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A1-reactive astrocytes and IFNAR signaling collectively induce neuronal cell death during infection of IFNAR1−/− mice by severe fever with thrombocytopenia syndrome virus 严重发热伴血小板减少综合征病毒感染 IFNAR1-/- 小鼠时,A1 反应性星形胶质细胞和 IFNAR 信号共同诱导神经细胞死亡。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-10-01 DOI: 10.1002/jmv.29949
Morgan Brisse, Hinh Ly
<p>Severe fever with thrombocytopenia syndrome (SFTS) is caused by the SFTS virus (SFTSV), a bunyavirus that is endemic throughout eastern Asia. SFTSV was first discovered in 2009 in central China<span><sup>1</sup></span> and has since infected about 5500 people in China<span><sup>2</sup></span> and approximately 800 each in Japan and South Korea.<span><sup>3</sup></span> The disease (SFTS) is characterized by fever, thrombocytopenia, and central nervous system (CNS) symptoms including headache, vertigo, coma, and encephalitis<span><sup>4, 5</sup></span> which has impacted as many as 45% of SFTS patients.<span><sup>6</sup></span> The mortality rate caused by SFTSV infection varies by region and by year with reported rates as high as 27%.<span><sup>7, 8</sup></span> There are currently no therapeutics or vaccines available for SFTS treatment and prevention.</p><p>While clinical manifestations such as decreased blood flow to the brain resulting from systemic SFTSV infection likely contribute to the disease pathology,<span><sup>9, 10</sup></span> some studies have shown that direct viral infection of the brain may also play an important role in disease pathogenesis. Evidence from a newborn mouse-infection model has shown that SFSTV can infect microglia to cause inflammasome-mediated neuronal cell death,<span><sup>11</sup></span> which could in part explain how some immunocompromised individuals are more likely to develop severe disease as a result of the infection,<span><sup>4-6</sup></span> whereas most patients who succumb to SFTS show symptoms of severe encephalitis before death. Nevertheless, the molecular mechanisms of virus-induced neuronal pathogenesis and the location of virus-induced brain damage have not been fully characterized.</p><p>Kim et al. have recently published a paper in <i>Journal of Medical Virology</i>,<span><sup>12</sup></span> in which they infected the interferon-alpha receptor knock-out (IFNAR1−/−) adult mice intraperitoneally with SFTSV to deliver the virus systematically and to show that the virus could successfully cross the blood–brain barrier (BBB) to invade the CNS as evidenced by the presence of the viral protein and genomic content being detectable throughout the CNS 4 days after the infection. They showed that SFTSV infected the brainstem and spinal cord of the IFNAR1−/− mice and that A1-reactive astrocytes were activated by virus infection, leading to neuronal cell death. Because the brainstem and spinal cord are regions of the brain that have been associated with respiratory function and motor neurons in IFNAR1−/− mice, SFTSV infection leading to lethal neuroinflammation and neuronal cell death may underlie the cause of disease pathogenesis, pathology, and mortality of some SFTS patients.</p><p>Specifically, the authors showed that viral gene expressions were significantly higher in the olfactory bulb, cortex, cerebellum, brainstem, and spinal cord of the IFNAR1−/− mice. They also characterized the immunological
严重发热伴血小板减少综合征(SFTS)由SFTS病毒(SFTSV)引起,SFTSV是一种布尼亚病毒,在整个东亚地区流行。SFTSV 于 2009 年首次在中国中部被发现1 ,至今已在中国感染了约 5500 人2 ,在日本和韩国各感染了约 800 人3 。该病(SFTS)的特征是发热、血小板减少和中枢神经系统(CNS)症状,包括头痛、眩晕、昏迷和脑炎4,5 多达 45% 的 SFTS 患者受到影响6。SFTSV感染导致的死亡率因地区和年份而异,有报道称死亡率高达27%。7, 8 目前还没有治疗和预防SFTS的疗法或疫苗。虽然全身性SFTSV感染导致脑血流量减少等临床表现可能是疾病病理的原因之一,9, 10 但一些研究表明,病毒直接感染大脑也可能在疾病发病机制中发挥重要作用。来自新生小鼠感染模型的证据显示,SFSTV 可感染小胶质细胞,导致炎性体介导的神经元细胞死亡,11 这在一定程度上解释了为什么一些免疫力低下的人更容易因感染而发展成严重疾病,4-6 而大多数死于 SFTS 的病人在死前会表现出严重脑炎的症状。然而,病毒诱导神经元发病的分子机制以及病毒诱导脑损伤的部位尚未完全确定。Kim 等人最近在《医学病毒学杂志》(Journal of Medical Virology)12 上发表了一篇论文,他们用 SFTSV 感染α干扰素受体基因敲除(IFNAR1-/-)的成年小鼠腹腔,以系统性地传递病毒,并证明病毒可成功穿过血脑屏障(BBB)侵入中枢神经系统,感染 4 天后整个中枢神经系统均可检测到病毒蛋白和基因组内容。他们发现,SFTSV感染了IFNAR1-/-小鼠的脑干和脊髓,病毒感染激活了A1反应性星形胶质细胞,导致神经细胞死亡。由于脑干和脊髓是与IFNAR1-/-小鼠呼吸功能和运动神经元相关的大脑区域,SFTSV感染导致致命的神经炎症和神经细胞死亡可能是一些SFTS患者发病、病理和死亡的原因。他们还描述了SFTSV感染大脑的免疫学效应,并发现IFNAR缺乏也会增加神经元细胞的死亡,这表现在感染后第4天存活的神经元明显减少。他们发现大多数测试的促炎细胞因子,如IFNγ、白细胞介素(IL)1α、IL1β、IL6和肿瘤坏死因子-α的表达水平都有所下降。两个例外是 C1q 和 C3 细胞因子,它们在病毒感染的 IFNAR1-/- 小鼠中含量较高。由于这两种细胞因子与 A1 反应性星形胶质细胞的活化有关,因此作者通过研究星形胶质细胞的信号转导进一步扩展了这一发现,并发现在病毒感染的 IFNAR1-/- 小鼠中,活化的星形胶质细胞和 A1-星形胶质细胞基因表达水平明显更高。为此,他们研究了受感染的神经元与小胶质细胞或星形胶质细胞之间的相互作用,方法是从胚胎或新生野生型(WT)小鼠和IFNAR1-/-小鼠幼崽中分离出原发性神经元、小胶质细胞和星形胶质细胞,在培养过程中用SFTSV感染这些细胞,然后用从受感染的小胶质细胞或星形胶质细胞中收集的细胞培养基上清培养受感染的神经元。从受感染的 WT 星形胶质细胞和 IFNAR1-/- 星形胶质细胞中收集的条件培养基增加了神经元细胞的死亡,而从小胶质细胞中收集的条件培养基没有增加神经元细胞的死亡,这在受感染的 IFNAR1-/- 神经元中达到了统计学意义。此外,与来自 WT 星形胶质细胞的条件培养基相比,来自受感染 IFNAR1-/- 星形胶质细胞的条件培养基对神经细胞死亡的增加程度更大。用感染的小胶质细胞或星形胶质细胞的条件培养基培养未感染的神经元表明,条件培养基上清液不会将感染性病毒传递给神经元。不过,这种细胞培养模式没有考虑到细胞-细胞直接接触的潜在影响,这可以在今后的共培养模式实验中进行研究。 值得注意的是,虽然作者也描述了几种 SFTSV 基因型在 IFNAR1-/- 小鼠中的发病率和死亡率,但他们没有直接比较感染 SFTSV 的 WT 小鼠的发病率和死亡率,因此限制了对所使用的病毒株和/或小鼠模型导致的潜在疾病进展的直接比较。另外值得注意的是,IFNAR1-/- 小鼠以前也被证明会受到西尼罗河病毒的影响,病毒突破 BBB 导致神经元感染。在慢性病毒感染过程中,它们还可充当持续时间较长的病毒库21 ,因此在整个感染过程中,它们对病毒感染的炎症反应可能与神经元的发病机制有关。相比之下,尽管其他研究显示成年小鼠的布尼亚病毒感染会激活小胶质细胞,但迄今为止只有在细胞培养22-24 和新生小鼠11 或人源化小鼠14 中显示了小胶质细胞的生产性布尼亚病毒感染、24 因此,本研究12 是研究 SFTSV 诱导的成年动物神经发病机制的重要的第一步。总之,本研究12 的作者证明,在全身注射 SFTSV 后,可在成年小鼠大脑中观察到神经细胞死亡和免疫激活,IFNAR 细胞信号的缺失会对其产生显著影响。具体来说,与小胶质细胞相比,A1 反应性星形胶质细胞似乎与神经细胞死亡的关系更为密切。虽然没有直接涉及,但A1反应性星形胶质细胞也可能与更高水平的SFTSV感染有关,因为大脑中受IFNAR信号影响最大的部位与与BBB相关的星形胶质细胞长期接触。这可能会使集中在 BBB 中的大量易感星形胶质细胞在病毒突破 BBB 时成为产生感染的场所。因此,小胶质细胞与感染水平和神经元细胞死亡之间的关系可能不那么密切,因为它们在整个大脑中的存在更为分散。还应注意的是,星形胶质细胞25、26 和小胶质细胞27、28 会分泌趋化因子,以招募外周免疫细胞(如淋巴细胞),而淋巴细胞与整个大脑中的细胞之间存在着许多记录在案的促炎和抗炎相互作用。这些相互作用对病毒控制和疾病发病机制的贡献将是未来研究布尼亚病毒感染的另一个研究重点。本研究12 中描述的这种成年小鼠模型是研究 SFTSV 引起的疾病病理和发病机制的一种有趣的替代新生小鼠感染模型的方法。由于新生小鼠的小胶质细胞在出生后的前几周仍在继续发育29-31 ,因此开发一种替代性动物模型(如本研究中报道的模型12)来研究体内 SFSTV 感染非常重要。这反过来将有助于未来开发 SFSTV 治疗药物和疫苗的工作,如针对大脑中的特定细胞类型并优化其在患者(包括免疫力低下者,他们最容易患上严重的 SFTS 疾病)中的表现。
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引用次数: 0
Exploring the effects of Merkel cell polyomavirus T antigens expression in REH and MCC13 cells by methylome and transcriptome profiling 通过甲基组和转录组图谱分析探索梅克尔细胞多瘤病毒T抗原在REH和MCC13细胞中表达的影响。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-30 DOI: 10.1002/jmv.29938
Amanda Macamo, Dan Liu, Martina Färber, Felix Borman, Joost van den Oord, Véronique Winnepenninckx, Faisal Klufah, Emil Chteinberg, Axel zur Hausen

