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C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe? C1酯酶抑制剂介导的COVID-19免疫抑制:是敌是友?
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.05.001
Melissa A. Hausburg , Jason S. Williams , Kaysie L. Banton , Charles W. Mains , Michael Roshon , David Bar-Or

From asymptomatic to severe, SARS-CoV-2, causative agent of COVID-19, elicits varying disease severities. Moreover, understanding innate and adaptive immune responses to SARS-CoV-2 is imperative since variants such as Omicron negatively impact adaptive antibody neutralization. Severe COVID-19 is, in part, associated with aberrant activation of complement and Factor XII (FXIIa), initiator of contact system activation. Paradoxically, a protein that inhibits the three known pathways of complement activation and FXIIa, C1 esterase inhibitor (C1-INH), is increased in COVID-19 patient plasma and is associated with disease severity. Here we review the role of C1-INH in the regulation of innate and adaptive immune responses. Additionally, we contextualize regulation of C1-INH and SERPING1, the gene encoding C1-INH, by other pathogens and SARS viruses and propose that viral proteins bind to C1-INH to inhibit its function in severe COVID-19. Finally, we review the current clinical trials and published results of exogenous C1-INH treatment in COVID-19 patients.

从无症状到严重,COVID-19的病原体SARS-CoV-2可引起不同的疾病严重程度。此外,了解对SARS-CoV-2的先天和适应性免疫反应是必要的,因为Omicron等变异会对适应性抗体中和产生负面影响。严重的COVID-19在一定程度上与补体和因子XII(接触系统激活的启动者)的异常激活有关。矛盾的是,一种抑制补体激活和FXIIa三种已知途径的蛋白,C1酯酶抑制剂(C1- inh),在COVID-19患者血浆中增加,并与疾病严重程度相关。本文综述了C1-INH在先天和适应性免疫反应调控中的作用。此外,我们分析了其他病原体和SARS病毒对C1-INH和编码C1-INH基因SERPING1的调控,并提出病毒蛋白结合C1-INH抑制其在重症COVID-19中的功能。最后,我们回顾了目前外源性C1-INH治疗COVID-19患者的临床试验和已发表的结果。
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引用次数: 2
Reduced immune system responsiveness in fibromyalgia - A pilot study 纤维肌痛患者免疫系统反应性降低-一项初步研究
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.02.003
Sophia Björkander , Malin Ernberg , Indre Bileviciute-Ljungar

Fibromyalgia is characterized by widespread musculoskeletal and joint pain, stiffness, fatigue, and sleep and mood disorders. However, the involvement of the immune system in the pathways of fibromyalgia is unclear. The aim of this study was to explore the role of the immune system in comparison with healthy controls and in association with clinical symptoms. Thirteen women with fibromyalgia and 14 controls were included. Peripheral blood mononuclear cells were stimulated and analysed by flow cytometry, and interferon gamma (IFN-γ) and interleukins were measured. Among clinical symptoms, the fibromyalgia group showed decreased cold pain threshold. Immunologically, they had a higher percentage of monocytes, a lower percentage of CD19+ B-cells, and lower secretion of IFN-γ after stimulation. Decreased capacity to secrete IFN-γ was significantly correlated with decreased cold pain threshold in the fibromyalgia group. These results confirm the presence of immune aberrations in fibromyalgia, at least partially responsible for the associated pain.

纤维肌痛的特点是广泛的肌肉骨骼和关节疼痛,僵硬,疲劳,睡眠和情绪障碍。然而,免疫系统参与纤维肌痛的途径尚不清楚。本研究的目的是探讨免疫系统的作用,与健康对照,并与临床症状的关系。包括13名患有纤维肌痛的女性和14名对照组。流式细胞术对外周血单个核细胞进行刺激和分析,并测定干扰素γ (IFN-γ)和白细胞介素。临床症状中,纤维肌痛组冷痛阈值降低。免疫方面,刺激后小鼠单核细胞百分比较高,CD19+ b细胞百分比较低,IFN-γ分泌较低。纤维肌痛组IFN-γ分泌能力下降与冷痛阈值降低显著相关。这些结果证实了纤维肌痛中存在免疫异常,至少部分导致了相关的疼痛。
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引用次数: 3
Inhibiting VEGF in cancer immunotherapy 抑制肿瘤免疫治疗中的VEGF
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2021.12.003
Masahiko Shibata , Koji Kono , Seiichi Takenoshita
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引用次数: 2
A case of de novo seronegative inflammatory oligoarthritis associated with COVID-19 infection 新发血清阴性炎性少关节炎合并COVID-19感染1例
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.10.001
Lily H. Sung MD , Natalya Surmachevska DO , Jose E. Rubio MD

