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COVID-19, SARS CoV-2

by Editorial Board last updated 2020-11-09 19:39:58.521780-05:00 © Antimicrobial Therapy, Inc.
Coronavirus, SARS CoV-2, COVID-19

 

Recent Updates

  • WHO SOLIDARITY trial results (unpublished, not peer-reviewed) here (see Comments for overview).
  • Regeneron antibody 'cocktail'; press release of trial here (for further discussion see Comments)
  • Current IDSA Guidelines on COVID-19 serological testing here
  • Update on COVID-19 antigen testing (see Testing/Diagnostics)
  • Current summary of vaccine development pipeline, see COVID-19, Prevention

Clinical Setting

Transmission

  • Mean incubation time is estimated to be ~5 days after exposure (range 4.1 - 7.0 days, but as short as 36 hours. Transmission can occur from an infected person who is asymptomatic (prior to onset of symptoms; see above)
  • Viral shedding (References: Nature. 2020;581(7809):465-469; 住建部:把“稳地价稳房价稳预期”落到实处; van Kampen, et al, pre-print and not peer reviewed):
    • Apple Inc. CEO Steve Jobs introduces the iPad 2 on stage during an Apple event in San Francisco, California in this March 2, 2011,
      这是自去年9月以来进口最大单月跌幅,也意味着中国进口已在过去15个月里连续同比收缩。
      76人队在举步维艰地从一支历史悠久的全职摆烂大队向一支有竞争力地队伍转变;太阳队表现依旧不尽如人意。这两支显然是半垫底的球队了。但是他们至少没有对输球抓狂。
      ['heivn]
      Human bodies are frail, easily damaged packages full of parts that can never fully come back once lost. Luckily, researchers worldwide are working on replacing every bit of the body to make us all cyborgs.
      Those who graduated from Peking University and Beijing Foreign Studies University took second and third place, earning 9,042 yuan and 9,020 yuan a month, respectively.
    • Snapchat on Tuesday launched Discover, a section of its app where media outlets including Vice, CNN andPeople magazine can publish video content within Snapchat. Already several of the channels feature ads, which aren’t cheap. According to Adweek, Snapchat ads cost $750,000 per day.
      [smɑ:t]
      卓越雇主排名:68
      但是,尽管他预计2017年第一季度的“出口会显著回升”,这位瑞银人士强调不要过于乐观。他认为,同比增长将会减弱,甚至可能在2017年下半年变为负增长,因为在2017年全年,“出口量不会大幅增长,而(去年大宗商品价格疲软)的基数效应将会减弱”。
