sars-cov-2 (covid-19)

SARS - CoV - 2 (COVID - 19)
  • 文章类型: Journal Article
    解决怀孕期间管理病毒感染的复杂性对于明智的医疗决策至关重要。这篇全面的综述深入探讨了影响孕妇的关键病毒感染的管理,即人类免疫缺陷病毒(HIV),乙型肝炎病毒/丙型肝炎病毒(HBV/HCV),流感,巨细胞病毒(CMV),和SARS-CoV-2(COVID-19)。我们评估了每种感染的抗病毒治疗的安全性和有效性,同时还探索创新途径,如基因疫苗及其在减轻怀孕期间病毒威胁方面的潜力。此外,审查审查了克服挑战的策略,包括预防性和治疗性疫苗研究,监管方面的考虑,和安全协议。利用先进的方法,包括PBPK建模,机器学习,人工智能,和因果推断,我们可以在这个复杂的领域中增强我们的理解力和决策能力。这篇叙述性评论旨在阐明不同的方法和正在进行的进步,这篇综述旨在促进孕妇抗病毒治疗的进展,改善产妇和胎儿的健康结局。
    Addressing the complexities of managing viral infections during pregnancy is essential for informed medical decision-making. This comprehensive review delves into the management of key viral infections impacting pregnant women, namely Human Immunodeficiency Virus (HIV), Hepatitis B Virus/Hepatitis C Virus (HBV/HCV), Influenza, Cytomegalovirus (CMV), and SARS-CoV-2 (COVID-19). We evaluate the safety and efficacy profiles of antiviral treatments for each infection, while also exploring innovative avenues such as gene vaccines and their potential in mitigating viral threats during pregnancy. Additionally, the review examines strategies to overcome challenges, encompassing prophylactic and therapeutic vaccine research, regulatory considerations, and safety protocols. Utilizing advanced methodologies, including PBPK modeling, machine learning, artificial intelligence, and causal inference, we can amplify our comprehension and decision-making capabilities in this intricate domain. This narrative review aims to shed light on diverse approaches and ongoing advancements, this review aims to foster progress in antiviral therapy for pregnant women, improving maternal and fetal health outcomes.
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  • 文章类型: Journal Article
    自世界卫生组织(WHO)宣布COVID-19大流行以来三年多,这仍然是一个全球性的负担。由SARS-CoV-2引起的针对COVID-19的疫苗是可用的,可有效预防疾病。然而,它们的保护作用不是100%。目前,美国食品和药物管理局(FDA)仅批准了数量有限的COVID-19住院治疗,如雷姆德西韦,baricitinib,和托珠单抗。这些药物具有适用于选定患者群体的适应症和禁忌症。寻找其他有效的治疗方法,广泛使用,风险有限,对于优化这种病毒性疾病的治疗策略至关重要。一些维生素和补充剂已被确定为管理COVID-19的潜在选择。维生素D(VD)缺乏与呼吸道感染有关。此外,α-硫辛酸(ALA)是一种强大的抗氧化剂,有助于减少许多病理条件下的炎症反应。这篇综述旨在分析目前关于VD和α-硫辛酸在门诊和住院患者COVID-19感染中有效性的证据。从2021年1月1日至2023年12月31日,通过PubMed数据库确定了相关的随机对照试验(RCT)。纳入标准如下:研究设计为随机对照试验(RCT),在干预期间使用恒定剂量,没有任何额外的推注,一个研究伦理委员会批准了。排除标准包括缺乏结果或明显的干预,额外的丸剂,或所有介入组的单剂量方案。共有11项研究,总样本量为35,717例患者符合本综述的标准。共有10个RCT检查了VD的疗效,并确定了一个回顾ALA疗效的RCT。所有文章都研究了VD或ALA在COVID-19治疗过程中的使用。每一项研究的终点各不相同,包括住院时间,病毒载量,SARS-CoV-2感染率,机械通气,炎症标志物,临床症状,序贯器官衰竭评估(SOFA)评分,和死亡率。在8/10VD补充试验中,在上述参数方面,介入组和安慰剂组之间存在显著差异.在2/10的VD补充试验中,没有发现显著差异。ALA补充剂RCT发现,干预组和安慰剂组在SOFA评分和30天全因死亡率方面没有差异。目前的文献表明,VD可以潜在地降低SARS-CoV-2感染率,氧气需求,炎症标志物,临床症状,和死亡率。关于ALA,虽然有好处的建议,没有统计学意义。不同研究中的共同限制包括相对较小的样本量,研究中不同的患者地理位置,和剂量的差异。应进行研究高剂量VD补充剂对SARS-CoV-2感染的影响的试验。需要更多的研究来确定在COVID-19中使用VD的最佳实践和最佳给药方案。
    Over three years since the World Health Organization (WHO) declared COVID-19 a pandemic, it is still a global burden. Vaccines against COVID-19, caused by SARS-CoV-2, are available and effective for preventing disease. However, their protective effects are not 100%. Currently, the U.S. Food and Drug Administration (FDA) has only approved a limited number of inpatient treatments for COVID-19, such as remdesivir, baricitinib, and tocilizumab. These medications have indications and contraindications applicable to a select patient population. Finding additional effective therapies that are widely available with limited risk could be vital in optimizing treatment strategies for this viral illness. Some vitamins and supplements have been identified as potential options for managing COVID-19. Vitamin D (VD) deficiency