Infection with SARS-CoV-2 (COVID-19) virus is characterized by an acute respiratory viral illness, often accompanied by extrapulmonary manifestations. Musculoskeletal symptoms such as myalgias and arthralgias are observed in 60 – 70% of cases. Inflammatory arthritis associated with SARS-CoV-2 infection has been reported in the literature, however, nearly all such cases describe a post-viral or reactive phenomenon occurring a few weeks following the infection. We report a unique case of de novo arthritis at the onset of a confirmed COVID-19 infection in a 55-year-old woman. Magnetic resonance imaging demonstrated synovial enhancement consistent with synovitis. Her disease was deemed refractory after failing several immunosuppressive agents. Lastly, we compare our patient's clinical presentation with two other similar cases to understand the natural history of this emerging syndrome.

SARS-CoV-2 (COVID-19)病毒感染的特征是急性呼吸道病毒性疾病,通常伴有肺外表现。肌肉骨骼症状,如肌痛和关节痛在60 - 70%的病例中观察到。文献中已经报道了与SARS-CoV-2感染相关的炎症性关节炎,然而,几乎所有此类病例都描述了感染后几周发生的病毒后或反应性现象。我们报告了一例独特的新发关节炎在确诊的COVID-19感染发病的55岁女性。磁共振成像显示滑膜增强与滑膜炎一致。她的疾病在几种免疫抑制剂无效后被认为是难治性的。最后,我们将患者的临床表现与其他两个类似病例进行比较,以了解这种新出现综合征的自然历史。
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引用次数: 1
SARS-CoV-2 antibody determination in a vaccinated and recovered cohort in Austria 奥地利接种疫苗和康复队列的SARS-CoV-2抗体测定
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.08.001
Elisabeth Mara, Tobias Mader, Johannes Gratzer, Stefanie Hochegger, Thomas Pekar

Since December 2019 the world has been dealing with a severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. The first SARS-CoV-2 vaccine was made available in Europe at the end of 2020. 202 volunteers from the vicinity of the University of Applied Sciences Wiener Neustadt took part in this study; their IgG levels recognizing the RBD of SARS-CoV-2 were determined. The aim was to evaluate the SARS-CoV-2 titer levels of vaccinated, recovered and vaccinated plus recovered persons. We could show that there is a significant difference in the antibody levels of vaccinated, vaccinated plus recovered and only recovered probands. Additionally, the highest antibody levels were found in triple vaccinated persons. Furthermore, the Moderna vaccine seems to have a higher immune response.

自2019年12月以来,世界一直在应对严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)大流行。首支SARS-CoV-2疫苗于2020年底在欧洲上市。来自维也纳新城应用科技大学附近的202名志愿者参加了这项研究;检测识别SARS-CoV-2 RBD的IgG水平。目的是评估接种者、康复者和接种者加康复者的SARS-CoV-2滴度水平。我们可以证明,接种疫苗的、接种疫苗加恢复的和仅恢复的先证者的抗体水平有显著差异。此外,在三次接种者中发现抗体水平最高。此外,现代疫苗似乎有更高的免疫反应。
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引用次数: 1
Myocarditis following Coronavirus vaccination 冠状病毒疫苗接种后心肌炎
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.11.001
Khouloud Ferchichi , Imen Aouinti , Ahmed Zaiem , Ghozlane Lakhoua , Widd Kaabi , Ons Charfi , Sarrah Kastalli , Riadh Daghfous , Sihem El Aidli

Introduction

Myocarditis is an adverse reaction discovered after the marketing of SARS-CoV-2 mRNA vaccines. Nevertheless, this effect is not mentioned as an adverse reaction in the summary of product characteristics of other types of vaccines against this disease.

