新型冠状病毒快速检测研究进展

当前全球大流行的新型冠状病毒肺炎(COVID-19)是由新型冠状病毒(SARS-CoV-2)感染的一种高传染性肺炎,其通过呼吸道飞沫、气溶胶、直接或间接接触、粪口传播或者冷链运输等途径在人群中进行传播,处在潜伏期或尚无明显症状的患者也具备传染他人的能力。SARS-CoV-2是一种有包膜的单股正链RNA病毒,拥有线性RNA片段,每个病毒粒子直径为60～140 nm。与其他冠状病毒相似,SARS-CoV-2主要包括4种结构蛋白,即：刺突蛋白(S)、膜蛋白(M)、包膜蛋白(E)和核衣壳蛋白(N)。迄今为止,基于病毒结构基础和病原学特点开发出了多种检测SARS-CoV-2的方法,为疑似COVID-19患者的确诊和疫情防控提供了有力的保障。简要介绍了SARS-CoV-2的病原学特征,并综述了核酸检测、免疫学检测和新型生物传感器等最新检测方法的研究进展,以期为COVID-19的早期诊断与防控提供帮助。     

SARS-CoV-2 NP和NP-FlaB融合蛋白的免疫原性研究

新型冠状病毒严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染引发的新型冠状病毒肺炎(COVID-19)疫情在全球持续流行,疫苗的研发和推广使用是阻止新冠疫情的关键手段.SARS-CoV-2核衣壳蛋白(NP)作为病毒的主要结构蛋白,是疫苗开发的潜在候选靶点.鞭毛素B(FlaB)可作为免疫佐剂,增强抗原的免疫原性....     

微生态疗法抗新型冠状病毒肺炎研究进展

2019年底湖北省武汉市出现新型冠状病毒肺炎（coronavirus disease 2019,COVID-19）疫情,传染性强,传播速度快,流行范围广,引起国内外学者高度关注。该病作为急性呼吸道传染病已纳入《中华人民共和国传染病防治法》规定的乙类传染病,按甲类传染病管理。WHO宣布将COVID-19疫情列为国际关注的突发公共卫生事件。目前针对新型冠状病毒（SARS-CoV-2）感染的临床治疗主要以改善症状为主,尚缺少直接针对SARS-CoV-2的特效药。本文通过文献检索就COVID-19现有主要治疗方法和微生态疗法相关研究进行综述,以期为微生态辅助治疗提供参考。     

CpG联合铝佐剂增强RBD-Fc重组蛋白诱导小鼠免疫反应效果的研究

由严重急性呼吸系统综合征冠状病毒2(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)引起的2019冠状病毒病（Coronavirus disease 2019,COVID-19）大流行对全球健康和经济构成了严重威胁,SARS-CoV-2关切变异株（Variants of concern,VOCs）的出现更增加了疫苗研发的难度,因此,优化设计对突变株具有广谱免疫反应的疫苗显得尤为重要。本研究选取具有大量显性中和表位的受体结合域（Receptor-binding domain,RBD）蛋白作为目标抗原,在SARS-CoV-2经典株RBD序列的基础上引入多个VOCs的关键突变位点,将其与人IgG1 Fc片段融合表达,并结合CpG单佐剂、氢氧化铝单佐剂或CpG与氢氧化铝复合佐剂两剂次免疫小鼠,比较CpG联合铝佐剂相比单独使用铝或CpG佐剂诱导细胞免疫和体液免疫反应的增强作用,同时观察小鼠产生抗不同VOCs活病毒的交叉中和抗体滴度。结果显示,与单佐剂相比,RBD-Fc蛋白结合CpG与氢氧化铝复合佐剂免疫小鼠可产生最高的IgG结...     

用于临床新型冠状病毒核酸检测的分子诊断新技术

目前新型冠状病毒肺炎(corona virus disease 2019, COVID-19)在全球仍呈现大流行趋势,该病潜伏期长、传染性强,给全世界人民的健康安全带来严重威胁。新型冠状病毒(severe acute respiratory syndrome coronavirus2, SARS-CoV-2)核酸检测作为COVID-19确诊的重要依据之一,在疫情防控工作中发挥了巨大的作用。截至2020年8月17日,国家药品监督管理局已应急批准15个新型冠状病毒核酸检测试剂盒,其中10个试剂盒是以逆转录-实时荧光定量PCR (RT-qPCR)为主要技术原理,其余试剂盒分别采用了不同于RT-qPCR的5种分子诊断技术。本文对上述检测试剂盒所使用的技术原理、反应时间、优缺点等方面进行了介绍,以期为COVID-19及类似传染病的快速筛查、确诊、防控提供更多的方案思路。     