has been associated with respiratory tract infections. Moreover, alpha-lipoic acid (ALA) is a powerful antioxidant and helps reduce inflammatory responses in many pathologic conditions. This review aims to analyze the current evidence regarding the effectiveness of VD and alpha-lipoic acid in COVID-19 infection in both outpatient and hospitalized patients. Relevant randomized controlled trials (RCTs) were identified via the PubMed database from January 1, 2021, to December 31, 2023. Inclusion criteria were as follows: the study design was a randomized controlled trial (RCT), the usage of a constant dose during the intervention period without any additional boluses, and a research ethics committee approved it. Exclusion criteria included a lack of an outcome or apparent intervention, additional boluses, or a single-dose regimen in all the interventional groups. There were 11 studies with a total sample size of 35,717 patients that met the criteria for this review. A total of 10 RCTs examined the efficacy of VD, and one RCT that reviewed the efficacy of ALA was identified. All of the articles investigated the use of VD or ALA during the treatment of COVID-19. The endpoints of each study varied, including length of stay in hospital, viral load, SARS-CoV-2 infection rate, mechanical ventilation, inflammatory markers, clinical symptoms, Sequential Organ Failure Assessment (SOFA) score, and mortality. In 8/10 VD supplementation trials, significant differences were identified between the interventional and placebo groups in the aforementioned parameters. In 2/10 VD supplementation trials, no significant differences were identified. The ALA supplementation RCT found no differences between the interventional and placebo groups in the SOFA score and 30-day all-cause mortality rate. The current literature suggests that VD can potentially reduce the SARS-CoV-2 infection rate, oxygen requirements, inflammatory markers, clinical symptoms, and mortality. Regarding ALA, although there was a suggestion of benefit, it was not statistically significant. Common limitations among the different studies included relatively small sample sizes, different geographical patient locations among studies, and differences in dosages. Trials investigating the effects of higher doses of VD supplementation on SARS-CoV-2 infection should be conducted. More research is needed to define best practices and optimal dosing protocols for the use of VD in COVID-19.
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  • 文章类型: Journal Article
    背景:COVID-19疫苗现在在紧急使用许可下可用于6个月至5岁的儿童。我们检查了父母为5岁以下儿童接种疫苗的意图,并评估了他们对疫苗接种做出明智决定的信心(决定自我效能)是否与这些意图相关。
    方法:我们在2022年3月23日至4月5日期间对美国父母进行了一项横断面在线调查。我们研究了父母为年幼的孩子(<5岁)接种疫苗的意愿与对疫苗决策(决策自我效能)的信心之间的关系。使用多变量多项逻辑回归模型来获得父母意图的调整比值比(AORs)和95%置信区间(CIs)(归类为打算接种疫苗,不确定,或不打算接种疫苗)。
    结果:在此样本中的591个父母中,49%的人表示他们打算给孩子接种疫苗,29%的人报告说他们不会,21%的人尚未决定。在双变量分析中,种族/民族,健康保险,在过去的12个月内接种流感疫苗,和父母的COVID-19疫苗接种状况与父母为其孩子(ren)接种疫苗的意愿显着相关。在多变量分析中,控制了这些因素,与不确定接种疫苗的父母相比,打算给孩子(人)接种疫苗的父母对自己做出关于COVID-19疫苗接种的知情决定的能力更有信心.决策自我效能评分中的每一个标准差与对接种疫苗不确定的意愿增加39%相关(AOR1.39,95%CI1.09,1.77)。
    结论:不确定为孩子接种COVID-19疫苗的父母可能会从旨在提高其获得能力的干预措施中受益,理解,并利用信息做出明智的决定。
    BACKGROUND: COVID-19 vaccines are now available under Emergency Use Authorization for children ages 6 months to 5 years. We examined parents\' intentions to vaccinate their children under the age of 5 years and assessed whether their confidence in making an informed decision about vaccination (decision self-efficacy) was associated with these intentions.
