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1.
Mutations and transient conformational movements of the receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To mitigate viral escape, we developed a cocktail of neutralizing antibodies (NAbs) targeting epitopes located on different domains of spike (S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting the N-terminal domain (NTD) and RBD domain of S, effective at nM concentrations. Remarkably, a combination of RBD-targeting NAbs and NTD-binding NAbs, FC05, enhanced the neutralization potency in cell-based assays and an animal model. Results of competitive surface plasmon resonance assays and cryo-electron microscopy (cryo-EM) structures of antigen-binding fragments bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in the NTD and RBD of S, when immunized in rabbits and macaques, elicited potent protective immune responses against SARS-CoV-2. More importantly, two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection. These results provide a proof of concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD.  相似文献   

2.
Minks are raised in many countries and have transmitted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans. However, the biologic properties of SARS-CoV-2 in minks are largely unknown. Here, we investigated and found that SARS-CoV-2 replicates efficiently in both the upper and lower respiratory tracts, and transmits efficiently in minks via respiratory droplets; pulmonary lesions caused by SARS-CoV-2 in minks are similar to those seen in humans with COVID-19. We further found that a spike protein-based subunit vaccine largely prevented SARS-CoV-2 replication and lung damage caused by SARS-CoV-2 infection in minks. Our study indicates that minks are a useful animal model for evaluating the efficacy of drugs or vaccines against COVID-19 and that vaccination is a potential strategy to prevent minks from transmitting SARS-CoV-2.  相似文献   

3.
Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global health problem, India being the second most affected country. The kinetics of antibody response to SARS-CoV-2 in Indian population is not studied yet. To understand serological response in relation to age, gender, time period and severity of disease, Roche Elecsys anti-SARS-CoV-2 test was used which analysed both IgM and IgG. One hundred and three COVID-19 patients were enrolled. Seropositivity was seen in 64% of patients, with 33% at ≤ 7 days, 62% between 8 and 15 days and 81% at ≥ 16 days from the time of admission. Men (65%) showed higher antibody response than women (59%), whereas no difference was observed in seropositivity with respect to age of the patients. Dynamics of antibody responses revealed individual variations. Patients in ICU had higher antibody reactivity with 67% positivity as compared to 60% positivity in non-ICU patients. Kinetics of antibody response during COVID-19 disease varied in relation to gender, age, time period and severity and these factors might play an important role in treatment and control of COVID-19.  相似文献   

4.
In December 2019, Wuhan city in the Hubei province of China reported for the first time a cluster of patients infected with a novel coronavirus, since then there has been an outburst of this disease across the globe affecting millions of human inhabitants. Severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), is a member of beta coronavirus family which upon exposure caused a highly infectious disease called novel coronavirus disease-2019 (COVID-19). COVID-19, a probably bat originated disease was declared by World Health Organization (WHO) as a global pandemic in March 2020. Since then, despite rigorous global containment and quarantine efforts, the disease has affected nearly 56,261,952 laboratory confirmed human population and caused deaths of over 1,349,506 lives worldwide. Virus passes in majority through respiratory droplets and then enters lung epithelial cells by binding to angiotensin converting enzyme 2 (ACE2) receptor and there it undergoes replication and targeting host cells causing severe pathogenesis. Majority of human population exposed to SARS-CoV-2 having fully functional immune system undergo asymptomatic infection while 5–10% are symptomatic and only 1–2% are critically affected and requires ventilation support. Older people or people with co-morbidities are severely affected by COVID-19. These categories of patients also display cytokine storm due to dysfunctional immune response which brutally destroys the affected organs and may lead to death in some. Real time PCR is still considered as standard method of diagnosis along with other serology, radiological and biochemical investigations. Till date, no specific validated medication is available for the treatment of COVID-19 patients. Thus, this review provides detailed knowledge about the different landscapes of disease incidence, etiopathogenesis, involvement of various organs, diagnostic criteria’s and treatment guidelines followed for management of COVID-19 infection since its inception. In conclusion, extensive research to recognize novel pathways and their cross talk to combat this virus in precarious settings is our future positive hope.  相似文献   