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a tripled incidence in the US and Europe over the past decade. Around 80% of MCC is linked to Merkel cell polyomavirus, but the cell of origin remains unknown. We stably introduced Merkel cell polyomavirus (MCPyV)-sT) and LT antigens to MCC13 and REH cell lines, analyzing DNA methylation and gene transcriptional regulation. Gene ontology analysis assessed MCPyV effects, and integrative analysis correlated gene expression and methylation. Expression patterns were compared with 15 previously sequenced primary MCCs. We found that MCPyV-LT induces DNA methylation changes in both cell lines, while MCPyV-sT only affected REH cells. Greater gene expression changes are observed in MCC13 cells, with upregulated genes associated with cellular components and downregulated genes related to biological processes. Integrative analysis of differentially expressed genes (DEG) and differentially methylated regions (DMR) of REH cell lines revealed that no genes were commonly methylated and differentially expressed. The study compared DEGs and DMG in MCC13 and REH cells to overlapping genes in MCPyV-positive cell lines (MKL1, MKL2, and WaGa), identifying hypomethylated genes in the gene body and hypermethylated genes at TSS1500. GO analysis of the two cell lines showed that MCPyV-TAs can downregulate genes in MHC-I pathways; this downregulation offers a target that can be used to create novel and efficient MCC immunotherapy approaches. Finally, it was confirmed that MCPyV-LT controls gene expression in MCC tissues using an integrative investigation of DNA methylation and gene expression.