    METHODS: We conducted a cross-sectional online survey of U.S. parents between 23 March and 5 April 2022. We examined associations between parental intention to vaccinate their young children (RESULTS: Of the 591 parents in this sample, 49% indicated that they intended to vaccinate their child(ren), 29% reported that they would not, and 21% were undecided. In bivariate analyses, race/ethnicity, health insurance, flu vaccination in the past 12 months, and parental COVID-19 vaccination status were significantly related to parental intention to vaccinate their child(ren). In the multivariable analyses, which controlled for these factors, parents who intended to vaccinate their child(ren) had greater confidence in their ability to make informed decisions about COVID-19 vaccinations compared to those who were unsure about vaccination. Each one standard deviation in the Decision Self-Efficacy score was associated with a 39% increase in intention to vaccinate one\'s child versus being unsure about vaccination (AOR 1.39, 95% CI 1.09, 1.77).
    CONCLUSIONS: Parents who are unsure about vaccinating their children against COVID-19 may benefit from interventions designed to increase their ability to obtain, understand, and utilize information to make informed decisions.
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  • 文章类型: Journal Article
    SARS-CoV-2非结构蛋白13(nsp13)解旋酶是病毒复制的必需酶,已被确定为开发新抗病毒药物的有吸引力的靶标。详细来说,解旋酶催化双链DNA或RNA以5'至3'方向解链,并与复制-转录复合物(nsp7/nsp8/nsp12)协同作用。在这项工作中,生物信息学和计算工具使我们能够对SARS-CoV-2解旋酶基因组进行详细的保守性分析,并进一步预测可药用酶的结合袋。因此,基于结构的虚拟筛选被用于鉴定能够识别多个nsp13口袋的有价值的化合物.从食品和药物管理局(FDA)已经批准的大约4000种药物的数据库开始,我们选择了14种能够识别4个位点中的3个的共有化合物.最后,通过目视检查分析并根据其商业可用性,五种有希望的化合物被提交体外试验。其中,PF-03715455能够在微摩尔范围内阻断nsp13的展开和NTPase活性。
    The SARS-CoV-2 non-structural protein 13 (nsp13) helicase is an essential enzyme for viral replication and has been identified as an attractive target for the development of new antiviral drugs. In detail, the helicase catalyzes the unwinding of double-stranded DNA or RNA in a 5\' to 3\' direction and acts in concert with the replication-transcription complex (nsp7/nsp8/nsp12). In this work, bioinformatics and computational tools allowed us to perform a detailed conservation analysis of the SARS-CoV-2 helicase genome and to further predict the druggable enzyme\'s binding pockets. Thus, a structure-based virtual screening was used to identify valuable compounds that are capable of recognizing multiple nsp13 pockets. Starting from a database of around 4000 drugs already approved by the Food and Drug Administration (FDA), we chose 14 shared compounds capable of recognizing three out of four sites. Finally, by means of visual inspection analysis and based on their commercial availability, five promising compounds were submitted to in vitro assays. Among them, PF-03715455 was able to block both the unwinding and NTPase activities of nsp13 in a micromolar range.
