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1 Phys.org,2月21日,Why natural killer cells react to COVID-19 2022-03-03

Little has been known to date about how the immune system's natural killer(NK)cells detect which cells have been infected with SARS-CoV-2.An international team of scientist led by researchers from Karolinska Institutet now shows that NK cells respond to acertain peptide on the surface of infected cells.The study,which is published in Cell Reports,is an important piece of the puzzle in our understanding of how the immune system reacts to COVID-19. NK cells are white blood cells that are part of the innate immune system.Unlike cells in the adaptive immune defense,they are able to recognize and kill cancer cells and virus-infected cells immediately without having encountered them before.This ability is controlled by abalance between the NK cells'activating and inhibiting receptors,which can react to different molecules on the surface of other cells. The virus is revealed by apeptide A new study shows why certain NK cells are activated when encountering acell infected with SARS-CoV-2.The infected cells contain apeptide from the virus that triggers areaction in NK cells that carry aparticular receptor,NKG2A,able to detect the peptide. "Our study shows that SARS-CoV-2 contains apeptide that is displayed by molecules on the cell surface,"says Quirin Hammer,researcher at the Center for Infectious Medicine(CIM),Karolinska Institutet."The activation of NK cells is acomplex reaction,and here the peptide blocks the inhibition of the NK cells,which allows them to be activated.This new knowledge is an important piece of the puzzle in our understanding of how our immune system reacts in the presence of this viral infection." The study was amajor collaboration between Karolinska Institutet,Karolinska University Hospital and research laboratories and universities in Italy,Germany,Norway and the U.S.The first phase was to test their hypothesis using computer simulations that were then confirmed in the laboratory.The decisive phase was the infection of human lung cells with SARS-CoV-2 in acontrolled environment,whereupon the researchers could show that NK cells with the receptor in question are activated to agreater degree than the NK cells without it. 查看详细>>

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2 ScienceDaily,2月18日,T-cell responses may help predict protection against SARS-CoV-2 infection in individuals with and without cancer 2022-03-03

The efficacy of COVID-19 vaccines has been typically measured by antibody levels,but this may not be areliable metric,explained Laurence Zitvogel,MD,PhD,a professor at the Gustave Roussy Institute in Villejuif,France."Humoral immune responses monitored by antibody titers are only transiently helpful and not well correlated with protection,"she said."Antibodies do not last more than acouple of weeks in agiven individual post-infection or post-vaccination.Data show that antibodies against the SARS-CoV-2 spike protein have failed to predict actual protection against reinfection or breakthrough infection." Measuring antibody levels is away to monitor the presence and the activity of memory Bcells,which are immune cells that produce antibodies and represent the first arm of adaptive immunity.T cells,another type of immune cell,represent the second arm of long-term immunity and can be amplified during infection to kill infected cells directly. In this study,Zitvogel and colleagues examined whether T-cell responses could be areliable indicator of protection against SARS-CoV-2 infection in healthy individuals and in patients with cancer who had not been exposed to the virus during the first wave of the pandemic.Using blood samples collected prior to infection with SARS-CoV-2,they performed various in vitro experiments to assess how the polarity and repertoire of T-cell responses correlated with susceptibility to infection with SARS-CoV-2 during subsequent waves of the pandemic. T-cell polarity was assessed by identifying the types of cytokines--which are immune-stimulating proteins--released by the Tcells of each individual when exposed to aviral antigen.The release of the IL-2 cytokine was indicative of Th1 Tcells,whereas the release of the IL-5 cytokine indicated Th2 Tcells.Zitvogel and colleagues examined the makeup of each individual's T-cell pool to determine the proportion of Th1 and Th2 Tcells. They found pre-existing SARS-CoV-2-specific Tcell responses in about 20-25 percent of the population,both in healthy individuals and in cancer patients.In addition,they observed that the types of cytokines released by memory Tcells were associated with protection against SARS-CoV-2 infection.An imbalance between the IL-2 and IL-5 cytokines was associated with ahigher susceptibility to SARS-CoV-2 infection,with an IL-2/IL-5 ratio less than 1predicting infection,regardless of cancer status.This suggests that the relative levels of cytokines released by Tcells may provide insight into susceptibility to SARS-CoV-2 infection,explained Zitvogel. Further analysis revealed that Tcells from individuals who had developed aprimary infection,breakthrough infection post-vaccination,or reinfection with SARS-CoV-2 did not react to the receptor-binding domain of the spike protein,despite having immune responses against other regions of the viral genome.Zitvogel and colleagues proposed that the lack of reactivity to the spike receptor-binding domain may have made these individuals more susceptible to infection.Additionally,Zitvogel proposed that T-cell reactivity to the receptor-binding domain could even drive evolution of the spike protein,potentially contributing to the emergence of new viral variants. 查看详细>>

