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新冠病毒与细胞因子风暴有紧密联系?约翰霍普金斯大学学者研究成果发表

  • 责任编辑:siyu.zhang
  • 来源:互联网
  • 时间:2020-06-30 16:07:16

  新冠病毒导致了很多严重的结果,尤其是对人体免疫系统的伤害,近日约翰霍普金斯大学医学专家也在努力研究细胞因子与新冠病毒的联系,希望能够对控制新冠病毒有所帮助。

  风暴电池

  约翰霍普金斯大学的研究人员正在加紧研究SARS-CoV-2与一种称为细胞因子风暴的致命免疫系统故障之间的联系

  作者:Marlene Cimons/20小时前出版

  “细胞因子风暴”这个名字很贴切,它描述了人体免疫系统释放出的一股猛烈的狂风,它会导致极度的炎症、组织损伤甚至死亡。来自希腊细胞的细胞因子和运动的kinos在对抗病毒感染方面很重要。但它们会使同样的感染恶化到极致,这一现象证明对老年COVID-19患者是致命的。

  “免疫系统是一把双刃剑,”约翰·霍普金斯医学院的医学教授安德烈·考克斯说它在抗病毒反应中起着关键作用。但它也可能是一种病理性的促炎症。就像是想用锤子杀死一只虫子。你可以在墙上打个洞,而你正想把虫子弄脏。”

  考克斯是霍普金斯大学研究细胞因子风暴及其与新冠病毒关系的科学家之一。她的实验室,包括传染病博士后研究员安德鲁卡拉巴(andrewkaraba)正在分析感染患者的血液和肺组织样本,以确定相关的特定细胞因子。他们想知道为什么他们变得危险,尤其是在老年人中。

  其他研究人员正在测试药物,他们希望这些药物能够防止细胞因子风暴的发生,或者在细胞因子风暴开始后阻止它们。最终的目标是拯救那些最危险的人,使他们免于这种潜在的致命的SARS-CoV-2感染并发症。

  考克斯和她的团队正在研究一系列疾病,“寻找在非常严重的疾病中发现的东西,以及那些没有非常严重疾病的人,以了解为什么有些人生病,而另一些人没有,”她说我们想把范围缩小到小组之间一致的最小数量。细胞因子是作为先天感应途径的一部分产生的。如果我们能识别出这种过度活跃的途径,我们就能找到阻止它的方法。”

  “这就像是想用锤子杀死一只虫子。你可以在墙上打个洞,而你正想把虫子弄脏。”

  安德烈·考克斯

  医学教授有几十种影响免疫系统的细胞因子蛋白信使。在某些情况下,它们会激活某些反应,而在另一些情况下,它们会减慢反应速度。有时系统会出问题,触发太多的细胞因子,速度太快。这种情况也发生在自身免疫疾病、其他感染以及某些免疫疗法的副作用中。

  在COVID-19中,细胞因子风暴不成比例地袭击老年人,“原因尚不清楚,”考克斯说免疫系统的平衡在不同的年龄段受到不同的调节。这并不是说老年人和年轻人的免疫系统较弱或更强,而是有所不同。老年人可能比年轻人产生更具破坏性的免疫反应。”

  最常见的情况是,患者在突然病情严重之前似乎对最初的SARS-CoV-2感染保持着自己的抵抗力。通常,结果是可怕的。

  “细胞因子告诉其他细胞做一些事情,在这种情况下可能会增加组织损伤和疾病的严重程度,”考克斯说以血管为例,它会导致血管系统漏出液体和血液,使氧气更难到达它应该去的地方,因为氧气所在的地方有液体,比如肺部。”

  了解细胞因子风暴在COVID-19中的作用是霍普金斯大学一项多学科的工作,包括研究人员对旧药物进行新的研究。

  医学院外科学助理教授、移植外科医生罗素·韦斯森说:“在JHU看到来自不同领域的人们做出反应真是太棒了。”人们正在研究使用不同的药物来观察它们对COVID的影响,而且几乎所有这些努力都涉及到重新调整其他药物的用途。”

  Wesson正在与主要研究者Nada Alachkar,医学副教授和不相容性肾移植项目的医学主任,以及肾病学和传染病组的科学家一起进行一项多中心研究,测试Clazakizumab,一种防止肾移植受者器官排斥的药物。它通过抑制白细胞介素-6(IL-6)发挥作用,白细胞介素-6是一种免疫系统细胞因子,在病情最严重的COVID-19患者中被发现升高。

  这项临床试验是双盲和安慰剂对照的,这意味着研究人员和病人都不知道谁能得到这种药物或无害的替代品。研究对象包括重病患者,包括使用呼吸机的患者。”Wesson说:“我们知道这种药物非常直接地影响IL-6,并且相信中和它将有助于阻止细胞因子风暴,或者阻止它的进展。”这项研究是盲目的,但我们看到了令人鼓舞的结果,其中包括恢复迅速的患者。”