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  • 文章类型: Journal Article
    感染性微生物疾病是一种主要的公共卫生危害,呼吁更多创新的抗菌药物。在这里,聚乳酸(PLA)低聚物已被探索和报道为生物安全和生态友好的抗病原体的功能抗菌剂,如病毒(H1N1,H3N2和SARS-CoV-2),细菌(E.大肠杆菌金黄色葡萄球菌,肺炎克雷伯菌,MRSA),和真菌(C.albicans).通过1-乳酸单体的无催化剂直接缩聚制备PLA低聚物,并通过FT-IR和1H-NMR进行表征。抗病毒结果表明,PLA寡聚体具有强大的(抑制率>99%)和快速(<20分钟)抗病毒活性对两种大流行的ssRNA病毒,包括甲型流感病毒(IAV)和冠状病毒(CoV)。此外,PLA低聚物对革兰氏阴性(G-)和革兰氏阳性(G+)细菌都表现出高的抗菌活性。在10mg/mL的浓度下,PLA低聚物还有效地杀死高达105cfu/mL至零的大量白色念珠菌。因此,广谱抗微生物活性赋予PLA低聚物有前途的杀生物选择,除了抗生素的广泛应用,例如医用纺织品,食品保存,水消毒,和个人卫生,鉴于其独特的生物降解性和生物相容性。
    Infectious microbial diseases are a major public health hazard, calling for more innovative antimicrobials. Herein, polylactic acid (PLA) oligomers have been explored and reported as a bio-safe and eco-friendly functional antimicrobial agent against pathogens, such as viruses (H1N1, H3N2, and SARS-CoV-2), bacteria (E. coli, S. aureus, K. pneumoniae, MRSA), and fungi (C. albicans). The PLA oligomers were prepared by direct catalyst-free condensation polymerization of l-lactic acid monomers and characterized by FT-IR and 1H-NMR. The antiviral results demonstrate that PLA oligomers possess robust (inhibiting rate > 99%) and rapid (<20 min) antiviral activity against two pandemic ssRNA viruses, including influenza A virus (IAV) and coronavirus (CoV). Furthermore, the PLA oligomers exhibit high antibacterial activities against both Gram negative (G−) and Gram positive (G+) bacteria. The PLA oligomers also perform efficiently in killing a large amount of C. albicans as high as 105 cfu/mL down to zero at the concentration of 10 mg/mL. Thus, the broad-spectrum antimicrobial activity endowed the PLA oligomers with a promising biocidal option, except antibiotics in a wide range of applications, such as medical textiles, food preservation, water disinfection, and personal hygiene, in light of their unique biodegradability and biocompatibility.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Case Reports
    COVID-19的急性期已经得到了很好的研究,然而,随着急性后COVID-19综合征的增加,很多关于它的长期影响是未知的。急性和急性后阶段的常见症状是疲劳,主要定性评估。在这里,我们提出了一个案例研究,客观地评估了一名年轻男性的神经肌肉疲劳性(27岁,1.85米,78公斤),继续经历COVID-19相关的疲劳和认知功能障碍,包括其他症状,感染后12个月以上。在感染之前,他是神经肌肉研究的一部分,该研究构成了我们在COVID-19之前的结果的基础.该研究在COVID-19感染后12个月重复。肌肉力量,耐力,扭矩稳定,自愿激活,twitch属性,肌电图,并获得复合肌肉动作电位,并对COVID-19前后进行比较。所有测量均使用背屈测力计进行,其中还要求参与者产生一分钟的疲劳最大自愿收缩。肌肉力量,自愿激活,和易疲劳性(扭矩斜率)没有显示有意义的差异,提示内在神经肌肉特性不受影响。然而,与前COVID-19测试相比,后扭矩稳定性受损3倍。参与者还报告了主观上较高的运动感和持续的疲劳抱怨。这些结果表明,急性COVID-19综合征后的肌肉疲劳可能不是肌肉及其激活的限制,而是由与身体努力有关的认知障碍引起的感知脱节。该病例报告表明,旨在评估急性COVID-19综合征后这些特征的大型研究具有潜在价值。
    The acute phase of COVID-19 has been well studied, however with increasing post-acute COVID-19 syndrome, much is unknown about its long-term effects. A common symptom in both the acute and post-acute phases has been fatigue, assessed predominantly qualitatively. Here we present a case study objectively assessing neuromuscular fatiguability in a young male (27 year, 1.85 m, 78 kg) who continues to experience COVID-19 related fatigue and cognitive dysfunction, including other symptoms, 12+ months post-infection. Prior to infection, he was part of a neuromuscular study forming the basis of our pre-COVID-19 results. The study was repeated 12 months post-COVID-19 infection. Muscle strength, endurance, torque steadiness, voluntary activation, twitch properties, electromyography, and compound muscle action potential were obtained and compared pre- and post-COVID-19. All measurements were done using a dorsiflexion dynamometer in which the participant also was asked to produce a one-minute fatiguing maximal voluntary contraction. Muscle strength, voluntary activation, and fatigability (slope of torque) showed no meaningful differences, suggesting intrinsic neuromuscular properties are not affected. However, torque steadiness was impaired three-fold in the post- compared with pre-COVID-19 test. The participant also reported a higher level of perceived exertion subjectively and a continued complaint of fatigue. These findings indicate that muscle fatiguability in post-acute COVID-19 syndrome may not be a limitation of the muscle and its activation, but a perceptual disconnect caused by cognitive impairments relating to physical efforts. This case report suggests the potential value of larger studies designed to assess these features in post-acute COVID-19 syndrome.
