为何中国抑制住了COVID-19的大爆发;冠状病毒的突破——地塞米松

冠状病毒的突破——地塞米松

几天前,在最新一期的《nature》杂志上报告了针对SARS-CoV-2冠状病毒的大型临床试验结果,一种廉价且广泛使用的类固醇——地塞米松可使重症COVID-19患者的死亡人数减少三分之一。

 

这项针对COVID-19命名为RECOVERY的试验于3月启动,是全球最大的冠状病毒治疗随机对照试验之一。目前,RECOVERY试验的最新发现6日22日发布在medRxiv的预印本中。

 

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这项试验最新的报告比较了给予患者长达10天每天一次6 mg地塞米松与只进行常规护理的初步结果。主要终点是28天的死亡率。目前有2104例患者随机分配接受地塞米松治疗,同时4321例患者分配到常规治疗。总体而言,地塞米松组的454例(21.6%)患者和常规护理组的1065例(24.6%)患者在28天内死亡(年龄校正率[RR]0.83;95%置信区间[CI]0.74至0.92;P<0.001)。地塞米松使有创机械通气患者死亡率降低三分之一(29.0%比40.7%,RR 0.65[95%CI 0.51至0.82];p<0.001)。但地塞米松对COVID-19病情较轻的人(未接受氧气或通气的人)没有显著影响。

 

地塞米松是一种廉价且常用的类固醇,是第一个被证明可减少冠状病毒患者死亡药物。结果发布后不久,英国政府宣布立即授权地塞米松用于接受氧气的COVID-19住院患者,包括用了呼吸机的患者。

 

英国牛津大学的传染病专家,试验的首席研究员彼得·霍比说指出,使用类固醇治疗病毒性呼吸道感染(例如COVID-19)一直存在争议,但这是一项重大突破。相关冠状病毒引起的严重急性呼吸系统综合症和中东呼吸系统综合症爆发期间的类固醇试验数据尚无定论。尽管如此,鉴于地塞米松的广泛使用以及以前类似疾病爆发中类固醇研究的一些积极的结果,RECOVERY研究人员认为在严格的临床试验中对该治疗方案进行试验很重要。

 

世界卫生组织(WHO)和许多国家/地区的治疗指南均告诫不要使用类固醇治疗冠状病毒患者,并且一些研究人员担心有关类固醇广泛治疗会产生的副作用。该药物可抑制免疫系统,从而缓解了肺部过度的免疫反应(有时表现在严重的COVID-19病例中)。但是这些患者可能仍需要功能齐全的免疫系统来抵御病毒本身。RECOVERY试验表明,在所测试的剂量下,类固醇治疗的益处可能超过潜在的危害。该研究目前未发现明显的不良事件。

 

 

·与瑞德西韦的比较

 

迄今为止,在大型,随机,对照临床试验中,抗病毒药物瑞德西韦是之前唯一被证明了的使COVID-19患者受益的药物。然而,瑞德西韦已被证明缩短了患者可能需要在医院治疗的时间,但对死亡率没有明显影响。并且瑞德西韦供不应求,目前全球仅有限的医院可以使用瑞德西韦。它的给药方式很复杂:必须在几天内通过注射给药。相比之下,地塞米松是一种在世界各地都可以买到的廉价的药物。牛津大学的流行病学家Martin Landray和RECOVERY试验的另一位首席研究员说:“花费不到50英镑(63美元)就可以治疗8名患者并挽救一条生命。”

 



原文阅读:


Coronavirus Breakthrough: Dexamethasone Is First Drug Shown to Save Lives


An inexpensive and commonly used steroid can save the lives of people seriously ill with COVID-19, a randomized, controlled clinical trial in the United Kingdom has found. The drug, called dexamethasone, is the first shown to reduce deaths from the coronavirus that has killed more than 440,000 people globally. In the trial, it cut deaths by about one-third in patients who were on ventilators because of coronavirus infection.


“It’s a startling result,” says Kenneth Baillie, an intensive-care physician at the University of Edinburgh, UK, who serves on the steering committee of the trial, called RECOVERY. “It will clearly have a massive global impact.” The RECOVERY study announced the findings in a press release on 16 June, and in a preprint posted to medRxiv on 22 June1.