Objective

In this work, we aim to present the cases of myocarditis after vaccination against COVID-19 reported to the national Tunisian centre of pharmacovigilance.

Method

We present the cases of myocarditis reported after the COVID-19 vaccination. All cases are diagnosed according to Brighton's case definition of myocarditis. The vaccines causality assessment was estimated by the French imputability updated method of Bégaud et al.

Results

We included five patients. The sex ratio (M/F) was 4. The mean age was 30 years. All patients had no notable cardiovascular history and did not report any significant past medical history. The onset of symptoms was two days post-vaccination in three patients. The predominant reported symptoms are chest pain and dyspnea in the five cases. Cardiac magnetic resonance imaging (MRI) confirmed the myocarditis diagnosis in four patients (not performed for one patient).

All cases were classified as definitive cases according to the Brighton case definition of myocarditis. No patient required hospitalization in a cardiac intensive care unit. All the patients recovered from acute myocarditis within a few days.

Conclusion

Reported cases of myocarditis post-COVID-19 vaccination in our population are rare, not severe, and have a quick favorable outcome.

心肌炎是SARS-CoV-2 mRNA疫苗上市后发现的不良反应。然而,在其他类型的抗此病疫苗的产品特性摘要中,这种作用并未作为不良反应提及。目的在本工作中,我们旨在介绍向突尼斯国家药物警戒中心报告的COVID-19疫苗接种后心肌炎病例。方法对新冠肺炎疫苗接种后报告的心肌炎病例进行分析。所有病例均根据布莱顿心肌炎病例定义诊断。疫苗的因果关系评估采用法国的bassagaud等人的归因更新方法。结果纳入5例患者。性别比(M/F)为4。平均年龄为30岁。所有患者均无显著的心血管病史,也未报告任何显著的既往病史。3例患者在接种疫苗后2天出现症状。报告的主要症状是胸痛和呼吸困难。心脏磁共振成像(MRI)证实了4例患者的心肌炎诊断(1例未行)。所有病例均根据布莱顿心肌炎病例定义归为确诊病例。没有病人需要在心脏重症监护病房住院。所有急性心肌炎患者均在几天内痊愈。结论我市人群新型冠状病毒肺炎疫苗接种后发生心肌炎病例少见,病情不严重,预后迅速良好。
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引用次数: 2
Potential role of uric acid to activate NLRP3 inflammasome triggering endothelial dysfunction in preeclampsia 尿酸激活NLRP3炎性体引发子痫前期内皮功能障碍的潜在作用
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.03.003
Priscila Rezeck Nunes , Mariana Romao-Veiga , Maria Terezinha Serrao Peracoli , Jose Carlos Peracoli , Valeria Cristina Sandrim

Preeclampsia (PE) is a pregnancy-related disorder associated with increasing maternal death rates and affecting 2–8% of pregnant women worldwide. Arterial hypertension and proteinuria, followed by other maternal dysfunctions are classic clinical parameters to identify this disease. Furthermore, hyperuricemia is strictly related to PE, and high plasmatic levels of uric acid have been associated with disease severity. The inflammation in the endothelium caused by danger signals, such as uric acid crystals, is persistent and stimulates the release of inflammatory cytokines, and activates the NLRP3 inflammasome. The mechanisms underlying endothelial dysfunction induced by the metabolism of uric acid, and consequently increased levels of inflammation and oxidative stress in women with PE could be ameliorated with interventions related to inhibition of the NLRP3 activation MSU-mediated and may improve the prognostics of this disease.

