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Stability and infectivity of enteroviruses on dry surfaces: Potential for indirect transmission control 肠道病毒在干燥表面的稳定性和感染性:间接传播控制的潜力
Q1 Medicine Pub Date : 2023-12-01 DOI: 10.1016/j.bsheal.2023.07.001
Pichamon Sittikul , Pimolpachr Sriburin , Jittraporn Rattanamahaphoom , Warisa Nuprasert , Nipa Thammasonthijarern , Janjira Thaipadungpanit , Weerawan Hattasingh , Nathamon Kosoltanapiwat , Pilaipan Puthavathana , Supawat Chatchen

Hand, foot, and mouth disease (HFMD) is a contagious disease mainly occurring in young children, and outbreaks commonly occur among young children in the Asia–Pacific region including Thailand. Moreover, the World Health Organization (WHO) monitors HFMD in the Western Pacific region to detect outbreaks and other significant events by the Regional Event Based Surveillance System. HFMD is mainly caused by a group of enteroviruses (EVs) transmitted through direct contact (person to person) and indirect contact with contaminated objects (surface-to-hand). However, few studies have examined the surface stability of EVs. In this study, we investigated the stability of enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16) on three different dry surfaces (wood, plastic, and stainless steel) using the endpoint titration using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) staining of viable cells and real-time polymerase chain reaction (viral genome detection). The results revealed that virus infectivity dramatically decreased within a few hours on dry surfaces. However, viral RNA could be detected on dry surfaces for up to 28 days. Concerning heat inactivation, both EV-A71 and CVA16 were inactivated after exposure to 60°C for 15 min. Information on virus stability on different dry surfaces will provide useful information for HFMD transmission control.

手足口病是一种主要发生在幼儿身上的传染性疾病,在包括泰国在内的亚太地区,幼儿中经常爆发手足口病。此外,世界卫生组织(WHO)通过区域事件监测系统对西太平洋地区的手足口病进行监测,以发现疫情爆发和其他重大事件。手足口病主要由一组肠道病毒(EVs)引起,通过直接接触(人与人之间)和间接接触受污染物体(手与手之间)传播。然而,很少有研究探讨肠道病毒的表面稳定性。在本研究中,我们使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-溴化四氮唑(MTT)染色法和实时聚合酶链反应(病毒基因组检测)研究了肠病毒 A71(EV-A71)和柯萨奇病毒 A16(CVA16)在三种不同干燥表面(木材、塑料和不锈钢)上的稳定性。结果表明,在干燥的表面上,病毒的感染力在几小时内急剧下降。不过,在干燥表面上检测病毒 RNA 的时间可长达 28 天。关于热灭活,EV-A71 和 CVA16 在暴露于 60°C 15 分钟后均失活。有关病毒在不同干燥表面稳定性的信息将为手足口病传播控制提供有用信息。
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引用次数: 0
Epidemiology and characteristics of identified early mpox cases in Guangdong Province, China: Implications for prevention and control 中国广东省已发现的早期天花病例的流行病学和特征:对预防和控制的影响
Q1 Medicine Pub Date : 2023-12-01 DOI: 10.1016/j.bsheal.2023.10.003
Yinan Zong , Yuwei Yang , Dongfeng Kong , Jianxiong Xu , Zimian Liang , Fengxiang Shi , Jianhua Huang , Min Kang , Haojie Zhong , Wenjia Liang , Yan Li

In June 2023, the 2022 global mpox (monkeypox) outbreak began to affect Guangdong Province, one of the first regions in mainland China to report mpox cases. By July 10, 2023, 93 mpox cases had been reported in Guangdong Province. This study describes the epidemiological characteristics of these patients by collecting and analyzing data on demographics, sexual behavior, medical history, travel history, clinical symptoms, and diagnostic pathways and processes. The 93 mpox cases were all men aged 20-48 years, 95.70 % were men who have sex with men (MSM), and 48.39 % were HIV-positive. A few cases were married (to women) or living with children. The rash was present in almost all cases (98.91 %), with the most common sites being the genital and perianal areas (70.33 %). Intimate sexual contact was suspected to be the main route of infection, with a median incubation period of 8.5 days (IQR 5.0–11.8). The number of cases increased rapidly, and most patients had no history of international travel, suggesting sustained community transmission within the MSM population in Guangdong Province. In addition, 93.55 % of cases were detected by medical institutions, and more than half of these patients had two or more hospital visits before being diagnosed as an mpox case, indicating that clinicians need further training to increase their sensitivity to mpox. Targeted interventions should prioritize MSM while remaining vigilant for transmission to other populations, such as women and children.