梅克尔细胞癌(MCC)是一种罕见的侵袭性皮肤癌,在过去十年中,美国和欧洲的发病率增加了两倍。约80%的梅克尔细胞癌与梅克尔细胞多瘤病毒有关,但起源细胞仍然未知。我们将梅克尔细胞多瘤病毒(MCPyV)-sT)和LT抗原稳定导入MCC13和REH细胞系,分析DNA甲基化和基因转录调控。基因本体分析评估了MCPyV的影响,综合分析则关联了基因表达和甲基化。表达模式与之前测序的 15 个原发性 MCC 进行了比较。我们发现,MCPyV-LT会诱导两种细胞系的DNA甲基化发生变化,而MCPyV-sT只影响REH细胞。在 MCC13 细胞中观察到了更大的基因表达变化,上调的基因与细胞成分有关,下调的基因与生物过程有关。对 REH 细胞系差异表达基因(DEG)和差异甲基化区域(DMR)的整合分析表明,没有基因普遍甲基化和差异表达。研究将MCC13和REH细胞中的DEG和DMG与MCPyV阳性细胞系(MKL1、MKL2和WaGa)中的重叠基因进行了比较,确定了基因体内的低甲基化基因和TSS1500处的高甲基化基因。对这两种细胞系进行的GO分析表明,MCPyV-TAs能下调MHC-I通路中的基因;这种下调提供了一个靶点,可用于创建新型高效的MCC免疫疗法方法。最后,通过对 DNA 甲基化和基因表达的综合研究,证实了 MCPyV-LT 可控制 MCC 组织中的基因表达。
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引用次数: 0
Coinfection of human adenovirus and recombinant human astrovirus in a case of acute gastroenteritis: A report from China 一例急性肠胃炎患者同时感染人腺病毒和重组人星状病毒:中国的一份报告
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-26 DOI: 10.1002/jmv.29940
Xin Wang, Wanqiu Liu, Mingda Hu, Yaqing He, Boqian Wang, Kexin Li, Rui Zhang, Hailong Zhang, Tianyi Wang, Yuxin Wang, Long Chen, Xiaofeng Hu, Hongguang Ren, Hongbin Song

Diarrhea is one of the major public health issues worldwide. Although the infections of individual enteric virus have been extensively studied, elucidation of the coinfection involving multiple viruses is still limited. In this study, we identified the coinfection of human adenovirus (HAdV) and human astrovirus (HAstV) in a child with acute gastroenteritis, analyzed their genotypes and molecular evolution characteristics. The sample was collected and identified using RT-PCR and subjected to whole-genome sequencing on the NovaSeq (Illumina) platform. Obtained sequences were assembled into the complete genome of HAdV and the ORF1 of HAstV. We conducted phylogenetic analysis using IQ-TREE software and conducted recombination analysis with the Recombination Detection Program. The sequenced HAdV was confirmed to be genotype 41, and was genetically close to some European strains. Phylogenetic analysis revealed that the HAstV was genetically close to both HAstV-2 and HAstV-4 and was different from the genotype prevalent in Shenzhen before. The recombination analysis confirmed that the sequenced HAstV strain is a recombinant of HAstV-2 and HAstV-4. Our analysis has shown that the strains in this coinfection are both uncommon variants in this geographical region, instead of dominant subtypes that have prevailed for years. This study presents a coinfection of HAdV and HAstV and conducts an evolutionary analysis on involved viruses, which reveals the genetic diversity of epidemic strains in Southern China and offers valuable insights into vaccine and medical research.

腹泻是全球主要的公共卫生问题之一。虽然对单个肠道病毒感染的研究已经非常广泛,但对多种病毒合并感染的研究仍然有限。在本研究中,我们在一名急性肠胃炎患儿身上发现了人类腺病毒(HAdV)和人类星状病毒(HAstV)的合并感染,并分析了它们的基因型和分子进化特征。采集的样本经 RT-PCR 鉴定后,在 NovaSeq(Illumina)平台上进行了全基因组测序。获得的序列被组装成HAdV的完整基因组和HAstV的ORF1。我们使用 IQ-TREE 软件进行了系统进化分析,并使用重组检测程序进行了重组分析。经过测序的HAdV被确认为基因型41,在基因上与一些欧洲毒株接近。系统进化分析表明,该 HAstV 与 HAstV-2 和 HAstV-4 的基因相似,与之前在深圳流行的基因型不同。重组分析证实,已测序的 HAstV 株系是 HAstV-2 和 HAstV-4 的重组株。我们的分析表明,此次合并感染的病毒株都是这一地区不常见的变异株,而不是多年来流行的优势亚型。本研究展示了 HAdV 和 HAstV 的混合感染,并对相关病毒进行了进化分析,揭示了华南地区流行株的遗传多样性,为疫苗和医学研究提供了有价值的见解。
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引用次数: 0
Pretreatment drug resistance among people living with HIV from 2018 to 2022 in Guangzhou, China 2018年至2022年中国广州艾滋病病毒感染者治疗前耐药性情况
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-25 DOI: 10.1002/jmv.29937
Shiyun Lv, Yun Lan, Yaozu He, Quanmin Li, Xuemei Ling, Junbin Li, Liya Li, Pengle Guo, Fengyu Hu, Weiping Cai, Xiaoping Tang, Jingliang Chen, Linghua Li

The presence of pretreatment drug resistance (PDR) is posing an increasing threat to HIV control. Here we investigated drug resistance mutations (DRMs) and PDR among 6831 HIV-infected individuals from 2018 to 2022 in Guangzhou, China. DRMs were detected among 24.5% of the patients. The overall prevalence of PDR was 7.4%, with resistance rate to nucleotide reverse transcriptase inhibitor (NRTI) being 1.3%, nonnucleoside reverse transcriptase inhibitor (NNRTI) 4.8%, and protease inhibitor (PI) 1.4%. Abacavir (0.8%) resistance was the most common in NRTI, followed by resistance to emtricitabine (0.6%), lamivudine (0.6%), and tenofovir disoproxil fumarate (0.3%). In NNRTI, nevirapine (3.7%) resistance was the most common, followed by efavirenz (3.5%) and rilpivirine (3.4%). Among PI, resistance to tipranavir (0.8%), nelfinavir (0.6%), fosamprenavir (0.2%) and lopinavir (0.1%) was most frequent. Annual prevalence of PDR showed an increase trend from 2018 to 2022, although not significant. In the multivariable logistic regression model, hepatitis B surface antigen positivity, circulating recombinant form (CRF) 55_01B, CRF08_BC, CRF59_01B, and subtype B were demonstrated as associated risk factors for PDR. The overall prevalence of PDR in Guangzhou was moderate, with relatively severe NNRTI resistance. Therefore, it remains crucial to continue monitoring PDR among newly diagnosed HIV-infected individuals.