5.
Early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and diagnosis of coronavirus disease 2019 (COVID-19) are priorities during the pandemic. Symptomatic and suspected asymptomatic individuals should be tested for COVID-19 to confirm infection and to be excluded from social interactions. As molecular testing capacity is overloaded during the pandemic, rapid antigen tests, such as lateral flow immunoassays (LFIAs), can be a useful tool as they allow greater test availability and obtain results in a very short time. This short review aims to present the analytical properties of LFIAs in the detection of SARS-CoV-2 in nasopharyngeal swabs. Lateral flow immunoassay is a method that combines thin-layer chromatography and indirect immunochemical sandwich method and allows the detection of a specific SARS-CoV-2 antigen in nasopharyngeal swabs. Swab specimens should be adequately collected and tested as soon as possible. Users should pay attention to quality control and possible interferences. Antigen tests for SARS-CoV-2 show high sensitivity and specificity in cases with high viral loads, and should be used up to five days after the onset of the first symptoms of COVID-19. False positive results may be obtained when screening large populations with a low prevalence of COVID-19 infection, while false negative results may happen due to improper specimen collection or insufficient amount of antigen in the specimen. So as to achieve reliable results, a diagnostic accuracy study of a specific rapid antigen test should be performed.  相似文献   

6.
IntroductionThe data on the coronavirus disease (COVID-19) in solid-organ transplant recipients (SOTRs) in Croatia is unknown. The aim of this study was to analyze the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Croatian SOTRs.Materials and methodsFrom 7 September to 27 November 2020 (beginning of the second COVID-19 pandemic wave), a cross-sectional screening for COVID-19 was performed in the adult outpatient liver (LTRs; N = 280) and kidney transplant recipients (KTRs; N = 232). Serum samples were initially tested for SARS-CoV-2 IgG antibodies using a commercial enzyme-linked immunosorbent assay (ELISA; Vircell Microbiologists, Granada, Spain). All positive samples were confirmed using a virus neutralization test (VNT). Data on risk exposure and COVID-19 related symptoms were collected using a questionnaire.ResultsThe transplanted cohort’s seroprevalence detected by ELISA and VNT was 20.1% and 3.1%, respectively. Neutralizing (NT) antibodies developed in 15.6% of anti-SARS-CoV-2 ELISA IgG positive SOTRs. The difference in seropositivity rates between LTRs and KTRs was not statistically significant (ELISA 21.1% vs. 19.0%, P = 0.554; VNT 3.6% vs. 2.6%, P = 0.082). Overall VNT positivity rates were higher in patients who reported participation in large community events (5.9% vs. 1.0%; P = 0.027) as well as in patients who reported COVID-19 related symptoms in the past six months. In addition, symptomatic VNT positive patients showed significantly higher (P = 0.031) NT antibody titers (median 128, interquartile range (IQR) = 32-128) compared to asymptomatic patients (median 16, IQR = 16-48).ConclusionsThis study showed that 15.6% of anti-SARS-CoV-2 ELISA positive Croatian SOTRs developed NT antibodies indicating protective immunity. Further studies are needed to determine the dynamic of NT antibodies and COVID-19 immunity duration in immunocompromised populations such as LTRs and KTRs.  相似文献   

7.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of coronavirus disease-2019 (COVID-19), is a highly contagious pathogenic coronavirus to emerge and spread in human populations. Although substantial exertions have been laid to avert spread of COVID-19 by therapeutic and preventive countermeasures, but emergence of SARS-CoV-2 variants as a result of mutations make the infection more ominous. New viral confers a higher nasopharyngeal viral load, increased viral transmissibility, higher infectiousness, immune escape, increased resistance to monoclonal/polyclonal antibodies from convalescence sera/vaccine, and an enhanced virulence. Thus, it is pertinent to monitor evolving mutations and genetic diversity of SARS-CoV-2 as it is decisive for understanding the viral variants. In this review we provide an overview of colloquial nomenclature and the genetic characteristics of different SARS-CoV-2 variants in the context of mutational changes of the circulating strains, transmissibility potential, virulence and infectivity.  相似文献   