SARS-CoV-2（新冠病毒）变异流行株命名系统

SARS-CoV-2(Severe acute respiratory syndrome coronavirus 2),又称“新型冠状病毒”或“新冠病毒”,正不断进化和变异,产生了大量的病毒变异株（Variant）,其致病性、宿主适应性和传播性变化显著,给COVID-19(Coronavirus disease-19),又称“新型冠状病毒肺炎”或“新冠肺炎”的防治带来巨大挑战。变异株的命名对COVID-19的分子流行病学调查和防控技术研究起到关键性的辨识作用。本文综述了GISAID、Nextstrain、Pango、TILE和希腊字母5种SARS-CoV-2变异株的命名原则、适用范围和重要的流行变异株,为SARS-CoV-2变异株的监测、研究SARS-CoV-2变异株的进化机制、传播特性及抗原位点设计提供一定的参考。     

新型冠状病毒(SARS-CoV-2)核酸检测技术

新型冠状病毒(SARS-CoV-2)的迅速传播,导致了新冠肺炎(COVID-19)的全球大流行。COVID-19给世界各国的经济发展和健康生活带来了巨大影响,已成为全球公共卫生关注的核心问题。控制COVID-19大流行的一种有效策略是开发快速识别和隔离SARS-CoV-2感染者的高精度方法。因此,本文总结了SARS-CoV-2病毒核酸检测的技术方法、标本类型和质量控制,对比了各种核酸检测技术的优势和不足及其研究进展和应用,分析了标本和质量控制对检测结果的影响,以期为未来的发展趋势与面临的挑战提供思路。     

新型冠状病毒实验室检测方法研究进展

世界范围内流行的SARS-CoV-2已造成大批新型冠状病毒肺炎(COVID-19)患者,严重威胁着全人类生命健康.新型冠状病毒肺炎尚没有特效药,也没有疫苗,实验室确诊新型冠状病毒肺炎,隔离传染源,尽早治愈患者对整个疫情防控起着非常重要的作用.目前实验室检测方法有病毒分离培养、实时荧光定量PCR、环介导等温扩增技术、CRISPR/Cas技术、测序技术、基因芯片和抗原抗体检测.本文就上述几种方法做一综述,为确诊COVID-19提供参考.     

微量元素硒在对抗COVID-19中的作用研究进展

自新型冠状病毒肺炎（corona virus disease 2019，COVID-19）疫情爆发以来，严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome-coronavirus 2， SARS-CoV-2）引起的各类临床表现和后续并发症受到了广泛关注。有研究发现，COVID-19死亡率具有地域差异性，中度或重度缺硒地区感染人群常常具有更高的死亡率，因此硒可能在对抗COVID-19中具有一定的作用。总结了硒缺乏COVID-19患者的临床表现、硒对抗COVID-19的临床效应、以及硒对抗COVID-19的作用机制等方面的研究进展。从目前的研究结果来看，硒在应对感染SARS-CoV-2以及避免过激免疫反应导致的细胞因子风暴过程中具有积极作用，但仍然缺乏临床试验研究证据。     

冠状病毒对天然免疫的抑制作用

由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肺炎(corona virus disease 2019, COVID-19),至今仍在全球范围内流行。21世纪以来,数次冠状病毒感染疫情促使人类更加重视冠状病毒,尤其是COVID-19疫情的暴发与大流行,更将新冠病毒提升为全球的研究重点。免疫反应与病毒的感染、清除以及病理损伤等密切相关。天然免疫是机体防御体系的重要组成部分和首道防线,在病毒感染早期对于抑制病毒的复制和扩散具有至关重要的作用,并且在获得性免疫的启动及后续的发展中也发挥着关键的调控功能。研究表明,免疫逃逸是冠状病毒的重要致病机制,冠状病毒能够通过多种方式抑制宿主的天然免疫应答。现对SARS-CoV-2等主要的冠状病毒抑制天然免疫的分子机制作一概述,以期为抗冠状病毒感染的疫苗及治疗性药物的研发提供帮助。     

Targeting ACLY efficiently inhibits SARS-CoV-2 replication

The Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the biggest public health challenge the world has witnessed in the past decades. SARS-CoV-2 undergoes constant mutations and new variants of concerns (VOCs) with altered transmissibility, virulence, and/or susceptibility to vaccines and therapeutics continue to emerge. Detailed analysis of host factors involved in virus replication may help to identify novel treatment targets. In this study, we dissected the metabolome derived from COVID-19 patients to identify key host factors that are required for efficient SARS-CoV-2 replication. Through a series of metabolomic analyses, in vitro, and in vivo investigations, we identified ATP citrate lyase (ACLY) as a novel host factor required for efficient replication of SARS-CoV-2 wild-type and variants, including Omicron. ACLY should be further explored as a novel intervention target for COVID-19.     

