2019冠状病毒病的发病机制研究进展

由严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)引起的病毒性肺炎已经扩散到全球200多个国家和地区,导致了数十万人死亡。2019冠状病毒病(coronavirus disease 19,COVID-19)的流行病学、致病机制和临床治疗方法成为各国政府以及科研界亟待研究解决的重大问题。本文对SARS-CoV-2的病原学特征及COVID-19的发病机制、病理学研究进展进行综述,重点评述病毒受体人血管紧张素转换酶Ⅱ (human angiotensin-converting enzyme 2,ACE2)与病毒致病机制的相关性,为后续研究与防治提供参考。     

2019新型冠状病毒及其诊疗与防控:回顾与展望

2019新型冠状病毒的暴发持续至今,导致了世界各地数以百万计的感染个例,更夺去了数十万人的生命。世界卫生组织在2020年2月将此病毒引起的疾病定名为2019冠状病毒病(Coronavirus disease 2019,COVID-19),而国际病毒分类委员会也将此病毒命名为SARS-Co V-2。COVID-19的典型临床症状类似感冒,少数病人可发展为重症甚至死亡。21世纪以来,人类冠状病毒有3次大暴发,分别是2003年暴发的严重急性呼吸综合征(SARS)、2012年暴发的中东呼吸综合征(MERS)和本次的新型肺炎。自2003年以来,对SARS和MERS冠状病毒的研究从未间断,对其自然起源、致病机理、药物筛选及疫苗研发等已取得一定进展。鉴于SARS-Co V-2和SARS-Co V的基因组序列高度相似,以往对SARS-Co V的研究对深入探讨SARS-Co V-2生物学特性、诊断、治疗和防控有很强的借鉴性。文中通过回顾过往的研究进展,对比SARS-Co V和SARS-Co V-2的生物学特性,分析当前亟需的防控和诊疗措施,探讨疫苗研发所面对的一些难题,并展望疫情发展趋势及对本领域研究与开发的主要挑战,冀为我国和全世界有效控制COVID-19疫情提供参考。     

2019冠状病毒病对肺外系统的影响及可能机制探讨

2019冠状病毒病(coronavirus 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)导致的感染性疾病。SARS-CoV-2感染人体后除作用于肺部的SARS-CoV-2功能受体外,还可以作用于心脏、消化道、肝脏、肾脏、中枢系统的SARS-CoV-2功能受体,引起肺外脏器的损伤,诱发多器官功能衰竭,增加COVID-19的病死率。但目前对SARS-CoV-2引起肺外各脏器损伤的具体作用机制还不是很清楚,需要更多临床和实验室数据支持。通过检索COVID-19相关的文献,对SARS-CoV-2导致的肺外系统影响及其可能作用机制作一综述。     

新型冠状病毒与系统损伤研究

自2019年12月全国及世界范围爆发了新型冠状病毒性肺炎(corona virus disease 2019,COVID-19),给中国和全球公共卫生安全带来了极大的挑战.研究发现,新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)不仅损...     

Summary of the Detection Kits for SARS-CoV-2 Approved by the National Medical Products Administration of China and Their Application for Diagnosis of COVID-19

Virologica Sinica - The on-going global pandemic of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been...     

值得关切的严重急性呼吸综合征冠状病毒2型变异株

自2019年12月2019冠状病毒病暴发流行以来,严重急性呼吸综合征冠状病毒 2 型已经产生了1万个以上的变异株。其中有些可能获得更强的传染性,有的致病性得以提高,有的或许不能被现有的检测试剂检测出来,还有的也许能够逃逸疫苗的免疫保护作用。世界卫生组织于2021年5月31日发布了针对这些变异株的新的命名系统。本文对当前世界上流行较广的4个变异株进行综述,包括最近在广州市引起小暴发的δ变异株。     

Viral and Antibody Kinetics of COVID-19 Patients with Different Disease Severities in Acute and Convalescent Phases: A 6-Month Follow-Up Study

Virologica Sinica - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly around the world, posing a major threat to human...     

COVID-19: Antiviral agents and enzyme inhibitors/receptor blockers in development

Novel 2019 coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) and coronavirus disease 2019 (COVID-19), the respiratory syndrome it causes, have shaken the world to its core by infecting and claiming the lives of many people since originating in December 2019 in Wuhan, China. World Health Organization and several states have declared a pandemic situation and state of emergency, respectively. As there is no treatment for COVID-19, several research institutes and pharmaceutical companies are racing to find a cure. Advances in computational approaches have allowed the screening of massive antiviral compound libraries to identify those that may potentially work against SARS-CoV-2. Antiviral agents developed in the past to combat other viruses are being repurposed. At the same time, new vaccine candidates are being developed and tested in preclinical/clinical settings. This review provides a detailed overview of select repurposed drugs, their mechanism of action, associated toxicities, and major clinical trials involving these agents.     