8.
Currently, world is facing a global outbreak causing a pandemic threat known as COVID-19. This infectious disease is triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Gut microbiota harbours multi species community with a strong impact on host immune homeostasis. However, our knowledge about this gut microbiota and its symbiotic relationship with immune activation in association with SARS-CoV-2 is limited. Unbalanced bacterial flora with too many opportunistic infections can shift immune system towards a cascade of inflammatory responses leading to multi organ damage. This review will highlight immune-regulation via various mechanisms in SARS-CoV-2 infection. Diet has an unbelievable influence on gut microbiome that allows a new state of homeostasis to be reached through timing, frequency and duration of intake. This review article focuses on gut, lung microbiota and immunomodulation with specific attention on immune activation by gut microbiota.  相似文献   

9.
The origin of SARS-CoV-2,the causative virus of COVID-19,has been a mys-tery since the beginning of the out-break and has been heavily debated lately.One of the...  相似文献   

10.
Political polarization remains perhaps the “greatest barrier” to effective COVID-19 pandemic mitigation measures in the United States. Social media has been implicated in fueling this polarization. In this paper, we uncover the network of COVID-19 related news sources shared to 30 politically biased and 2 neutral subcommunities on Reddit. We find, using exponential random graph modeling, that news sources associated with highly toxic – “rude, disrespectful” – content are more likely to be shared across political subreddits. We also find homophily according to toxicity levels in the network of online news sources. Our findings suggest that news sources associated with high toxicity are rewarded with prominent positions in the resultant network. The toxicity in COVID-19 discussions may fuel political polarization by denigrating ideological opponents and politicizing responses to the COVID-19 pandemic, all to the detriment of mitigation measures. Public health practitioners should monitor toxicity in public online discussions to familiarize themselves with emerging political arguments that threaten adherence to public health crises management. We also recommend, based on our findings, that social media platforms algorithmically promote neutral and scientific news sources to reduce toxic discussion in subcommunities and encourage compliance with public health recommendations in the fight against COVID-19.  相似文献   

11.
The current pandemic of COVID-19, with its climbing number of cases and deaths, has us searching for tools for rapid, reliable, and affordable methods of detection on one hand, and novel, improved therapeutic strategies on the other. The currently employed RT-PCR method, despite its all-encompassing utility, has its shortcomings. Newer diagnostic tools, based on the Clustered Regularly Interspaced Short Palindromic Repeats/Cas(CRISPR-Cas) system, with its better diagnostic accuracy measures, have come up to fill that void. These assay platforms are expected to slowly take up the place of COVID-19 diagnostics. Further, the current therapeutic options focus mainly on counteracting the viral proteins and components and their entry into host cells. The CRISPR-based system, especially through the RNA-guided Cas13 approach, can identify the genomic characteristics of SARS-CoV-2 and provide a novel inhibition strategy for coronaviruses. In this mini-review, we have discussed the available and upcoming CRISPR-based diagnostic assays and the potential of the CRISPR/Cas system as a therapeutic or prevention strategy in COVID-19. CRISPR-Cas system shows promise in both diagnostics as well as therapeutics and may as well change the face of molecular diagnosis and precision medicine.  相似文献   

12.
Coronavirus disease 2019 (COVID-19) pandemic represents a scientific and social crisis. One of the main unmet needs for coronavirus disease 2019 is its unpredictable clinical course, which can rapidly change in an irreversible outcome. COVID-19 patients can be classified into mild, moderate, and severe. Several haematological parameters, such as platelets, white blood cell total count, lymphocytes, neutrophils, (together with neutrophil-lymphocyte and platelet-lymphocyte ratio), and haemoglobin were described to be associated with COVID-19 infection and severity. The purpose of these review is to describe the current state of the art about complete blood count alterations during COVID-19 infection, and to summarize the crucial role of some haematological parameters during the course of the disease. Decreased platelet, lymphocyte, haemoglobin, eosinophil, and basophil count, increased neutrophil count and neutrophil-lymphocyte and platelet-lymphocyte ratio have been associated with COVID-19 infection and a worse clinical outcome. Our study adds some novelty about the identification of effective biomarkers of progressive disease, and might be helpful for diagnosis, prevention of complications, and effective therapy.  相似文献   