2023 年 6 月,2022 年全球猴痘疫情开始影响广东省,这是中国大陆最早报告猴痘病例的地区之一。截至2023年7月10日,广东省共报告93例猴痘病例。本研究通过收集和分析人口统计学、性行为、病史、旅行史、临床症状、诊断途径和过程等方面的数据,描述了这些患者的流行病学特征。93 例艾滋病病毒感染者均为 20-48 岁的男性,95.70% 为男男性行为者(MSM),48.39% 为 HIV 阳性。少数病例已婚(与女性)或与子女同住。几乎所有病例都出现皮疹(98.91%),最常见的部位是生殖器和肛周(70.33%)。亲密的性接触被怀疑是主要的感染途径,中位潜伏期为 8.5 天(IQR 5.0-11.8)。病例数量增长迅速,大多数患者无国际旅行史,这表明广东省男男性行为者人群中存在持续的社区传播。此外,93.55%的病例由医疗机构发现,其中半数以上的患者在被诊断为麻痘病例前曾两次或两次以上到医院就诊,这表明临床医生需要进一步培训以提高对麻痘的敏感性。有针对性的干预措施应优先考虑男男性行为者,同时警惕向妇女和儿童等其他人群传播。
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引用次数: 0
Genetic characterizations and molecular epidemiology of human echovirus 30 isolated from Ningxia, China 从中国宁夏分离的人类埃可病毒 30 的遗传特征和分子流行病学研究
Q1 Medicine Pub Date : 2023-12-01 DOI: 10.1016/j.bsheal.2023.10.001
Fang Yuan , Xinfeng Wei , Xueping Ma , Jiangtao Ma , Xuemin Ma , Xiaoqiang Sun , Min Cao , Juan Zhou , Wei Zhang , Hui Chen , Rui Wang , Jichen Li , Qiang Sun

In October 2017, a small outbreak of echovirus 30 (E30) associated with aseptic meningitis in nine cases occurred at a primary school in the Ningxia Hui Autonomous Region. That year, we observed a significant increase in E30 levels in an acute flaccid paralysis (AFP) case surveillance system. To investigate their phylogenetic relationships, we determined the whole genomic sequences of 12 strains isolated from aseptic meningitis cases, AFP cases, and healthy children. We found that the E30 strains circulating in Ningxia belong to two lineages (H and J). The strains isolated in 2010, 2012, and 2016 belonged to the H lineage. In 2017, a new lineage, J, emerged as the dominant lineage. Phylogenetic trees were constructed based on the whole genome and P1, P2, and P3 regions; clustering with other types of enterovirus species B was found, suggesting that recombination events had occurred. The recombination sites were mainly in regions 2B, 2C, and 3D. This study confirmed that the E30 strains in Ningxia in 2010, 2012, and 2016 had different recombination patterns and were recombined with different enteroviruses. The 2017 epidemic E30 originated from another new lineage with a complex recombination pattern and formed an independent transmission chain in Ningxia.