子痫前期(PE)是一种妊娠相关疾病,与孕产妇死亡率上升有关,影响全世界2-8%的孕妇。动脉高血压和蛋白尿,其次是其他产妇功能障碍是诊断该病的典型临床参数。此外,高尿酸血症与PE密切相关,高血浆尿酸水平与疾病严重程度相关。尿酸结晶等危险信号引起的内皮炎症是持续性的,刺激炎症因子的释放,激活NLRP3炎性小体。尿酸代谢诱导的内皮功能障碍的机制,以及由此导致的PE女性炎症和氧化应激水平的升高,可以通过抑制msu介导的NLRP3激活的干预措施得到改善,并可能改善该疾病的预后。
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引用次数: 2
High neutrophil/lymphocyte ratio and low lymphocyte percentage are independent risk factors for new-onset CKD 中性粒细胞/淋巴细胞比值高和淋巴细胞百分比低是新发CKD的独立危险因素
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.11.003
Mengyuan Guo , Zhaohui Wang , Rui Yang , Kun Liu , Junchao Zeng , Tianhui An

Chronic kidney disease (CKD) is one of the major public health problems worldwide, and inflammation is a noticeable cause of CKD. A total of 5508 non-CKD patients were enrolled in our prospective study and followed for three years, with 1.25% (n = 69) participants having newonset CKD at the endpoint. After adjustment for potential confounders, we found that High NLR and low LYMPH% are two independent risk factors for new-onset CKD: Compared with the lowest NLR tertile, the multifactor corrected OR (95% CI) of the highest tertile was 2.47(1.20–5.09), P = 0.014; And adjusted OR (95% CI) was 0.31(0.16–0.62) for the highest LYMPH% tertile, P = 0.001. The model constructed with NLR, LYMPH%, and other risk factors had favourable predictive power for new-onset CKD with an AUC of 0.82 (95% CI, 0.76–0.88). Assessment of NLR and LYMPH% may be helpful for early warning of CKD occurrence.

慢性肾脏疾病(CKD)是世界范围内主要的公共卫生问题之一,炎症是CKD的一个显著原因。我们的前瞻性研究共纳入了5508名非CKD患者,随访3年,其中1.25% (n = 69)的参与者在终点时患有新发CKD。在对潜在混杂因素进行校正后,我们发现高NLR和低LYMPH%是新发CKD的两个独立危险因素:与最低NLR分位数相比,最高分位数的多因素校正OR (95% CI)为2.47(1.20-5.09),P = 0.014;最高淋巴百分比的校正OR (95% CI)为0.31(0.16-0.62),P = 0.001。由NLR、LYMPH%和其他危险因素构建的模型对新发CKD具有良好的预测能力,AUC为0.82 (95% CI, 0.76-0.88)。评估NLR和LYMPH%可能有助于CKD发生的早期预警。
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引用次数: 0
Meningoradiculitis post-COVID-19 mRNA vaccination: A case report covid -19 mRNA疫苗接种后脑膜根炎1例报告
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.03.004
Alexandre Landry , Stéphanie Crapoulet , Luc H. Boudreau , Christine Bourque , Lyle Weston , Nicholas Pilote , Guillaume Desnoyers , Ludivine Chamard-Witkowski

We present a rare case of meningoradiculitis occurring after mRNA COVID-19 vaccination.

This patient, with a history of inflammatory arthritis following rubella vaccination, presented to the emergency department 4 days after her vaccination with both central and radicular nervous system symptoms. Symptoms included pain, sensory and motor deficits in L5 roots distribution, along with signs of central irritation, such as headache, difficulty concentrating and a Babinski sign. MRI showed bilateral L5 nerve roots enhancement. Lumbar puncture showed elevated protein and IgG, and relevant serologies excluded common causes. Prednisone and physical therapy helped the patient to achieve near complete recovery nine weeks after presentation.

We concluded that this patient presented meningoradiculitis probably secondary to her vaccination in a context of possible overactive immune system. While such presentations might be rare, and do not constitute a general reason to abstain from vaccination, they must be well recognized and treated.

