COVID - 19

COVID - 19
  • 文章类型: Journal Article
    在不同的疾病修饰疗法(DMT)和Omicron和武汉的SARS-COV-2变种的中和作用下,尚无LATAM与多发性硬化症(pwMS)患者对基于腺病毒的COVID-19疫苗的纵向体液和细胞反应有关的报道。
    IgG抗SARS-COV-2的峰值滴度在芬戈莫德下的101pwMS队列中测量,富马酸二甲酯,在第2剂(SputnikV或AZD1222)和第3剂(同源或异源时间表)接种后6周,测量了克拉屈滨和抗CD20以及28名健康对照(HC)。中和能力针对Omicron(BA.1)和武汉(D614G)变体,并分析了假型颗粒和细胞反应。
    多元回归分析显示抗cd20(β=-,349,95%CI:-3655.6--369.01,p=0.017)和芬戈莫德(β=-,399,95%CI:-3363.8--250.9,p=0.023)治疗作为与低抗体反应相关的独立因素(r2调整=0.157)。在第2次剂量后,我们发现总滴度和中和滴度对D614G之间存在相关性(rho=0.6;p<0.001;斜率0.8,95CI:0.4-1.3),DMT之间没有差异。BA.1的中和能力较低(斜率0.3,95CI:0.1-0.4)。第三次给药后,BA.1的中和改善(斜率:0.995CI:0.6-1.2),没有DMT之间的差异。一部分pwMS产生抗-SpikeCD4+和CD8+T细胞应答。相比之下,pwMS在抗CD20下产生CD8+TNF+IL2+反应,与HC无差异,即使没有体液反应。第三剂量显著增加了对Omicron的中和作用,在免疫活性人群中观察到的。
    关于体液和细胞反应的发现与以前的报告一致。
    UNASSIGNED: There are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2.
    UNASSIGNED: IgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2nd dose (Sputnik V or AZD1222) and 3nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed.
    UNASSIGNED: Multivariate regression analysis showed anti-cd20 (β= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (β=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95%CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population.
    UNASSIGNED: Findings regarding humoral and cellular response are consistent with previous reports.
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  • 文章类型: Journal Article
    急性呼吸窘迫综合征(ARDS)是严重COVID-19的常见并发症,并导致患者的发病率和死亡率。ARDS是由各种侮辱引起的异质性综合征,并导致急性低氧性呼吸衰竭。来自COVID-19的ARDS患者可能代表ARDS患者的一个亚组,具有不同的分子谱,可驱动疾病结局。这里,我们假设纵向转录组分析可能在COVID-19ARDS过程中识别出不同的动态病理生物学途径。
    我们从现有的ICU生物储存库中确定了一个患者队列,并建立了三组进行比较:1)住院存活的COVID-19ARDS患者(COVID幸存者,n=4),2)住院期间未能存活的COVID-19ARDS患者(COVID非幸存者,n=5),和3)其他原因引起的ARDS患者作为对照组(ARDS对照,n=4)。在4个时间点(ICU入院后第1、3、7和10天)从外周血单核细胞(PBMC)中分离RNA,并通过批量RNA测序进行分析。
    我们首先在各个时间点比较了组间的转录组,并观察到差异表达基因(DEGs)的显着异质性。接下来,我们利用似然比检验来识别3组之间随时间变化的不同模式的基因,并在时间上识别出341个DEG,包括血红蛋白亚基α2(HBA1,HBA2),血红蛋白亚基β(HBB),血管性血友病因子C和EGF域(VWCE),和碳酸酐酶1(CA1),与COVID幸存者相比,COVID非幸存者均表现出持续的上调。在341个DEG中,314显示,与幸存者相比,COVID非幸存者的基因表达持续增加的模式相似,与铁稳态信号传导的经典途径相关,红细胞与氧气和二氧化碳的相互作用,促红细胞生成素信号,血红素生物合成,卟啉的代谢,以及铁的吸收和运输。
    这些发现描述了COVID-19ARDS幸存者和非幸存者在患者ICU过程中基因调控的显着差异。我们确定了表明血红素和红细胞代谢有助于疾病结局的多种途径。这种方法可推广到更大的队列,并支持ARDS分子谱分析研究中的纵向采样方法。这可能会发现新的可靶向的损伤和解决途径。
    UNASSIGNED: The acute respiratory distress syndrome (ARDS) is a common complication of severe COVID-19 and contributes to patient morbidity and mortality. ARDS is a heterogeneous syndrome caused by various insults, and results in acute hypoxemic respiratory failure. Patients with ARDS from COVID-19 may represent a subgroup of ARDS patients with distinct molecular profiles that drive disease outcomes. Here, we hypothesized that longitudinal transcriptomic analysis may identify distinct dynamic pathobiological pathways during COVID-19 ARDS.