2017年10月,宁夏回族自治区一所小学发生了9例与无菌性脑膜炎相关的埃可病毒30(E30)小规模暴发疫情。同年,我们在急性弛缓性麻痹(AFP)病例监测系统中观察到 E30 的水平显著上升。为了研究它们之间的系统发育关系,我们测定了从无菌性脑膜炎病例、急性弛缓性麻痹病例和健康儿童中分离出的 12 株菌株的全基因组序列。我们发现,在宁夏流行的E30菌株属于两个系(H系和J系)。2010年、2012年和2016年分离到的菌株属于H系。2017 年,一个新的品系 J 出现,成为优势品系。根据全基因组和P1、P2和P3区构建了系统发生树;发现了与其他类型肠道病毒B种的聚类,表明发生了重组事件。重组位点主要分布在 2B、2C 和 3D 区。这项研究证实,2010年、2012年和2016年宁夏的E30毒株具有不同的重组模式,并与不同的肠道病毒重组。2017年流行的E30来源于另一个新品系,具有复杂的重组模式,并在宁夏形成了独立的传播链。
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引用次数: 0
Establishment and application of national reference panels for SARS-CoV-2 antigen detection kit 建立和应用国家 SARS-CoV-2 抗原检测试剂盒参考面板
Q1 Medicine Pub Date : 2023-12-01 DOI: 10.1016/j.bsheal.2023.10.002
Tingting Ma , Donglai Liu , Keliang Lyu , Tingting Gao , Dawei Shi , Lanqing Zhao , Shu Shen , Yabin Tian , Sihong Xu , Haiwei Zhou

To develop a national reference panel for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen detection kit and establish a quality standard. The cultures of SARS-CoV-2 and other pathogens were collected to establish a national reference panel for SARS-CoV-2 antigen detection. The stability and homogeneity of the reference panel were evaluated. Based on World Health Organization (WHO) guidance and nucleic acid quantitative results, a quality standard reference panel was established. Currently, three generations of SARS-CoV-2 antigen national reference materials with batch numbers 370095–202001, 370095–202202, and 370095–202203 have been successfully established. These national reference panels comprised 8 positive samples, 20 negative samples, 1 repetitive sample, and 1 lower detection limit sample. The stability and homogeneity of the reference panel meet the requirements. The quality standards are as follows: the positive and negative coincidence rates are 8/8 and 20/20, respectively. The 10 test results of the medium and low-concentration repetitive reference materials should be positive, and the color rendering should be uniform (or the coefficient of variance should not be higher than 20.0%). The lower detection limit should be at least 5 × 105 U/mL (equivalent to copies/mL), and higher concentrations above the lower detection limit must be positive. A national reference panel for the SARS-CoV-2 antigen detection kit has been established. As the standard of SARS-CoV-2 antigen reagents, the reference panel has played a crucial role in the pre-marketing quality evaluation and post-marketing quality supervision in China.

开发严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)抗原检测试剂盒的国家参考试剂盒,并制定质量标准。收集 SARS-CoV-2 和其他病原体的培养物,建立 SARS-CoV-2 抗原检测国家参考试剂盒。对参考面板的稳定性和同质性进行了评估。根据世界卫生组织(WHO)的指导意见和核酸定量结果,建立了质量标准参考板。目前,已成功建立了三代 SARS-CoV-2 抗原国家参考材料,批号分别为 370095-202001、370095-202202 和 370095-202203。这些国家参考样本包括 8 份阳性样本、20 份阴性样本、1 份重复样本和 1 份检测下限样本。参比板的稳定性和均一性均符合要求。质量标准如下:阳性和阴性重合率分别为 8/8 和 20/20。中、低浓度重复性参比物的 10 次检测结果均应为阳性,显色均匀(或方差系数不高于 20.0%)。检测下限应至少为 5 × 105 U/mL(相当于拷贝数/毫升),高于检测下限的浓度必须为阳性。SARS-CoV-2 抗原检测试剂盒的国家参考面板已经建立。作为SARS-CoV-2抗原试剂的标准,参比架在我国SARS-CoV-2试剂上市前的质量评价和上市后的质量监管中发挥了重要作用。
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引用次数: 0
Advances in treatment strategies for COVID-19: Insights from other coronavirus diseases and prospects 新冠肺炎治疗策略的进展:来自其他冠状病毒疾病的见解和前景
Q1 Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.bsheal.2023.08.003
Yingwen Li , Jiaming Lan , Gary Wong

The coronavirus disease 2019 (COVID-19) pandemic is the third human disease outbreak caused by an emerging coronavirus in the 21st century. Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pandemic has been the most devastating, with millions of deaths. Medical countermeasures are needed to limit the number of infections and fatalities. Here, we discuss advances in clinical and research-based treatment methods for SARS-CoV-2 that were initially derived from treatments for other coronaviruses. Recent advances in SARS-CoV-2 treatments, from traditional drugs and immunotherapies to artificial intelligence to predict potential future treatment methods, are summarized and discussed.

