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Failure of bamlanivimab with selection of E484K mutation in an allogeneic stem cell transplant recipient with nosocomial SARS-CoV-2 infection. 在一名感染 SARS-CoV-2 的同种异体干细胞移植受者中,选择 E484K 突变的巴马伊单抗治疗失败。
IF 1.2 4区 医学 Q4 INFECTIOUS DISEASES Pub Date : 2024-02-01 DOI: 10.1177/13596535221097495
Inès Boussen, Maud Salmona, Flore Sicre De Fontbrune, Aliénor Xhaard, Nathalie De Castro, Constance Delaugerre, Marie-Laure Chaix, Jean-Michel Molina

We report the case of an allogeneic stem cell transplant recipient with nosocomial acquisition of SARS-CoV-2 infection who received antispike neutralizing monoclonal antibody bamlanivimab 2 days after diagnosis of SARS-CoV-2 infection but progressed to severe COVID-19 pneumonia and died with the selection of E484K/Q resistance mutations to bamlanivimab.

我们报告了一例异体干细胞移植受者的病例,该受者在确诊感染 SARS-CoV-2 2 天后接受了抗梭形病毒中和单克隆抗体巴马替尼,但病情恶化为严重的 COVID-19 肺炎,并因对巴马替尼产生 E484K/Q 抗性突变而死亡。
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引用次数: 0
Cross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA. CAPELLA 研究第 52 周的入口抑制剂交叉耐药性和来那卡韦耐药性。
IF 1.2 4区 医学 Q4 INFECTIOUS DISEASES Pub Date : 2023-12-01 DOI: 10.1177/13596535231220754
Nicolas Margot, Nina Pennetzdorfer, Vidula Naik, Martin Rhee, Christian Callebaut

Background: Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function for the treatment of heavily treatment-experienced people with HIV (PWH) harbouring multidrug resistance in combination with an optimized background regimen (OBR). Here, we describe in vitro analysis of the interplay between entry inhibitors (EI; enfuvirtide, fostemsavir, ibalizumab, and maraviroc) susceptibility and LEN susceptibility in samples from 72 participants in the phase 2/3 CAPELLA study, as well as the emergence of resistance in CAPELLA through 52 weeks.

Methods: The phenotypic susceptibility to EIs of screening samples from participants was analysed using entry assays, and susceptibility to LEN was generated. Genotypic and phenotypic resistance to LEN was evaluated for subjects with virological failure through Week 52.

Results: Overall, viruses with resistance to EIs showed no cross-resistance to LEN, with a mean fold change from wild type close to 1.0. Of the 22 participants analysed for resistance through Week 52, 9 participants (13%) had emergence of capsid resistance mutation(s) while the remaining 13 participants (18%) had no change in the capsid sequence.

Conclusion: The gag sequence from EI-resistant isolates did not affect LEN susceptibility. The lack of cross-resistance to LEN across ARV-resistant isolates supports the use of LEN in PWH regardless of their treatment history. During the second half-year period of the CAPELLA Study, development of LEN resistance was rare and was overall associated with functional LEN monotherapy due to either nonadherence or resistance-driven non-susceptibility to OBR.

