Viral gastroenteritis

病毒性胃肠炎
  • 文章类型: Journal Article
    背景:胃肠炎是全球发病率和死亡率的常见原因。它的原因包括一系列的代理人,包括病毒,细菌,寄生虫,毒素,和毒品。在所有年龄组的胃肠炎病例中,病毒占相当大的一部分,通常表现为恶心等症状,呕吐,腹泻,脱水,厌食症,和减肥。虽然发生了零星的病例,病毒性肠胃炎更常见于日托机构等紧密联系社区的暴发中,疗养院,和游轮。因此,有必要确定医疗保健提供者何时应在鉴别诊断中考虑这种情况,并制定最有效的策略来确认诊断。
    方法:使用患者队列浏览器,在五年的时间内收集胃肠炎患者的去识别数据,密西西比大学医学中心的电子健康记录。验证性实验室测试采用BioFire®FilmArray®多重聚合酶链反应治疗胃肠道病原体。在与胃肠炎相关的22种最常见的药物中,只有病毒病原体,特别是腺病毒,星状病毒,诺如病毒,轮状病毒,和萨波病毒,包括在分析中。如果可用,回顾了组织病理学。
    结果:在胃肠炎的各种原因中,传染性和非传染性,我们的研究结果显示,25.46%的病例与病毒病原体有关。与成人(27.07%)相比,儿科患者的比例(72.73%)明显更高,p值为0.015。诺如病毒I型和II型是所有年龄组中最常见的病毒,在成年人中患病率很高。没有观察到明显的基于性别的差异。组织病理学发现包括炎症,溃疡,侵蚀,建筑扭曲,以及与腺病毒相关的致病病毒包涵体。
    结论:我们对病毒性胃肠炎病例的综合分析突出了这种情况的巨大负担,尤其是儿科患者。诺如病毒成为流行的罪魁祸首,强调了警惕监测和及时诊断的重要性,尤其是在爆发很常见的环境中。
    BACKGROUND: Gastroenteritis is a common cause of morbidity and mortality globally. Its cause encompasses a spectrum of agents, including viruses, bacteria, parasites, toxins, and drugs. Viruses account for a considerable portion of gastroenteritis cases across all age groups, typically presenting with symptoms like nausea, vomiting, diarrhea, dehydration, anorexia, and weight loss. While sporadic cases occur, viral gastroenteritis is more frequently observed in outbreaks within closely knit communities such as daycare facilities, nursing homes, and cruise ships. Therefore, it becomes necessary to determine when healthcare providers should consider this condition in their differential diagnosis and to develop the most effective strategy to confirm the diagnosis.
    METHODS: De-identified data of patients with gastroenteritis were collected over a five-year period utilizing the Patient Cohort Explorer, an electronic health record at the University of Mississippi Medical Center. Confirmatory laboratory tests employed the BioFire® FilmArray® multiplex polymerase chain reaction for gastrointestinal pathogens. Out of the 22 most common agents associated with gastroenteritis, only viral pathogens, specifically adenovirus, astrovirus, norovirus, rotavirus, and sapovirus, were included in the analysis. When available, histopathology was reviewed.
    RESULTS: Among the various causes of gastroenteritis, both infectious and non-infectious, our findings revealed that 25.46% of the cases were linked to viral pathogens. This included a significantly higher percentage of pediatric patients (72.73%) when compared to adults (27.07%), with a p-value of 0.015. Norovirus genogroups I and II emerged as the most frequently detected viruses across all age groups, with a significant prevalence among adults. No discernible gender-based differences were observed. The histopathological findings included inflammation, ulceration, erosion, architectural distortion, and the pathognomonic viral inclusion bodies associated with adenovirus.
    CONCLUSIONS: Our comprehensive analysis of viral gastroenteritis cases highlights the substantial burden of this condition, particularly among pediatric patients. Norovirus emerges as a prevalent culprit which emphasizes the importance of vigilant surveillance and timely diagnosis, especially in settings where outbreaks are common.