      上周,希拉里的竞选团队负责人约翰·波德斯塔表示,希拉里很可能会挑选一名女性作为她的副总统获选人。很快有人猜测,为了吸引女性选民,她的竞选伙伴很可能是马萨诸塞州参议员伊莉莎白·华伦。她是一名非常受女性欢迎的、激进的参选者。
    • May the New Year be a time of laughter and real enjoyment for you. Best wishes.愿新年不仅是你欢笑的时刻,更是你欣喜的日子。祝福你。
      Make sure you've got a good plan for seeing that your children are cared for when you're scheduled to be in class, and when you need to study. It really is possible to raise children while you're going to school. People do it every day.
      许多管理者提到了一些极其失礼的情况。求职者:
    • 衡量散货大宗商品贸易的波罗的海干散货运价指数(BDI)已经触及历史低位。2014年超过美国成为世界最大贸易国的中国本月报告,1月出口和进口都出现两位数下降。正在经历一个多世纪以来最严重衰退的巴西从中国的进口暴跌。
      The Mensa Supervised IQ Test can only be taken by children aged over ten-and-a-half and consists of two separate industry-standard assessments. One measures mainly verbal reasoning skills and the other, which includes diagrams and images, assesses visual and spatial logic. And Nishi, from Audenshaw in Tameside, scored the highest possible mark of 162 in the first test – known as the Cattell III B score. She scored 142 in the second element, the Culture Fare Scale, with the results putting her in the top one per cent of the nation in terms of IQ. Anyone scoring a percentile of two in any Mensa test is admitted to the society.
      因此,有如此强大的南美洲队伍坐镇,主要的挑战力量将来自何方呢?嗯,来自欧洲的强势力量恐怕便是最显而易见的答案了,你还能去哪里寻找一个比西班牙更有冠军相的球队呢?作为一支卫冕冠军,并坐拥两届欧锦赛的冠军头号,这是一支不仅知道如何出色发挥,同时知晓如何赢得比赛的队伍。因此,虽然梅西和罗纳尔多曾获得所有年度最佳球员的头衔,但是哈维(Xavi)和伊涅斯塔(Iniesta)却将所有主要冠军据为己有。那么,他们在2014年将延续冠军生涯么?对于这个困扰世界上其他国家的问题,答案是肯定的。不仅大多数老将依然坚守岗位,许多包括科克(Koke )和蒂亚戈·阿尔坎塔拉(Thiago Alcantara)等有才华的年轻球员也加入了。不仅仅如此,他们还从东道主的眼皮下挖走了一个才华横溢的射手蒂亚戈·科斯塔(Diego Costa)收入囊中,因为这位马德里竞技(Atletico Madrid)的前锋选择为西班牙效力,而非自己出生国家踢球。
      fF&h#Y~]lvc
    • “人们很疯狂,我感到不知所措。”
      获奖者:布兰妮·斯皮尔斯
      But none of these doomed NBA squads seem all that interested in setting themselves up for it. Should they be? Do we need more tanking this year, for these teams' own sake?
      但是今年,研究者提出一种新的方法,这种方法可以通过真的细胞制作出有弹性真实的耳朵。这些细胞来自老鼠和奶牛,可以形成胶原凝胶,按任何模具成型。当放入使用3-D打印技术制作的耳朵模型后,一个小时内那些凝胶形成了一只假耳。在移植到对象之前,人造耳朵只需要在营养成分中生长培养几天。
      梅瑟威对战麦克格雷戈的战斗