背景:来那卡韦(LEN)是第一类人类免疫缺陷病毒1型(HIV-1)衣壳功能抑制剂,用于治疗存在多药耐药性的重度治疗经验HIV感染者(PWH),并与优化背景方案(OBR)联合使用。在此,我们描述了在体外分析2/3期CAPELLA研究中72名参与者样本中入口抑制剂(EI;恩夫韦地、福斯替沙韦、伊巴利珠单抗和马拉韦罗)敏感性和LEN敏感性之间的相互作用,以及CAPELLA在52周内出现耐药性的情况:方法:使用入口检测法分析了参与者筛选样本对 EIs 的表型药敏性,并生成了对 LEN 的药敏性。对第 52 周之前出现病毒学失败的受试者的基因型和表型对 LEN 的耐药性进行了评估:总体而言,对 EIs 产生耐药性的病毒对 LEN 没有交叉耐药性,与野生型相比的平均折叠变化接近 1.0。在第 52 周耐药性分析的 22 名参与者中,9 名参与者(13%)出现了囊膜耐药性突变,其余 13 名参与者(18%)的囊膜序列没有变化:结论:耐 EI 分离物的 gag 序列不会影响 LEN 的敏感性。耐抗逆转录病毒药物的分离株对 LEN 没有交叉耐药性,这支持了在 PWH 中使用 LEN,无论其治疗史如何。在CAPELLA研究的后半年期间,LEN耐药性的产生非常罕见,总体上与功能性LEN单药治疗有关,原因是不坚持治疗或对OBR产生耐药性。
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引用次数: 0
Dolutegravir and rilpivirine as successful initial antiretroviral therapy in a treatment-naive patient with HIV-1: A case report. 多替格拉韦和利匹韦林作为HIV-1初次治疗患者成功的初始抗逆转录病毒治疗:一个病例报告。
IF 1.2 4区 医学 Q4 INFECTIOUS DISEASES Pub Date : 2023-12-01 DOI: 10.1177/13596535231218875
S Jawad Zafar, Bruce L Gilliam, Sarah A Schmalzle
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引用次数: 0
RVX-208, an inducer of Apolipoprotein A-I, inhibits the particle production of hepatitis B virus through activation of cGAS-STING pathway. 载脂蛋白A-I诱导剂RVX-208通过激活cGAS-STING途径抑制乙型肝炎病毒颗粒的产生。
IF 1.2 4区 医学 Q4 INFECTIOUS DISEASES Pub Date : 2023-12-01 DOI: 10.1177/13596535231219639
Dan Shu, Lin Cheng, Kefei Yuan, Dan Liu, He Wei

Background: Previously, we have demonstrated that Apolipoprotein A-I (ApoA-I) could inhibit the secretion of Hepatitis B virus (HBV), suggesting that stimulation of ApoA-I may block particle production. In the present study, we evaluated the anti-HBV effect of RVX-208, a small-molecule stimulator of ApoA-I gene expression.

Methods: RVX-208 was used to treat HepG2.2.15 cell, a HepG2 derived cell line stably producing HBV virus. Real-time PCR was performed to examine the HBV DNA levels. Magnetic particles, which were coated with anti-HBS or anti-HBE antibody, were used to examine the HBsAg and HBeAg levels in the supernatant of cultured HepG2.2.15 cells in combination with the enzyme conjugates that were prepared with horseradish peroxidase labelled anti-HBS or anti-HBE antibody in a double antibody sandwich manner. RNA-seq, immunoblots and real-time PCR were used to analyze the functional mechanism of RVX-208.

Results: RVX-208 could elevate the ApoA-I protein levels in HepG2.2.15 cells. In the meantime, RVX-208 significantly repressed HBV DNA, HBsAg and HBeAg levels in the supernatants of HepG2.2.15 cells. RNA-seq data revealed that RVX-208 treatment not only affected the cholesterol metabolism, which is closely related to ApoA-I, but also regulated signalling pathways that are associated with antiviral immune response. Moreover, mechanistic studies demonstrated that RVX-208 could activate cGAS-STING pathway and upregulate the transcription of a series of interferons, pro-inflammatory cytokines and chemokines with antiviral potential that are at the downstream of cGAS-STING pathway.

Conclusion: Our study demonstrated that RVX-208, an inducer of ApoA-I, could suppress HBV particle production through activation of cGAS-STING pathway.

