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。     

新型冠状病毒肺炎感染防治研究进展

摘要：2019年12月,武汉发生了一种新型冠状病毒(SARS-CoV-2)感染导致的肺炎(COVID-19)疫情,并在全国范围内迅速流行,严重危害了人类健康。目前对于SARS-CoV-2的相关研究尚处于起步阶段,本文整理了关于COVID-19相关最新研究成果,总结了COVID-19病原学特征、致病机制、流行病学特征、临床特点及治疗,为后续的研究及防治提供参考。     

新型冠状病毒肺炎患者恢复期肛拭子中SARS-CoV-2核酸检测结果评价

目的 分析新型冠状病毒肺炎（COVID-19）患者在恢复期肛拭子标本中新型冠状病毒（SARS-CoV-2）核 酸的检出率及其临床价值。方法 对我院确诊的COVID-19患者痰液、咽拭子和肛拭子3种来源的标本同期进行 SARS-CoV-2核酸检测。分析3种标本类型的病毒核酸阳性率及肛拭子病毒核酸阳性时痰液标本和咽拭子标本中 病毒核酸检出情况。结果 共收集50例COVID-19患者的156份样本,其中痰液标本41份,检出SARS-CoV-2阳性 8份（19.5%）;咽拭子标本55份,检出SARS-CoV-2阳性6份（10.9%）;肛拭子标本60份,检出SARS-CoV-2阳性11份 （18.3%）。50例COVID-19患者在恢复期出现病毒核酸阳性者痰液、咽拭子和肛拭子样本核酸检测阳性分别有8例 （19.5%）、6例（12.0%）和10例（20.0%）。10例肛拭子核酸检测阳性患者的呼吸道标本核酸检测显示9例为阴性。结 论 COVID-19患者恢复期肛拭子SARS-CoV-2核酸阳性检出率较咽拭子和痰液标本检出率稍高。患者恢复期的 呼吸道标本SARS-CoV-2核酸连续检测阴性时,应考虑添加肛拭子检测作为出院或者隔离标准。     

新型冠状病毒肺炎与传染性非典型肺炎特点及药物治疗的对比分析

2019年12月在中国武汉陆续发现多例新型冠状病毒肺炎(corona virus disease 2019,COVID-19)患者,并迅速在全世界范围内造成了严重疫情。因此针对COVID-19的研究成为热点。目前尚没有针对COVID-19的特效药物或疫苗。引起COVID-19的严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)和2003年在中国引起传染性非典型肺炎(severe acute respiratory syndrome,SARS)的病毒(severe acute respiratory syndrome coronavirus,SARS-CoV)都属于冠状病毒,有许多相似之处。本文从流行病学、病原学、临床表现、药物治疗4个方面对2次疫情进行了系统的比较分析,详细对比了2次疫情的治疗方案,并整理出当前临床药物治疗方案以及一些具有临床治疗前景的药物,以方便临床医疗团队能够借鉴SARS治疗的经验和教训,顺利开展COVID-19的治疗。     

我国新型冠状病毒疫苗研发进展及思考

新型冠状病毒(SARS-CoV-2)是继SARS冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)之后又一严重危害人类的病毒。SARS-CoV-2引起的疾病被世界卫生组织命名为COVID-19,具有较高的传染性和病死率。为控制疫情蔓延,我国正应急开展多种技术路线的COVID-19疫苗研发,包括灭活疫苗、重组蛋白疫苗、病毒载体疫苗和核酸疫苗(DNA和mRNA)等,在加快疫苗研发进程的同时把握应急研发进度和科学性之间的平衡,并行解决相关科学问题,在满足安全性的前提下保证疫苗的有效性和质量可控。目前我国研发的腺病毒载体疫苗已率先进入Ⅰ期临床试验,多家企业进入注册检验和滚动提交审评资料阶段。本文对COVID-19疫苗研究进展进行综述,并提出现阶段对此种新疫苗研发的考虑。     

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。     

天然产物来源的抗SARS-CoV-2药物研究进展

广谱高效的小分子药物是应对新型冠状病毒感染(COVID-19)及未来可能爆发疫情的重要武器。天然产物是药物先导化合物的重要来源,在抗COVID-19的药物研发中得到了广泛关注。本文综述了抗新型冠状病毒(SARS-CoV-2)药物的关键靶点和具有抗SARS-CoV-2活性的天然产物的研究进展,以期为抗SARS-CoV-2药物的研发提供参考。     