13.
Coronavirus disease 2019 (Covid-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic disease which has affected more than 6.2 million people globally, with numbers mounting considerably daily. However, till date, no specific treatment modalities are available for Covid-19 and also not much information is known about this disease. Recent studies have revealed that SARS-CoV-2 infection is associated with the generation of thrombosis and coagulopathy. Fundamentally, it has been believed that a diverse array of signalling pathways might be responsible for the activation of coagulation cascade during SARS-CoV-2 infection. Henceforth, a detailed understanding of these probable underlying molecular mechanistic pathways causing thrombosis in Covid-19 disease deserves an urgent exploration. Therefore, in this review, the hypothetical crosstalk between distinct signalling pathways including apoptosis, inflammation, hypoxia and angiogenesis attributable for the commencement of thrombotic events during SARS-CoV-2 infection has been addressed which might further unravel promising therapeutic targets in Covid-19 disease.  相似文献   

14.
科技智库是以科技战略政策研究和科技支撑公共政策为主要职能的专业研究和咨询机构,在国家科技战略和政策布局等方面发挥关键作用。面对突如其来的新冠疫情,我国相关科技智库在战略咨询研究与国际合作交流等方面发挥了重要作用。同时,疫情防控和复工复产过程中所面临的挑战,也为科技智库的进一步发展带来了启示、指明了工作方向。为进一步助力我国疫情常态化防控和复工复产、推进新时代我国科技智库的健康发展,提出科技智库下一步发展的若干建议,包括科技智库机制体制、前瞻性战略咨询研究、跨学科人才教育和培养、国际交流与合作等方面,以供相关部门和学者参考。  相似文献   

15.
《Research Policy》2022,51(1):104393
In this paper we draw a parallel between the insights developed within the framework of the current COVID-19 health crisis and the views and insights developed with respect to the long term environmental crisis, the implications for science, technology and innovation (STI) policy, Christopher Freeman analyzed already in the early 90′s. With at the time of writing, the COVID-19 pandemic entering in many countries a third wave with a very differentiated implementation path of vaccination across rich and poor countries, drawing such a parallel remains of course a relatively speculative exercise. Nevertheless, based on the available evidence of the first wave of the pandemic, we feel confident that some lessons from the current health crisis and its parallels with the long-term environmental crisis can be drawn. The COVID-19 pandemic has also been described as a “syndemic”: a term popular in medical anthropology which marries the concept of ‘synergy’ with ‘epidemic’ and provides conceptually an interesting background for these posthumous Freeman reflections on crises. The COVID-19 crisis affects citizens in very different and disproportionate ways. It results not only in rising structural inequalities among social groups and classes, but also among generations. In the paper, we focus on the growing inequality within two particular groups: youngsters and the impact of COVID-19 on learning and the organization of education; and as mirror picture, the elderly many of whom witnessed despite strict confinement in long-term care facilities, high mortality following the COVID-19 outbreak. From a Freeman perspective, these inequality consequences of the current COVID-19 health crisis call for new social STI policies: for a new “corona version” of inclusion versus exclusion.  相似文献   

16.
Documenting the emergent social representations of COVID-19 in public communication is necessary for critically reflecting on pandemic responses and providing guidance for global pandemic recovery policies and practices. This study documents the dynamics of changing social representations of the COVID-19 pandemic on one of the largest Chinese social media, Weibo, from December 2019 to April 2020. We draw on the social representation theory (SRT) and conceptualize topics and topic networks as a form of social representation. We analyzed a dataset of 40 million COVID-19 related posts from 9.7 million users (including the general public, opinion leaders, and organizations) using machine learning methods. We identified 12 topics and found an expansion in social representations of COVID-19 from a clinical and epidemiological perspective to a broader perspective that integrated personal illness experiences with economic and sociopolitical discourses. Discussions about COVID-19 science did not take a prominent position in the representations, suggesting a lack of effective science and risk communication. Further, we found the strongest association of social representations existed between the public and opinion leaders and the organizations’ representations did not align much with the other two groups, suggesting a lack of organizations’ influence in public representations of COVID-19 on social media in China.  相似文献   