    UNASSIGNED: We identified a patient cohort from an existing ICU biorepository and established three groups for comparison: 1) patients with COVID-19 ARDS that survived hospitalization (COVID survivors, n = 4), 2) patients with COVID-19 ARDS that did not survive hospitalization (COVID non-survivors, n = 5), and 3) patients with ARDS from other causes as a control group (ARDS controls, n = 4). RNA was isolated from peripheral blood mononuclear cells (PBMCs) at 4 time points (Days 1, 3, 7, and 10 following ICU admission) and analyzed by bulk RNA sequencing.
    UNASSIGNED: We first compared transcriptomes between groups at individual timepoints and observed significant heterogeneity in differentially expressed genes (DEGs). Next, we utilized the likelihood ratio test to identify genes that exhibit different patterns of change over time between the 3 groups and identified 341 DEGs across time, including hemoglobin subunit alpha 2 (HBA1, HBA2), hemoglobin subunit beta (HBB), von Willebrand factor C and EGF domains (VWCE), and carbonic anhydrase 1 (CA1), which all demonstrated persistent upregulation in the COVID non-survivors compared to COVID survivors. Of the 341 DEGs, 314 demonstrated a similar pattern of persistent increased gene expression in COVID non-survivors compared to survivors, associated with canonical pathways of iron homeostasis signaling, erythrocyte interaction with oxygen and carbon dioxide, erythropoietin signaling, heme biosynthesis, metabolism of porphyrins, and iron uptake and transport.
    UNASSIGNED: These findings describe significant differences in gene regulation during patient ICU course between survivors and non-survivors of COVID-19 ARDS. We identified multiple pathways that suggest heme and red blood cell metabolism contribute to disease outcomes. This approach is generalizable to larger cohorts and supports an approach of longitudinal sampling in ARDS molecular profiling studies, which may identify novel targetable pathways of injury and resolution.
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  • 文章类型: Journal Article
    自2019年冠状病毒病(COVID-19)大流行以来,人们很少关注大流行对心血管健康系统的间接影响,特别是在急性冠脉综合征(ACS)患者中。这项研究的目的是比较可能的流行病学,在因ACS住院的患者组中,四个流行波之间的临床和管理差异,以突出大流行对该综合征管理的负担.
    在这项回顾性观察性研究中,我们纳入了在2020年3月至2022年3月期间因ACS进入冠状动脉重症监护病房(CICU)的98例患者,这些患者使用经皮冠状动脉成形术(PCI)进行了血运重建手术。所检查的患者分为四组,代表影响我国的四个流行病。
    与第一波相比,第三波中ACS的住院率逐渐增加到178%(p=0.003),如果我们仅考虑非ST段抬高型心肌梗死(NSTEMI),则增加900%(占第三组ACS诊断的54%,而第一组为14.3%)。由于NSTEMI的存在增加,在第三波中记录了更长的门到气球时间。第三波中平均住院时间较低,为5±2天(p=0.007),死亡率较低(第三波中为5.1%;第四波中最高,为9.5%)。
    研究表明,在第一波大流行期间,ACS的管理受到的间接影响最大,既是因为医院设施的准备不足,也是因为害怕感染,这阻止了人们寻求帮助。
    UNASSIGNED: Since the beginning of the COronaVIrus Disease 2019 (COVID-19) pandemic, poor attention has been paid to the indirect effects of the pandemia on cardiovascular health system, in particular in patients with Acute Coronary Syndrome (ACS). The aims of this study is to compare possible epidemiological, clinical and management differences between the four epidemic waves in groups of patients hospitalized for ACS with a view to highlighting the burden of the pandemic on the management of this syndrome.