2019冠状病毒病(新冠肺炎)大流行是21世纪由新出现的冠状病毒引起的第三次人类疾病爆发。由严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)引起的新冠肺炎大流行是最具破坏性的,有数百万人死亡。需要采取医疗对策来限制感染和死亡人数。在这里,我们讨论了严重急性呼吸系统综合征冠状病毒2型的临床和研究治疗方法的进展,这些方法最初来源于其他冠状病毒的治疗。综述和讨论了严重急性呼吸系统综合征冠状病毒2型治疗的最新进展,从传统药物和免疫疗法到预测未来潜在治疗方法的人工智能。
{"title":"Advances in treatment strategies for COVID-19: Insights from other coronavirus diseases and prospects","authors":"Yingwen Li ,&nbsp;Jiaming Lan ,&nbsp;Gary Wong","doi":"10.1016/j.bsheal.2023.08.003","DOIUrl":"10.1016/j.bsheal.2023.08.003","url":null,"abstract":"<div><p>The coronavirus disease 2019 (COVID-19) pandemic is the third human disease outbreak caused by an emerging coronavirus in the 21st century. Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pandemic has been the most devastating, with millions of deaths. Medical countermeasures are needed to limit the number of infections and fatalities. Here, we discuss advances in clinical and research-based treatment methods for SARS-CoV-2 that were initially derived from treatments for other coronaviruses. Recent advances in SARS-CoV-2 treatments, from traditional drugs and immunotherapies to artificial intelligence to predict potential future treatment methods, are summarized and discussed.</p></div>","PeriodicalId":36178,"journal":{"name":"Biosafety and Health","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41556220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
HLA-E-restricted Hantaan virus-specific CD8+ T cell responses enhance the control of infection in hemorrhagic fever with renal syndrome hla - e限制性汉滩病毒特异性CD8+ T细胞反应增强对肾综合征出血热感染的控制
Q1 Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.bsheal.2023.06.002
Kang Tang , Yusi Zhang , Xinyu Li , Chunmei Zhang , Xiaozhou Jia , Haifeng Hu , Lihua Chen , Ran Zhuang , Yun Zhang , Boquan Jin , Ying Ma

Infection with the Hantaan virus (HTNV) may result in severe hemorrhagic fever with renal syndrome (HFRS). The functions of HLA-E-restricted CD8+ T lymphocytes in virus control and vaccine development have recently received increased attention. The purpose of this research is to discover HLA-E-restricted CD8+ T cell epitopes on HTNV as well as the features of these epitope-specific CD8+ T cells in HFRS patients. To anticipate HLA-E-restricted HTNV epitopes, the NetMHCpan servers were utilized. The K562/HLA-E cell binding test and the enzyme-linked immunospot assay were used to confirm epitope binding to HLA-E. The number and features of HLA-E-restricted epitope-specific CD8+ T lymphocytes in HFRS patients were investigated using tetramer staining, intracellular cytokine labeling, proliferation, and cytotoxicity assays. Six HTNV-derived HLA-E-restricted CD8+ T cell epitopes were found in this study. In mild/moderate HFRS patients, the frequency of HLA-E-restricted epitope-specific CD8+ T cells was greater than in severe/critical patients. CD38+HLA-DR+ HLA-E-restricted CD8+ T cells were identified. Meanwhile, CD45RA+CCR7 effector memory-re-expressing CD45RA T cells with early and intermediate maturation and differentiation characteristics predominated. Notably, CD8+ T cells from milder HFRS patients produced more interferon-γ, interleukin-2, and granzyme B, had a stronger proliferative potential, and were inversely linked with the amount of plasma HTNV virus load. Furthermore, HLA-E-restricted epitope-specific CD8+ T cells demonstrated improved cytotoxic activity in vitro during the acute stage of HFRS. Taken together, the findings demonstrate the protective effects of HLA-E-restricted CD8+ T cells during HTNV infection, suggesting that HLA-E-targeted vaccines against HTNV might be developed for HLA-diverse populations.

