Does post-COVID reactive arthritis exist? Experience of a tertiary care centre with a review of the literature

BackgroundRheumatological manifestations following COVID-19 are various, including Reactive Arthritis (ReA), which is a form of asymmetric oligoarthritis mainly involving the lower limbs, with or without extra-articular features. The current case series describes the clinical profile and treatment outcome of 23 patients with post-COVID-19 ReA.MethodsA retrospective, observational study of patients with post-COVID-19 arthritis over one year was conducted at a tertiary care centre in India. Patients (n = 23) with either a positive polymerase chain reaction test for SARS-CoV2 or an anti-COVID-19 antibody test were included. Available demographic details, musculoskeletal symptoms, inflammatory markers, and treatment given were documented.ResultsSixteen out of 23 patients were female. The mean age of the patients was 42.8 years. Nineteen patients had had symptomatic COVID-19 infection in the past. The duration between onset of COVID-19 symptoms and arthritis ranged from 5 to 52 days with a mean of 25.9 days. The knee was the most involved joint (16 out of 23 cases). Seven patients had inflammatory lower back pain and nine had enthesitis. Most patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and steroids – either depot injection or a short oral course. Three patients required treatment with hydroxychloroquine and methotrexate which were eventually stopped. No relapse was reported in any of the patients.ConclusionOn combining our data with 21 other case reports of ReA, a lower limb predominant, oligoarticular, asymmetric pattern of arthritis was seen with a female preponderance. The mean number of joints involved was 2.8. Axial symptoms and enthesitis were often coexistent. Treatment with NSAIDs and intra-articular steroids was effective. However, whether COVID-19 was the definitive aetiology of the arthritis is yet to be proven.     

GRIM-19在卵巢癌细胞株中的高表达及其意义

将高表达GRIM-19的重组质粒经脂质体转染到卵巢癌细胞株（SK-OV-3）中,构建稳定高表达GRIM-19的SK-OV-3/GRIM-19细胞株,并设SK-OV-3/Control对照细胞株。通过逆转录聚合酶链反应和免疫印迹法检测GRIM-19及其下游基因信号转导和转录激活子3（STAT3）的表达,运用四甲基偶氮唑蓝法检测细胞增殖情况。结果成功建立了高表达GRIM-19的SK-OV-3/GRIM-19细胞株,并发现STAT3的表达明显下调;MTT检测结果显示,SK-OV-3/GRIM-19细胞株增殖较SK-OV-3/Control细胞株明显下调（P〈0.05）。提示GRIM-19的高表达可以抑制卵巢癌细胞株的增殖,并且下调STAT3的表达。     

Med19在肿瘤领域的研究

中介体(Mediator,Med)是RNA聚合酶Ⅱ通用转录装置的重要组成部分,在真核mRNA合成的活化和阻抑中起着关键作用.其最早是在研究酵母RNA聚合酶Ⅱ转录功能时发现的[1],并在近年的研究中发现Med复合物的亚基组成及其相关的可能功能活性.     

GRIM-19表达与人子宫颈癌移植瘤细胞凋亡关系的研究

目的通过裸鼠体内实验探讨GRIM-19基因对子宫颈癌细胞凋亡的影响。方法将HeLa/Control、He-La/GRIM-19接种到裸鼠皮下7周,利用Tunel实验检测移植瘤细胞的凋亡情况,采用Western blot检测移植瘤组织中p53及puma蛋白的表达情况。结果与对照组相比,GRIM-19高表达的移植瘤细胞生长减慢、凋亡增多,p53及其下游基因puma表达增加。结论 GRIM-19可能通过上调p53蛋白的表达促进子宫颈癌细胞的凋亡。     

Med19在人胃癌中的表达及其临床意义

目的 研究Med19基因在人胃癌组织中的表达情况及临床意义.方法 应用免疫组化和RT-PCR方法检测Med19 基因在胃癌组织、癌旁胃组织及正常胃组织中的表达.结果 胃癌组织中Med19表达阳性率为71.7%(43/60),显著高于癌旁胃组织和正常胃组织(P<0.01).癌旁胃组织和正常胃组织中Med19多为阴性表达,少数为弱阳性表达,二者间差异无显著性(P> 0.05).Med19的表达与胃癌的细胞分化程度、淋巴结转移情况、TNM分期相关(P<0.05),而在不同年龄、性别、肿瘤大小、浸润深度的胃癌样本中表达差异无显著性(P> 0.05). 结论 Med19参与了胃癌的发生、发展过程,有望成为一个新的肿瘤治疗靶向因子.     