治疗前耐药性(PDR)的存在对艾滋病的控制构成了越来越大的威胁。在此,我们调查了2018年至2022年中国广州6831名HIV感染者的耐药突变(DRMs)和PDR情况。24.5%的患者检测到 DRMs。PDR总发生率为7.4%,其中核苷酸逆转录酶抑制剂(NRTI)耐药率为1.3%,非核苷酸逆转录酶抑制剂(NNRTI)耐药率为4.8%,蛋白酶抑制剂(PI)耐药率为1.4%。阿巴卡韦(0.8%)耐药是 NRTI 中最常见的,其次是恩曲他滨(0.6%)、拉米夫定(0.6%)和富马酸替诺福韦二吡呋酯(0.3%)耐药。在 NNRTI 中,最常见的是奈韦拉平(3.7%)耐药,其次是依非韦伦(3.5%)和利匹韦林(3.4%)。在 PI 中,对替拉那韦(0.8%)、奈非那韦(0.6%)、福沙那韦(0.2%)和洛匹那韦(0.1%)的耐药性最为常见。从2018年到2022年,PDR的年患病率呈上升趋势,但并不显著。在多变量逻辑回归模型中,乙肝表面抗原阳性、循环重组型(CRF)55_01B、CRF08_BC、CRF59_01B和B亚型被证明是PDR的相关风险因素。广州 PDR 的总体流行率为中度,NNRTI 耐药性相对严重。因此,继续监测新诊断的HIV感染者的PDR仍然至关重要。
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引用次数: 0
Determinants of HBeAg loss during follow-up of a multiethnic pediatric cohort 多种族儿童队列随访期间 HBeAg 消失的决定因素
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-25 DOI: 10.1002/jmv.29936
David Mutimer, Sowsan F. Atabani, Maxine Brown, Jacqueline Logan, Chayarani Kelgeri

Hepatitis B e antigen (HBeAg) loss is a key event in the natural history of chronic hepatitis B virus infection. The rate and determinants of HBeAg loss depend upon cohort characteristics at baseline. Few studies have examined the age-dependent rate, and none have examined the effect of patient sex and ethnicity on the age-dependant rate. The study of age-dependent rates requires the identification and long-term follow-up of a pediatric cohort. We have studied the age-dependent rate of HBeAg loss, and the rate of HBeAg loss measured from baseline, in a multi-ethnic cohort of 454 pediatric patients. During observation, HBeAg loss was observed in 121/303 (39.9%) HBeAg-positive patients. The rate of HBeAg loss was greater in the second versus the first and third decades of life. The age-related rate of HBeAg loss was clearly affected by patient sex and ethnicity, with earlier loss observed for males and for White versus both South Asian and Chinese ethnicities. When measured from baseline, Chinese patients had a slower rate of HBeAg loss in comparison with White patients. In multivariate analysis of HBeAg loss during prolonged follow-up, male sex, older age, and White ethnicity were associated with HBeAg loss, but antiviral treatment was not.

乙型肝炎 e 抗原(HBeAg)丢失是慢性乙型肝炎病毒感染自然史中的一个关键事件。HBeAg 消失的速度和决定因素取决于基线时的队列特征。很少有研究探讨了与年龄相关的比率,也没有研究探讨患者性别和种族对与年龄相关比率的影响。研究与年龄相关的比率需要确定一个儿科队列并对其进行长期随访。我们在一个由 454 名儿科患者组成的多种族队列中研究了 HBeAg 随年龄变化的丢失率,以及从基线开始测量的 HBeAg 丢失率。在观察期间,121/303(39.9%)名 HBeAg 阳性患者的 HBeAg 消失。HBeAg丢失率在生命的第二个十年高于第一个十年和第三个十年。与年龄相关的 HBeAg 阳性丢失率明显受到患者性别和种族的影响,男性和白人与南亚和华裔相比,HBeAg 阳性丢失率更早。从基线开始测量,华裔患者的 HBeAg 消失速度比白人患者慢。在对长期随访期间 HBeAg 消失情况进行的多变量分析中,男性、高龄和白人与 HBeAg 消失有关,但与抗病毒治疗无关。
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引用次数: 0
Divergent autoantibody and cytokine levels in COVID-19 sepsis patients influence survival COVID-19 败血症患者的自身抗体和细胞因子水平差异影响存活率
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-25 DOI: 10.1002/jmv.29935
Daniel Kühn, Natalie Heinen, Kathrin Sutter, Simon T. Herrmann, Maximilian K. Nocke, Daniel Todt, Peter D. Burbelo, Eike Steinmann, Dominik Ziehe, Björn Koos, Michael Adamzik, Christian Putensen, Alexander Zarbock, Ute Gravemann, Christine Jork, Stephanie Pfaender, SepsisDataNet.NRW and CovidDataNet.NRW research group

Studies have pointed to a decisive role of autoantibodies in the context of sepsis and severe Coronavirus disease 2019 (COVID-19), which itself often fulfills the criteria for sepsis, including dysregulated immune responses and organ dysfunction. To directly compare and further analyze the autoantibody profiles of sepsis patients with and without COVID-19, the luciferase immunoprecipitation systems (LIPS) assay was used to measure the levels of autoantibodies against a variety of clinically relevant cytokines, lung-associated proteins, other autoantigens, and antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, cytokine titers were measured with the LEGENDplex™ Human Antivirus Response Panel. We observed significantly increased levels of autoantibodies in 59% of the COVID-19-Sepsis group compared to 48% of the Sepsis group. Significant differences were identified between the groups for the levels of autoantibodies against gATPase. The cytokine levels of interferon (IFN)-λ1 and IP-10 were higher in the COVID-19-Sepsis group compared to the Sepsis group. Additional correlations between autoantibodies, cytokines and 30-day survival could be demonstrated, suggesting varied underlying pathological mechanisms. Elevated levels of cytokines and autoantibodies may serve as prognostic indicators for the survival probability of sepsis patients, highlighting the intricate relationship between immune responses and patient outcomes in the context of both sepsis and COVID-19.