感染汉坦病毒可能导致严重的肾综合征出血热。HLA-E限制性CD8+T淋巴细胞在病毒控制和疫苗开发中的作用最近受到越来越多的关注。本研究的目的是发现HTNV上的HLA-E限制性CD8+T细胞表位,以及这些表位特异性CD8+T淋巴细胞在HFRS患者中的特征。为了预测HLA-E限制性HTNV表位,使用NetMHCpan服务器。K562/HLA-E细胞结合试验和酶联免疫斑点试验用于证实表位与HLA-E的结合。使用四聚体染色、细胞内细胞因子标记、增殖和细胞毒性分析研究了HFRS患者中HLA-E限制性表位特异性CD8+T淋巴细胞的数量和特征。在本研究中发现了6个HTNV衍生的HLA-E限制性CD8+T细胞表位。在轻度/中度HFRS患者中,HLA-E限制性表位特异性CD8+T细胞的频率高于重症/危重症患者。鉴定出CD38+HLA-DR+HLA-E限制性CD8+T细胞。同时,CD45RA+CR7效应记忆重表达CD45RA T细胞具有早期和中期成熟和分化特征,占主导地位。值得注意的是,来自较轻HFRS患者的CD8+T细胞产生更多的干扰素-γ、白细胞介素-2和颗粒酶B,具有更强的增殖潜力,并且与血浆HTNV病毒载量呈负相关。此外,在HFRS急性期,HLA-E限制性表位特异性CD8+T细胞在体外表现出改善的细胞毒性活性。总之,这些发现证明了HLA-E限制性CD8+T细胞在HTNV感染期间的保护作用,表明针对HTNV的HLA-E靶向疫苗可能针对HLA不同的人群开发。
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引用次数: 0
Investigation into the epidemiology, genetic characteristics, and clinical manifestations of the first monkeypox outbreak in Shenzhen, China 深圳市首次猴痘疫情流行病学、遗传特征及临床表现调查
Q1 Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.bsheal.2023.08.001
Jia Wan , Xiaomin Zhang , Jing Qu , Bo Peng , Dongfeng Kong , Jianhua Lu , Qinghua Hu , Zhifeng Zhou , Haiduan Lin , Xiangjie Yao , Yulin Fu , Qing Xu , Ying Lin , Yan Yang , Jinzhen Tang , Lin Lin , Huimin Li , Ziquan Lv , Zhen Zhang , Xuan Zou , Xiaolu Shi

This paper comprehensively analyses the first-ever monkeypox outbreak in Shenzhen, China, encompassing clinical symptomatology, therapeutic approaches, epidemiological research, and comprehensive laboratory tests, aiming to establish a robust reference for future monkeypox mitigation and management strategies. The investigation involved a thorough investigation of all identified positive cases, including extensive molecular analysis by nucleic acid detection and whole-genome sequencing of the monkeypox virus. Contact tracing and containment of the infected individuals were also undertaken. Three distinct monkeypox cases were identified in this unique outbreak, exhibiting mild and atypical clinical manifestations, primarily fever and rash. All cases were associated with a single transmission chain, primarily facilitated through close contact and homosexual behavior, indicative of a high-risk factor for monkeypox transmission.

本文全面分析了中国深圳首次爆发的猴痘,包括临床症状、治疗方法、流行病学研究和综合实验室检测,旨在为未来的猴痘缓解和管理策略提供有力的参考。调查包括对所有已确认的阳性病例进行彻底调查,包括通过核酸检测和猴痘病毒全基因组测序进行广泛的分子分析。还对感染者进行了接触者追踪和控制。在这次独特的疫情中发现了三例不同的猴痘病例,表现出轻微和非典型的临床表现,主要是发烧和皮疹。所有病例都与单一传播链有关,主要通过密切接触和同性恋行为促进,这表明猴痘传播的高危因素。
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引用次数: 0
Molecular phylogenomic analysis reveals a single origin of monkeypox virus transmission in Guangzhou, China in June 2023 分子系统发育分析揭示了2023年6月中国广州猴痘病毒传播的单一起源
Q1 Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.bsheal.2023.08.002
Mengling Jiang , Xizi Deng , Qinghong Fan , Fei Gu , Huiqin Yang , Jian Wang , Xiaoping Tang , Fengyu Hu , Yun Lan , Feng Li

