新型冠状病毒抗原快速检测研发现状及展望*

新型冠状病毒肺炎疫情的全球大流行,对全球公共健康、社会和经济运转造成了重大影响。在药物研发迟滞及疫苗有效性未得到充分验证的情况下,对人群进行大规模的快速筛查,寻找潜在的感染者(尤其是轻症和无症状患者),并进行集中隔离,切断传播途径和保护易感人群是首要的任务。因此对于SARS-CoV-2感染,早期诊断尤为重要。总结现有市场上的新冠病毒抗原快速检测产品,对全球抗原快速检测市场进行分析,概述其研发的动向并展望了我国在新冠抗原检测新方法、新技术方面的自主创新能力。     

Humoral Immunity against SARS-CoV-2 and the Impact on COVID-19 Pathogenesis

It has been more than a year since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged. Many studies have provided insights into the various aspects of the immune response in coronavirus disease 2019 (COVID-19). Especially for antibody treatment and vaccine development, humoral immunity to SARS-CoV-2 has been studied extensively, though there is still much that is unknown and controversial. Here, we introduce key discoveries on the humoral immune responses in COVID-19, including the immune dynamics of antibody responses and correlations with disease severity, neutralizing antibodies and their cross-reactivity, how long the antibody and memory B-cell responses last, aberrant autoreactive antibodies generated in COVID-19 patients, and the efficacy of currently available therapeutic antibodies and vaccines against circulating SARS-CoV-2 variants, and highlight gaps in the current knowledge.     

Isolation and Growth Characteristics of SARS-CoV-2 in Vero Cell

The coronavirus disease 2019 (COVID-19) broke out in early December 2019 in Wuhan, China and escalated into a global pandemic. There is an urgent need to understand the biology of SARS-CoV-2. In this letter, we report the isolation and characterization of seven isolates of SARS-CoV-2. Results show that our viruses have 99% sequence identity with published virus sequences. In addition, all viruses grew well in Vero cells, and one of the viruses had a deletion mutation after short passage. These results shall facilitate the understanding of the characteristics of SARS-CoV-2 in vitro.     

Clinical and immunological features of convalescent pediatric patients infected with the SARS-CoV-2 Omicron variant in Tianjin,China

COVID-19 has spread surprisingly fast worldwide, and new variants continue to emerge. Recently, the World Health Organization acknowledged a new mutant strain “Omicron”, with children were accounting for a growing share of COVID-19 cases compared with other mutant strains. However, the clinical and immunological characteristics of convalescent pediatric patients after Omicron infection were lacking. In this study, we comparatively analyzed the clinical data from pediatric patients with adult patients or healthy children and the effects of SARSCoV-2 vaccine on the clinical and immune characteristics in convalescent pediatric patients. Our results indicated that convalescent pediatric patients had unique clinical and immune characteristics different from those of adult patients or healthy children, and SARS-CoV-2 vaccination significantly affected on the clinical and immune characteristics and the prevention of nucleic acid re-detectable positive (RP) in convalescent patients. Our study further deepens the understanding of the impact of Omicron on the long-term health of pediatric patients and provides a valuable reference for the prevention and treatment of children infected with Omicron.     

Structural basis of human ACE2 higher binding affinity to currently circulating Omicron SARS-CoV-2 sub-variants BA.2 and BA.1.1

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新型冠状病毒感染相关嗅觉障碍的流行现状、机制和康复

新型冠状病毒感染（coronavirus disease 2019,COVID-19）,下简称“新冠”,是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）引发的全球流行传染病。鉴于嗅觉障碍是其主要神经症状,明确相关流行现状、机制和康复对促进公共健康非常重要。文献报道的新冠相关嗅觉障碍的发生率存在差异,与评估工具、人群以及变异毒株3个因素有关。其中,不同毒株之间嗅觉障碍发生率的差异可能源于刺突糖蛋白和侵入方式的变异。在外周嗅觉系统,SARS-CoV-2主要引发嗅裂炎症、支持细胞死亡和宿主免疫反应,而关于SARS-CoV-2入侵中枢的途径和机制仍存争议。部分“长新冠”患者存在持续的嗅觉障碍,SARS-CoV-2诱发慢性炎症反应和对嗅上皮再生的破坏是其潜在的病理基础。根据嗅觉媒介假说,SARS-CoV-2可能借由嗅觉系统影响中枢功能并最终诱发神经退行性变。嗅觉训练、药物等方法可帮助新冠相关嗅觉障碍的康复。     