  “很高兴看到我们实验室的工作转化为可能有所帮助的东西。随着这场大流行的蔓延,我感到有点无能为力。”

  切坦贝特戈达

  来自金梅尔癌症中心、风湿病和传染病科以及神经内科和神经外科的神经外科教授正在测试另一种药物哌唑嗪,一种用于治疗高血压、前列腺肥大和创伤后应激障碍的α受体阻滞剂。他们认为它可以通过阻断儿茶酚胺(儿茶酚胺)的激增来防止细胞因子风暴,儿茶酚胺是一种在早期小鼠研究的基础上产生的物质,通常在细胞因子风暴出现之前。

  研究人员首先检查了一个全国性的急性呼吸窘迫综合征(ARDS)患者的数据库,ARDS是一种以肺部积液为特征的疾病,与COVID-19的情况相似。他们发现在服用哌唑嗪等药物的患者中,死亡人数较少,对呼吸机的需求也较低,因此他们推测,这种药物同样可以使COVID-19患者受益。

  “在动物模型的临床前数据和人类的回顾性数据之间,我们认为用COVID-19来测试这个概念是有很好的理由的,”Chetan Bettegowda说,他是医学院神经外科的教授和脑瘤专家。这个研究小组还包括路德维希中心主任、肿瘤学和病理学教授伯特·沃格尔斯坦(Bert Vogelstein)、霍华德休斯医学院研究员、风湿病学家马克西米利安·科尼格(Maximilian Konig)最近开始了一项对照试验,以观察在感染后早期给予哌唑嗪是否能避免细胞因子风暴。”“这是一种预防性的方法,”Bettegowda说如果患者已经出现细胞因子风暴的迹象,那就不太可能奏效。”

  就她而言,考克斯长期研究传染病,因此她意识到一种新发现的病毒所带来的挑战。

  “这些大流行病毒的问题是,世界上没有人见过类似的病毒,”考克斯说没有豁免权。更糟糕的是,这种病毒对谁做得好谁坏的规则与其他病毒不同,而现在,我们根本不理解这些规则。”

  对其他人来说,这项研究代表了一种背离,尽管这是一个值得欢迎的转变,因为他们很高兴参与到这场斗争中来。

  Bettegowda说:“看到这么多人独自过世,他们不能与亲人在一起,这让人心碎,所以很高兴看到我们实验室的工作转化为可能有所帮助的东西。”随着这场大流行的蔓延,我感到有点无能为力。”

  在健康中发布

  标记冠状病毒,covid-19

  附上原文,以供参考,拒绝转载,侵权必删:

  STORM CELLS

  Researchers at Johns Hopkins are racing to understand the connection between SARS-CoV-2 and a deadly immune system malfunction called a cytokine storm

  By Marlene Cimons / Published 20 hours ago

  The name "cytokine storm" is apt. It describes a furious gale-force swarm of molecules unleashed by the body's immune system that causes extreme inflammation, tissue damage, even death. Cytokines—from the Greek cyto for cells and kinos for movement—are important in the fight against viral infections. But they worsen those same infections in the extreme, a phenomenon that is proving lethal for older COVID-19 patients.

  "The immune system is a double-edged sword," says Andrea Cox, a professor of medicine in the Johns Hopkins School of Medicine. "There's a critical role for it in an antiviral response. But it also can be pro-inflammatory in a pathological way. It's like trying to kill a bug with a hammer. You can put a hole in the wall while you're trying to smush the bug."

  Cox is among several Hopkins scientists studying cytokine storms and their relationship to COVID-19. Her lab, which includes infectious disease postdoctoral fellow Andrew Karaba, is analyzing blood and lung tissue samples from infected patients to identify specific cytokines involved. They want to know why they turn dangerous, especially among the elderly.

  Other researchers are testing drugs they hope will prevent the onset of cytokine storms, or stop them after they begin. The goal, ultimately, is to save those at greatest risk from this potentially deadly complication of SARS-CoV-2 infection.

  Cox and her team are studying a range of illness, "looking for things found in very severe illness, and in those who are not very severely ill, to understand why some are getting sick and others not," she says. "We want to narrow it down to the smallest number of things consistent among the groups. Cytokines are produced as part of an innate sensing pathway. If we can identify that overly active pathway, we can find ways to block it."

  "IT'S LIKE TRYING TO KILL A BUG WITH A HAMMER. YOU CAN PUT A HOLE IN THE WALL WHILE YOU'RE TRYING TO SMUSH THE BUG."

  Andrea Cox

  Professor of medicineThere are several dozen cytokines—protein messengers—that affect the immune system. In some cases, they activate certain responses, while in others, they slow them down. Sometimes the system goes awry, triggering too many cytokines, too rapidly. This also occurs in auto-immune diseases, other infections, and as a side effect of certain immunotherapies.