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  • 文章类型: Journal Article
    腹泻,通常由轮状病毒(RV)和诺如病毒(NV)引起,是全球健康问题。本研究集中于济宁市2021年至2022年的RV和NV。在2021年至2022年之间,共收集了1052个腹泻样本。实时定量荧光逆转录酶-PCR检测RV-A,NVGI,和NVGII。对于RV-A阳性样本,VP7和VP4基因测序用于基因型分析,其次是进化树的建造。同样,对于NV-GII阳性样本,对VP1和RdRp基因进行测序以进行基因型分析,随后建造了进化树。在2021年至2022年之间,济宁市的检出率各不相同:仅RV-A(不包括RV-A和NVGII的合并感染)为7.03%,NVGI为0.10%,仅NVGII(不包括RV-A和NVGII的共感染)为5.42%,RV-A和NVGII共感染1.14%。最高的RV-A比率显示在≤1岁和2-5岁的儿童中。济宁,金乡县,和梁山县的RV-A比率明显较高,分别为24.37%(不包括RV-A和NVGII的合并感染)和18.33%(不包括RV-A和NVGII的合并感染),分别。济宁,曲阜市,微山没有RV-A阳性。微山的NVGII比率最高,为35.48%(不包括RV-A和NVGII的共感染)。基因型分析显示,2021年,G9P[8]和G2P[4]占主导地位,分别为94.44%和5.56%,分别。2022年,G8P[8],G9P[8],G1P[8]突出,为75.86%,13.79%,10.35%,分别。2021年,GII.3[P12],GII.4[P16],GII.4[P31]占71.42%,14.29%,和14.29%,分别。2022年,GII.3[P12]和GII.4[P16]分别占55.00%和45.00%,分别。RV-A和NV在不同的时间范围内显示出不同的模式,年龄组,和济宁市内的地区。从2021年到2022年,济宁市流行的RV-A和NVGII菌株也发生了基因型变化。建议对RV-A和NV进行持续监测,以进行有效的预防和控制。
    Diarrhea, often caused by viruses like rotavirus (RV) and norovirus (NV), is a global health concern. This study focuses on RV and NV in Jining City from 2021 to 2022. Between 2021 and 2022, a total of 1052 diarrhea samples were collected. Real-Time Quantitative Fluorescent Reverse Transcriptase-PCR was used to detect RV-A, NV GI, and NV GII. For RV-A-positive samples, VP7 and VP4 genes were sequenced for genotype analysis, followed by the construction of evolutionary trees. Likewise, for NV-GII-positive samples, VP1 and RdRp genes were sequenced for genotypic analysis, and evolutionary trees were subsequently constructed. Between 2021 and 2022, Jining City showed varying detection ratios: RV-A alone (excluding co-infection of RV-A and NV GII) at 7.03%, NV GI at 0.10%, NV GII alone (excluding co-infection of RV-A and NV GII) at 5.42%, and co-infection of RV-A and NV GII at 1.14%. The highest RV-A ratios were shown in children ≤1 year and 2-5 years. Jining, Jinxiang County, and Liangshan County had notably high RV-A ratios at 24.37% (excluding co-infection of RV-A and NV GII) and 18.33% (excluding co-infection of RV-A and NV GII), respectively. Jining, Qufu, and Weishan had no RV-A positives. Weishan showed the highest NV GII ratios at 35.48% (excluding co-infection of RV-A and NV GII). Genotype analysis showed that, in 2021, G9P[8] and G2P[4] were dominant at 94.44% and 5.56%, respectively. In 2022, G8P[8], G9P[8], and G1P[8] were prominent at 75.86%, 13.79%, and 10.35%, respectively. In 2021, GII.3[P12], GII.4[P16], and GII.4[P31] constituted 71.42%, 14.29%, and 14.29%, respectively. In 2022, GII.3[P12] and GII.4[P16] accounted for 55.00% and 45.00%, respectively. RV-A and NV showed varying patterns for different time frames, age groups, and regions within Jining. Genotypic shifts were also observed in prevalent RV-A and NV GII strains in Jining City from 2021 to 2022. Ongoing monitoring of RV-A and NV is recommended for effective prevention and control.