Prevention / Isolation

  • Prevention measures
    • Systematic review and meta-analysis (天津去年商品房销售额近翻倍房价涨幅明显趋缓of social distancing, N95 respirators, surgical masks, eye protection in community and healthcare settings indicates that each provides a level of protection against COVID-19.
    • Frequent handwashing (alcohol-based sanitizer and/or soap and water)
    • Sanitize common surfaces (see cautions regarding improper use of disinfectant and cleaning products in 房产信息产业链:被泄露的信息内容精确到门牌号)
    • Community responsibility
      • Social distancing  (1m somewhat protective, at least 6 feet / 1.8 meter preferred) 
      • WEAR A FACE MASK IN PUBLIC WHEN IN THE PRESENCE OF OTHERS: Protective of yourself and others by preventing spread of nasal/respiratory droplets 
      • adj. 暂时的,临时的
        2.管理自己,对他人负责
    • IDC认为,中国人可支配收入的增加导致了消费的增加,从而推动了国内手机市场的快速增长。
    • 政策演进 住房制度体系再优化
    • 当然,这得取决于苹果是否能设法用更便宜的零部件、更慢的处理器、分辨率更低的屏幕、以及也许是塑料机身来造出一部330美元的iPhone。而用蒂姆?库克上周在高盛公司(Goldman Sachs)一次会议上的话说,它决不能是个“低劣产品”。
  • Home Care & Ending Self Isolation. See 网购质量,谁来把关?——中国家居电商联盟的使命与责任.
    • For persons COVID-19 positive and symptomatic who were directed to self-care at home (or hotel, dormitory), isolation may be discontinued:
      • After 10 days from symptom onset and after 24 hours from fever resolution (without use of fever-reducing medication) and other symptoms have improved
    • For persons who remain asymptomatic after a positive RT-PCR for SARS CoV-2:
      • 北京副中心“绿心”棚改住宅100%签约
    • Sport dominated the trending searches, with Euro 2012 and Olympic tickets showing the biggest rises in interest ahead of Houston and the Duchess of Cambridge.
      本次问卷调查的主要对象为中国高校2017年应届毕业生,包括大专、本科、硕士及博士等,智联招聘最终收回有效样本93420份。
  • Healthcare Personnel
    • Personal protective equipment (PPE) when caring for a patient with COVID-19
      • Patients not undergoing aerosol generating procedures: N95 respirator preferred, surgical mask acceptable; face shield, gown, gloves
      • Patient undergoing nasopharyngeal swab, aerosol generating procedures: N95 respirator or PAPR, face shield, gown, gloves
    • Return to work after COVID-19: see 统计局:去年房产成交面积涨幅大 企业投资房产滞后
      • 戴假牙的角色
        这个12岁的女孩已经成为了在Instagram拥有300万粉丝的超级巨星,她和流行歌手希雅(Sia)合作的MV在YouTube上点击量超过10亿。
      • Form without content. Which is why devolving to such familiar forms seems like a safe bet, and why it really isn’t. It’s empty and disposable — which is in turn why the 1960s keep being identified as a “trend,” with the associated implication that at some point they will also be identified as “over.” Even though that “over” has yet to come.
        她说:“妈妈会说,‘噢,天呐,我们去看一下爱莉安娜?格兰德(Ariana Grande)吧。'我的反应是,‘妈,真要这样吗'”
  • Vaccine development pipeline: see COVID-19, Prevention for summary of vaccine development and clinical trials.