SARS-CoV-2重组S1和S蛋白疫苗诱导保护性免疫的研究*

目的:评价新型冠状病毒(SARS-CoV-2)重组S1蛋白和S蛋白疫苗对SARS-CoV-2的免疫保护效果。方法:将SARS-CoV-2重组S1蛋白和S蛋白分别联合氢氧化铝佐剂以0.1 μg/只、1 μg/只、5 μg/只、10 μg/只不同剂量接种6~8周BALB/c纯系健康雌性小鼠。第二次免疫后采血通过酶联免疫吸附试验(ELISA)检测血清中IgG抗体效价,通过假病毒中和试验比较免疫小鼠血清对SARS-CoV-2野生型株(WT)、英国株(B.1.1.7)、巴西株(P.1)、印度株(B.1.617.2)、Mu毒株(B.1.621)和南非株(501Y.V2-1)六种假病毒毒株中和活性效价,取脾细胞通过酶联免疫斑点技术(ELISpot)检测免疫小鼠的细胞免疫水平。结果:SARS-CoV-2重组S和S1蛋白都能诱导小鼠产生较强的IgG抗体水平。免疫S1蛋白的小鼠血清对SARS-CoV-2野生型株、英国株、巴西株有明显的中和活性,免疫S蛋白的小鼠血清除了对SARS-CoV-2野生型株、英国株、巴西株有明显中和活性之外,对印度株也有明显的中和活性,两种蛋白质免疫的小鼠血清均对野生型株中和效果最强。S蛋白免疫的小鼠脾细胞能够显著诱导出γ干扰素(IFN-γ)和白介素-4(IL-4)的产生。S蛋白诱导产生的IgG抗体、中和抗体、细胞免疫水平均高于S1。结论:SARS-CoV-2重组S蛋白疫苗能够诱导产生较强的保护性免疫应答。     

Assessment of global asymptomatic SARS-CoV-2 infection and management practices from China

With ongoing research, it was found that asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was widespread in coronavirus disease 2019 (COVID-19) populations. Studies have confirmed asymptomatic patients with COVID-19 have potential infectivity, and most of the transmission occurred before symptoms appear. Asymptomatic infection rates varied widely in different countries and regions. Identifying the asymptomatic infected persons and cutting off the infection source is an effective way to prevent the spread of this disease. However, asymptomatic patients have hidden clinical symptoms, and screening based only on the clinical symptoms of COVID-19 can easily lead to a missed diagnosis. Therefore, determining asymptomatic infection patients by SARS-CoV-2 nucleic acid testing is the gold standard. A series of prevention and control measures adopted by the Chinese government, especially the “Four Early” policy, have achieved outstanding achievements, which are worth learning from by other countries.     

Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2

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Downregulation of ACE2 expression by SARS-CoV-2 worsens the prognosis of KIRC and KIRP patients via metabolism and immunoregulation

Background: Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) allow entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells and play essential roles in cancer therapy. However, the functions of ACE2 and TMPRSS2 in kidney cancer remain unclear, especially as kidneys are targets for SARS-CoV-2 infection.Methods: UCSC Xena project, the Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases ({"type":"entrez-geo","attrs":{"text":"GSE30589","term_id":"30589"}}GSE30589 and {"type":"entrez-geo","attrs":{"text":"GSE59185","term_id":"59185"}}GSE59185) were searched for gene expression in human tissues, gene expression data, and clinical information. Several bioinformatics methods were utilized to analyze the correlation between ACE2 and TMPRSS2 with respect to the prognosis of kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP).Results: ACE2 expression was significantly upregulated in tumor tissue, while its downregulation was associated with low survival in KIRC and KIRP patients. TMPRSS2 was downregulated in KIRC and KIRP, and its expression was not correlated with patient survival. According to clinical risk factor-based prediction models, ACE2 exhibits predictive accuracy for kidney cancer prognosis and is correlated with metabolism and immune infiltration. In an animal model, ACE2 expression was remarkably downregulated in SARS-CoV-2-infected cells compared to in the control.Conclusion: ACE2 expression is highly correlated with various metabolic pathways and is involved in immune infiltration.it plays a crucial role than TMPRSS2 in diagnosing and prognosis of kidney cancer patients. The overlap in ACE2 expression between kidney cancer and SARS-CoV-2 infection suggests that patients with KIRC or KIRP are at high risk of developing serious symptoms.     

