺炎(corona virus disease 2019,COVID-19)。冠状病毒(coronavirus,CoV)属冠状病毒科,是一组具有外套膜的正链单股RNA病毒,可导致动物和人类不同程度的呼吸道、肠道、肝脏和神经系统疾病[1-3]。包括4属:α-CoV、β-CoV、γ-CoV、δ-CoV。短短20年来,冠状病毒已引发了包括严重急性呼吸综合征冠状病毒(severe acute respiratory syndrome coronavirus,SARS-CoV)感染、中东呼吸综合征冠状病毒(middle east respiratory syndrome coronavirus,MERS-CoV)感染和目前的SARS-CoV-2感染在内的3次传染病大流行[4-6]。三种冠状病毒均属于β-CoV,传播速度快,重症可导致严重呼吸综合征和死亡。目前,COVID-19已成为全球关注的突发公共卫生事件,但仍缺乏直接抗病毒治疗药物。     

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。     

洛匹那韦/利托那韦治疗冠状病毒感染的研究进展

洛匹那韦/利托那韦(LPV/r)是国家卫生健康委员会和国家中医药管理局推荐的新型冠状病毒肺炎(COVID-19)抗病毒治疗药物之一。几项体外试验研究结果显示,LPV/r有抑制SARS病毒和中东呼吸综合征(MERS)冠状病毒的作用,但也有研究并未发现其有抑制SARS病毒的活性或活性较弱。2篇文献报道了LPV/r治疗SARS有一定临床疗效,1篇文献报道了LPV/r治疗1例MERS患者取得成功。近来也有少量LPV/r治疗COVID-19的报道,但是均尚缺乏高质量的对照研究。     

新型冠状病毒肺炎治疗药物研发现状

目的 探讨新型冠状病毒肺炎(简称新冠肺炎)治疗药物研发现状、成效和存在的问题,并提出改进建议。方法 以国家卫生健康委员会《新型冠状病毒肺炎诊疗方案》中药物治疗的演变为切入点,结合临床治疗现状,总结各种治疗新型冠状病毒感染药物的特点,分析新冠肺炎疫情暴发以来登记注册拟开展的药物临床试验研究情况及存在的问题。结果 对于新冠肺炎,目前尚无特效抗病毒治疗方法,国家卫生健康委员会《新型冠状病毒肺炎诊疗方案》中所推荐的药物治疗也是基于突发疫情条件下的试用建议,且需严格监控。针对新冠肺炎疫情下登记注册拟开展的药物临床试验项目整体上普遍存在立题依据、研究基础和研究条件不充分,缺乏必要的临床前试验数据和质量保证体系等问题。结论 针对新冠肺炎,药物选择都是基于既往的严重急性呼吸综合征(SARS)、中东呼吸综合征(MERS)或其他新型流感病毒的治疗经验,积极的对症支持治疗仍是治疗的关键。针对新型冠状病毒的新药研发应回归到认真做好基于药物作用靶点、作用机制的活性筛选的基础工作。     

儿童新型冠状病毒肺炎抗病毒药物治疗选择与思考

2019年末,中国湖北省武汉市出现一组不明原因肺炎病例,并在全国乃至世界范围内迅速蔓延,随后被证实是由一种新型冠状病毒引起。2020年2月11日,国际病毒分类委员会宣布其正式分类名为严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)。世界卫生组织(WHO)同日宣布,由这一病毒导致的疾病的正式名称为2019冠状病毒病(COVID-19)[1]。截至北京时间2020年2月19日24时,全国共31个省累计报告确诊74576例,儿童确诊病例最小年龄仅出生30 h[2]。儿童患者多以发热、咳嗽为主要表现,与成人相比病情更轻,但也有危重型病例报道[3]。目前对于SARS-CoV-2的认识尚不全面和深入,且尚无预防和治疗的特效药物,临床上大多以经验性治疗、支持治疗和控制并发症为主。本文结合SARS-CoV-2的特性与临床实践提出儿童新型冠状病毒感染的抗病毒药物治疗选择与未来研发思考。     