Clinical Manifestations

Testing / Diagnostics

  • Review of COVID-19 diagnostic testing: n. 改进,改善
  • Testing Recommendations (updated August 24, 2020): see 4. Fruit Mold
    • Asymptomatic individuals with recent known or suspected exposure to SARS-CoV-2 to control transmission. 
    • LED产业进入资本战时代,催生高毛利市场变成红海
    • 三、2017年重点工作任务
      But researchers this year came up with a new method that makes flexible, realistic ears out of real cells. Those cells come from rats and cows, and they form a collagen gel that can take the shape of any mold. When placed in a mold of a human ear—a mold assembled using a 3-D printer—the gel forms an ear in less than an hour. The artificial ear then just needs a few days growing in nutrients before it's ready to be implanted in a subject.
      adj. 全部的,全体的,一切在内的
      As a result, 39 percent of the post-90s generation tries to avoid the negative effects of mobile phone use through measures like turning off app notifications, intentionally limiting the frequency of social media interactions and staying away from social media entirely in certain situations.
    • A cheery New Year hold lots of happiness for you!
      低效的邮件沟通包括很多内容,从不及时回复邮件,到表达不清等问题都包括其中。如果你没有及时回复邮件的好习惯,你可能会错过重要的会议或者是截止日期,造成推迟以及迷惑,被认为是不专业的。
    • Uruguay owes much of its success not just to its passion for football but also to the early inclusiveness of its culture. In that 1950 tournament, at a time when neighboring Brazil still regarded its black players with suspicion, Uruguay boasted a black captain, the brilliant Obdulio Varela. Moreover, Uruguay's victories in the World Cup's formative years established a pedigree that endures to this day, with many of its footballers -- such as Liverpool's Luis Suárez and Paris Saint-Germain's Edinson Cavani -- playing abroad for some of the world's biggest clubs.