The monkeypox (mpox) virus has caused worldwide transmission since its initial report in England in early May 2022. Available data from the World Health Organization (WHO) show that Europe and the Americas experienced a huge wave of mpox virus infection. Now the number of infected cases is on the rise in Asia. Several sporadic infections have been reported in China. In this study, we obtained high-quality whole viral genomic sequences using a mpox virus-specific amplicon-based sequencing strategy. Our analysis of the phylogenomic characteristics indicated that all eight mpox virus sequences from Guangzhou belonged to the clade IIb lineage B.1.3 cluster. However, we could not locate the exact origins where the virus was imported, based on all the available mpox virus sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database (https://gisaid.org/), except for their closest sequence similarity to that was reported from Japan. Novel amino acid mutations were found among the eight cases, suggesting that a local transmission may have occurred in Guangzhou, China.

自2022年5月初在英格兰首次报告以来,猴痘(猴痘)病毒已在全球范围内传播。世界卫生组织(世界卫生组织)的现有数据显示,欧洲和美洲经历了一次巨大的猴痘病毒感染浪潮。现在,亚洲的感染病例数量呈上升趋势。中国报告了几例散发性感染病例。在这项研究中,我们使用基于猴痘病毒特异性扩增子的测序策略获得了高质量的全病毒基因组序列。我们的系统发育特征分析表明,8个猴痘病毒序列均属于分支IIb谱系B.1.3簇。然而,根据全球禽流感数据共享倡议(GISAID)数据库中所有可用的猴痘病毒序列,我们无法找到病毒输入的确切来源(https://gisaid.org/),除了它们与日本报道的序列最相似之外。在8例病例中发现了新的氨基酸突变,这表明中国广州可能发生了本地传播。
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引用次数: 0
Viral rebound and safety of nirmatrelvir/ritonavir for lung-transplant recipients infected with SARS-CoV-2 尼马特雷韦/利托那韦治疗严重急性呼吸系统综合征冠状病毒2型肺移植受者的病毒反弹和安全性
Q1 Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.bsheal.2023.08.004
Hui Li , Li Zhao , Ke Huang , Xiaoxing Wang , Fei Zhou , Yiming Feng , Liang Ma , Bin Cao , Wenhui Chen

Data on the viral rebound and safety of nirmatrelvir/ritonavir in lung transplant (LTx) recipients are limited. The study prospectively followed four LTx recipients. Clinical characteristics, viral RNA dynamic in throat swabs, and tacrolimus blood concentration were monitored regularly. All four LTx recipients, aged 35–74 years, were not vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They got coronavirus disease 2019 (COVID-19) after more than one week of admission during the era of Omicron. All cases received nirmatrelvir/ritonavir (NM/r) within two days of infection, and the relative viral RNA copies dropped quickly. Viral load rebound was observed in all four cases after discontinuation of the first five days of NM/r treatment. Three of them received another 5-days antiviral therapy with NM/r. The duration of positive viral PCR testing was 25-28 days. None of them progressed into severe or critical COVID-19. Tacrolimus was stopped 12 h before NM/r and held during the 5-day course of antiviral therapy. Blood concentration of tacrolimus were maintained at a baseline level during these five days. Tacrolimus was re‐initiated at its baseline daily dose 3-4 days after NM/r therapy. However, during the second round of antiviral therapy with NM/r, the concentration of tacrolimus fluctuated wildly. In conclusion, the 5-day course of NM/r treatment was not sufficient for LTx recipients and the viral rebound was common. More data are needed to clarify whether LTx recipients with SARS-CoV-2 viral rebound could benefit from additional treatment with NM/r.