新型冠状病毒疫苗研究策略分析

新型冠状病毒(SARS-CoV-2)是一种可引起人新型冠状病毒肺炎(COVID-19)的新发呼吸道病原体,与重症急性呼吸道综合症冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)同属于β-冠状病毒,具有较高的传染性和一定的致死率。2019年12月在我国武汉被发现,随后蔓延到我国大部分省份,给我国人民健康和经济发展造成巨大损失。疫苗接种是预防和控制传染病的常规和有效手段,国内外多个机构已启动COVID-19疫苗研究工作。文中基于SARS和MERS疫苗研究的经验和教训,对COVID-19疫苗的研究策略和需要注意的关键问题进行了阐述,为相关研究人员提供参考。     

COVID-19疫苗研究现状*

2019年底于中国武汉暴发的新型冠状病毒肺炎疫情来势凶猛,迅速蔓延全球,并被世界卫生组织列为“国际关注的突发公共卫生事件”,给全人类的健康及经济发展造成难以估量的损害。新型冠状病毒对人群普遍易感且传染性强,在无特效药物及治疗手段的情况下,疫苗接种是防控COVID-19疫情最有效且最经济的途径。目前全球疫苗研发正在加速进行,各国之间通力合作,共同应对此次疫情。主要对目前正在研发的针对SARS-CoV-2的灭活疫苗、病毒载体疫苗、基因工程重组亚单位疫苗、核酸疫苗的研究进展进行综述。     

Facing the wrath of enigmatic mutations: a review on the emergence of severe acute respiratory syndrome coronavirus 2 variants amid coronavirus disease-19 pandemic

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging respiratory virus responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic. More than a year into this pandemic, the COVID-19 fatigue is still escalating and takes hold of the entire world population. Driven by the ongoing geographical expansion and upcoming mutations, the COVID-19 pandemic has taken a new shape in the form of emerging SARS-CoV-2 variants. These mutations in the viral spike (S) protein enhance the virulence of SARS-CoV-2 variants by improving viral infectivity, transmissibility and immune evasion abilities. Such variants have resulted in cluster outbreaks and fresh infection waves in various parts of the world with increased disease severity and poor clinical outcomes. Hence, the variants of SARS-CoV-2 pose a threat to human health and public safety. This review enlists the most recent updates regarding the presently characterized variants of SARS-CoV-2 recognized by the global regulatory health authorities (WHO, CDC). Based on the slender literature on SARS-CoV-2 variants, we collate information on the biological implications of these mutations on virus pathology. We also shed light on the efficacy of therapeutics and COVID-19 vaccines against the emerging SARS-CoV-2 variants.     

A systematic review of Vaccine Breakthrough Infections by SARS-CoV-2 Delta Variant

Vaccines are proving to be highly effective in controlling hospitalization and deaths associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as shown by clinical trials and real-world evidence. However, a deadly second wave of coronavirus disease 2019 (COVID-19), infected by SARS-CoV-2 variants, especially the Delta (B.1.617.2) variant, with an increased number of post-vaccination breakthrough infections were reported in the world recently. Actually, Delta variant not only resulted in a severe surge of vaccine breakthrough infections which was accompanied with high viral load and transmissibility, but also challenged the development of effective vaccines. Therefore, the biological characteristics and epidemiological profile of Delta variant, the current status of Delta variant vaccine breakthrough infections and the mechanism of vaccine breakthrough infections were discussed in this article. In addition, the significant role of the Delta variant spike (S) protein in the mechanism of immune escape of SARS-CoV-2 was highlighted in this article. In particular, we further discussed key points on the future SARS-CoV-2 vaccine research and development, hoping to make a contribution to the early, accurate and rapid control of the COVID-19 epidemic.     

SARS-CoV-2 VOCs,Mutational diversity and clinical outcome: Are they modulating drug efficacy by altered binding strength?

The global COVID-19 pandemic continues due to emerging Severe Acute Respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC). Here, we performed comprehensive analysis of in-house sequenced SARS-CoV-2 genome mutations dynamics in the patients infected with the VOCs - Delta and Omicron, within Recovered and Mortality patients. Statistical analysis highlighted significant mutations - T4685A, N4992N, and G5063S in RdRp; T19R in NTD spike; K444N and N532H in RBD spike, associated with Delta mortality. Mutations, T19I in NTD spike, Q493R and N440K in the RBD spike were significantly associated with Omicron mortality. We performed molecular docking for possible effect of significant mutations on the binding of Remdesivir. We found that Remdesivir showed less binding efficacy with the mutant Spike protein of both Delta and Omicron mortality compared to recovered patients. This indicates that mortality associated mutations could have a modulatory effect on drug binding which could be associated with disease outcome.     