17.
提出“合作创新韧性”的概念，认为合作创新韧性是区域稳定合作创新网络对抗新冠疫情冲击的重要能力。基于演化经济地理学的相关理论，利用2017—2020年中国合作专利申请微观数据及30个省域数据，探讨创新投入多样化对合作创新韧性的直接作用，及其通过经济结构影响合作创新韧性的间接作用。研究发现，新冠疫情期间，由于研发预算软约束、市场不确定性和线下交互受阻等因素，疫情冲击具有结构偏向性，对基础研究和应用研究的影响更大，表现为创新投入越多样化的省份创新韧性（对冲击的抵抗能力）则越弱；创新投入多样化通过调节产业结构的升级和企业结构影响创新韧性，疫情对不同产业结构和企业结构的地区影响具有异质性；产业结构具有完全中介效应，企业结构具有部分中介效应。  相似文献   

18.
Various technology innovations and applications have been developed to fight the coronavirus pandemic. The pandemic also has implications for the design, development, and use of technologies. There is an urgent need for a greater understanding of what roles information systems and technology researchers can play in this global pandemic. This paper examines emerging technologies used to mitigate the threats of COVID-19 and relevant challenges related to technology design, development, and use. It also provides insights and suggestions into how information systems and technology scholars can help fight the COVID-19 pandemic. This paper helps promote future research and technology development to produce better solutions for tackling the COVID-19 pandemic and future pandemics.  相似文献   

19.
【目的/意义】社会化问答社区在健康信息传播中具有关键作用,了解用户偏好的信息类型对提高信息质 量、促进与用户之间的有效沟通至关重要。【方法/过程】本研究利用多值集定性比较分析（mvQCA）方法,选取知乎 中有关COVID-19的答案,从信息特征和来源的角度确定8个前因变量,通过组态视角构建多重并发的因果关系, 最终获取不同偏好答案对应的条件组态以及特征。【结果/结论】研究发现：（1）偏好高的答案对应的组态有3种,其 中字数多和可视化是必要条件,此外用户更偏好具有损失框架、统计证据、积极情感、可视化以及包含具体链接特 征的答案;偏好低的答案对应的组态有4种,其中字数少和不包含专家是必要条件,此外用户不喜欢无框架、叙事证 据、无情感、纯文本以及无具体源特征的答案;（2）偏好高的答案其主题分布在记录各国新冠时政情况、介绍新冠预 防治疗、反映医患相关资讯以及热点“人物”介绍。本研究丰富了健康信息传播以及用户偏好信息类型的相关理论 研究,同时对提高社会化问答社区中健康信息的整体质量以及用户之间有效沟通提供参考。【创新/局限】不同于以 往研究视角,本研究通过组态视角能够更有效地挖掘多重并发的因果关系,进而获取用户偏好的不同答案类型,然 而本研究仅以小样本展开分析,未来可考虑更多样本的研究。  相似文献   

20.
COVID-19 has emerged as a global pandemic. It is mainly manifested as pneumonia which may deteriorate into severe respiratory failure. The major hallmark of the disease is the systemic inflammatory immune response characterized by Cytokine Storm (CS). CS is marked by elevated levels of inflammatory cytokines, mainly interleukin-6 (IL-6), IL-8, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Of these, IL-6 is found to be significantly associated with higher mortality. IL-6 is also a robust marker for predicting disease prognosis and deterioration of clinical profile. In this review, the pivotal role played by IL-6 in the immuno-pathology of COVID-19 has been illustrated. The role of IL-6 as a pleiotropic cytokine executing both pro and anti-inflammatory activities has been reviewed. ADAM 10, a metalloproteinase switches the anti-inflammatory pathway of IL-6 to pro inflammatory hence blocking the action of ADAM 10 could be a new therapeutic strategy to mitigate the proinflammatory action of IL-6. Furthermore, we explore the role of anti-IL6 agents, IL-6 receptor antibodies which were being used for autoimmune diseases but now are being repurposed for the therapy of COVID-19.  相似文献   

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