背景:以前,我们已经证明载脂蛋白A-I (ApoA-I)可以抑制乙型肝炎病毒(HBV)的分泌,这表明ApoA-I的刺激可能会阻断颗粒的产生。在本研究中,我们评估了RVX-208的抗hbv作用,RVX-208是一种ApoA-I基因表达的小分子刺激剂。方法:RVX-208作用于HepG2衍生细胞系HepG2.2.15细胞,该细胞系稳定产生HBV病毒。实时荧光定量PCR检测HBV DNA水平。用磁性颗粒包被抗hbs或抗hbe抗体,结合辣根过氧化物酶标记的抗hbs或抗hbe抗体制备的酶偶联物,双抗体夹心法检测HepG2.2.15细胞培养上清中HBsAg和HBeAg的水平。采用RNA-seq、免疫印迹和实时荧光定量PCR分析RVX-208的作用机制。结果:RVX-208可提高HepG2.2.15细胞的ApoA-I蛋白水平。同时,RVX-208显著抑制HepG2.2.15细胞上清液中HBV DNA、HBsAg和HBeAg水平。RNA-seq数据显示,RVX-208治疗不仅影响与ApoA-I密切相关的胆固醇代谢,而且还调节与抗病毒免疫应答相关的信号通路。此外,机制研究表明,RVX-208可激活cGAS-STING通路,上调cGAS-STING通路下游一系列干扰素、促炎细胞因子和具有抗病毒潜力的趋化因子的转录。结论:我们的研究表明,ApoA-I诱导剂RVX-208可以通过激活cGAS-STING途径抑制HBV颗粒的产生。
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引用次数: 0
Waitlist-controlled trial of an online intervention to address mental health among older people living with HIV. 在线干预解决老年艾滋病毒感染者心理健康问题的候补对照试验。
IF 1.2 4区 医学 Q4 INFECTIOUS DISEASES Pub Date : 2023-12-01 DOI: 10.1177/13596535231216311
Jeff Berko, Peter Mazonson, Duncan Short, Maile Karris, Lynsay Ehui, Cassidy A Gutner, Frank Spinelli, Andrew Zolopa

Background: Older people living with HIV (PLWH) often experience elevated levels of depression, anxiety, and loneliness.Methods: This waitlist-controlled trial examined the effectiveness of online audio mindfulness lessons in impacting these feelings among older PLWH.Results: Among 214 participants, the mean (SD) age was 60.4 (5.9) years, 89% were male, and 69% were white. After 25 days, the intervention group showed significant improvements versus the waitlist control group in symptoms of depression (20.3% improvement, p < .01) and symptoms of anxiety (22.4% improvement, p = .03), but not in loneliness as measured by a Daily Diary (12.9% improvement, p = .07) or the 3-Item Loneliness Scale (4.8% improvement, p = .27). Secondary analyses among participants with elevated baseline symptoms of depression showed a 26.3% improvement (p < .01), with a moderate effect size (Hedge's g = 0.69). Similarly, those with elevated baseline symptoms of anxiety showed a 25.6% improvement (p < .01), a moderate effect size (g = 0.54), while those with moderate or severely elevated loneliness showed an 18.9% improvement in daily loneliness (p < .01), a moderate effect size (g = 0.55).Conclusion: This waitlist-controlled trial is the first to show that a series of brief, online audio mindfulness lessons improves mental health outcomes among older PLWH. For many patients, this intervention may offer relief that is both accessible and affordable.

背景:老年艾滋病毒感染者(PLWH)经常经历高水平的抑郁、焦虑和孤独。方法:这项候补对照试验检验了在线音频正念课程对老年PLWH患者这些感受的影响。结果:在214名参与者中,平均(SD)年龄为60.4(5.9)岁,89%为男性,69%为白人。25天后,干预组在抑郁症状(改善20.3%,p < 0.01)和焦虑症状(改善22.4%,p = 0.03)方面与等候名单对照组相比有显著改善,但在每日日记(改善12.9%,p = 0.07)或3项孤独量表(改善4.8%,p = 0.27)方面没有改善。在基线抑郁症状升高的参与者中进行的二次分析显示改善26.3% (p < 0.01),具有中等效应大小(Hedge’s g = 0.69)。同样,焦虑基线症状升高的患者表现出25.6%的改善(p < 0.01),中等效应量(g = 0.54),而孤独感中度或重度升高的患者表现出18.9%的日常孤独感改善(p < 0.01),中等效应量(g = 0.55)。结论:这项候补对照试验首次表明,一系列简短的在线音频正念课程可以改善老年PLWH患者的心理健康状况。对于许多患者来说,这种干预可能提供既容易获得又负担得起的缓解。
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引用次数: 0
Andrographolide inhibits infectious bronchitis virus-induced apoptosis, pyroptosis, and inflammation. 穿心莲内酯抑制传染性支气管炎病毒诱导的细胞凋亡、pyroptosis和炎症。
IF 1.2 4区 医学 Q4 INFECTIOUS DISEASES Pub Date : 2023-10-01 DOI: 10.1177/13596535231207499
Jiachen Shen, Qiuchi Xu, Lu Chen, Xinyu Chang, Ruiting Shen, Zhenhua Zhao, Lifei Zhu, Yifei Wu, Xiaolin Hou