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  • 文章类型: Journal Article
    Galahad™是一种与多糖复合的原花青素,可使病毒失活,并显示出制造保护性疫苗的创新方法的潜力。Galahad™的多糖部分主要由阿拉伯聚糖和阿拉伯半乳聚糖组成。在一项为期七天的大鼠毒性研究中,即使未经稀释测试,它也没有毒性。Galahad™灭活了广泛的DNA和RNA病毒,包括腺病毒,冠状病毒,如SARS-CoV-2和流感病毒。电子显微镜研究表明,暴露于Galahad™会导致病毒体的大量结块,随后在较长时间的暴露后无法检测到病毒体。根据病毒灭活数据,所测试的假设是Galahad™灭活病毒可用于配制保护性灭活病毒疫苗。为了评估这个假设,将具有105.7CCID50/0.1ml滴度的传染性甲型流感病毒(H5N1,Duck/MN/1525/81)暴露于Galahad™10分钟。这种处理导致感染性病毒滴度降低到低于可检测的限度。使用多种给药途径和给药方案将不含佐剂或防腐剂的Galahad™灭活的流感制剂给予BALB/c小鼠。最保护性的给药途径和给药方案是当小鼠鼻内两次给予疫苗时,第二剂是在主要疫苗剂量后14天。所有接受该疫苗方案的小鼠在病毒攻击中存活,而接受安慰剂的小鼠中只有20%存活。这表明Galahad™灭活的流感病毒疫苗甚至可以在不使用佐剂的情况下引发保护性免疫应答。应进一步研究该技术制造有效人类疫苗的潜力。
    Galahad™ is a proanthocyanidin complexed with polysaccharides that inactivates viruses and indicates potential for an innovative approach to making protective vaccines. The polysaccharide portion of Galahad™ consists mainly of arabinan and arabinogalactan. In a seven-day toxicity study in rats, it was not toxic even when tested undiluted. Galahad™ inactivated a wide range of DNA and RNA viruses including adenoviruses, corona viruses such as SARS-CoV-2, and influenza viruses. Electron microscopy studies showed that exposure to Galahad™ caused extensive clumping of virions followed by lack of detection of virions after longer periods of exposure. Based on the viral inactivation data, the hypotheses tested is that Galahad™ inactivation of virus can be used to formulate a protective inactivated virus vaccine. To evaluate this hypothesis, infectious influenza A virus (H5N1, Duck/MN/1525/81) with a titer of 105.7 CCID50/0.1 ml was exposed for 10 min to Galahad™. This treatment caused the infectious virus titer to be reduced to below detectable limits. The Galahad™ -inactivated influenza preparation without adjuvant or preservative was given to BALB/c mice using a variety of routes of administration and dosing regimens. The most protective route of administration and dosing regimen was when mice were given the vaccine twice intranasally, the second dose coming 14 days after the primary vaccine dose. All the mice receiving this vaccine regimen survived the virus challenge while only 20% of the mice receiving placebo survived. This suggests that a Galahad™-inactivated influenza virus vaccine can elicit a protective immune response even without the use of an adjuvant. This technology should be investigated further for its potential to make effective human vaccines.