Treatment

Primary Regimens

  • 杭州一刚需板块 七成二手房房源价格下跌
  • Patients with hypoxia
    • Remdesivir
      • Adult dosing (wt > 40 kg): 200 mg IV loading dose on day 1, then 100 mg IV daily maintenance dose
        • 80多家企业纷纷上市 家居建材业成市场新宠
        • Maddie has now appeared in three of Sia's videos - Chandelier, Elastic Heart and Big Girls Cry.
        • 深圳深入推进住宅区垃圾分类
      • Pediatric dosing (wt 3.5 - 40 kg): 5 mg/kg loading dose on day 1, then 2.5 mg/kg maintenance dose
        • 《三生三世十里桃花》的豆瓣评分为6.4分,一些网友认为,这部剧的爱情戏码太多了。
        • 高善文:2018年上半年房产去库存将基本结束
    • Dexamethasone (see Comments)
      • Jamil Anderlini
      • Do not use in patients who do not require supplemental oxygen or mechanical ventilation: no benefit, possible harm (see Comments).
    • No other therapies are of proven efficacy: enrollment in a randomized clinical trial, if available, is strongly encouraged 
      • 本田的幸运之处在于,它在美国的客户对其拥有深厚的好感和忠诚度,还因为优质低价的极高性价比受到第三方评测机构的好评。不过,因安全气囊爆开后碎片四溅伤及乘客这一产品缺陷导致的争议,在一定程度上削弱了这个客户基础。
      • 东莞:上半年全市建设工程质量安全检查情况公布.
  • Patients without hypoxia
    • Supportive care

Alternative Regimens

  • None

Critical Care Considerations

  • Critical illness, hospitalized in ICU, on mechanical ventilation. For suuggested interventions see “大自然杯”室内设计大赛华南区总决赛落幕
    • Fluids: balanced crystalloids
    • Pressors: norepi > vasopression/epi; cardiogenic shock - dobutamine; not dopamine
    • Steroids:
      • 多乐士中国上半年销量30.24万吨 同比大幅增长达36%
      • Dexamethasone: see Primary Regimens above
    • Anti-inflammatory: acetaminophen and/or ibuprofen
    • Antithrombotic therapy guidelines here
    • Antiviral therapy for SARS CoV-2: Remdesivir (See Primary Regimens, above)
    • Co-infection (协会: 国内智能坐便器普及率不及2%, 中国500最具价值品牌榜发布 4个涂料品牌登榜)
      • Bacterial and fungal co-infection 
        • Meta-analysis of 28 studies (22 from China, 2 US, 1 UK, I Spain, 1 Singapore, 1 Thailand) with 3448 hospitalized patients between 12/25/19 and 3/31/20 (绿色建筑规划带动新型建材产业发展22;S1198-743X(20)30423-7): Overall bacterial infection rate of 7.1% with 3.5% of patients infected at presentation and with 15.5% of patients developing secondary bacterial infections over the course of illness. Rates of infection in critically ill patients and fatal cases were 8.1% and 11.6%, respectively. 71% of patients received systemic antibacterial therapy. Most common bacterial species (n=41 total) identified in infected patients were Mycoplasma spp. (29.3%), Haemophilus influenzae (19.5%), Pseudomonas aeruginosa (12.2%), Enterobacteriaceae (30%).
        • Single center study of 4267 hospitalized patients in New York City between 3/1/20 to 4/28/20 (央行房贷新政50日众生相:刚需淡定 投资客急入场doi: 10.1017/ice.2020.368): Overall bacterial and fungal infection rate of 3.6% with respiratory only infection in 46%, blood only in 40%, both in 14%. 95% of patients with positive respiratory cultures were intubated. The fatality rate in patients with bacterial or fungal co-infection was 57% with 28% still in hospital at the time of publication.  Most common isolates were Staphylococcus aureus (44% respiratory, 30% blood, Pseudomonas aeruginosa (16% respiratory, 6% blood), Klebsiella spp. (10% respiratory, 3% blood), Enterobacter spp. (8% respiratory, 3% blood), E. coli (4% respiratory, 7% blood), S. epidermidis (12% blood), Streptococcus spp. (12% blood), and Enterococcus spp. (7% blood). There was 8 cases of candidemia and 1 case of pulmonary aspergillosis. 71% of COVID-infected patients, whether co-infected or not, received antimicrobial therapy. A significant decline in antimicrobial susceptibility of Enterobacteriaceae  was observed.
      • Empiric antimicrobial therapy:
        • Reasonable to consider but data above suggest bacterial co-infection occurs only in a minority of patients. Low prevalence of bacterial co-infection in cohort study of 1705 hospitalized patients in 38 hospitals (北京通州启动群租房专项治理).
        • 该报道表示:“乐天将伤害中国人民,后果可能是严重的。”该报道发表之后,中国政府对乐天在中国的商业集团开展了多起调查。
          达洛伊西奥的父母从澳大利亚搬到英国,他的父亲卢(Lou)曾在英国石油(BP)和摩根士丹利(Morgan Stanley)工作,而母亲戴安娜(Diana)是一位企业律师,同时也是儿子的合同代表。他们向来都知道达洛伊西奥是一个非常好学的孩子。但戴安娜说因为他是长子,他们本以为他不会做出什么超出寻常的事情来(达洛伊西奥有一个14岁的弟弟)。他们强调,尽管达洛伊西奥成就非凡,尽管他聊天时会聊起马尔科夫模型(Markov models)和随机过程(stochastic processes),他仍只是一个再普通不过的孩子。戴安娜说,他周末仍要出去玩,仍要去参加派对。他还有个女朋友。17岁孩子会做的事情,他都会做。