HIV蛋白酶抑制剂在冠状病毒感染中应用的研究进展

新型冠状病毒肺炎(corona virus disease 2019,COVID-19)疫情发生以来,建议的治疗方案在持续更新中。目前没有特效药物,很多药物仅仅是推荐试用,也有一些新药在开展临床研究,如瑞德西韦。相对于新药,开发已上市药物新的适应证在安全性方面更有优势,如人类免疫缺陷病毒(human immunodeficiency virus,HIV)蛋白酶抑制剂(protease inhibitors,PIs)。此类药物目前为HIV感染治疗的二线用药,但曾被推荐试用于严重急性呼吸综合征(severe acute respiratory syndrome,SARS)、中东呼吸综合征(Middle East respiratory syndrome,MERS)以及COVID-19。本文拟对HIV PIs在冠状病毒(coronavirus,CoV)感染中应用的研究情况进行综述,以期为HIV PIs用于COVID-19治疗的可行性研究提供参考。     

SARS-CoV-2刺突蛋白抑制剂活性筛选方法研究进展

严重急性呼吸综合征冠状病毒2 (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)引起的新型冠状病毒感染(corona virus disease 2019, COVID-19)对全球公共卫生和经济造成了前所未有的影响。SARSCoV-2通过其表面的刺突蛋白与宿主细胞膜上的血管紧张素转换酶2相结合是入侵宿主细胞的关键步骤,以刺突蛋白为靶标的小分子药物成为抗SARS-CoV-2研究的热点。活性筛选是小分子药物研发的关键步骤。鉴于此,本文综述了SARS-CoV-2刺突蛋白小分子抑制剂的活性筛选方法,以期为靶向刺突蛋白的抗病毒药物研发提供参考。     

Written consent to use the drug in children: the problem of off-label drugs

Cardiac arrhythmias in pediatric patients have different mechanisms and frequencies compared to adult patients. There are many physiological differences between children and adults that may affect the pharmacodynamic and pharmacokinetic of the antiarrhythmic drugs in pediatric population. Children, and specially breast feeding children, cannot be considered low weighted adults to select antiarrhythmic drug doses. Although radiofrequency ablation has experienced great technological advances, it is performed in selected pediatric patients. Therefore, the main therapeutic strategy is the use of antiarrhythmic drugs in children. The medical management of arrhythmias in pediatric patients is challenging and complex. There are few clinical guidelines. There is scarce and incomplete information about the efficacy and safety of antiarrhythmic drugs in pediatric population. Most of the doses and drug administration intervals are extrapolated from adult population and applied to children. Antiarrhythmic drug doses have been extensively studied in adult population. However, in pediatric population, there are very few clinical trials and the safety of these drugs is not well known. In general, dose regimens are based on small uncontrolled studies, extrapolation of drug doses from studies performed in the adult population or physician experience. As a consequence, there is a need for further studies to assess the most effective antiarrhythmic drug regimens in children reducing the risk of side effects. Evidence suggests that medical research in pediatric population is necessary and morally valuable. But investigators involved must take care of moral and ethical values, including the respect for the child-subject and his parents or legal representatives, and this respect compels them to consider the patient and family in the decision making process. The participation request and the informed consent must be obtained according to the competitions the patient exhibits, trying to anticipate information about benefits and possible damages derived from the investigation in an understandable language for him. In our opinion the pharmacologic clinical investigation of antiarrhythmic treatments in pediatrics is necessary. More clinical studies must be carried out under rigorous scientific rules that contemplate the particular ethical dilemmas this population faces.     

Recent progress in understanding 2019 novel coronavirus (SARS-CoV-2) associated with human respiratory disease: detection,mechanisms and treatment

Viral respiratory diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) always pose a severe threat to people. First identified in late December 2019, a novel coronavirus (2019-nCoV; SARS-CoV-2) has affected many provinces in China and multiple countries worldwide. The viral outbreak has aroused panic and a public-health emergency around the world, and the number of infections continues to rise. However, the causes and consequences of the pneumonia remain unknown. To effectively implement epidemic prevention, early identification and diagnosis are critical to disease control. Here we scrutinise a series of available studies by global scientists on the clinical manifestations, detection methods and treatment options for the disease caused by SARS-CoV-2, named coronavirus disease 2019 (COVID-19), and also propose potential strategies for preventing the infection.     