Background: Avian infectious bronchitis virus (IBV), a coronavirus, causes a huge economic loss to the poultry industry. Andrographolide (APL) is a compound with a variety of pharmacological properties, including antiviral and anti-inflammatory effects. In this study, APL was evaluated for antiviral activity by its anti-apoptotic, anti-pyroptosis, and anti-inflammatory effects.

Methods: The cytotoxicity of APL was determined by the MTT method. We investigated the therapeutic impact of APL on IBV through a plate assay. We explored that APL inhibited IBV-induced apoptosis, pyroptosis, and inflammation in HD11 cells by RT-qPCR and immunofluorescence. Also, it was verified in the clinical chicken embryo trial.

Results: We found that APL down-regulated apoptosis-related genes Caspase-3, Caspase-8, Caspase-9, Bax, Bid, and Bak, down-regulated pyroptosis gene DFNA5, and down-regulated inflammation-related genes (NF-κB, NLRP3, iNOS, TNF-α, and IL-1β). In addition, APL reduced the reactive oxygen species (ROS) production in cells. Finally, clinical trials showed that APL inhibited IBV-induced apoptosis, pyroptosis, and inflammation, as well as reduced the mortality and malformation of chicken embryos.

Conclusions: In this study, we delved into the antiviral properties of APL in the context of chicken macrophage (HD11) infection with IBV. Our findings confirm that andrographolide effectively inhibits apoptosis, pyroptosis, and inflammation by IBV infection. Furthermore, this inhibition was verified on chicken embryos in vivo. This inhibition suggests a substantial potential for APL as a therapeutic agent to mitigate the harmful effects of IBV on host cells.