有研究指出,自身抗体在败血症和严重冠状病毒病2019(COVID-19)中起着决定性作用,而冠状病毒病2019本身往往符合败血症的标准,包括免疫反应失调和器官功能障碍。为了直接比较和进一步分析有COVID-19和无COVID-19的脓毒症患者的自身抗体谱,研究人员使用荧光素酶免疫沉淀系统(LIPS)测定法来测量各种临床相关细胞因子、肺相关蛋白、其他自身抗原和严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2)抗体的自身抗体水平。此外,细胞因子滴度是用 LEGENDplex™ 人类抗病毒反应面板测定的。我们观察到,与败血症组的 48% 相比,COVID-19-败血症组的 59% 自身抗体水平明显升高。各组间针对 gATPase 的自身抗体水平存在显著差异。与败血症组相比,COVID-19-败血症组的干扰素 (IFN)-λ1 和 IP-10 细胞因子水平更高。自身抗体、细胞因子和 30 天存活率之间还存在其他相关性,这表明潜在的病理机制各不相同。细胞因子和自身抗体水平的升高可作为脓毒症患者生存概率的预后指标,凸显了脓毒症和 COVID-19 免疫反应与患者预后之间错综复杂的关系。
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引用次数: 0
Interim safety and immunogenicity analysis of the EuCorVac-19 COVID-19 vaccine in a Phase 3 randomized, observer-blind, immunobridging trial in the Philippines 菲律宾 EuCorVac-19 COVID-19 疫苗 3 期随机、观察盲法免疫桥接试验的中期安全性和免疫原性分析
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-24 DOI: 10.1002/jmv.29927
Jonathan F. Lovell, Kazutoyo Miura, Yeong Ok Baik, Chankyu Lee, YoungJin Choi, Howard Her, Jeong-Yoon Lee, Michelle Ylade, Roxas Lee-Llacer, Norman De Asis, Mitzi Trinidad-Aseron, Jose Manuel Ranola, Loreta Zoleta De Jesus

EuCorVac-19 (ECV-19) is a recombinant receptor binding domain (RBD) COVID-19 vaccine that displays the RBD (derived from the SARS-CoV-2 Wuhan strain) on immunogenic liposomes. This study compares the safety and immunogenicity of ECV-19 to the COVISHIELDTM (CS) adenoviral-vectored vaccine. Interim analysis is presented of a randomized, observer-blind, immunobridging Phase 3 trial in the Philippines in 2600 subjects, with treatment and biospecimen collection between October 2022 and January 2023. Healthy male and female adults who received investigational vaccines were 18 years and older, and randomly assigned to ECV-19 (n = 2004) or CS (n = 596) groups. Immunization followed a two-injection, intramuscular regimen with 4 weeks between prime and boost vaccination. Safety endpoints were assessed in all participants and immunogenicity analysis was carried out in a subset (n = 585 in ECV-19 and n = 290 in CS groups). The primary immunological endpoints were superiority of neutralizing antibody response, as well as noninferiority in seroresponse rate (defined as a 4-fold increase in RBD antibody titers from baseline). After prime vaccination, ECV-19 had a lower incidence of local solicited adverse events (AEs) (12.0% vs. 15.8%, p < 0.01), and solicited systemic AEs (13.1 vs. 17.4%, p < 0.01) relative to CS. After the second injection, both ECV-19 and CS had lower overall solicited AEs (7.8% vs. 7.6%). For immunological assessment, 98% of participants had prior COVID-19 exposure (based on the presence of anti-nucleocapsid antibodies) at the time of the initial immunization, without differing baseline antibody levels or microneutralization (MN) titers against the Wuhan strain in the two groups. After prime vaccination, ECV-19 induced higher anti-RBD IgG relative to CS (1,464 vs. 355 BAU/mL, p < 0.001) and higher neutralizing antibody response (1,303 vs. 494 MN titer, p < 0.001). After boost vaccination, ECV-19 and CS maintained those levels of anti-RBD IgG (1367 vs. 344 BAU/mL, p < 0.001) and neutralizing antibodies (1128 vs. 469 MN titer, p < 0.001). ECV-19 also elicited antibodies that better neutralized the Omicron variant, compared to CS (763 vs. 373 MN titer, p < 0.001). Women displayed higher responses to both vaccines than men. The ECV-19 group had a greater seroresponse rate compared to CS (83% vs. 30%, p < 0.001). In summary, both ECV-19 and CS had favorable safety profiles, with ECV-19 showing diminished local and systemic solicited AE after prime immunization. ECV-19 had significantly greater immunogenicity in terms of anti-RBD IgG, neutralizing antibodies, and seroresponse rate. These data establish a relatively favorable safety and immunogenicity profile for ECV-19. The trial is registered on ClinicalTrials.gov (NCT05572879).