  In COVID-19, cytokine storms disproportionately strike the elderly, "for reasons that are not clear," Cox says. "Immune system balance is regulated differently at different ages. It's not that the immune system is weaker or stronger in older versus younger–but different. It's possible that older people make a more damaging immune response than the young."

  Most commonly, patients seem to be holding their own against the initial SARS-CoV-2 infection before suddenly turning gravely ill. Often, the outcome is grim.

  "Cytokines tell other cells to do things that in this case may enhance tissue damage and disease severity," Cox says. "With blood vessels, for example, it can cause the vascular system to leak fluids and blood, and make it harder for oxygen to go where it's supposed to go because there is fluid where oxygen should be, like in the lungs."

  Understanding a cytokine storm's role in COVID-19 is a multidisciplinary effort at Hopkins, including researchers taking a new look at old drugs.

  "It has been terrific to see people from all different fields [at JHU] respond," says Russell Wesson, assistant professor of surgery in the School of Medicine, and a transplant surgeon. "People are looking at using different drugs to see their effect on COVID, and almost all of these efforts involve repurposing other drugs."

  Wesson is working with principal investigator Nada Alachkar, associate professor of medicine and medical director of the Incompatible Kidney Transplant Program, and scientists from the nephrology and infectious diseases groups in a multicenter study testing Clazakizumab, a medication that prevents organ rejection in kidney transplant recipients. It works by suppressing interleukin-6 (IL-6), an immune system cytokine found elevated in the sickest COVID-19 patients.

  The clinical trial is double-blinded and placebo controlled, meaning neither the researchers nor the patients know who gets the drug or a harmless substitute. The subjects include patients who are seriously ill, including those on ventilators. "We know this drug very directly affects IL-6 and believe that neutralizing it will help stop cytokine storm, or prevent it from progressing," Wesson says. "The study is blinded, but we have seen encouraging results, among them patients who have recovered rapidly."

  "IT'S GRATIFYING TO SEE THE WORK OF OUR LAB TRANSLATE INTO SOMETHING THAT MIGHT HELP. IT MAKES ME FEEL A LITTLE LESS POWERLESS AS THIS PANDEMIC UNFOLDS."

  Chetan Bettegowda

  Professor of neurosurgeryResearchers from the Kimmel Cancer Center, the divisions of rheumatology and infectious diseases, and the departments of neurology and neurosurgery, are testing another drug, Prazosin, an alpha blocker used to treat hypertension, enlarged prostate, and post-traumatic stress disorder. They think it could prevent cytokine storms by blocking a surge of molecules known as catecholamines, substances made in the brain and adrenal glands that—based on an earlier mouse study—typically precedes the onset of a cytokine storm.

  The researchers first examined a national database of patients with Acute Respiratory Distress Syndrome, or ARDS, a condition characterized by fluid accumulation in the lungs, not unlike what happens with COVID-19. They found fewer deaths and less need for ventilators among those who had been taking drugs like Prazosin, leading them to speculate that the drug could similarly benefit patients with COVID-19.

  "Between the preclinical data from animal models and the retrospective data from humans, we felt there was good rationale to test this concept with COVID-19," says Chetan Bettegowda, a brain tumor specialist and professor of neurosurgery in the School of Medicine. The team, which also includes Bert Vogelstein, director of the Ludwig Center, professor of oncology and pathology, and a Howard Hughes Medical Institute investigator, and rheumatologist Maximilian Konig, a postdoctoral fellow, recently began a controlled trial to see if Prazosin, given early after infection, can stave off a cytokine storm. "This is a preventive approach," Bettegowda says. "If patients are already manifesting signs of cytokine storm, it's unlikely to work."

  For her part, Cox has long studied infectious diseases, so she is aware of the challenges posed by a newly identified virus.

  "The problem with these pandemic viruses is that no one in the world has seen anything like them," Cox says. "There is no immunity. What's worse, the rules for who does well and who does badly are different for this virus than for other viruses, and, right now, we don't understand the rules at all."

  For the others, the research represents a departure, albeit a welcome one, as they are glad to be involved in the fight.

  "It's heartbreaking to see so many people who pass away alone, who can't have their loved ones with them, so it's gratifying to see the work of our lab translate into something that might help," Bettegowda says. "It makes me feel a little less powerless as this pandemic unfolds."

  Posted in Health

  Tagged coronavirus, covid-19

  Source of articles:https://hub.jhu.edu/

  Author:Marlene Cimons

  以上就是新冠病毒的最新研究结果了,这对人体免疫系统是个巨大伤害,希望约翰霍普金斯大学研究学者能够早日发现更好的治疗方法。


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