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  • 文章类型: Journal Article
    背景:本研究的目的是确定在沙特阿拉伯东部省一家医院接受22年病毒性胃肠炎评估的儿科患者中轮状病毒和腺病毒的分布。
    方法:这是一项基于沙特阿拉伯二级医疗中心的回顾性研究。从2000年1月至2022年12月通过轮状病毒/腺病毒抗原检测试剂盒评估病毒性胃肠炎的所有儿科患者(最大14岁)的医院记录中收集实验室和人口统计学数据。数据采用SPSS28.0版进行分析。分类数据以频率和百分比表示,而平均值和标准偏差是计算连续变量的。采用卡方检验和t检验确定统计学意义。
    结果:轮状病毒抗原检测的总产率为13.6%,腺病毒为2.6%。在0.5%的研究人群中记录了两种病毒的共感染。在过去的二十年中,轮状病毒以不同的频率被持续检测到,但是腺病毒的检测显示,至少连续三年有零确诊病例。在2013年之前,当轮状病毒疫苗在沙特阿拉伯推出时,轮状病毒比腺病毒流行得多(30%,2010年为3.8%),但是在引入疫苗十年后,它们变得同样普遍。轮状病毒胃肠炎在一年中出现了三个不同的高峰,在三月,七月,和十二月。每个高峰之后,在下一个高峰之前,患病率逐渐下降。腺病毒,相比之下,全年以2%到5%的比率持续检测到。
    结论:在过去的二十年中,轮状病毒和腺病毒胃肠炎的患病率发生了变化。我们发现与轮状病毒和腺病毒胃肠炎相关的不同季节模式。鼓励将病毒学测试与综合征测试小组一起用于小儿胃肠炎,以提高对肠道病毒真实流行的认识。
    BACKGROUND: The aim of this study was to determine the distribution of rotavirus and adenovirus in pediatric patients evaluated for viral gastroenteritis in a hospital in the Eastern Province of Saudi Arabia for 22 years.
    METHODS: This was a retrospective study based in a secondary healthcare center in Saudi Arabia. Laboratory and demographic data were collected from hospital records for all pediatric patients (up to 14 years old) evaluated for viral gastroenteritis by rotavirus/adenovirus antigen detection kit from January 2000 to December 2022. Data were analyzed utilizing SPSS version 28.0. Categorical data were presented as frequency and percentages, whereas mean and standard deviations were computed for continuous variables. Chi-square test and t-test were used to determine statistical significance.
    RESULTS: The overall yields of antigen detection were 13.6% for rotavirus and 2.6% for adenovirus. Coinfection with both viruses was documented in 0.5% of the study population. Rotavirus was persistently detected in the past two decades with varying frequency, but the detection of adenovirus showed intervals of at least three consecutive years of zero confirmed cases. Before 2013, when the rotavirus vaccine was introduced in Saudi Arabia, rotavirus was much more prevalent than adenovirus (30% compared to 3.8% in 2010), but they became equally prevalent a decade after the introduction of the vaccine. Rotavirus gastroenteritis showed three different peaks in the year, in March, July, and December. Each peak was followed by a gradual decrease in prevalence before the next peak. Adenovirus, in contrast, was detected consistently around the year at rates between 2% and 5%.
    CONCLUSIONS: Rotavirus and adenovirus gastroenteritis have changed in prevalence in the past two decades. We found distinct seasonal patterns associated with rotavirus and adenovirus gastroenteritis. The utilization of virological testing for pediatric gastroenteritis with syndromic testing panels is to be encouraged to improve the knowledge of the true prevalence of enteric viruses.
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  • 文章类型: Journal Article
    背景:急性胃肠炎(AGE)在全世界儿童中引起显著发病率;然而,在中国,很少描述病毒性胃肠炎住院儿童的疾病负担。通过这项研究,我们对病毒性胃肠炎住院患儿的资料进行分析,探讨中国大陆病毒性胃肠炎的流行病学和临床特征的变化.
    方法:数据来自福唐儿童医学发展研究中心(FRCPD),2016年至2020年,在7个地区的27家医院中。人口统计,地理分布,致病性检查结果,并发症,入院日期,住院时间,收集并分析了住院费用和结局.