EuCorVac-19(ECV-19)是一种重组受体结合域(RBD)COVID-19疫苗,其免疫原性脂质体上显示了RBD(来源于SARS-CoV-2武汉株)。这项研究比较了 ECV-19 与 COVISHIELDTM (CS) 腺病毒载体疫苗的安全性和免疫原性。该研究对在菲律宾进行的一项随机、观察盲、免疫桥接的 3 期试验进行了中期分析,共有 2600 名受试者参加,治疗和生物样本采集时间为 2022 年 10 月至 2023 年 1 月。接种研究疫苗的健康男性和女性成人年龄在 18 岁及以上,随机分配到 ECV-19 组(n = 2004)或 CS 组(n = 596)。免疫接种采用两次肌肉注射的方案,两次接种之间的间隔时间为 4 周。对所有参与者进行了安全性终点评估,并对部分参与者(ECV-19 组 585 人,CS 组 290 人)进行了免疫原性分析。主要免疫学终点是中和抗体反应的优越性以及血清反应率的非劣效性(定义为 RBD 抗体滴度比基线增加 4 倍)。初次接种后,ECV-19 的局部诱发不良事件 (AE) 发生率(12.0% 对 15.8%,p < 0.01)和诱发全身不良事件发生率(13.1% 对 17.4%,p < 0.01)均低于 CS。第二次注射后,ECV-19和CS的总招致AE较低(7.8% vs. 7.6%)。在免疫学评估方面,98%的参与者在初次免疫时曾接触过COVID-19(基于抗核头壳抗体的存在),两组的基线抗体水平或针对武汉毒株的微中和(MN)滴度没有差异。初次接种后,相对于 CS,ECV-19 诱导了更高的抗 RBD IgG(1,464 对 355 BAU/mL,p <0.001)和更高的中和抗体反应(1,303 对 494 MN 滴度,p <0.001)。加强免疫后,ECV-19 和 CS 能维持较高水平的抗 RBD IgG(1367 vs. 344 BAU/mL,p <0.001)和中和抗体(1128 vs. 469 MN 滴度,p <0.001)。与 CS 相比,ECV-19 也能产生更好的中和 Omicron 变种的抗体(763 对 373 MN 滴度,p < 0.001)。女性对两种疫苗的反应均高于男性。与 CS 相比,ECV-19 组的血清反应率更高(83% 对 30%,p < 0.001)。总之,ECV-19和CS都具有良好的安全性,ECV-19在初次免疫后的局部和全身诱发性AE减少。就抗 RBD IgG、中和抗体和血清反应率而言,ECV-19 的免疫原性明显更高。这些数据表明,ECV-19 具有相对良好的安全性和免疫原性。该试验已在 ClinicalTrials.gov 上注册(NCT05572879)。
{"title":"Interim safety and immunogenicity analysis of the EuCorVac-19 COVID-19 vaccine in a Phase 3 randomized, observer-blind, immunobridging trial in the Philippines","authors":"Jonathan F. Lovell,&nbsp;Kazutoyo Miura,&nbsp;Yeong Ok Baik,&nbsp;Chankyu Lee,&nbsp;YoungJin Choi,&nbsp;Howard Her,&nbsp;Jeong-Yoon Lee,&nbsp;Michelle Ylade,&nbsp;Roxas Lee-Llacer,&nbsp;Norman De Asis,&nbsp;Mitzi Trinidad-Aseron,&nbsp;Jose Manuel Ranola,&nbsp;Loreta Zoleta De Jesus","doi":"10.1002/jmv.29927","DOIUrl":"https://doi.org/10.1002/jmv.29927","url":null,"abstract":"<p>EuCorVac-19 (ECV-19) is a recombinant receptor binding domain (RBD) COVID-19 vaccine that displays the RBD (derived from the SARS-CoV-2 Wuhan strain) on immunogenic liposomes. This study compares the safety and immunogenicity of ECV-19 to the COVISHIELD<sup>TM</sup> (CS) adenoviral-vectored vaccine. Interim analysis is presented of a randomized, observer-blind, immunobridging Phase 3 trial in the Philippines in 2600 subjects, with treatment and biospecimen collection between October 2022 and January 2023. Healthy male and female adults who received investigational vaccines were 18 years and older, and randomly assigned to ECV-19 (<i>n</i> = 2004) or CS (<i>n</i> = 596) groups. Immunization followed a two-injection, intramuscular regimen with 4 weeks between prime and boost vaccination. Safety endpoints were assessed in all participants and immunogenicity analysis was carried out in a subset (<i>n</i> = 585 in ECV-19 and <i>n</i> = 290 in CS groups). The primary immunological endpoints were superiority of neutralizing antibody response, as well as noninferiority in seroresponse rate (defined as a 4-fold increase in RBD antibody titers from baseline). After prime vaccination, ECV-19 had a lower incidence of local solicited adverse events (AEs) (12.0% vs. 15.8%, <i>p</i> &lt; 0.01), and solicited systemic AEs (13.1 vs. 17.4%, <i>p</i> &lt; 0.01) relative to CS. After the second injection, both ECV-19 and CS had lower overall solicited AEs (7.8% vs. 7.6%). For immunological assessment, 98% of participants had prior COVID-19 exposure (based on the presence of anti-nucleocapsid antibodies) at the time of the initial immunization, without differing baseline antibody levels or microneutralization (MN) titers against the Wuhan strain in the two groups. After prime vaccination, ECV-19 induced higher anti-RBD IgG relative to CS (1,464 vs. 355 BAU/mL, <i>p</i> &lt; 0.001) and higher neutralizing antibody response (1,303 vs. 494 MN titer, <i>p</i> &lt; 0.001). After boost vaccination, ECV-19 and CS maintained those levels of anti-RBD IgG (1367 vs. 344 BAU/mL, <i>p</i> &lt; 0.001) and neutralizing antibodies (1128 vs. 469 MN titer, <i>p</i> &lt; 0.001). ECV-19 also elicited antibodies that better neutralized the Omicron variant, compared to CS (763 vs. 373 MN titer, <i>p</i> &lt; 0.001). Women displayed higher responses to both vaccines than men. The ECV-19 group had a greater seroresponse rate compared to CS (83% vs. 30%, <i>p</i> &lt; 0.001). In summary, both ECV-19 and CS had favorable safety profiles, with ECV-19 showing diminished local and systemic solicited AE after prime immunization. ECV-19 had significantly greater immunogenicity in terms of anti-RBD IgG, neutralizing antibodies, and seroresponse rate. These data establish a relatively favorable safety and immunogenicity profile for ECV-19. The trial is registered on ClinicalTrials.gov (NCT05572879).</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Analyzing infections caused by 11 respiratory pathogens in children: Pre- and post-COVID-19 pandemic trends in China 分析由 11 种呼吸道病原体引起的儿童感染:中国 COVID-19 大流行前后的趋势。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-23 DOI: 10.1002/jmv.29929
Huamei Li, Ying yang, Ran Tao, Shiqiang Shang

With the lifting of coronavirus disease 2019 (COVID-19) restrictions in December 2022 in China, the population was widely infected with COVID-19. We aim to analyzed changes in the epidemiological characteristics of other respiratory pathogens in children before and after the COVID-19 pandemic. We conducted a retrospective analysis of 44 704 children with acute respiratory infections who underwent 11 respiratory pathogen tests based on multiplex polymerase chain reaction between February and December in both 2022 and 2023. The total pathogen detection rate (24861, 74.80% vs. 6423, 56.01%; p = 0.000) and detection rates of coinfection (4059, 12.21% vs. 676, 5.89%; p = 0.000) in 2023 was significantly higher than that in 2022. The detection rates of influenza A (2567, 7.72% vs. 222, 1.94%; p = 0.000), influenza B (383, 1.15% vs. 37, 0.32%; p = 0.000), human parainfluenza virus (2175, 6.54% vs. 602, 5.25%; p = 0.000), human metapneumovirus (1354, 4.07% vs. 346, 3.01%; p = 0.000), respiratory syncytial virus (3148, 9.47% vs. 870, 7.59%; p = 0.000), and Mycoplasma pneumonia (MP; 9494, 28.56% vs. 1790, 15.61%; p = 0.000) in 2023 were significantly higher than those in 2022, whereas the detection rates of human adenovirus (1124, 3.38% vs. 489, 4.26%; p = 0.000) and human bocavirus (629, 1.89% vs. 375, 3.27%; p = 0.000) were significantly lower than those in 2022. Chlamydia, human rhinovirus, and human coronavirus showed similar detection rates between 2023 and 2022. In 2023, the influenza virus and human parainfluenza virus regained seasonal characteristic, an outbreak of MP infection occurred, the epidemic season of respiratory syncytial virus changed, and the proportion of children with acute respiratory infection aged 0–28 days and over 3 years old increased. Influenza B, metapneumovirus, and human bocavirus were detected in children aged 0–28 days in 2023, but not in 2022. After the COVID-19 pandemic, we should be alert to the increase of respiratory diseases and the change of epidemic season and susceptible age.