关于肺移植(LTx)受者的病毒反弹和尼马特雷韦/利托那韦的安全性的数据有限。该研究对四名LTx接受者进行了前瞻性随访。定期监测临床特征、咽拭子中的病毒核糖核酸动态和他克莫司血液浓度。所有四名年龄在35-74岁之间的LTx接种者均未接种严重急性呼吸综合征冠状病毒2型疫苗。在奥密克戎时代,他们在入院一周多后感染了2019冠状病毒病(新冠肺炎)。所有病例在感染后两天内接受了尼马特雷韦/利托那韦(NM/r)治疗,相对病毒RNA拷贝数迅速下降。在停止NM/r治疗的前五天后,在所有四个病例中都观察到病毒载量反弹。其中3人接受了NM/r的5天抗病毒治疗。病毒PCR检测呈阳性的持续时间为25-28天。他们都没有进展为严重或危重的新冠肺炎。他克莫司在NM/r前12小时停药,并在抗病毒治疗的5天疗程中停药。在这五天内,他克莫司的血液浓度维持在基线水平。他克莫司在NM/r治疗后3-4天以其基线日剂量重新启动。然而,在第二轮NM/r抗病毒治疗期间,他克莫司的浓度波动很大。总之,5天疗程的NM/r治疗对LTx接受者来说是不够的,病毒反弹很常见。需要更多的数据来澄清患有严重急性呼吸系统综合征冠状病毒2型病毒反弹的LTx接受者是否可以从NM/r的额外治疗中受益。
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引用次数: 0
Incorporation of Escherichia coli heat-labile enterotoxin B subunit into rabies virus particles enhances its immunogenicity in mice and dogs 将大肠杆菌热不稳定肠毒素B亚基掺入狂犬病毒颗粒中,增强了狂犬病毒在小鼠和犬体内的免疫原性
Q1 Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.bsheal.2023.05.005
Zhiyuan Gong , Hailun Li , Meichen Qian , Yujie Bai , Hongli Jin , Jingxuan Sun , Mengyao Zhang , Cuicui Jiao , Pei Huang , Yuanyuan Li , Haili Zhang , Hualei Wang

Although inactivated vaccines against rabies have the advantage of high safety, effective protection against rabies virus (RABV) infection often requires multiple, high-dose immunization. Incorporating a molecular adjuvant into the viral particles has been found to be a useful strategy to promote the immune effectiveness of inactivated vaccines. In this study, we constructed a recombinant virus, rCVS11-LTB, which chimerically expresses a molecular adjuvant heat-labile enterotoxin B subunit (LTB) protein on the surface of the RABV particles. Immunogenicity in vivo was found to be promoted by rCVS11-LTB through the activation of dendritic cells (DCs). Our results demonstrated that inactivated rCVS11-LTB was able to induce higher levels of virus-neutralizing antibodies (VNAs) in both mice and dogs than the parent virus rCVS11, to enhance the cellular immune response and T cell immune memory in mice, and was also able to provide 100% protection in mice from lethal doses of rabies virus, indicating its potential as a safe and effective inactivated rabies vaccine candidate.

尽管狂犬病灭活疫苗具有高安全性的优点,但对狂犬病病毒(RABV)感染的有效保护通常需要多次、高剂量的免疫接种。在病毒颗粒中加入分子佐剂已被发现是提高灭活疫苗免疫效力的有用策略。在本研究中,我们构建了一种重组病毒rCVS11-LTB,该病毒在RABV颗粒表面嵌合表达分子佐剂热不稳定肠毒素B亚基(LTB)蛋白。发现rCVS11-LTB通过激活树突状细胞(DC)来促进体内免疫原性。我们的结果表明,与亲本病毒rCVS11相比,灭活的rCVS11-LTB能够在小鼠和狗中诱导更高水平的病毒中和抗体(VNA),以增强小鼠的细胞免疫反应和T细胞免疫记忆,并且还能够在小鼠中提供100%的保护,使其免受狂犬病病毒的致命剂量,表明其作为安全有效的狂犬病灭活候选疫苗的潜力。
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