背景:鸡传染性支气管炎病毒(IBV)是一种冠状病毒,给家禽业造成了巨大的经济损失。穿心莲内酯(APL)是一种具有多种药理特性的化合物,包括抗病毒和抗炎作用。在本研究中,APL通过其抗细胞凋亡、抗pyroptosis和抗炎作用来评估其抗病毒活性。方法:采用MTT法测定APL的细胞毒性。我们通过平板试验研究了APL对IBV的治疗作用。我们通过RT-qPCR和免疫荧光研究了APL对IBV诱导的HD11细胞凋亡、pyroptosis和炎症的抑制作用。并在临床鸡胚试验中得到验证。结果:APL下调凋亡相关基因Caspase-3、Caspase-8、Caspase-9、Bax、Bid和Bak,下调pyroptosis基因DFNA5,下调炎症相关基因(NF-κB、NLRP3、iNOS、TNF-α和IL-1β)。此外,APL降低了细胞中活性氧(ROS)的产生。最后,临床试验表明,APL抑制了IBV诱导的细胞凋亡、焦下垂和炎症,并降低了鸡胚的死亡率和畸形率。结论:在本研究中,我们深入研究了APL在鸡巨噬细胞(HD11)感染IBV的情况下的抗病毒特性。我们的研究结果证实,穿心莲内酯有效抑制IBV感染引起的细胞凋亡、pyroptosis和炎症。此外,这种抑制作用在体内的鸡胚上得到了验证。这种抑制作用表明APL作为一种治疗剂有很大的潜力来减轻IBV对宿主细胞的有害影响。
{"title":"Andrographolide inhibits infectious bronchitis virus-induced apoptosis, pyroptosis, and inflammation.","authors":"Jiachen Shen, Qiuchi Xu, Lu Chen, Xinyu Chang, Ruiting Shen, Zhenhua Zhao, Lifei Zhu, Yifei Wu, Xiaolin Hou","doi":"10.1177/13596535231207499","DOIUrl":"10.1177/13596535231207499","url":null,"abstract":"<p><strong>Background: </strong>Avian infectious bronchitis virus (IBV), a coronavirus, causes a huge economic loss to the poultry industry. Andrographolide (APL) is a compound with a variety of pharmacological properties, including antiviral and anti-inflammatory effects. In this study, APL was evaluated for antiviral activity by its anti-apoptotic, anti-pyroptosis, and anti-inflammatory effects.</p><p><strong>Methods: </strong>The cytotoxicity of APL was determined by the MTT method. We investigated the therapeutic impact of APL on IBV through a plate assay. We explored that APL inhibited IBV-induced apoptosis, pyroptosis, and inflammation in HD11 cells by RT-qPCR and immunofluorescence. Also, it was verified in the clinical chicken embryo trial.</p><p><strong>Results: </strong>We found that APL down-regulated apoptosis-related genes Caspase-3, Caspase-8, Caspase-9, Bax, Bid, and Bak, down-regulated pyroptosis gene DFNA5, and down-regulated inflammation-related genes (NF-κB, NLRP3, iNOS, TNF-α, and IL-1β). In addition, APL reduced the reactive oxygen species (ROS) production in cells. Finally, clinical trials showed that APL inhibited IBV-induced apoptosis, pyroptosis, and inflammation, as well as reduced the mortality and malformation of chicken embryos.</p><p><strong>Conclusions: </strong>In this study, we delved into the antiviral properties of APL in the context of chicken macrophage (HD11) infection with IBV. Our findings confirm that andrographolide effectively inhibits apoptosis, pyroptosis, and inflammation by IBV infection. Furthermore, this inhibition was verified on chicken embryos in vivo. This inhibition suggests a substantial potential for APL as a therapeutic agent to mitigate the harmful effects of IBV on host cells.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"28 5","pages":"13596535231207499"},"PeriodicalIF":1.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41231919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Computer-assisted drug discovery of potential natural inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase through a multi-phase in silico approach. 通过多阶段计算机辅助药物发现严重急性呼吸系统综合征冠状病毒2型RNA依赖性RNA聚合酶的潜在天然抑制剂。
IF 1.2 4区 医学 Q4 INFECTIOUS DISEASES Pub Date : 2023-10-01 DOI: 10.1177/13596535231199838
Eslam B Elkaeed, Bshra A Alsfouk, Tuqa H Ibrahim, Reem K Arafa, Hazem Elkady, Ibrahim M Ibrahim, Ibrahim H Eissa, Ahmed M Metwaly

Background: The COVID-19 pandemic has led to significant loss of life and economic disruption worldwide. Currently, there are limited effective treatments available for this disease. SARS-CoV-2 RNA-dependent RNA polymerase (SARS-CoV-2 RdRp) has been identified as a potential target for drug development against COVID-19. Natural products have been shown to possess antiviral properties, making them a promising source for developing drugs against SARS-CoV-2.

Objectives: The objective of this study is to identify the most effective natural inhibitors of SARS-CoV-2 RdRp among a set of 4924 African natural products using a multi-phase in silico approach.

Methods: The study utilized remdesivir (RTP), the co-crystallized ligand of RdRp, as a starting point to select compounds that have the most similar chemical structures among the examined set of compounds. Molecular fingerprints and structure similarity studies were carried out in the first part of the study. The second part of the study included molecular docking against SARS-CoV-2 RdRp (PDB ID: 7BV2) and Molecular Dynamics (MD) simulations including the calculation of RMSD, RMSF, Rg, SASA, hydrogen bonding, and PLIP. Moreover, the calculations of Molecular mechanics with generalised Born and surface area solvation (MM-GBSA) Lennard-Jones and Columbic electrostatic interaction energies have been conducted. Additionally, in silico ADMET and toxicity studies were performed to examine the drug likeness degrees of the selected compounds.

Results: Eight compounds were identified as the most effective natural inhibitors of SARS-CoV-2 RdRp. These compounds are kaempferol 3-galactoside, kaempferol 3-O-β-D-glucopyranoside, mangiferin methyl ether, luteolin 7-O-β-D-glucopyranoside, quercetin-O-β-D-3-glucopyranoside, 1-methoxy-3-indolylmethyl glucosinolate, naringenin, and asphodelin A 4'-O-β-D-glucopyranoside.