    UNASSIGNED: In this retrospective observational study we included 98 patients admitted to Coronary Intensive Care Unit (CICU) for ACS between March 2020 and March 2022, who underwent revascularization procedure using percutaneous coronary angioplasty (PCI). The patients examined were divided into four groups representative of the four epidemic waves that affected our country.
    UNASSIGNED: The rate of hospitalization for ACS increased progressively to a 178 % increase in the third wave compared to the first (p = 0.003), with an increase of 900 % if we consider only Non-ST-Elevation Myocardial Infarction (NSTEMI) (representing 54 % of the ACS diagnoses of the third group against 14.3 % in the first). Longer door-to-balloon times were recorded in the third wave for the increased presence of NSTEMI. The average hospital stay was lower in the third wave with 5 ± 2 days (p = 0.007) as well as mortality (5.1 % in the third wave; the highest in the fourth wave with 9.5 %).
    UNASSIGNED: The study show that the management of ACS suffered most from the indirect effects of the pandemic during the first wave, both because of the unpreparedness of hospital facilities and because of the fear of infection that has dissuaded people from asking for help.
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  • 文章类型: Journal Article
    外泌体存在于身体的各种组织中,并携带丰富的内容物,包括核酸,蛋白质,和代谢物,它在各种组织的细胞之间不断流动,并介导重要的细胞间通讯。此外,来自不同细胞来源的外泌体具有不同的生理病理免疫调节作用,与正常或异常器官组织的免疫再生密切相关。这里,我们专注于外泌体和人体免疫系统之间的机械相互作用,介绍外泌体在常见临床免疫相关疾病中的免疫再生治疗潜力,如传染病,自身免疫性疾病,和肿瘤,并揭示了外泌体作为一种新型无细胞免疫再生疗法的安全性和有效性。
    Exosomes are found in various tissues of the body and carry abundant contents including nucleic acids, proteins, and metabolites, which continuously flow between cells of various tissues and mediate important intercellular communication. In addition, exosomes from different cellular sources possess different physiopathological immunomodulatory effects, which are closely related to the immune regeneration of normal or abnormal organs and tissues. Here, we focus on the mechanistic interactions between exosomes and the human immune system, introduce the immuno-regenerative therapeutic potential of exosomes in common clinical immune-related diseases, such as infectious diseases, autoimmune diseases, and tumors, and reveal the safety and efficacy of exosomes as a novel cell-free immune regenerative therapy.
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  • 文章类型: Editorial
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  • 文章类型: Journal Article
    固有淋巴样细胞(ILC)富集在粘膜表面,在那里它们对环境刺激迅速反应并有助于组织炎症和愈合。
    为了深入了解ILC在COVID-19感染的病理和恢复中的作用,我们采用由Abseq和靶向mRNA测序组成的多组学方法来分别探测表面标记表达,与健康对照组相比,COVID-19患者外周血ILC的转录谱和异质性。
    我们发现,在COVID-19患者中,ILC1和ILC2细胞的频率显着增加。此外,所有ILC亚群都显示出明显更高频率的CD69表达细胞,表明激活状态增强。来自COVID-19患者的ILC2s具有最高数量的显著差异表达(DE)基因。COVID-19与健康参与者相比,最显着的基因DE包括a)与病毒感染反应相关的基因和b)支持ILC自我增殖的基因,激活和体内平衡。此外,差异基因调控网络分析揭示了ILC特异性调控子及其相互作用驱动每个ILC中的差异基因表达。
    总的来说,这项研究提供了对COVID-19感染期间激活的ILC亚群特征的机制见解。
    UNASSIGNED: Innate lymphoid cells (ILCs) are enriched at mucosal surfaces where they respond rapidly to environmental stimuli and contribute to both tissue inflammation and healing.