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3 2月18日_研究发现伊维菌素对轻度至中度COVID-19无效 2022-03-03

CIDRAP网站2月18日消息,发表在《美国医学会内科杂志》(JAMA Internal Medicine)上的一项研究表明,使用抗寄生虫药物伊维菌素(ivermectin)进行早期治疗并不能降低轻度至中度COVID-19患者患重症的风险。 研究人员于2021年5月31日至10月25日进行了一项开放性的随机临床试验,以研究50岁及以上、患有轻或中度疾病和潜在疾病的成人住院患者在COVID-19症状出现的第一周使用伊维菌素治疗的效果。患者的平均年龄为62.5岁,54.5%为女性,51.8%接种了两剂COVID-19疫苗,75.3%患有高血压,53.5%患有糖尿病,37.6%患有胆固醇水平异常,23.9%患有肥胖。患者以1:1的比例随机分配,口服伊维菌素5天加标准治疗(241名患者)或仅标准治疗(249名)。标准治疗包括症状治疗和临床表现监测、实验室检查结果和胸部影像学检查,以监测疾病进展的迹象。重症的具体表现为缺氧(低氧水平),需要使用辅助氧气将血氧饱和度维持在95%或更高。伊维菌素组的241例患者中有52例(21.6%)、标准护理组249例患者中有43例(17.3%)患者的病情更为严重(相对风险[RR]:1.25;95%可信区间[CI]:0.87-1.80)。两组在症状消退或机械通气、重症监护病房(ICU)入院、28天住院死亡或不良事件发生率方面没有显著差异。4名伊维菌素接受者(1.7%)需要机械通气,而标准护理组为10名(4.0%)(RR:0.41;95%CI:0.13-1.30)。伊维菌素组有6名患者(2.4%)入院ICU,对照组8名(3.2%)(RR:0.78;95%CI:0.27-2.20),3名服用伊维菌素者(1.2%)和10名对照组患者(4.0%)在28天内死亡(RR:0.31;95%CI:0.09-1.11)。44名患者(9.0%)中有55例不良事件,其中33例为伊维菌素组。最常见的不良事件是腹泻,在伊维菌素组中发生14例(5.8%),在标准护理组中发生4例(1.6%)。在整个试验中,一共发生了五起严重不良事件,其中伊维菌素组有四起。两名患者心脏病发作,一名患有严重贫血,一名患者因严重腹泻导致液体流失而休克,而对照组的一名患者腹部有动脉出血。不良事件导致六名患者停止服用伊维菌素,三名患者退出研究。13例患者(2.7%)死亡,其中大多数死于COVID-19肺炎,没有死亡归因于伊维菌素。伊维菌素组中不良事件的发生率较高,在试验环境之外需谨慎使用这种药物。 查看详细>>

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4 2月17日_抗磷脂自身抗体可使COVID-19患者出现血栓 2022-03-03

ScienceDaily网站2月17日消息,研究发现,在COVID-19患者血液中循环的抗磷脂自身抗体有可能使COVID-19患者出现血栓现象。研究人员分析了近250名COVID-19住院患者的血液样本,结果发现患者体内的抗磷脂自身抗体水平高于预期,这种抗体可使自身免疫性疾病(包括狼疮和抗磷脂综合征)患者的动脉和静脉产生血液凝块。自身抗体是由免疫系统产生的抗体,其错误地靶向并可能损害人体自身的系统和器官。 研究人员发现,COVID-19患者体内的自身抗体可使小鼠体内发生严重的凝血现象。这可能是因为自身抗体似乎对构成血管内壁的内皮细胞造成压力,进而导致细胞失去防止血栓形成的能力。当内皮细胞被激活时,其会使健康的血管变得“粘稠”,并将其他细胞吸引到血管壁上,进而使血栓现象更易发生,这可能会影响患者体内的多种基本器官。相关研究发表在期刊《关节炎与风湿病学》(Arthritis&Rheumatology)上。 研究人员发现,如果将抗磷脂自身抗体从COVID-19患者的血液样本中去除,内皮细胞促进凝血的活化功能就会丧失。但需要进行更多的研究来分析患者体内的自身抗体是否是导致凝血和COVID-19疾病严重程度增加的确切原因。该研究还表明,也许可以将用于治疗抗磷脂综合征的方法重新用于COVID-19疾病。 查看详细>>

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