Conclusion: The results of this study provide valuable information for the development of natural product-based drugs against COVID-19. However, the elected compounds should be further studied in vitro and in vivo to confirm their efficacy in treating COVID-19.

背景:新冠肺炎大流行已在全球范围内造成重大生命损失和经济混乱。目前,这种疾病的有效治疗方法有限。SARS-CoV-2 RNA依赖性RNA聚合酶(SARS-CoV-2 RdRp)已被确定为针对新冠肺炎的药物开发的潜在靶点。天然产物已被证明具有抗病毒特性,使其成为开发抗严重急性呼吸系统综合征冠状病毒2型药物的有前景的来源。方法:该研究以RdRp的共结晶配体瑞德西韦(RTP)为起点,在所检查的一组化合物中选择化学结构最相似的化合物。研究的第一部分进行了分子指纹图谱和结构相似性研究。研究的第二部分包括针对严重急性呼吸系统综合征冠状病毒2型RdRp的分子对接(PDB ID:7BV2)和分子动力学(MD)模拟,包括RMSD、RMSF、Rg、SASA、氢键和PLIP的计算。此外,还用广义Born和表面积溶剂化(MM-GBSA)Lennard-Jones和Columbic静电相互作用能计算了分子力学。此外,还进行了计算机ADMET和毒性研究,以检查所选化合物的药物相似程度。结果:8个化合物被鉴定为最有效的严重急性呼吸系统综合征冠状病毒2型RdRp的天然抑制剂。这些化合物是山奈酚3-半乳糖苷、山奈酚3-O-β-D-吡喃葡萄糖糖苷、芒果苷甲醚、木犀草素7-O-β-D-吡喃葡萄糖苷、槲皮素-O-β-D-3-吡喃葡萄糖甙、1-甲氧基-3-吲哚甲基硫代葡萄糖苷、柚皮素、,结论:本研究结果为开发抗新冠肺炎的天然产物药物提供了有价值的信息。然而,应在体外和体内进一步研究所选化合物,以确认其治疗新冠肺炎的疗效。
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引用次数: 2
Subacute thyroiditis following COVID-19 vaccination: Case presentation. 新冠肺炎疫苗接种后的亚急性甲状腺炎:病例介绍。
IF 1.2 4区 医学 Q4 INFECTIOUS DISEASES Pub Date : 2023-10-01 DOI: 10.1177/13596535231208831
Aleksandra Z Tomic, Sonja S Zafirovic, Zoran M Gluvic, Vladimir S Samardzic, Mirjana T Macvanin, Maja Lj Radunovic, Esma R Isenovic

Background: Subacute thyroiditis (SAT) is an organ-specific disease that various drugs, including COVID-19 vaccines, can trigger. COVID-19 infection has been associated with thyroid gland damage and disease SARS-CoV-2 direct action, euthyroid sick syndrome, and immune-mediated mechanisms are all potential mechanisms of thyroid damage. It denotes thyroid gland inflammation, most commonly of viral origin, and belongs to the transitory, self-limiting thyroid gland diseases group, causing complications in approximately 15% of patients in the form of permanent hypothyroidism. Some authors say SAT is the most common thyroid disease associated with COVID-19.Purpose: The occurrence of SAT many weeks after administering the second COVID-19 vaccine is rare and has limited documentation in academic literature. This study aims to present the occurrence of SAT after administering the COVID-19 vaccine. We present the case of a 37-year-old man who developed SAT 23 days after receiving the second dose of Pfizer BioNTech's COVID-19 mRNA vaccine.Research design and study sample: Due to neck pain and an elevated body temperature (up to 38.2°C), a 37-year-old male subject presented for examination 23 days after receiving the second Pfizer BioNTech mRNA vaccine against SARS-CoV-2 viral infection. The patient denied ever having an autoimmune disease or any other disease. Painful neck palpation and a firm, slightly enlarged thyroid gland with no surrounding lymphadenopathy were identified during the exam. The heart rate was 104 beats per minute. All of the remaining physical findings were normal.Data collection and/or Analysis: Data collected during the disease are integral to the medical record.Results: Hematology and biochemistry analyses at the initial and follow-up visits revealed minor leukocytosis, normocytic anaemia, and thrombocytosis, followed by a mild increase in lactate dehydrogenase and decreased iron levels. The patient's thyroid function and morphology had recovered entirely from post-vaccine SAT.Conclusions: Results from this study emphasise the need for healthcare professionals to promptly report any case of SAT related to COVID-19 vaccination. Further investigation is warranted to understand the immunopathogenesis of COVID-19-associated thyroiditis and the impact of COVID-19 immunization on this condition.