    结果:病毒病原体包括轮状病毒(RV),腺病毒(ADV),诺如病毒(NV)和柯萨奇病毒(CV)在25,274(89.6%)中检测到,1,047(3.7%),441例(1.5%)和83例(0.3%)。3岁以下儿童的RV和NV感染率较高。RV和NV在冬季的检出率最高,而ADV在夏天。病毒性胃肠炎患儿常伴有其他疾病,如心肌疾病(10.98-31.04%),上呼吸道疾病(1.20-20.15%),和缉获量(2.41-14.51%)。在这些案例中,与其他病原体的共感染率为6.28%,肺炎支原体(M.肺炎),EB病毒(EBV)流感病毒(FLU)是最常见的病原体。平均住院时间为5天,住院费用中位数为587美元。
    结论:这一发现表明病毒性胃肠炎,尤其是那些由房车引起的,是年幼儿童中的一种普遍疾病。共感染和其他疾病的存在是常见的。病毒病原体的季节性和区域差异突出了有针对性的预防和控制措施的必要性。虽然病毒性胃肠炎很少导致死亡,这也给医疗保健系统带来了巨大的经济负担。
    BACKGROUND: Acute gastroenteritis (AGE) causes significant morbidity in children worldwide; however, the disease burden of children hospitalized with viral gastroenteritis in China has been rarely described. Through this study, we analyzed the data of hospitalized children with viral gastroenteritis to explore the changes in the epidemiology and clinical characteristics of viral gastroenteritis in the mainland of China.
    METHODS: Data were extracted from Futang Children\'s Medical Development Research Center (FRCPD), between 2016 and 2020, across 27 hospitals in 7 regions. The demographics, geographic distribution, pathogenic examination results, complications, hospital admission date, length of hospital stays, hospitalization charges and outcomes were collected and analyzed.
    RESULTS: Viral etiological agents included rotavirus (RV), adenovirus (ADV), norovirus (NV) and coxsackievirus (CV) that were detected in 25,274 (89.6%), 1,047 (3.7%), 441 (1.5%) and 83 (0.3%) cases. There was a higher prevalence of RV and NV infection among children younger than 3 years of age. RV and NV had the highest detection rates in winter, while ADV in summer. Children with viral gastroenteritis were often accompanied by other diseases, such as myocardial diseases (10.98-31.04%), upper respiratory tract diseases (1.20-20.15%), and seizures (2.41-14.51%). Among those cases, the co-infection rate with other pathogens was 6.28%, with Mycoplasma pneumoniae (M. pneumoniae), Epstein-Barr virus (EBV), and influenza virus (FLU) being the most common pathogens. The median length of stay was 5 days, and the median cost of hospitalization corresponded to587 US dollars.
    CONCLUSIONS: This finding suggests that viral gastroenteritis, especially those caused by RV, is a prevalent illness among younger children. Co-infections and the presence of other diseases are common. The seasonality and regional variation of viral etiological agents highlight the need for targeted prevention and control measures. Although viral gastroenteritis rarely leads to death, it also results in a significant economic burden on healthcare systems.
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  • 文章类型: Journal Article
    背景:定量分子测定越来越多地用于检测肠道病毒。
    方法:我们使用常规测定法(轮状病毒和腺病毒40/41的酶免疫测定[EIA]和星状病毒的常规聚合酶链反应检测肠道病毒的改良Vesikari评分(mVS)比较了临床严重程度,sapovirus,和诺如病毒)和全球肠道多中心研究中0-59个月儿童的定量分子测定(TaqMan阵列卡[TAC])。对于轮状病毒和腺病毒40/41,我们使用不同的周期阈值(CT)截止值比较了EIA阳性和TAC阳性病例的严重程度。
    结果:使用常规测定法,轮状病毒的中位数(四分位距)mVS为10(8,11),9(7,11)为腺病毒40/41,8(6,10)为星状病毒,sapovirus,诺如病毒GII,诺如病毒GI为7(6,9)。与轮状病毒EIA阳性病例相比,对于CT<32.6和32.6≤CT<35的EIA阴性/TAC阳性病例,mVS中位数分别低2和3分(p值<.0001).腺病毒40/41EIA阳性和EIA阴性/TAC阳性病例相似,不管CT截止。
    结论:定量分子测定与常规测定相比,比如EIA,可能会影响已识别病例的严重程度,尤其是轮状病毒。在肠道病毒研究的设计和解释中,应考虑为定量测定分配病因的截止值。
    BACKGROUND: Quantitative molecular assays are increasingly used for detection of enteric viruses.