The RECOVERY trial, launched in March, is one of the world’s largest randomized, controlled trials for coronavirus treatments; it is testing a range of potential therapies. The dexamethasone arm enrolled 2,100 participants who received the drug at a low-to-moderate dose of 6 milligrams per day for 10 days, and compared how they fared against about 4,300 people who received standard care for coronavirus infection.


The effect of dexamethasone was most striking among critically ill patients on ventilators. Those who were receiving oxygen therapy but were not on ventilators also saw improvement: their risk of dying was reduced by 20%. The steroid had no effect on people with less severe cases of COVID-19 — those not receiving oxygen or ventilation.


Shortly after the results were released, the UK government announced that it had immediately authorized the use of dexamethasone for patients hospitalized with COVID-19 who required oxygen, including those on ventilators. The researchers say that they are also sharing their findings with regulators in the United Kingdom and internationally.


Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report


Abstract


Background: 


Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death.


Methods: 


The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality.


Results: 


2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14).


Conclusions: 


In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.


Clinical Trial


The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).


参考文献


Heidi L. Coronavirus Breakthrough: Dexamethasone Is First Drug Shown to Save Lives[J]. Nature.


Horby P, Lim W S, Emberson J, et al. Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report[J]. medRxiv, 2020.



为何中国抑制住了COVID-19的大爆发


冠状病毒(COVID-19)大流行对数百万人的日常生活施加了更严格的限制,但之前一直没有明确的数据统计社交限制措施对COVID-19的影响程度。随着世界上其它许多国家病毒传播的加剧,年龄,接触方式,社会距离,感染易感性和COVID-19动态之间的相互作用尚不清楚。

 

2020年6月26日,《science》杂志上发表了一项研究成果证明了中国采取的强有力的非药物干预措施阻止新型冠状病毒COVID-19传播的成效。这个研究团队分析了暴发之前和期间武汉和上海的接触者调查数据以及湖南省的接触者追踪信息,研究了从患者管理到社会隔离等干预措施的影响。在COVID-19社交隔离期间,人们的日常接触减少了7到8倍,大多数互动仅限于家庭成员之间。研究发现,一旦人们将他们的平均每日接触人数从14-20个减少到2个,传播则迅速降至流行阈以下。另外,研究发现0至14岁的儿童比15至64岁的成年人更不易感染SARS-CoV-2(优势比0.34,95%置信区间0.24至0.49),而65岁以上的人更容易感染(优势比1.47,95%置信区间1.12至1.92)。基于这些数据,研究团队建立了一个传输模型来研究社会距离和学校关闭对传输的影响,发现在COVID-19爆发期间,中国实施的社会距离足以控制COVID-19。虽然主动关闭学校不能使传播终止,但可以将高峰发病率降低40%至60%,延缓疫情的发生。值得注意的是,武汉和上海实行的严格的社会疏离措施并未完全消除工作场所的接触。

 

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上图为按年龄划分的联系矩阵


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上图表示了接触方式对流行病传播的影响


这项研究提供了证据表明在武汉和上海进行的干预措施以及由此产生的人类行为变化极大地减少了日常接触,从实质上减少了与家庭互动的时间。这很大程度上减少了SARS-CoV-2的传播。展望未来,为COVID-19的长期控制设计针对性的策略尤其重要,包括基于学校和工作的控制策略,以及大规模的测试和联系人追踪。研究应集中于细化针对感染,疾病和传染性的特定年龄估计,这对于评估这些策略的影响至关重要。

 

原文阅读


Abstract


Intense nonpharmaceutical interventions were put in place in China to stop transmission of the novel coronavirus disease 2019 (COVID-19). As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact survey data for Wuhan and Shanghai before and during the outbreak and contact-tracing information from Hunan province. Daily contacts were reduced seven- to eightfold during the COVID-19 social distancing period, with most interactions restricted to the household. We find that children 0 to 14 years of age are less susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than adults 15 to 64 years of age (odds ratio 0.34, 95% confidence interval 0.24 to 0.49), whereas individuals more than 65 years of age are more susceptible to infection (odds ratio 1.47, 95% confidence interval 1.12 to 1.92). Based on these data, we built a transmission model to study the impact of social distancing and school closure on transmission. We find that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. Although proactive school closures cannot interrupt transmission on their own, they can reduce peak incidence by 40 to 60% and delay the epidemic.


参考文献


Zhang J, Litvinova M, Liang Y, et al. Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China. Science. 2020;368(6498):1481-1486. doi:10.1126/science.abb8001





       




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