新型冠状病毒肺炎:实验室检测、治疗及疫苗

新型冠状病毒肺炎(2019 novel coronavirus disease,COVID-19),一种由动物来源的新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SRAS-CoV-2)感染所致的疾病在全球范围内急速传播,严重的危害人类的健康.快速、准确的诊...     

SARS-CoV-2抗原表位分析及相关疫苗研发的进展与挑战

疫苗的接种被认为是阻止时下2019冠状病毒病(Corona Virus Disease 2019,COVID-19)疫情进一步蔓延的最有效手段.目前,国内外多个研究团队采用了不同的技术路线开展严重急性呼吸综合征冠状病毒2(Severe Acute Respiratory Syndrome Coronavirus 2,S...     

新型冠状病毒及泛β冠状病毒广谱中和单抗的研究进展

新型冠状病毒的全球大流行,给人类的生命健康和社会秩序带来了巨大的危害。疫苗、小分子药物及各类抗体药物的研发在遏制新型冠状病毒感染传播、降低重症率和死亡风险上发挥了积极的作用。然而,由于新冠病毒庞大的感染基数及自身易突变的特征,当前已经演化出多种能逃逸疫苗及中和抗体的变异株,显著削弱了抗体的保护效果。研发新型冠状病毒广谱甚至泛β冠状病毒广谱的中和抗体对于未来新冠变异株及其他高致病性β冠状病毒的防治具有重要意义。本文从新型冠状病毒中和抗体的筛选制备策略、作用机制、中和效果及广谱性等方面进行了系统综述,并对当前面临的挑战和未来的发展方向进行了讨论和展望,以期为后续相关研究提供参考。     

Pathogenesis and treatment of cytokine storm in COVID-19

COVID-19 is a viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that killed a large number of patients around the world. A hyperinflammatory state resulting in a cytokine storm and adult respiratory distress syndrome seems to be the major cause of the death. Many mechanisms have been suggested in the pathogenesis of COVID-19 associated cytokine storm (COVID-CS). Insufficient viral clearance and persistence of a strong cytokine response despite inadequate antiviral immunity seem to be the main mechanisms underlying the pathogenesis. The diagnosis of COVID-19 is based on relatively constant clinical symptoms, clinical findings, laboratory tests, and imaging techniques, while the diagnosis of COVID-CS is a rather dynamic process, based on evolving or newly emerging findings during the clinical course. Management of COVID-19 consists of using antiviral agents to inhibit SARS-CoV-2 replication and treating potential complications including the cytokine storm together with general supportive measures. COVID-CS may be treated using appropriate immunosuppressive and immunomodulatory drugs that reduce the level of inappropriate systemic inflammation, which has the potential to cause organ damage. Currently corticosteroids, IL-6 blockers, or IL-1 blockers are most widely used for treating COVID-CS.     

Expression Analyses of MicroRNAs in Hamster Lung Tissues Infected by SARS-CoV-2

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease with multiple severe symptoms, such as fever over 37.5°C, cough, dyspnea, and pneumonia. In our research, microRNAs (miRNAs) binding to the genome sequences of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory-related coronavirus (MERS-CoV), and SARS-CoV-2 were identified by bioinformatic tools. Five miRNAs (hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-16-5p, and hsa-miR-196a-1-3p) were found to commonly bind to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2. The expression patterns of those miRNAs were examined in hamster lung samples infected by SARS-CoV-2. Five miRNAs (hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-221-3p, hsa-miR-140-3p, and hsa-miR-422a) showed differential expression patterns in lung tissues before and after infection. Especially, hsa-miR-15b-5p and hsa-miR-195-5p showed a large difference in expression, indicating that they may potentially be diagnostic biomarkers for SARS-CoV-2 infection.     

Mesenchymal stem cells as living anti-inflammatory therapy for COVID-19 related acute respiratory distress syndrome

Coronavirus disease 2019(COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2(SARS-Co V2), is growing at an exponential rate worldwide. Manifestations of this disease are heterogeneous; however, advanced cases often exhibit various acute respiratory distress syndrome-like symptoms, systemic inflammatory reactions, coagulopathy, and organ involvements. A common theme in advanced COVID-19 is unrestrained immune activation, classically referred to as a "cytokine storm", as well as deficiencies in immune regulatory mechanisms such as T regulatory cells. While mesenchymal stem cells(MSCs) themselves are objects of cytokine regulation, they can secrete cytokines to modulate immune cells by inducing antiinflammatory regulatory Treg cells, macrophages and neutrophils; and by reducing the activation of T and B cells, dendritic and nature killer cells. Consequently, they have therapeutic potential for treating severe cases of COVID-19. Here we discuss the unique ability of MSCs, to act as a "living antiinflammatory", which can "rebalance" the cytokine/immune responses to restore equilibrium. We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome.     