    UNASSIGNED: To gain insight into the role of ILCs in the pathology and recovery from COVID-19 infection, we employed a multi-omics approach consisting of Abseq and targeted mRNA sequencing to respectively probe the surface marker expression, transcriptional profile and heterogeneity of ILCs in peripheral blood of patients with COVID-19 compared with healthy controls.
    UNASSIGNED: We found that the frequency of ILC1 and ILC2 cells was significantly increased in COVID-19 patients. Moreover, all ILC subsets displayed a significantly higher frequency of CD69-expressing cells, indicating a heightened state of activation. ILC2s from COVID-19 patients had the highest number of significantly differentially expressed (DE) genes. The most notable genes DE in COVID-19 vs healthy participants included a) genes associated with responses to virus infections and b) genes that support ILC self-proliferation, activation and homeostasis. In addition, differential gene regulatory network analysis revealed ILC-specific regulons and their interactions driving the differential gene expression in each ILC.
    UNASSIGNED: Overall, this study provides mechanistic insights into the characteristics of ILC subsets activated during COVID-19 infection.
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  • 文章类型: Journal Article
    Omicron时代血液病(HD)患者中COVID-19管理的真实数据很少。
    为了评估诊断的SARS-CoV-2感染的当前临床管理和结果,根据真实世界环境中的HD特征和细胞治疗程序,确定严重结局的危险因素.
    分析了由西班牙移植小组(GETH-TC)领导的回顾性观察性注册表,该注册表于2021年12月至2023年5月期间连续692例HD患者。
    近三分之一(31%)的患者未接受治疗,COVID-19相关死亡率较低(0.9%)。Nirmatrelvir/利托那韦主要用于门诊的轻度COVID-19病例(32%),死亡率低(1%),而在住院期间的中度至重度SARS-CoV-2感染病例中(35%),死亡率为8.6%,则优先使用remdesivir进行治疗。住院率为23%,而18%发展为肺炎。入院患者中COVID-19相关死亡率为14%。年纪大了,自体造血干细胞移植(SCT),嵌合抗原受体T细胞疗法,糖皮质激素和不完全疫苗接种是与COVID-19严重程度独立相关的因素,并且与更高的住院率和肺炎发生率显著相关.不完全疫苗接种状态,用先前的抗CD20单克隆抗体治疗,和共病心肌病被确定为COVID-19死亡率的独立危险因素。
    结果支持,尽管程度较低,Omicron时代的COVID-19仍然是HD患者的一个重要问题。在这些免疫功能低下的患者中,应优先考虑完全接种(3剂)。确定的危险因素可能有助于改善COVID-19的管理,以降低严重疾病的发生率,ICU入院率和死亡率。
    UNASSIGNED: Scarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era.
    UNASSIGNED: To assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting.
    UNASSIGNED: A retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed.
    UNASSIGNED: Nearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality.
    UNASSIGNED: The results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality.
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  • 文章类型: Journal Article
    当前的SARS-CoV-2毒株继续突变并试图逃避由先前的暴露和疫苗接种引起的抗体反应。2022年9月,首批更新的SARS-CoV-2疫苗,被设计用于产生对2022年流行的变体具有特异性的免疫反应,获得批准。这些新疫苗,通常被称为二价升压(呃),包括编码原始武汉-Hu-1刺突蛋白以及对OmicronBA.4和BA.5变体具有特异性的刺突蛋白的mRNA。
    我们招募了马萨诸塞州大学学生的志愿者,教职员工在四个不同的时间点提供血液和唾液样本,包括前加强和三次后加强和分析样品的抗体生产以及中和病毒。
    我们的数据提供了在6个月的时间内单剂量的二价加强后的抗体应答的全面分析,并且支持先前的发现,即在二价加强后诱导的应答不产生强烈的BA4/BA.5特异性抗体应答。
    我们没有发现任何证据表明随着时间的推移会产生特定的抗BA.4/BA.5反应,包括在单剂量的二价加强剂后感染的个体亚群中。此外,我们提供的数据支持使用唾液样本作为血液的可靠替代方法来检测针对特定SARS-CoV-2抗原的抗体。
    UNASSIGNED: Current SARS-CoV-2 strains continue to mutate and attempt to evade the antibody response elicited by previous exposures and vaccinations. In September of 2022, the first updated SARS-CoV-2 vaccines, designed to create immune responses specific for the variants circulating in 2022, were approved. These new vaccines, known commonly as the bivalent boost(er), include mRNA that encodes both the original Wuhan-Hu-1 spike protein as well as the spike protein specific to the Omicron BA.4 and BA.5 variants.