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。     

Antiviral Efficacy of Pralatrexate against SARS-CoV-2

Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global community. However, only limited access has been allowed to COVID-19 vaccines and antiviral treatment options. Here, we report the efficacy of the anticancer drug pralatrexate against SARS-CoV-2. In Vero and human lung epithelial Calu-3 cells, pralatrexate reduced viral RNA copies of SARS-CoV-2 without detectable cytotoxicity, and viral replication was successfully inhibited in a dose-dependent manner. In a time-to-addition assay, pralatrexate treatment at almost half a day after infection also exhibited inhibitory effects on the replication of SARS-CoV-2 in Calu-3 cells. Taken together, these results suggest the potential of pralatrexate as a drug repurposing COVID-19 remedy.     

Plasma exchange in the treatment of complex COVID-19-related critical illness: controversies and perspectives

COVID-19 (coronavirus disease 2019), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), emerged in Wuhan, China, and has spread worldwide, resulting in over 73 million cases and more than 1 600 000 deaths as of December 2020. Although the disease is asymptomatic in most cases, some patients develop life-threatening disease characterised by acute respiratory distress syndrome, sepsis, multisystem organ failure (MSOF), extrapulmonary manifestations, thromboembolic disease and associated cytokine release syndrome. The rationale for applying therapeutic plasma exchange (TPE) early in the course of fulminant COVID-19 is the suppression of thromboinflammation and amelioration of microangiopathy, thus preventing the ensuing MSOF. In the course of complicated critical illness due to COVID-19, immune dysregulation may be as important as viral replication itself. Moreover, the natural course of SARS-CoV-2 infection remains obscure, as re-infections and/or recurrently positive real-time PCR results have been reported. Although concerns still exist regarding its potential immunosuppressive effects and safety, TPE shows promise in the management of life-threatening COVID-19 as documented by various pilot studies, which remain to be confirmed by future randomised controlled trials. However, current data suggest that TPE could be an adjunctive rescue therapy in complex COVID-19 critical illness.     

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.     

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.     

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.     

Short-term celecoxib (celebrex) adjuvant therapy: a clinical trial study on COVID-19 patients

Inflammopharmacology - It is known that severe acute respiratory coronavirus 2 (SARS-CoV-2) is the viral strain responsible for the recent coronavirus disease 2019 (COVID-19) pandemic. Current...     

New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?

Recently, a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Despite drastic containment measures, the spread of this virus is ongoing. SARS-CoV-2 is the aetiological agent of coronavirus disease 2019 (COVID-19) characterised by pulmonary infection in humans. The efforts of international health authorities have since focused on rapid diagnosis and isolation of patients as well as the search for therapies able to counter the most severe effects of the disease. In the absence of a known efficient therapy and because of the situation of a public-health emergency, it made sense to investigate the possible effect of chloroquine/hydroxychloroquine against SARS-CoV-2 since this molecule was previously described as a potent inhibitor of most coronaviruses, including SARS-CoV-1. Preliminary trials of chloroquine repurposing in the treatment of COVID-19 in China have been encouraging, leading to several new trials. Here we discuss the possible mechanisms of chloroquine interference with the SARS-CoV-2 replication cycle.     

Repurposing carrimycin as an antiviral agent against human coronaviruses,including the currently pandemic SARS-CoV-2

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.     

新型冠状病毒肺炎患者血常规及淋巴细胞亚群的变化特点

目的 探讨新型冠状病毒肺炎（COVID-19）患者血常规及淋巴细胞亚群的变化。方法 选取2020年1 月—2 月在阜阳市第二人民医院收治的确诊 COVID-19 患者 66 例,将同期住院的疑似并最终排除新型冠状病毒 （SARS-CoV-2）感染的56例患者作为对照组。比较2组患者血常规和淋巴细胞亚群水平的差异,Logistic回归分析 COVID-19 患病的血液细胞学影响因素。结果 与对照组相比,COVID-19 组白细胞计数（WBC）、中性粒细胞 （NEU）、淋巴细胞（LYM）、CD4+ T细胞、CD8+ T细胞、B淋巴细胞水平均降低（P＜0.05）。Logistic回归分析显示,CD4+T 细胞水平升高是COVID-19患者的保护因素（OR=0.997,95%CI：0.994~0.999）,同时CD4+ T细胞与LYM计数呈正相关 （rs=0.829,P＜0.01）。结论 COVID-19患者外周血T淋巴细胞水平下降,淋巴细胞亚群分析可为临床诊断SARS-CoV-2的感染和治疗提供参考。