The possible double-edged sword effects of vitamin D on COVID-19: A hypothesis

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gains access to host cells by attaching to angiotensin-converting enzyme 2 (ACE2). Vitamin D (VitD) can upregulate ACE2 and has an antagonistic effect on Renin, which exerts a vasodilatation and anti-inflammatory effect against coronavirus disease (COVID-19). However, it may also facilitate viral entry by increasing ACE2 as the main SARS-CoV-2 receptor and mediates ROS production through NADPH oxidase, as a double-edged sword effect. Lung function and the immune system are also influenced by VitD through several mechanisms, including increased natural antibiotics (Defensin and Cathelicidin) and upregulated transforming growth factor-β. A higher IgA, Th2/Th1 ratio, and T-regulatory cells are attributable to VitD effects on the immune cells, while these changes may also be a double-edged sword in COVID-19. Although VitD supplementation might be highly recommended in COVID-19, the administration's dosage and route could be challenging. Furthermore, this issue has not been mentioned in various studies so far. So, the report aimed to explain the current challenges with the application of VitD in COVID-19.     

严重急性呼吸综合征、中东呼吸综合征和2019冠状病毒病治疗研究进展

严重急性呼吸综合征2019(sever acute respiratory syndrome,SARS)、中东呼吸综合征(Middle East respiratory syndrome,MERS)和2019冠状病毒病(corona virus disease 2019,COVID-19)对全世界人民造成了严重的经济损...     

干扰素刺激基因与新型冠状病毒相互作用的研究进展

目前新型冠状病毒(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)感染所致的新型冠状病毒肺炎(corona virus disease, COVID-19)已成为威胁人类健康和安全的全球性流行性疾病。随着新突变株的不断出现,寻找有效治疗药物和靶点迫在眉睫。干扰素刺激基因(interferon-stimulated genes, ISGs)是由干扰素(interferons, IFNs)诱导后表达上调的一类基因,在宿主抵抗病毒感染过程中发挥着至关重要的作用。研究表明,ISGs能够靶向许多病毒复制的不同阶段发挥抗病毒作用,然而SARS-CoV-2也进化出各种策略干扰或逃避宿主天然免疫。因此,全面了解SARS-CoV-2与ISGs相互作用,对于设计抗病毒策略至关重要。本文简要综述不同ISGs抵抗SARS-CoV-2的作用机制,为开发新型的抗病毒药物提供思路和理论依据。     

Mesenchymal stem cells: a new front emerges in coronavirus disease 2019 treatment

Currently, treating coronavirus disease 2019 (COVID-19) patients, particularly those afflicted with severe pneumonia, is challenging, as no effective pharmacotherapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists. Severe pneumonia is recognized as a clinical syndrome characterized by hyper-induction of pro-inflammatory cytokine production, which can induce organ damage, followed by edema, dysfunction of air exchange, acute respiratory distress syndrome, acute cardiac injury, secondary infection and increased mortality. Owing to the immunoregulatory and differentiation potential of mesenchymal stem cells (MSCs), we aimed to outline current insights into the clinical application of MSCs in COVID-19 patients. Based on results from preliminary clinical investigations, it can be predicted that MSC therapy for patients infected with SARS-CoV-2 is safe and effective, although multiple clinical trials with a protracted follow-up will be necessary to determine the long-term effects of the treatment on COVID-19 patients.     

A Comprehensive Review of Animal Models for Coronaviruses: SARS-CoV-2, SARS-CoV,and MERS-CoV

The recent outbreak of coronavirus disease(COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has already affected a large population of the world. SARS-CoV-2 belongs to the same family of severe acute respiratory syndrome coronavirus(SARS-CoV) and Middle East respiratory syndrome coronavirus(MERSCoV). COVID-19 has a complex pathology involving severe acute respiratory infection, hyper-immune response, and coagulopathy. At present, there is no therapeutic drug or vaccine approved for the disease. There is an urgent need for an ideal animal model that can reflect clinical symptoms and underlying etiopathogenesis similar to COVID-19 patients which can be further used for evaluation of underlying mechanisms, potential vaccines, and therapeutic strategies. The current review provides a paramount insight into the available animal models of SARS-CoV-2, SARS-CoV, and MERS-CoV for the management of the diseases.