    METHODS: We compared the clinical severity using modified Vesikari score (mVS) of enteric viruses detected by conventional assays (enzyme immunoassays [EIA] for rotavirus and adenovirus 40/41 and conventional polymerase chain reaction for astrovirus, sapovirus, and norovirus) and a quantitative molecular assay (TaqMan Array Card [TAC]) among children aged 0-59 months in the Global Enteric Multicenter Study. For rotavirus and adenovirus 40/41, we compared severity between EIA-positive and TAC-positive cases assigned etiologies using different cycle threshold (CT) cutoffs.
    RESULTS: Using conventional assays, the median (interquartile range) mVS was 10 (8, 11) for rotavirus, 9 (7, 11) for adenovirus 40/41, 8 (6, 10) for astrovirus, sapovirus, and norovirus GII, and 7 (6, 9) for norovirus GI. Compared to rotavirus EIA-positive cases, the median mVS was 2 and 3 points lower for EIA-negative/TAC-positive cases with CT<32.6 and 32.6≤CT<35, respectively (p-value<.0001). Adenovirus 40/41 EIA-positive and EIA-negative/TAC-positive cases were similar, regardless of CT cutoff.
    CONCLUSIONS: Quantitative molecular assays compared to conventional assays, such as EIA, may influence severity of identified cases, especially for rotavirus. Cutoffs to assign etiology for quantitative assays should be considered in the design and interpretation of enteric virus studies.
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  • 文章类型: Journal Article
    背景:病毒性胃肠炎仍然是低收入国家的主要死亡原因。非药物干预(NPI)对COVID-19大流行期间引起胃肠炎的病毒传播的影响研究不足。
    目的:调查肠道病毒的10年趋势,并评估实施和缓解NPI的影响。
    方法:有关诺如病毒的数据,轮状病毒,腺病毒,星状病毒,在2013年1月至2023年4月期间,从5家韩国医院收集了沙斑病毒的检测结果。我们比较了大流行前的积极性,大流行,和大流行后时期。使用贝叶斯结构时间序列(BSTS)模型对实施和减轻NPI的因果影响进行了量化。
    结果:诺如病毒最常检出(9.9%),其次是轮状病毒(6.7%),腺病毒(3.3%),星状病毒(1.4%),和沙波病毒(0.6%)。大流行期间,所有五种病毒的阳性都下降了,范围从-1.0%到-8.1%,轮状病毒的下降幅度最大。在大流行后时期,除轮状病毒外,所有病毒的阳性率都有所回升。BSTS模型显示,NPI的实施对所有五种病毒的检测产生了负面影响,与预测相比,降幅从-73.0%到-91.0%,轮状病毒受影响最小。相反,NPI缓解对所有病毒的检测产生积极影响,从79.0%到200.0%,除了轮状病毒.
    结论:10年以来观察到的趋势表明,NPI对肠道病毒检测的变化产生了重大影响。疫苗的效果,除了NPI,关于轮状病毒的检测需要进一步调查。我们的发现强调了NPI在感染控制和预防中的重要性。
    BACKGROUND: Viral gastroenteritis continues to be a leading cause of death in low-income countries. The impact of nonpharmaceutical interventions (NPIs) on the transmission of gastroenteritis-causing viruses during the COVID-19 pandemic is understudied.
    OBJECTIVE: To investigate the 10-year trends of enteric viruses and estimate the impact of implementing and mitigating NPIs.
    METHODS: Data regarding norovirus, rotavirus, adenovirus, astrovirus, and sapovirus detection were collected from five Korean hospitals between January 2013 and April 2023. We compared positivity between the pre-pandemic, pandemic, and post-pandemic periods. The causal effects of implementing and mitigating NPIs were quantified using the Bayesian Structural Time Series (BSTS) model.