随着中国于 2022 年 12 月解除对 2019 年冠状病毒病(COVID-19)的限制,人群广泛感染 COVID-19。我们旨在分析 COVID-19 流行前后其他呼吸道病原体在儿童中的流行特征变化。我们对 44 704 名急性呼吸道感染患儿进行了回顾性分析,这些患儿在 2022 年和 2023 年的 2 月至 12 月期间接受了 11 次基于多重聚合酶链反应的呼吸道病原体检测。2023 年的病原体总检出率(24861,74.80% 对 6423,56.01%;P = 0.000)和合并感染检出率(4059,12.21% 对 676,5.89%;P = 0.000)明显高于 2022 年。甲型流感(2567,7.72% vs. 222,1.94%;p = 0.000)、乙型流感(383,1.15% vs. 37,0.32%;p = 0.000)、人类副流感病毒(2175,6.54% vs. 602, 5.25%; p = 0.000)、人类偏肺病毒(1354, 4.07% vs. 346, 3.01%; p = 0.000)、呼吸道合胞病毒(3148, 9.47% vs. 870, 7.59%; p = 0.000)、肺炎支原体(MP;9494,28.56% vs. 1790,15.61%;p = 0.000)在 2023 年的检出率明显高于 2022 年,而人类腺病毒(1124,3.38% vs. 489,4.26%;p = 0.000)和人类轮状病毒(629,1.89% vs. 375,3.27%;p = 0.000)的检出率则明显低于 2022 年。衣原体、人类鼻病毒和人类冠状病毒在 2023 年和 2022 年的检出率相似。2023 年,流感病毒和人类副流感病毒恢复季节性特征,MP 感染爆发,呼吸道合胞病毒流行季节发生变化,0-28 天和 3 岁以上急性呼吸道感染儿童比例上升。2023 年在 0-28 天儿童中检测到乙型流感病毒、偏肺病毒和人博卡病毒,而 2022 年未检测到。COVID-19 大流行后,我们应警惕呼吸道疾病的增加以及流行季节和易感年龄的变化。
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引用次数: 0
Israeli neonatal herpes simplex infection: Unique epidemiology and clinical profile 以色列新生儿单纯疱疹病毒感染:独特的流行病学和临床特征。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-23 DOI: 10.1002/jmv.29934
Tal Golan Lagziel, Menucha Jurkowicz, Oren Gordon, Merav Mor, Orli Megged, Elias Nasrallah, Ron Jacob, Rimma Melamed, Shani Levin Blustein, Diana Tasher, Alex Guri, Asaf Regev, Ilan Linder, Tal Brosh-Nissimov, Ellen Bamberger, Ronni Gur Lavy, Shelly Lipman-Arens, Shereen Shehadeh, Hanna Farah, Michal Stein

To gather national level data on Israeli neonatal HSV (NHSV) infection and to evaluate the distinct clinical characteristics of NHSV and neonatal enteroviral meningitis (NEM). Israeli NHSV patients, hospitalized between January 2015 and April 2022 in 22 medical centers were assessed, together with NEM patients, hospitalized at Sheba Medical Center during the same period. NHSV demographic and clinical characteristics were documented and compared to those of NEM. Eighty-five NHSV (73% males) and 130 NEM (62% males) patients were included. The incidence of NHSV was 5.9/100 000 live births, the common phenotype and HSV type were SEM (53%) and HSV1 (91%), respectively. Horizontal transmission was suspected in 50% cases (of which 67% underwent a Jewish ritual circumcision with direct wound sucking, 33% had relatives with highly suspicious herpetic lesions). Compared with NEM, NHSV tends to present with rash (14% vs. 60%, p-value < 0.01) and seizures (0% vs. 6%, p-value 0.02), while fever, irritability and poor feeding appear more frequently in NEM (94% vs. 18%, p-value < 0.01; 37% vs. 1%, p-value < 0.01; 25% vs. 1%, p-value < 0.01 respectively). Of NEM patients, 28% were treated with acyclovir. Our results mark a decrease in the incidence rate of NHSV in Israel and a prominent mode of horizontal infection acquisition. We underscore the unique localized phenotype of NHSV, in contrast to enterovirus, which tends to cause a systemic disease with constitutional symptoms. These findings should be considered when evaluating the need for comprehensive empirical treatment for HSV in the context of neonatal fever, or according to a certain clinical presentation.