细胞凋亡调节基因GRIM-19的研究进展

GRIM-19是维甲酸/干扰素联合应用诱导细胞凋亡相关基因中的一员,是由Angell等筛选出来的一个新的死亡相关基因,定位于人染色体19p 13.1,是线粒体复合体Ⅰ的组成成分.它可以特异性地与STAT3结合,通过下调STAT3的转录激活活性,抑制其靶基因的表达和细胞生长;此外还可以和蛋白GW112、NOD2等相互作用.国内外已经在原发性肾细胞癌等泌尿系统肿瘤、结直肠癌、甲状腺癌中对GRIM-19的表达进行了研究,提出GRIM-19可能成为一个新的肿瘤抑制基因,并可能成为评价疗效的有用的生物标记物和基因治疗的一个潜在的靶点.     

CK19 mRNA在大肠癌患者外周血中的表达及临床意义

目的 探讨CK19 mRNA在大肠癌患者外周血的表达及临床意义.方法 应用巢式RT-PCR技术检测20例健康人、20例大肠腺瘤疾病患者和90例大肠癌患者外周血CK19 mRNA的表达.结果 健康人中CK19 mRNA不表达,大肠良性腺瘤疾病患者外周血中CK19 mRNA有1例表达,表达率为5%,大肠癌患者外周血中CK19 mRNA有53例,表达率为58.9%,CK19 mRNA表达率与肿瘤分期,瘤细胞的分化程度,肿瘤转移有显著相关性(均P<0.05).结论 CK19 mRNA作为检测大肠癌患者外周血微转移的分子标记物具有良好的敏感度和特异性同时CK19 mRNA可作为判断大肠癌患者的预后的指标.     

MolecularphenotypesofhumanparvovirusB19inpatientswithmyocarditis Bock CT,Düchting A,Utta F,Brunner E,Sy BT,Klingel K,Lang F,Gawaz M,Felix SB,

AIM: To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy (DCM).METHODS: Endomyocardial biopsies (EMBs) from 498 B19V-positive patients with myocarditis and DCM were analyzed using molecular methods and functional experiments. EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers. Control tissues were obtained at autopsy from 34 victims of accidents, crime or suicide. Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining. Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction (PCR). For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism (RFLP)-PCR was established. B19V-genotyping was verified by direct DNA-sequencing and sequences were aligned using BLAST and BioEdit software. B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments. Transfection experiments were conducted using human endothelial cells 1. Luciferase reporter assays were performed to determine B19V-replication activity. Statistical analysis and graphical representation were calculated using SPSS and Prism5 software.RESULTS: The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy (iCMP) compared to uninflamed DCM (59.6% vs 35.3%) (P < 0.0001). The detection of B19V-mRNA replication intermediates proved that replication of B19V was present. RFLP-PCR assays showed that B19V-genotype 1 (57.4%) and B19V-genotype 2 (36.7%) were the most prevalent viral genotypes. B19V-genotype 2 was observed more frequently in EMBs with iCMP (65.0%) compared to DCM (35%) (P = 0.049). Although there was no significant difference in gender-specific B19V-loads, women were more frequently infected with B19V-genotype 2 (44.6%) than men (36.0%) (P = 0.0448). Coinfection with B19V and other cardiotropic viruses was found in 19.2% of tissue samples and was associated with higher B19V viral load compared to B19V-monoinfected tissue (P = 0.0012). The most frequent coinfecting virus was human herpes virus 6 (HHV6, 16.5%). B19V-coinfection with HHV6 showed higher B19V-loads compared to B19V-monoinfected EMBs (P = 0.0033), suggesting that HHV6 had transactivated B19V. In vitro experiments confirmed a 2.4-fold increased B19V P6-promoter activity by the HHV6 U94-transactivator.CONCLUSION: The finding of significantly increased B19V loads in patients with histologically proven cardiac inflammation suggests a crucial role of B19V-genotypes and reactivation of B19V-infection by HHV6-coinfection in B19V-associated iCMP. Our findings suggest that B19V-infection of the human heart can be a causative event for the development of an endothelial cell-mediated inflammatory disease and that this is related to both viral load and genotype.     