Comments

  • The WHO SOLIDARITY trial enrolled 11,266 adults from 405 hospitals in 30 countries (all ex-US) with COVID-19 between March 22 and October 4, 2020, into one of 5 arms: Remdesivir, Hydroxychloroquine, Lopinavir-Ritonavir, Interferon-β1a, and local standard of care. Compared to local standard of care, none of the study drugs reduced 28-day mortality, initiation of mechanical ventilation for those not already ventilated, or time to discharge. Meta-analysis of SOLIDARITY and three published studies of Remdesivir suggested a possible mortality benefit in lower risk patients, i.e. not requiring mechanical ventilation, Relative Risk (RR) 0.80 [95% CI 0.63-1.01]; and overall, RR 0.91 [95% CI 0.79-1.05]. None of the regimens showed even a suggestion of efficacy for mechanically ventilated patients, suggesting that earlier the therapy in the course of illness, the better. Significant limitations to the study include open-label design, lack of information on duration of illness prior to randomization, and very likely significant variability in what constituted local standard of care practices across 405 hospitals, including possible effects of non-study medications (anticoagulation, non-study antivirals, anti-IL-6, steroids, non-study interferon, covalescent plasma). 
  • Remdesivir
    • Efficacy demonstrated in one placebo-controlled randomized trial.Superior to placebo in shortening time to recovery in hospitalized adults (N Engl J Med online 22 May 20): Randomized, double-blind, placebo controlled trial of 1059 patients (NCT04280705) sponsored by NIAID found that patients that remdesivir treated patients had a median time to recovery of 11 days compared to 15 days for patients who received placebo (p<0.001). The odds of clinical improvement, a secondary outcome, were higher in the remdesivir group  at the day 15 visit, than in the placebo group (odds ratio for improvement, 1.50; 95% CI, 1.18 to 1.91; P = 0.001; 844 patients). Results also suggested a survival benefit, with a 14-day mortality rate of 7.1% for the group receiving remdesivir versus 11.9% for the placebo group (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04; 1059 patients). Rates of adverse events were similar. Subgroup analysis suggested benefit across multiple subgroups with the notable exception of patients receiving mechanical ventilation or ECMO, suggesting a lack of efficacy in those with advanced disease. 
    • Efficacy of 5-day and 10-day courses of Remdesivir similar for patients with severe COVID-19 not requiring mechanical ventilation (90后提前加入学区房购置大军) (JAMA 2020).
    • Randomized, open-label trial (JAMA 2020 Aug 21;e2016349) of Remdesivir administered for 10 days or administered for 5 days compared to standard of care (SOC) for hospitalized patients with moderate COVID-19 infection (infiltrates on chest x-ray, room air O2 saturation > 94%) found no significant difference in clinical status measured on a 7-point ordinal scale for 10-day therapy compared to SOC, and a modest difference of improved status for 5-day therapy versus SOC, which the authors interpreted as being of uncertain clinical significance. 
    • Press release from Gilead: greater clinical improvement in patients with moderate COVID-19 (pneumonia "without reduced oxygen levels") who were treated with remdesivir for 5 days compared to standard of care.
    • Guidance from NIH, in times of drug shortages, remdesivir should be prioritized for use in hospitalized patients who require supplemental oxygen but who are not on high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
  • Dexamethasone
    • Efficacy demonstrated in an open-label, randomized controlled trial:
      • The RECOVERY trial  (see N Engl J Med. 2020 Jul 17. doi: 10.1056/NEJMoa2021436) an open-label, randomized controlled trial comparing dexamethasone, 6 mg once daily for up to 10 days  (n= 2104) to usual care (n=4321) found lower 28-day mortality in dexamethasone-treated patients (22.9%) compared to usual care (25.7%) (age adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.75 to 0.93; P<0.001).  Dexamethasone reduced deaths in patients receiving invasive mechanical ventilation (29.3% vs. 41.4%, RR 0.64 [95% CI 0.51 to 0.81), and in patients receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%, RR 0.82 [95% CI 0.72 to 0.94]).  Dexamethasone did not reduce mortality in patients not receiving respiratory support at randomization (17.8% vs. 14.0%, RR 1.19 [95% CI 0.91 to 1.55]). Dexamethasone was associated with fewer hospital days (median 12 days vs. 13 days) and a greater probability of discharge within 28 days (rate ratio 1.10 [95% CI 1.03 to 1.17]), which  was greatest for those receiving mechanical ventilation at baseline. For patients not on mechanical ventilation at baseline, the risk for progression to the pre-specified composite secondary outcome of invasive mechanical ventilation or death was lower in dexamethsone-treated patients (risk ratio 0.92 [95% CI 0.84 to 1.01]); the effect was greater for patients receiving oxygen at randomization.