收集以色列全国新生儿 HSV(NHSV)感染数据,评估 NHSV 和新生儿肠道病毒脑膜炎(NEM)的不同临床特征。我们对 2015 年 1 月至 2022 年 4 月期间在 22 家医疗中心住院的以色列 NHSV 患者以及同期在谢巴医疗中心住院的 NEM 患者进行了评估。记录了 NHSV 的人口统计学特征和临床特征,并与 NEM 的特征进行了比较。其中包括 85 名 NHSV 患者(73% 为男性)和 130 名 NEM 患者(62% 为男性)。NHSV的发病率为5.9/100 000活产婴儿,常见的表型和HSV类型分别为SEM(53%)和HSV1(91%)。50%的病例怀疑是水平传播(其中67%的病例接受了犹太教仪式包皮环切术,伤口直接被吮吸,33%的病例的亲属有高度可疑的疱疹性病变)。与 NEM 相比,NHSV 多表现为皮疹(14% 对 60%,P 值
{"title":"Israeli neonatal herpes simplex infection: Unique epidemiology and clinical profile","authors":"Tal Golan Lagziel,&nbsp;Menucha Jurkowicz,&nbsp;Oren Gordon,&nbsp;Merav Mor,&nbsp;Orli Megged,&nbsp;Elias Nasrallah,&nbsp;Ron Jacob,&nbsp;Rimma Melamed,&nbsp;Shani Levin Blustein,&nbsp;Diana Tasher,&nbsp;Alex Guri,&nbsp;Asaf Regev,&nbsp;Ilan Linder,&nbsp;Tal Brosh-Nissimov,&nbsp;Ellen Bamberger,&nbsp;Ronni Gur Lavy,&nbsp;Shelly Lipman-Arens,&nbsp;Shereen Shehadeh,&nbsp;Hanna Farah,&nbsp;Michal Stein","doi":"10.1002/jmv.29934","DOIUrl":"10.1002/jmv.29934","url":null,"abstract":"<p>To gather national level data on Israeli neonatal HSV (NHSV) infection and to evaluate the distinct clinical characteristics of NHSV and neonatal enteroviral meningitis (NEM). Israeli NHSV patients, hospitalized between January 2015 and April 2022 in 22 medical centers were assessed, together with NEM patients, hospitalized at Sheba Medical Center during the same period. NHSV demographic and clinical characteristics were documented and compared to those of NEM. Eighty-five NHSV (73% males) and 130 NEM (62% males) patients were included. The incidence of NHSV was 5.9/100 000 live births, the common phenotype and HSV type were SEM (53%) and HSV1 (91%), respectively. Horizontal transmission was suspected in 50% cases (of which 67% underwent a Jewish ritual circumcision with direct wound sucking, 33% had relatives with highly suspicious herpetic lesions). Compared with NEM, NHSV tends to present with rash (14% vs. 60%, <i>p</i>-value &lt; 0.01) and seizures (0% vs. 6%, <i>p</i>-value 0.02), while fever, irritability and poor feeding appear more frequently in NEM (94% vs. 18%, <i>p</i>-value &lt; 0.01; 37% vs. 1%, <i>p</i>-value &lt; 0.01; 25% vs. 1%, <i>p</i>-value &lt; 0.01 respectively). Of NEM patients, 28% were treated with acyclovir. Our results mark a decrease in the incidence rate of NHSV in Israel and a prominent mode of horizontal infection acquisition. We underscore the unique localized phenotype of NHSV, in contrast to enterovirus, which tends to cause a systemic disease with constitutional symptoms. These findings should be considered when evaluating the need for comprehensive empirical treatment for HSV in the context of neonatal fever, or according to a certain clinical presentation.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.29934","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risk factors for post-coronavirus disease condition in the Alpha-, Delta-, and Omicron-dominant waves among adults in Japan: A population-based matched case-control study 日本成人中阿尔法波、德尔塔波和奥米克隆波主导的冠状病毒后疾病状况的风险因素:基于人群的匹配病例对照研究。
IF 6.8 3区 医学 Q1 VIROLOGY Pub Date : 2024-09-23 DOI: 10.1002/jmv.29928
Miyuki Hori, Mina Hayama-Terada, Akihiko Kitamura, Mariko Hosozawa, Yoko Muto, Arisa Iba, Yoshihiro Takayama, Takashi Kimura, Hiroyasu Iso

Vaccination is associated with a reduced risk of post-coronavirus disease (COVID-19) condition (PCC). Here, risk factors including vaccination for PCC in the Omicron-dominant waves among Japanese adults were investigated. This was a registry-based matched case-control study of individuals aged 18–79 years diagnosed with COVID-19 registered in a National database between March 2021 and April 2022 and matched noninfected individuals living in Yao City, Japan. A self-administered questionnaire was used to assess persistent symptoms and their risk factors. The COVID-19 vaccination status was obtained from the Vaccination Registry. PCC risk factors were analyzed using logistic regression after adjusting for potential confounding factors. Overall, 4185 infected (cases) and 3382 noninfected (controls) individuals were included in the analysis. The mean ages and proportions of women were 44.7 years and 60.2% and 45.5 years and 60.7% for cases and controls, respectively. A total of 3805 (90.9%) participants had asymptomatic or mild acute symptoms at the median (range) follow-up of 271 (185–605) days. The prevalence of PCC was 15.0% for cases while that of persistent symptoms was 4.4% for controls; among the cases, it was 27.0% in the Alpha- and Delta-dominant waves and 12.8% in the Omicron-dominant wave. Female sex, comorbidities, and hospitalization were positively associated with PCC. One or more vaccine doses of vaccination were inversely associated with PCC; the inverse association was stronger in the Alpha- and Delta-dominant waves (adjusted odds ratio [aOR]: 0.29, 95% confidence interval [CI]: 0.12–0.73) than in the Omicron-dominant wave (aOR: 0.79, 95% CI: 0.59–1.07).

接种疫苗与降低冠状病毒病(COVID-19)后病情(PCC)的风险有关。在此,研究人员调查了日本成年人中包括接种 PCC 疫苗在内的风险因素。这是一项基于登记的匹配病例对照研究,研究对象是 2021 年 3 月至 2022 年 4 月期间在国家数据库中登记的 18-79 岁确诊 COVID-19 感染者和居住在日本八尾市的匹配非感染者。研究采用自填问卷的方式评估持续性症状及其风险因素。COVID-19疫苗接种情况从疫苗接种登记处获得。在调整了潜在的混杂因素后,使用逻辑回归分析了 PCC 风险因素。共有 4185 名感染者(病例)和 3382 名非感染者(对照组)参与了分析。病例和对照组的平均年龄和女性比例分别为 44.7 岁和 60.2%,45.5 岁和 60.7%。共有 3805 人(90.9%)在中位数(范围)为 271 天(185-605 天)的随访中出现无症状或轻微急性症状。病例的 PCC 患病率为 15.0%,而对照组的持续症状患病率为 4.4%;在病例中,阿尔法和德尔塔主导波的 PCC 患病率为 27.0%,而奥米克主导波的 PCC 患病率为 12.8%。女性性别、合并症和住院治疗与 PCC 呈正相关。接种一剂或多剂疫苗与 PCC 呈反向关系;与 Omicron 主导波(aOR:0.79,95% 置信区间:0.59-1.07)相比,Alpha 和 Delta 主导波的反向关系更强(调整后的几率比 [aOR]:0.29,95% 置信区间 [CI]:0.12-0.73)。
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Journal of Medical Virology
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