Post-COVID-19 Arthritis and Sacroiliitis: Natural History with Longitudinal Magnetic Resonance Imaging Study in Two Cases and Review of the Literature

Severe acute respiratory coronavirus-2 syndrome (SARS-CoV-2) is a well-known pandemic infectious disease caused by an RNA virus belonging to the coronaviridae family. The most important involvement during the acute phase of infection concerns the respiratory tract and may be fatal. However, COVID-19 may become a systemic disease with a wide spectrum of manifestations. Herein, we report the natural history of sacroiliac inflammatory involvement in two females who developed COVID-19 infection with mild flu-like symptoms. After the infection they reported inflammatory back pain, with magnetic resonance imaging (MRI) studies showing typical aspects of sacroiliitis. Symptoms improved with NSAIDs therapy over the following months while MRI remained positive. A literature review was performed on this emerging topic. To our knowledge, this is the first MRI longitudinal study of post-COVID-19 sacroiliitis with almost one year of follow-up. Predisposing factors for the development of articular involvement are unclear but a long-lasting persistence of the virus, demonstrated by nasopharyngeal swab, may enhance the probability of altering the immune system in a favourable background.     

Post‑COVID‑19 Syndrome in Outpatients: a Cohort Study

BackgroundAfter mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed.ObjectivesTo characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors.ParticipantsOutpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative).DesignMonocentric cohort study with prospective phone interview between more than 3 months to 10 months after initial visit to the emergency department and outpatient clinics.Main MeasuresData of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey.Key ResultsThe study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p = 0.020) and healthcare workers (67% versus 82%; p = 0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p = 0.006) and proportions were stable among the periods of the phone interviews. Overall, 21% COVID-positive and 15% COVID-negative patients (p = 0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio 2.14, 95% CI 1.04–4.41), smell/taste disorder (26.5, 3.46–202), dyspnea (2.81, 1.10–7.16), and memory impairment (5.71, 1.53–21.3). Among COVID-positive, female gender (1.67, 1.09–2.56) and overweight/obesity (1.67, 1.10–2.56) were predictors of persistent symptoms.ConclusionsMore than half of COVID-positive outpatients report persistent symptoms up to 10 months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07242-1.     

Gastrointestinal manifestations of long-term effects after COVID-19 infection in patients with dialysis or kidney transplantation:An observational cohort study

BACKGROUND Prolonged symptoms after corona virus disease 2019(Long-COVID) in dialysisdependent patients and kidney transplant(KT) recipients are important as a possible risk factor for organ dysfunctions,especially gastrointestinal(GI)problems,during immunosuppressive therapy.AIM To identify the characteristics of GI manifestations of Long-COVID in patients with dialysis-dependent or KT status.METHODS This observational,prospective study included patients with COVID-19 infection,confirmed by rev...     

COVID-19 pandemic: Pathophysiology and manifestations from the gastrointestinal tract