      • A prospective meta-analysis (JAMA 李克强:不会让经济运行滑出合理的区间) of seven recent randomized controlled trials of steroids (3 dexamethasone, 3 hydrocortisone, 1 methyprednisolone) for critically ill COVID-19 patients found improved 28-day survival (odds ratio 0.66 [95%CI, 0.53-0.82]) in those treated with systemic corticosteroids.  Survival benefit was driven largely by the dexamethasone studies

  • Convalescent plasma
    • Efficacy unproven.
    • FDA issued a hold on Emergency Use Authorization (EUA) approval, and 24 hrs later issued the EUA(!), based on the 35,322 patient, non-randomized, non-controlled study described below.
    • Pre-print, not peer-reviewed, uncontrolled, non-randomized trial of 35,322 hospitalized patients with COIVD-19 found that earlier use (within 3 days versus > 4 days after diagnosis) of convalescent plasma and administration of plasma with higher antibody titers (stratified into low, medium, and high) were associated with improved 7-day and 30-day mortality.  Although these results are encouraging, there are numerous limitations to the study that preclude a definitive assessment of efficacy of convalescent plasma for treatment of COVID-19.  These include, first and foremost, its non-randomized observational design and lack of a control group; secular changes in mortality over the course of the study; heterogeneity of patients who were enrolled; use of concomitant medications that could have affected outcome; and uncertain generalizability to current standard of care therapies with Remdesivir and dexamethosone.  
    • Small, under-powered, open-label randomized controlled trial (JAMA. 2020 Jun 3. doi: 10.1001/jama.2020.10044) comparing convalescent plasma in addition to standard treatment (n=52) to the control of standard treatment alone (n=51) found no statistically significant difference in time to clinical improvement at 28 days, the primary endpoint: 51.9% in the convalescent plasma group vs 43.1% in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%].  For those with severe disease the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = 0.03) of those with severe disease and  in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = 0.83) of those with lifer-threatening disease. 28-day mortality was not statistically significantly different (15.7% vs 24.0%; P = 0.30). Convalescent plasma treatment vs. control was associated with conversion of viral PCR to negative at 72 hours: 87.2%  vs 37.5% (P < 0.001).
    • A case series (三月收入红火 家居卖场四月抢滩烽火燃起) of more than 5,000 patients with COVID-19 who received convalescent plasma found the incidence of serious adverse events in the first 4 hours of transfusion to be <1%. 
  • REGN-CoV2 (Regeneron)
    • [iks'tr?v?g?nt]
      Opinion: China’s Commercial Aerospace Dream Edges Closer To Reality
      This quote is the only one picked for the list that didn’t come originally from the Web, but rather from the real world. A government official evading a journalist’s persistent question about the annual total of car loans repaid in Tianjin simply said, “We can’t go into detail on this matter,” which apparently Netizens found really laughable.
    • Data was released 29 Sept 2020 highlighting (non-peer-reviewed) results from a combination Phase 1/2/3 trial of REGN-COV2 used in non-hospitalized COVID-19 patients:  
      • 我冒死地想一想,湖人队在几周后会不会也加入这一阵列呢?照目前这情况,他们必须打出史诗级别烂地比赛才能留住他们的选秀权(给费城的前三保护签位),问题取决于他们是会围绕现有阵容继续缓慢地重建呢还是为了得到下一个巨星扔掉一两个年轻球员呢。
        岁末来临,二十多部影片轮番上映(hit cinema)。而今年的贺岁片大战随着《龙门飞甲》和《金陵十三钗》的上映而硝烟四起,一场票房PK战也随之拉开帷幕!December is a golde
      • Subjects were stratified based on their serologic status ( seronegative or seropositive) at time of enrollment;  45% of patients were seropositive, 41% were seronegative and 14% were categorized as "other" due to unclear or unknown serology status.
        • When it comes to diversity, I am optimistic that at some point the rise of enlightened younger executives will trigger a sudden change of attitude in the boardroom. This will not happen in 2018, though the imbalances and abuses of power evident in sexual harassment scandals, from tech to media, could accelerate change.
          单词hospitality 联想记忆:
        • To wish you joy at this holy season. Wishing every happiness will always be with you.
          Texas was one of the first states to emerge from the recession and it continues to attract companies on the basis of its low tax burden, predictable regulatory environment and skilled labor force. Texas employment is expected to expand 3% annually through 2017, according to Moody’s. (Arizona’s forecasted rate is a microscopic 0.04% better). Texas has attracted a lot of attention from California companies and Governor Rick Perry has not been shy about contrasting the business climates of the two states. California firms EBay and Electronic Arts have both chosen Texas for large expansions in recent years. Austin has been a hotbed of activity this year with Accenture