    UNASSIGNED: We recruited volunteers from University of Massachusetts student, faculty and staff members to provide samples of blood and saliva at four different time points, including pre-boost and three times post boost and analyzed samples for antibody production as well as neutralization of virus.
    UNASSIGNED: Our data provide a comprehensive analysis of the antibody response following a single dose of the bivalent boost over a 6-month period and support previous findings that the response induced after the bivalent boost does not create a strong BA.4/BA.5-specific antibody response.
    UNASSIGNED: We found no evidence of a specific anti-BA.4/BA.5 response developing over time, including in a sub-population of individuals who become infected after a single dose of the bivalent booster. Additionally, we present data that support the use of saliva samples as a reliable alternative to blood for antibody detection against specific SARS-CoV-2 antigens.
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  • 文章类型: Editorial
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  • 文章类型: Case Reports
    背景:腹部脂肪成形术是当今最常见的腹部轮廓术之一;然而,它有严重并发症的风险。气胸是吸脂术的罕见并发症,while,静脉血栓栓塞具有较低的短期死亡率和长期发病率.
    方法:一名57岁女性,有糖尿病史,高血压,肥胖,三年前严重的COVID-19。患者接受了360度吸脂术和腹部成形术。在术后即刻,患者出现右侧气胸,随后出现深静脉血栓(DVT)和肺栓塞(PE),早期诊断和治疗。经过六个月的随访,患者完全康复。
    结论:气胸被认为是吸脂术的罕见并发症,在医学文献中仅限于病例报告和小病例系列,发生率为0.04%。在整形和美容手术中,身体轮廓手术如脂腹成形术与DVT和PE的风险为0.2-0.6%,0.3%,分别。此外,我们认为进行联合美容手术可能会增加并发症的风险。
    结论:这是首例气胸病例,身体轮廓手术后的DVT和PE。我们强调意识到这些并发症的重要性,以及对早期诊断和治疗的高度怀疑指数的必要性,这对患者的生存至关重要。
    BACKGROUND: Lipoabdominoplasty is one of the most common abdominal body contouring procedures performed today; however, it carries the risk of significant complications. Pneumothorax is a rare complication of liposuction, while, venous thromboembolism has a low short-term mortality and long-term morbidity.
    METHODS: A 57-year-old woman with a history of diabetes mellitus, hypertension, obesity, and severe COVID-19 three years earlier. The patient underwent 360-degree liposuction and abdominoplasty. In the immediate postoperative period, the patient developed a right pneumothorax and followed by deep vein thrombosis (DVT) and pulmonary embolism (PE), which were diagnosed and treated early. After six months of follow-up, the patient presented a complete recovery.
    CONCLUSIONS: Pneumothorax is recognized as a rare complication of liposuction and has been limited to case reports and small case series in the medical literature with an incidence of 0.04 %. In plastic and aesthetic surgery, body contouring procedures such as lipoabdominoplasty are associated with a risk of DVT and PE of 0.2-0.6 %, and 0.3 %, respectively. In addition, we believe that performing combined aesthetic procedures may increase the risk of complications.
    CONCLUSIONS: This is the first reported case of pneumothorax, DVT and PE after body contouring surgery. We highlight the importance of awareness of these complications and the need for a high index of suspicion for early diagnosis and treatment, which is critical for patient survival.
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