雾化吸入IFN-α治疗病毒性疾病的研究进展

目的探索IFN-α(IFN-α)在非典(SARS)、中东呼吸综合征(MERS)和儿童病毒性疾病中的作用,为IFN-α治疗新型冠状病毒肺炎(COVID-19)的临床研究提供一些可借鉴的思路。方法通过检索国内外数据库,获取与IFN-α相关的数据。结果目前尚缺乏IFN-α治疗NCP临床研究数据,IFN-α对SRAS的疗效尚未肯定,对MERS的最佳治疗方法仍未达成共识。但在儿童病毒性疾病中,雾化吸入IFN-α具有作用迅速、疗效可靠、用药剂量小、全身不良反应少等优点,在我国儿童中广泛应用。结论目前尚无NCP的特效药,IFN-α对新冠肺炎的疗效和安全性需要更进一步的临床研究。     

Recent findings on the Coronavirus disease 2019 (COVID-19); immunopathogenesis and immunotherapeutics

Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) is responsible for recent ongoing public health emergency in the world. Sharing structural and behavioral similarities with its ancestors [SARS and Middle East Respiratory Syndrome (MERS)], SARS-CoV-2 has lower fatality but faster transmission. We have gone through a long path to recognize SARS and MERS, therefore our knowledge regarding SARS-CoV-2 is not raw. Various responses of the immune system account for the wide spectrum of clinical manifestations in Coronavirus disease-2019 (COVID-19). Given the innate immune response as the front line of defense, it is immediately activated after the virus entry. Consequently, adaptive immune response is activated to eradicate the virus. However, this does not occur in every case and immune response is the main culprit causing the pathological manifestations of COVID-19. Lethal forms of the disease are correlated with inefficient and/or insufficient immune responses associated with cytokine storm. Current therapeutic approach for COVID-19 is in favor of suppressing extreme inflammatory responses, while maintaining the immune system alert and responsive against the virus. This could be contributing along with administration of antiviral drugs in such patients. Furthermore, supplementation with different compounds, such as vitamin D, has been tested to modulate the immune system responses. A thorough understanding of chronological events in COVID-19 contributing to the development of a highly efficient treatment has not figured out yet. This review focuses on the virus-immune system interaction as well as currently available and potential therapeutic approaches targeting immune system in the treatment of COVID-19 patients.     

Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics

At the time of writing this commentary (February 2020), the coronavirus COVID-19 epidemic has already resulted in more fatalities compared with the SARS and MERS coronavirus epidemics combined. Therapeutics that may assist to contain its rapid spread and reduce its high mortality rates are urgently needed. Developing vaccines against the SARS-CoV-2 virus may take many months. Moreover, vaccines based on viral-encoded peptides may not be effective against future coronavirus epidemics, as virus mutations could make them futile. Indeed, new Influenza virus strains emerge every year, requiring new immunizations. A tentative suggestion based on existing therapeutics, which would likely be resistant to new coronavirus mutations, is to use available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the aggressiveness and mortality from SARS-CoV-2 virus infections. This idea is based on observations that the angiotensin-converting enzyme 2 (ACE2) very likely serves as the binding site for SARS-CoV-2, the strain implicated in the current COVID-19 epidemic, similarly to strain SARS-CoV implicated in the 2002–2003 SARS epidemic. This commentary elaborates on the idea of considering AT1R blockers as tentative treatment for SARS-CoV-2 infections, and proposes a research direction based on datamining of clinical patient records for assessing its feasibility.     

1例儿童慢性肾衰竭伴反复泌尿道感染用药案例分析

目的：探讨临床药师在慢性肾衰竭伴泌尿道感染患儿治疗中的作用。方法：临床药师参与1例慢性肾衰竭伴泌尿道感染患儿的治疗过程,从药物治疗入手,通过查阅国内外指南和文献,提出合理用药建议,协助医师制定个体化给药方案。结果：在临床药师积极配合下,临床医师逐步完善了治疗方案,最终使患儿受益。结论：临床药师参与临床治疗实践可以使临床用药更加规范、合理     

Clinical management and infection control of SARS: Lessons learned

The outbreak of severe acute respiratory syndrome (SARS) in 2003 was the first emergence of an important human pathogen in the 21st century. Responding to the epidemic provided clinicians with extensive experience in diagnosing and treating a novel respiratory viral disease. In this article, we review the experience of the SARS epidemic, focusing on measures taken to identify and isolate patients, prevent the transmission of infection to healthcare workers and develop effective therapies. Lessons learned from the SARS epidemic will be especially important in responding to the current emergence of another highly pathogenic human coronavirus, the agent of Middle East respiratory syndrome (MERS), and to the recently emerging H7N9 influenza A virus in China. This paper forms part of a symposium in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.”     

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.