    RESULTS: Norovirus was most frequently detected (9.9 %), followed by rotavirus (6.7 %), adenovirus (3.3 %), astrovirus (1.4 %), and sapovirus (0.6 %). During the pandemic, the positivity of all five viruses decreased, ranging from -1.0 % to -8.1 %, with rotavirus showing the greatest decrease. In the post-pandemic period, positivity rebounded for all viruses except for rotavirus. The BSTS model revealed that NPI implementation negatively affected the detection of all five viruses, resulting in reductions ranging from -73.0 % to -91.0 % compared to the prediction, with rotavirus being the least affected. Conversely, NPI mitigation positively affected the detection of all viruses, ranging from 79.0 % to 200.0 %, except for rotavirus.
    CONCLUSIONS: Trends observed over 10 years show that NPIs have had a major impact on changes in enteric virus detection. The effect of vaccines, in addition to NPIs, on rotavirus detection requires further investigation. Our findings emphasize the importance of NPIs in infection control and prevention.
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  • 文章类型: English Abstract
    在亚眠妇产科中心进行了流行病学研究,目的是确定在两个月内影响部分新生儿的急性胃肠道疾病的病因。通过电子显微镜和酶联免疫吸附测定(ELISA),在16名婴儿(33%)中发现了轮状病毒。在一个案例中,一种小型圆形病毒与轮状病毒有关。在这种综合征中,仅分离了两次肠致病菌。感染似乎释放了医院污染。
    An epidemiological study has been carried on at the Amiens\' Gynecology-Obstetrical center with the aim to determinate the aetiology of acute gastrointestinal disorders who affected part of the newborns over a two months period. Rotavirus was found in 16 babies (33 %) by electronmicroscopy and Enzyme-linked-Immuno-sorbent-Assay (ELISA). In one case, a « small round viruswas associated with the Rotavirus. Enteropathogenic bacteria were isolated only two times in this syndrom. The infection seem to releave of nosocomial contamination.
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  • 文章类型: English Abstract
    许多病毒能够诱发胃肠炎,尤其是有免疫或营养缺陷的幼儿。最常见的观察,使用ELISA,是轮状病毒。其他人:诺沃克特工,冠状病毒,布雷达病毒,使用电子显微镜识别。使用对症治疗,预后与早熟水合有关。
    Many virus are able to induce gastroenteritis, especially in young children with immunological or nutritional defects. The most frequently observed, using ELISA, are Rotavirus. The others : Norwalk agent, Coronavirus, Breda virus, are identified using electron microscope. Using symptomatic therapy, prognosis is related to precocious hydratation.
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  • 文章类型: Journal Article
    共同可变免疫缺陷(CVID)是一种异质性原发性免疫缺陷疾病,以抗体产生受损为特征。导致反复感染和增加对病毒病原体的易感性。这篇文献综述旨在全面概述CVID与病毒感染的关系,包括疾病的发病机理,关键呈现功能,特定的单基因磁化率,COVID-19的影响和现有的治疗方案。CVID的发病机制涉及复杂的免疫失调,包括B细胞发育的缺陷,抗体类别转换,和浆细胞分化。这些异常导致对病毒因子的体液免疫应答受损。具有CVID的个体易患广泛的病毒感染。遗传因素在CVID中起着重要作用,通过先进的基因组研究,越来越多地确定了CVID样疾病的单基因驱动因素。CVID样表型的一些单基因原因似乎导致特定的病毒易感性,这些都在审查中进行了探讨。COVID-19大流行的出现凸显了CVID患者对病毒感染严重结局的易感性。本文就其临床表现、结果,以及CVID患者中COVID-19的潜在治疗方法。它评估了COVID-19预防措施的有效性,包括疫苗接种和免疫球蛋白替代疗法,以及试用疗法。
    Common Variable Immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disorder characterised by impaired antibody production, leading to recurrent infections and an increased susceptibility to viral pathogens. This literature review aims to provide a comprehensive overview of CVID\'s relationship with viral infections, encompassing disease pathogenesis, key presenting features, specific monogenic susceptibilities, the impact of COVID-19, and existing treatment options. The pathogenesis of CVID involves complex immunological dysregulation, including defects in B cell development, antibody class switching, and plasma cell differentiation. These abnormalities contribute to an impaired humoral immune response against viral agents, predisposing individuals with CVID to a broad range of viral infections. Genetic factors play a prominent role in CVID, and monogenic drivers of CVID-like disease are increasingly identified through advanced genomic studies. Some monogenic causes of the CVID-like phenotype appear to cause specific viral susceptibilities, and these are explored in the review. The emergence of the COVID-19 pandemic highlighted CVID patients\' heightened predisposition to severe outcomes with viral infections. This review explores the clinical manifestations, outcomes, and potential therapeutic approaches for COVID-19 in CVID patients. It assesses the efficacy of prophylactic measures for COVID-19, including vaccination and immunoglobulin replacement therapy, as well as trialled therapies.