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  • 文章类型: Journal Article
    严重急性呼吸道综合症冠状病毒2(SARS-CoV-2也称为COVID-19疾病)在室内环境中的传播途径是卫生系统与科学家之间争论的主要领域。在这种情况下,关于空气传播病毒脱落的收集研究很少。这里,我们从Zabol唯一的COVID-19患者护理中心内的24个地点收集了空气样本,伊朗,用于从2021年3月至5月筛选SARS-CoV-2RNA。地点包括ICU,COVID-19病房(CWs)房间,走廊,附近的护士站,和厕所。我们在CW的呼吸区鉴定了SARS-CoV-2RNA,在室内空气中,在浓度为17×103病毒基因组拷贝/m3空气时,阳性率为2.5%。它还调查了当地气候条件[即,温度和相对湿度]和COVID-19传播随着每日官方新病例数量数据的演变,住院治疗,和死亡。目前的数据表明,温度和湿度的差异可能会影响病毒的行为以及其他因素,即,人口密度,个体病毒脱落,和SARS-CoV-2的感染剂量(室内和室外)。我们的数据支持SARS-CoV-2在室内的潜在空中传播,这表明除了正确使用口罩和广泛的公共卫生干预措施外,还要对建筑物进行特定的安全评估,以改善通风解决方案。
    The transmission pathway of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 also called COVID-19 disease) in indoor environments are the main area of contention between health systems and scientists. In this context, little has been investigated about the collection of airborne viral shedding. Here, we collected air samples from 24 locations inside the sole COVID-19 patient care center in Zabol, Iran, for screening SARS-CoV-2 RNA from March to May 2021. Locations included the ICU, COVID-19 wards (CWs) rooms, corridors, nearby nurses\' stations, and toilets. We identified the SARS-CoV-2 RNA in breathing zone of CW, in room air, with the positivity rate of 2.5% at a concentration of 17 × 103 virus genome copies/m3 air. It also investigates the relationship between local climate conditions [i.e., temperature and relative humidity] and COVID-19 transmission with the evolution of daily official data on the number of new cases, hospitalizations, and deaths. Current data explained that the difference of temperature and humidity may affect the behavior of virus along with other factors, i.e., population density, individual viral shedding, and infectious dose of SARS-CoV-2 (both indoor and outdoor). Our data support the potential SARS-CoV-2 airborne transmission indoors suggesting the specific safety assessment of building to improve ventilation solutions besides proper using face masks and extensive public health interventions.
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  • 文章类型: Journal Article
    T细胞特异性结合抗原诱导适应性免疫应答使用高度特异性的分子识别,和具有抗原特异性克隆扩增的多种T细胞库可以指示感染或接种后的强烈免疫应答。对于炎症性肠病(IBD)患者,一系列通常需要免疫调节治疗的慢性肠道炎症性疾病,T细胞反应尚未得到很好的表征。了解导致强烈疫苗接种反应的患者因素对于指导疫苗接种时间表和识别IBD和其他免疫介导的疾病中的T细胞反应机制至关重要。在这里,我们使用T细胞受体测序显示IBD队列中的T细胞反应受人口统计学和免疫因素的影响。相对于卫生保健工作者(HCWs)的对照组。在接种SARS-CoV-2疫苗时对受试者进行采样,然后纵向进行;对TCRVβ基因库进行测序,并分析COVID-19特异性克隆。我们观察到不同年龄和疫苗类型的T细胞应答的总体强度存在显著差异。我们进一步将T细胞反应分为I类和II类特异性反应,显示Ad26。COV2.S载体疫苗诱导I类偏倚T细胞反应,而mRNA疫苗类型导致不同的反应,与BNT162b2相比,mRNA-1273疫苗诱导更多的I类缺陷型T细胞应答。最后,我们发现这些T细胞模式与同一患者的抗体水平一致.我们的结果解释了名义上免疫受损的IBD患者疫苗接种的惊人成功,同时表明,易于T细胞反应缺陷的IBD患者亚组可能需要加强加强方案。
    T-cells specifically bind antigens to induce adaptive immune responses using highly specific molecular recognition, and a diverse T-cell repertoire with expansion of antigen-specific clones can indicate robust immune responses after infection or vaccination. For patients with inflammatory bowel disease (IBD), a spectrum of chronic intestinal inflammatory diseases usually requiring immunomodulatory treatment, the T-cell response has not been well characterized. Understanding the patient factors that result in strong vaccination responses is critical to guiding vaccination schedules and identifying mechanisms of T-cell responses in IBD and other immune-mediated conditions. Here we used T-cell receptor sequencing to show that T-cell responses in an IBD cohort were influenced by demographic and immune factors, relative to a control cohort of health care workers (HCWs). Subjects were sampled at the time of SARS-CoV-2 vaccination, and longitudinally afterwards; TCR Vβ gene repertoires were sequenced and analyzed for COVID-19-specific clones. We observed significant differences in the overall strength of the T-cell response by age and vaccine type. We further stratified the T-cell response into Class-I- and Class-II-specific responses, showing that Ad26.COV2.S vector vaccine induced Class-I-biased T-cell responses, whereas mRNA vaccine types led to different responses, with mRNA-1273 vaccine inducing a more Class-I-deficient T-cell response compared to BNT162b2. Finally, we showed that these T-cell patterns were consistent with antibody levels from the same patients. Our results account for the surprising success of vaccination in nominally immuno-compromised IBD patients, while suggesting that a subset of IBD patients prone to deficiencies in T-cell response may warrant enhanced booster protocols.
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