Vaccine protection against the SARS-CoV-2 Omicron variant in macaques

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The One Hour COVID Test: A Rapid Colorimetric Reverse-Transcription LAMP–Based COVID-19 Test Requiring Minimal Equipment

At this writing, over 100 million people have tested positive for Corona Virus Disease-19 (COVID-19), and the global death toll from this disease has reached nearly 3 million. Despite the many tests currently available, we have not yet achieved the testing capacity needed to limit the spread of the virus and mitigate suffering worldwide. We have developed the One Hour COVID Test to address this challenge. Our test leverages an easy-to-use, commercially available oral swab kit for sample collection paired with a novel RNA processing protocol and a simple colorimetric assay that requires minimal equipment. The test can be easily scaled via automation and takes 1 h from sample collection to result.     

新型冠状病毒序列变异时空分析系统的设计与实现

新型冠状病毒肺炎目前已进入全球大流行状态,多个国家出现疫情爆发。美国疾病管制局期刊《新兴传染病》发表的关于新型冠状病毒的最新研究结论显示,新型冠状病毒基本传染数R0的中位数高达5.7,这意味着在未来较长时间内新型冠状病毒可能会在人群中持续传播并发生变异。在这一背景下,如何监视病毒的变异,对于冠状病毒的研究和药物研发具有重要意义。本文基于来自GISAID的病毒基因组序列数据,设计和实现了新型冠状病毒变异时空分析系统。该系统可对来自不同国家和地区的新型冠状病毒序列数进行统计,对病毒序列在不同时间、不同空间内的变异情况进行分析和可视化,同时还支持不同序列之间的差异比对。该系统可为新型冠状病毒肺炎的研究和政府的疾病控制机构的决策提供支持。     

Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants

Virologica Sinica - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies...     

Perspective on the status and behaviour of SARS-CoV-2 in soil

Soil contamination by SARS-CoV-2 is highly probable because soil can collect several transporters of the virus, such as fallout aerosols, wastewaters, relatively purified sludges, and organic residues. However, the fate and status of SARS-CoV-2 in soil and the possible risks for human health through contaminated food are unknown. Therefore, this perspective paper discusses the challenges of determining the SARS-CoV-2 in soil and the mechanisms concerning its adsorption, movement, and infectivity in soil, considering what has already been reported by perspective papers published up to May 2021. These issues are discussed, drawing attention to the soil virus bibliography and considering the chemical structure of the virus. The mechanistic understanding of the status and behavior of SARS-CoV-2 in soil requires setting up an accurate determination method. In addition, future researches should provide insights into i) plant uptake and movement inside the plant, ii) virus adsorption and desorption in soil with the relative infectivity, and iii) its effects on soil functions. Models should simulate spatial localization of virus in the soil matrix.     

Current development of COVID-19 diagnostics,vaccines and therapeutics

A novel coronavirus, designated as SARS-CoV-2, first emerged in Wuhan City, Hubei Province, China, in late December 2019. The rapidly increasing number of cases has caused worldwide panic. In this review, we describe some currently applied diagnostic approaches, as well as therapeutics and vaccines, to prevent, treat and control further outbreaks of SARS-CoV-2 infection.     

新型冠状病毒亚单位疫苗研究进展及现状*

自新型冠状病毒肺炎在2019年年末暴发以来,如何高效防控疫情一直是紧急的全球公共安全事件。疫苗是有效阻止病毒感染人体、保护高危人群免于疾病快速进展以及遏制疫情进一步扩大的手段之一,其中亚单位疫苗的主要成分为特定的病毒抗原蛋白或多肽,通过加入疫苗佐剂提高抗原的免疫原性。由于机体仅针对重组蛋白表面的特定抗原表位进行识别并产生抗体,因此亚单位疫苗具有较高的保护能力和安全性。通过对目前已上市及处于临床阶段的各类新型冠状病毒亚单位疫苗进行梳理,介绍了各类亚单位疫苗的抗原设计策略和佐剂选择、整体保护能力及研究进展,并对亚单位疫苗的应用及技术优势进行分析,期望能为亚单位疫苗研发及全球疫情防控提供参考。