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  • 文章类型: Journal Article
    人类诺如病毒(HuNoV)和人类轮状病毒(HRV)是胃肠道腹泻的主要原因。没有批准的抗病毒药物和轮状病毒疫苗不足以终止HRV相关的死亡率。此外,治疗慢性感染的免疫功能低下的患者是有限的疗效,仅限于超说明书同情使用再利用抗病毒药物,强调了HuNoV和HRV迫切需要有效和特异性的抗病毒药物。最近,在体外培养HuNoV和HRV方面取得了重大突破,这源于使用人肠类肠(HIE)。最终可以在相同的非转化和生理相关模型中研究多种循环HuNoV和HRV基因型的复制。先前描述的抗诺如病毒或抗轮状病毒药物的活性,如2'-C-甲基胞苷(2CMC),7-脱氮-2'-C-甲基腺苷(7DMA),硝唑尼特,favipiravir和dasabuvir,使用3D-HIE针对临床相关的人类基因型进行评估。2CMC显示出针对HuNoVGII.4的最佳活性,而7DMA是针对HRV的最有效的抗病毒剂。我们确定了莫努比拉韦及其活性代谢物的抗诺如病毒和轮状病毒活性,N4-羟胞苷(NHC),用于治疗2019年冠状病毒病的广谱抗病毒药物(COVID-19)。Molnupiravir和NHC抑制HuNoVGII.4,HRVG1P[8],G2P[4]和G4P[6]在3D-HIE中具有高选择性,显示出与2CMC相当的抗HuNoV的效力。此外,Molnupiravir和NHC阻断HRV病毒质形成,但不改变其大小或亚细胞定位。一起来看,Molnupiravir抑制HuNoV和HRV复制,这表明该药物可能是治疗慢性腹泻病毒中任何一种感染的患者的候选药物。
    Human norovirus (HuNoV) and human rotavirus (HRV) are the leading causes of gastrointestinal diarrhea. There are no approved antivirals and rotavirus vaccines are insufficient to cease HRV associated mortality. Furthermore, treatment of chronically infected immunocompromised patients is limited to off-label compassionate use of repurposed antivirals with limited efficacy, highlighting the urgent need of potent and specific antivirals for HuNoV and HRV. Recently, a major breakthrough in the in vitro cultivation of HuNoV and HRV derived from the use of human intestinal enteroids (HIEs). The replication of multiple circulating HuNoV and HRV genotypes can finally be studied and both in the same non-transformed and physiologically relevant model. Activity of previously described anti-norovirus or anti-rotavirus drugs, such as 2\'-C-methylcytidine (2CMC), 7-deaza-2\'-C-methyladenosine (7DMA), nitazoxanide, favipiravir and dasabuvir, was assessed against clinically relevant human genotypes using 3D-HIEs. 2CMC showed the best activity against HuNoV GII.4, while 7DMA was the most potent antiviral against HRV. We identified the anti-norovirus and -rotavirus activity of molnupiravir and its active metabolite, N4-hydroxycytidine (NHC), a broad-spectrum antiviral used to treat coronavirus disease 2019 (COVID-19). Molnupiravir and NHC inhibit HuNoV GII.4, HRV G1P[8], G2P[4] and G4P[6] in 3D-HIEs with high selectivity and show a potency comparable to 2CMC against HuNoV. Moreover, molnupiravir and NHC block HRV viroplasm formation, but do not alter its size or subcellular localization. Taken together, molnupiravir inhibits both HuNoV and HRV replication, suggesting that the drug could be a candidate for the treatment of patients chronically infected with either one of these diarrhea causing viruses.
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