The pandemic of coronavirus disease 2019(COVID-19), caused by a newly identified β-coronavirus(SARS-CoV-2) has emerged as a dire health problem, causing a massive crisis for global health. Primary method of transmission was firstly thought to be animal to human transmission. However, it has been observed that the virus is transmitted from human to human via respiratory droplets. Interestingly, SARS-CoV-2 ribonucleic acid(RNA) has been isolated from patient stools, suggesting a possible gastrointestinal(GI) involvement. Most commonly reported clinical manifestations are fever, fatigue and dry cough. Interestingly, a small percentage of patients experience GI symptoms with the most common being anorexia, diarrhea, nausea and vomiting. The presence of viral RNA in stools is also common and fecal tests can be positive even after negative respiratory samples. The exact incidence of digestive symptoms is a matter of debate. The distribution of Angiotensin converting enzyme type 2 receptors in multiple organs in the body provides a possible explanation for the digestive symptoms' mechanism. Cases with solely GI symptoms have been reported in both adults and children. Viral RNA has also been detected in stool and blood samples, indicating the possibility of liver damage, which has been reported in COVID-19 patients. The presence of chronic liver disease appears to be a risk factor for severe complications and a poorer prognosis, however data from these cases is lacking. The aim of this review is firstly, to briefly update what is known about the origin and the transmission of SARS-CoV-2, but mainly to focus on the manifestations of the GI tract and their pathophysiological background, so that physicians on the one hand, not to underestimate or disregard digestive symptoms due to the small number of patients exhibiting exclusively this symptomatology and on the other, to have SARS-CoV-2 on their mind when the "gastroenteritis" type symptoms predominate.     

鼻咽癌组织中EB病毒LMP1与hsa-miR-19b表达及其相关性分析

目的观察鼻咽癌（NPC）组织中EB病毒潜伏膜蛋白1（LMP1）和hsa—miR-19b表达变化及其与NPC临床病理特征的关系。方法采用免疫组化技术检测46例NPC放疗前活检标本中LMP1的表达情况,用实时定量PCR检测hsa-miR-19b表达情况。分析二者表达相关性及其与NPC临床病理特征的关系。结果NPC组织中LMP1阳性表达率为60．95％,hsa-miR-19b阳性表达量为68．27±69．00;LMP1、hsa-miR-19b表达均与NPC分期和淋巴结转移有关。LMP1表达与hsa—miR-19b表达呈正相关（r=0．390,P=0．007）。结论LMP1可能调控hsa-miR-19b的表达,两者的表达呈正相关关系。LMP1、hsa-miR-19b的高表达与NPC分期和转移有关。     

乳腺癌外周血细胞角蛋白19 mRNA的检测及临床价值

目的应用荧光定量RT-PCR检测乳腺癌外周血中的表达情况,并评价其表达的临床意义。方法用荧光定量RT-PCR方法检测49例乳腺癌患者外周血CK19mRNA表达。结果49例乳腺癌患者外周血中CK19mRNA检测阳性28例,阳性率57.1%,统计结果显示乳腺癌患者外周血CK19mRNA的表达阳性率在患者不同年龄、病理类别、临床分期、ER、PR状态的各组差异无显著性(P>0.05),在淋巴结转移状态间有显著差异。结论CK19mRNA可作为RT-PCR法检测乳腺癌患者外周血微转移的分子标志物,有助于早期预测乳腺癌发生血道微转移,指导临床治疗。     

慢性阻塞性肺疾病患者血中IL-19表达水平及与IL-8、IL-10、TNF-α的相关性研究

目的探讨白介素-19（Interleukin-19,IL-19）在慢性阻塞性肺疾病（COPD）患者血清中的表达水平。方法用酶联免疫吸附方法（ELISA）分别测定COPD组急性发作期、稳定期及正常对照组血清中IL-19、IL-8、IL-10、肿瘤坏死因子（Tumor Necrosis Factor,TNF-α）等细胞因子的水平,并同期检测各组肺通气功能。结果COPD组急性发作期、稳定期血清中IL-19水平均较对照组明显升高（P〈0.01）;急性发作期IL-19水平较缓解期升高（P〈0.05）。COPD组急性发作期、稳定期血清中IL-8、TNF-α水平均较对照组升高（P均〈0.05）;急性发作期IL-8、TNF-α水平均较缓解期升高（P均〈0.05）。COPD组急性发作期血清中IL-10水平较稳定期对照组升高（P均〈0.05）;缓解期IL-10水平较对照组无明显变化（P〉0.05）。COPD组急性发作期血IL-19水平与FEV1.0呈负相关,与同期IL-8、TNF-α水平呈正相关。结论IL-19可能参与了COPD气道炎症反应并导致气流阻塞的形成。