An update comprehensive review on the status of COVID-19: vaccines,drugs, variants and neurological symptoms

Various recently reported mutant variants, candidate and urgently approved current vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many current situations with severe neurological damage and symptoms as well as respiratory tract disorders have begun to be reported. In particular, drug, vaccine, and neutralizing monoclonal antibodies (mAbs) have been developed and are currently being evaluated in clinical trials. Here, we review lessons learned from the use of novel mutant variants of the COVID-19 virus, immunization, new drug solutions, and antibody therapies for infections. Next, we focus on the B 1.1.7, B 1.351, P.1, and B.1.617 lineages or variants of concern that have been reported worldwide, the new manifestations of neurological manifestations, the current therapeutic drug targets for its treatment, vaccine candidates and their efficacy, implantation of convalescent plasma, and neutralization of mAbs. We review specific clinical questions, including many emerging neurological effects and respiratory tract injuries, as well as new potential biomarkers, new studies in addition to known therapeutics, and chronic diseases of vaccines that have received immediate approval. To answer these questions, further understanding of the burden kinetics of COVID-19 and its correlation with neurological clinical outcomes, endogenous antibody responses to vaccines, pharmacokinetics of neutralizing mAbs, and action against emerging viral mutant variants is needed.     

Recipients of COVID-19 vaccines face challenges of SARS-CoV-2 variants

The coronavirus disease 19 (COVID-19) has been rampant since 2019, severely affecting global public health, and causing 5.75 million deaths worldwide. So far, many vaccines have been developed to prevent the infection of SARS-CoV-2 virus. However, the emergence of new variants may threat vaccine recipients as they might evade immunological surveillance that depends on the using of anti-SARS-CoV-2 antibody to neutralize the viral particles. Recent studies have found that recipients who received two doses of vaccination plus an additional booster shoot were able to quickly elevate neutralization response and immune response against wild-type SARS-CoV-2 virus and some initially appeared viral variants. In this review, we assessed the real-world effectiveness of different COVID-19 vaccines by population studies and neutralization assays and compared neutralization responses of booster vaccines in vitro. Finally, as the efficacy of COVID-19 vaccine is expected to decline over time, continued vaccination should be considered to achieve a long-term immune protection against coronavirus.     

Immunology of COVID-19

The immune response to SARS-CoV-2 reveals a delicate balance between protective effects and harmful pathological reactions and can possibly explain the highly variable disease manifestations in subjects infected with this novel coronavirus. A better understanding of the anti-viral immune response is not only critical for vaccine development but might also provide targets for pharmaceutical and immunological treatment options. Recent research literature on immune aspects of COVID-19 is summarized in this review with an outlook how bats have evolved to live with these viral infections.     

Genomic and epidemiological characteristics of SARS-CoV-2 in Africa

Since late 2019, the coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, has rapidly evolved to become a global pandemic. Each country was affected but with a varying number of infected cases and mortality rates. Africa was hit late by the pandemic but the number of cases rose sharply. In this study, we investigated 224 SARS-CoV-2 genome sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) in the early part of the outbreak, of which 69 were from Africa. We analyzed a total of 550 mutations by comparing them with the reference SARS-CoV-2 sequence from Wuhan. We classified the mutations observed based on country and region, and afterwards analyzed common and unique mutations on the African continent as a whole. Correlation analyses showed that the duo variants ORF1ab/RdRp 4715L and S protein 614G variants, which are strongly linked to fatality rate, were not significantly and positively correlated with fatality rates (r = -0.03757, P = 0.5331 and r = -0.2876, P = 0.6389, respectively), although increased number of cases correlated with number of deaths (r = 0.997, P = 0.0002). Furthermore, most cases in Africa were mainly imported from American and European countries, except one isolate with no mutation and was similar to the original isolate from Wuhan. Moreover, unique mutations specific to countries were identified in the early phase of the outbreak but these mutations were not regional-specific. There were common mutations in all isolates across the continent as well as similar isolate-specific mutations in different regions. Our findings suggest that mutation is rapid in SARS-CoV-2 in Africa and although these mutations spread across the continent, the duo variants could not possibly be the sole cause of COVID-19 deaths in Africa in the early phase of the outbreak.