背景:亚急性甲状腺炎(SAT)是一种器官特异性疾病,包括新冠肺炎疫苗在内的各种药物都可能引发。新冠肺炎感染与甲状腺损伤和疾病有关,SARS-CoV-2直接作用、甲状腺功能正常综合征和免疫介导机制都是甲状腺损伤的潜在机制。它表示甲状腺炎症,最常见的是病毒性炎症,属于短暂性、自限性甲状腺疾病组,约15%的患者会出现永久性甲状腺功能减退的并发症。一些作者表示,SAT是与新冠肺炎相关的最常见的甲状腺疾病。目的:在接种第二剂新冠肺炎疫苗数周后,SAT的发生是罕见的,学术文献中的文献也有限。本研究旨在介绍接种新冠肺炎疫苗后SAT的发生情况。我们介绍了一名37岁男子的病例,他在接种第二剂辉瑞-BioNTech的新冠肺炎mRNA疫苗23天后出现SAT。研究设计和研究样本:由于颈部疼痛和体温升高(高达38.2°C),一名37岁的男性受试者在接种第二种针对严重急性呼吸系统综合征冠状病毒2型病毒感染的辉瑞-BioNTech信使核糖核酸疫苗23天后接受检查。该患者否认曾患有自身免疫性疾病或任何其他疾病。检查中发现颈部触诊疼痛,甲状腺肿大,周围无淋巴结肿大。心率为每分钟104次。所有剩余的身体检查结果均正常。数据收集和/或分析:在疾病期间收集的数据是医疗记录的组成部分。结果:初次和随访时的血液学和生物化学分析显示有轻微的白细胞增多、正常细胞贫血和血小板增多,随后乳酸脱氢酶轻度升高,铁水平下降。患者的甲状腺功能和形态已从疫苗接种后的SAT中完全恢复。结论:这项研究的结果强调,医护人员需要及时报告任何与新冠肺炎疫苗接种有关的SAT病例。有必要进行进一步调查,以了解COVID-19相关甲状腺炎的免疫发病机制以及新冠肺炎免疫对这种情况的影响。
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引用次数: 0
HIV drug resistance in the era of contemporary antiretroviral therapy: A clinical perspective. 当代抗逆转录病毒治疗时代的艾滋病毒耐药性:临床视角。
IF 1.2 4区 医学 Q4 INFECTIOUS DISEASES Pub Date : 2023-10-01 DOI: 10.1177/13596535231201162
Andrew Carr, Nicola E Mackie, Roger Paredes, Kiat Ruxrungtham

Contemporary antiretroviral therapy (ART) regimens have high barriers to the development of drug resistance. However, resistance to earlier antiretrovirals and uncommon cases of resistance to contemporary ART illustrate the continued need for good clinical management of HIV drug resistance. Here, we describe HIV drug-resistance mechanisms, the interaction of HIV drug-resistant mutations and the patterns of drug resistance to contemporary ART. We then provide guidance on the management of HIV drug resistance, including how to limit the development of resistance and manage virologic failure that is complicated by resistance. To complement this, links to resources and treatment guidelines are provided that can assist with the interpretation of HIV drug resistance test results and optimal ART selection in the clinic.