我们报告一例罕见的mRNA - COVID-19疫苗接种后发生的脑膜根炎。该患者接种风疹疫苗后有炎症性关节炎史,接种后4天出现中枢和神经根系统症状。症状包括疼痛、L5根分布的感觉和运动缺陷,以及中枢刺激的迹象,如头痛、注意力难以集中和巴宾斯基征。MRI显示双侧L5神经根增强。腰椎穿刺显示蛋白和IgG升高,相关血清学排除常见原因。强的松和物理治疗帮助患者在9周后几乎完全康复。我们的结论是,这名患者出现脑膜根炎可能继发于她的免疫系统可能过度活跃的背景下接种疫苗。虽然这种表现可能是罕见的,并不构成放弃接种疫苗的一般理由,但它们必须得到很好的认识和治疗。
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引用次数: 2
Covid-19 Vaccine safety and adverse event analysis from Pakistan 巴基斯坦Covid-19疫苗安全性和不良事件分析
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.05.003
Syed Shahzad Hasan , Abdur Rashid , Sundus Osama , Zia Ul Mustafa , Hamid A. Merchant

Covid immunization commenced on 2nd Feb 2021 in Pakistan and as of 7th Sep 2021, over 84 million vaccine doses were administered in Pakistan, of which 72% procured by the government, 22% received through Covax and 6% were donated. The vaccines rolled out nationally included: Sinopharm, Sinovac and CanSinoBIO (China), AstraZeneca (UK), Moderna and Pfizer (USA), Sputnik (Russia), and PakVac (China/Pakistan). About half of the eligible population in Pakistan (63 m) had received at least one dose of Covid vaccine as of Sep 2021. Pakistan National Pharmacovigilance Centre (PNPC) in coordination with WHO, MHRA and Uppsala Monitoring Centre (UMC) established pharmacovigilance centers across Pakistan. The Covid vaccine AEFIs in Pakistan were mainly reported via NIMS (National Immunization Management System), COVIM (Covid-19 Vaccine Inventory Management System), 1166 freephone helpline and MedSafety. There have been 39,291 ADRs reported as of 30th Sept 2021, where most reported after the first dose (n = 27,108) and within 24–72 h of immunization (n = 27,591). Fever or shivering accounted for most AEFI (35%) followed by injection-site pain or redness (28%), headache (26%), nausea/vomiting (4%), and diarrhoea (3%). 24 serious AEFIs were also reported and investigated in detail by the National AEFI review committee. The rate of AEFIs reports ranged from 0.27 to 0.79 per 1000 for various Covid vaccines in Pakistan that was significantly lower than the rates in UK (∼4 per 1000), primarily atrributed to underreporting of cases in Pakistan. Finally, Covid vaccines were well tolerated and no significant cause for concern was flagged up in Pakistan's Covid vaccine surveillance system concluding overall benefits outweighed risks.

巴基斯坦于2021年2月2日开始进行Covid免疫接种,截至2021年9月7日,巴基斯坦接种了8400多万剂疫苗,其中72%由政府采购,22%通过Covax获得,6%为捐赠。在全国推广的疫苗包括:中国的国药、科兴和康西诺生物(中国)、英国的阿斯利康(AstraZeneca)、美国的Moderna和辉瑞(Pfizer)、俄罗斯的Sputnik和中巴的PakVac。截至2021年9月,巴基斯坦约有一半的符合条件的人口(6300万)至少接种了一剂新冠疫苗。巴基斯坦国家药物警戒中心(PNPC)与世卫组织、MHRA和乌普萨拉监测中心(UMC)协调,在巴基斯坦各地建立了药物警戒中心。巴基斯坦的新冠肺炎疫苗aefi主要通过NIMS(国家免疫管理系统)、COVIM(新冠肺炎疫苗库存管理系统)、1166免费电话热线和MedSafety进行报告。截至2021年9月30日,共报告了39,291例不良反应,其中大多数报告发生在首次接种后(n = 27,108)和免疫后24-72小时内(n = 27,591)。发热或寒战占大多数急性脑损伤(35%),其次是注射部位疼痛或发红(28%)、头痛(26%)、恶心/呕吐(4%)和腹泻(3%)。国家急性呼吸系统疾病审查委员会还对24起严重急性呼吸系统疾病进行了报告和详细调查。巴基斯坦各种Covid疫苗的aefi报告率为0.27至0.79 / 1000,显著低于英国的比率(约4 / 1000),这主要是由于巴基斯坦的病例漏报。最后,新冠病毒疫苗耐受性良好,在巴基斯坦的新冠病毒疫苗监测系统中没有发现值得担忧的重大问题,得出的结论是总体效益大于风险。
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引用次数: 5
期刊
Clinical Immunology Communications
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