当代抗逆转录病毒疗法(ART)方案对耐药性的发展具有很高的障碍。然而,对早期抗逆转录病毒药物的耐药性和对当代抗逆转录病毒疗法的罕见耐药性表明,仍然需要对艾滋病毒耐药性进行良好的临床管理。在这里,我们描述了HIV耐药性机制、HIV耐药性突变的相互作用以及对当代抗逆转录病毒疗法的耐药性模式。然后,我们就HIV耐药性的管理提供指导,包括如何限制耐药性的发展和管理因耐药性而复杂化的病毒学失败。为了补充这一点,提供了资源和治疗指南的链接,这些链接可以帮助解释HIV耐药性测试结果,并在临床上选择最佳的抗逆转录病毒疗法。
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引用次数: 0
Hepatitis C virus/Hepatitis B virus coinfection: Current prospectives. 丙型肝炎病毒/乙型肝炎病毒合并感染:当前展望。
IF 1.2 4区 医学 Q4 INFECTIOUS DISEASES Pub Date : 2023-08-01 DOI: 10.1177/13596535231189643
Quratulain Maqsood, Aleena Sumrin, Maryam Iqbal, Saima Younas, Nazim Hussain, Muhammada Mahnoor, Abdul Wajid

In endemic areas, hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection is common, and patients with coinfection have a higher risk of developing liver disease such as hepatocellular carcinoma, liver fibrosis and cirrhosis. In such cases, HCV predominates, and HBV replication is suppressed by HCV. HCV core proteins and interferons that are activated by HCV are responsible for the suppression of HBV. Immunosuppression is also seen in patients with HCV and HBV coinfections. A decrease in HCV-neutralizing antibody response and circulation of Th1-like Tfh cells is observed in patients with HCV and HBV coinfection. Both viruses interacted in the liver, and treatment of HCV/HBV coinfection is genotype-based and complex due to the interaction of both viruses. In HCV-dominant cases, direct-acting antiviral drugs and peg interferon plus ribavirin are used for the treatment, with continuous monitoring of AST and ALT. HBV-dominant cases are less common and are treated with peg interferon and nucleoside nucleotide analogues with monitoring of AST and ALT. The SVR rate in HCV-HBV coinfection is higher than that in monoinfection when treated with direct-acting antiviral drugs. But there is a risk of reactivation of HBV during and after therapy. The rate of reactivation is lower in patients treated with direct-acting antiviral drugs as compared to those treated with peg interferon plus ribavirin. Biomarkers of HBV such as HBcrAg, HBV DNA and HBVpg RNA are not effective in the prediction of HBV reactivation; only the hepatitis B surface antigen titre can be used as a biomarker for HBV reactivation. HCV can also be reactive, but this is found in very rare cases in which HBV is present and is treated first.

在流行地区,丙型肝炎病毒(HCV)/乙型肝炎病毒(HBV)合并感染很常见,合并感染的患者患肝细胞癌、肝纤维化和肝硬化等肝病的风险更高。在这种情况下,HCV占主导地位,并且HCV抑制HBV复制。HCV核心蛋白和被HCV激活的干扰素负责抑制HBV。HCV和HBV合并感染的患者也会出现免疫抑制。在HCV和HBV合并感染的患者中观察到HCV中和抗体反应和Th1样Tfh细胞循环的减少。两种病毒在肝脏中相互作用,由于两种病毒的相互作用,HCV/HBV合并感染的治疗是基于基因型的且复杂的。在HCV占优势的病例中,使用直接作用抗病毒药物和聚乙二醇干扰素加利巴韦林进行治疗,并持续监测AST和ALT。HBV占优势的患者不太常见,使用聚乙二醇干扰素和核苷类似物进行治疗,同时监测AST和ALT。用直接作用的抗病毒药物治疗,HCV-HBV合并感染的SVR率高于单一感染。但在治疗期间和治疗后存在HBV再激活的风险。与聚乙二醇干扰素加利巴韦林治疗的患者相比,直接作用抗病毒药物治疗的患者的再激活率较低。HBV的生物标志物如HBcrAg、HBVDNA和HBVpg RNA在预测HBV再激活方面无效;只有乙型肝炎表面抗原滴度可以用作HBV再激活的生物标志物。丙型肝炎病毒也可能是反应性的,但这是在非常罕见的情况下发现的,在这些情况下,乙型肝炎病毒是存在的,并首先进行治疗。
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引用次数: 1
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Antiviral Therapy
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