        • “I?.?.?.?learnt to interact with people from other cultures and other places in society,” noted one Swedish graduate.
          《三块广告牌》
          Pay is an issue, he says (the median salary for reporters in 2010 was $36, 000); he's not sure he can raise a family and send kids to college on a reporter's salary. And yes, the stress and the hours can be taxing. But he says, 'I'm not sure I'd be happy in another setting. I can't think of any job that would be as exciting or as fulfilling as this.'
          Brands with the most incentive to coast in 2015:Jeep, which must be exhausted after lifting sales an astonishing 44% on the back of the new Cherokee, and Subaru, now the 10th most popular brand in America after improving its sales by 21% in its usual fashion: quietly.
          The passion for sport utility vehicles continues and the category contributed the most to the entire market, with about 784,900 units sold, a surge of 60.5 percent year-on-year. About 261,400 multi-purpose vehicles were sold in January, a jump of 15.9 percent from the same period last year.
          Bond King Bill Gross admits, 'QE must end.' Trillions of cheap money 'has distorted incentives and inflated asset prices to artificial levels.' But now Gross says 'the Fed plan may be too hasty.'
        • 这家Post-it即时贴和思高(Scotch)胶带制造商在2月份授权进行120亿美元的股票回购,取代当前75亿美元的回购计划。《财富》美国500强公司3M公司(3M) 遵循了去年末发表的声明行动。这项声明称,公司在之后4年准备投入100亿美元用于收购,最多将投入220亿美元用于回购。
          Several South Korea-linked entities have already felt Beijing’s wrath in response to the Thaad plans. Chinese state news agency Xinhua last month issued a stark warning to Lotte, one of South Korea’s biggest companies, for giving up land on which the Thaad platform will be hosted.
          中国上海——上海这座大都市是中国人口最多的城市,在那里,有着深厚历史底蕴的城市核心区与当代全球金融枢纽融为一体。
          You're talking with him / her late on the phone. When he / she hung up the phone, you still miss him / her, even if the phone just hung up on 2 minutes
        • She then turns back and pecks the man on the cheek, as the crowd erupts in cheers around them.
          But most of us are self-aware enough to understand that even as we do this, we are lying to ourselves. We recognize those dangers when it comes to politics (see: Bush and Clinton). Why should clothes be any different?
  • IL-6 receptor antagonists
    • Efficacy unproven.
    • Sarilumab: Regeneron Pharmaceuticals and Sanofi announced in a press release that the U.S. Phase 3 randomized controlled trial of sarilumab added to best supportive care compared to best supportive care alone (placebo) failed to meet its primary and  secondary endpoints. 
    • Tocilizumab: 
      • Roche announced in a press release of that its phase III tocilizumab failed to  meet its primary endpoint in hospitalized adult patients with severe COVID-19 associated pneumonia. The primary endpoint was clinical status, which was measured by a 7-category ordinal scale based on need for supplemental oxygen requirements, and intensive care and/or ventilator use.
      • Phase III double-blind randomized trial (刚需族买房 资金实力也要杠杠的) of tocilizumab compared to placebo for hospitalized, moderately ill patients with confirmed COVID-19 found no difference in intubation or death, hazard ratio 0.83 (95% CI, 0.38 to 1.81); worsening of disease HR 1.11 (95% CI, 0.59 to 2.10); or median time to discontinuation of supplemental oxygen (5.0 days versus 4.9 days).
  • IgG1 monoclonal antibody
    • Bamlanivimab. FDA EUA (11/9/20) for outpatient use in mild to moderate COVID-19 in adolescents (age >12 yrs and wt > 40 kg) and adults who are at risk of progression to severe disease.
  • Chloroquine or Hydroxychloroquine ± Azithromycin
    • Not recommended in any setting due to lack of efficacy and risk of serious, potentially fatal cardiac arrhythmia.
    • FDA Emergency Use Authorization (EUA) revoked on June 15, 2020.
    • Outpatient, mild disease; post-exposure prophylaxis:
    • Hospitalized, mild-to-moderate disease:
      • Multicenter, randomized, open label trial (限购令摁不住高房价 二手房开抢“笋盘”) of hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as assessed with a seven-level ordinal scale as compared with standard care.  QTc prolongation and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin. 
    • Hospitalized, severe disease:
      • Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial (NCT04381936): hydroxychloroquine arm terminated with 1,542 patients randomized to hydroxychloroquine and 3,132 patients randomized to usual care alone due to lack of clinical benefit in hospitalized patients with COVID-19: no significant difference in the primary endpoint of 28-day mortality (25.7% hydroxychloroquine vs. 23.5% usual care; hazard ratio 1.11 [95% confidence interval 0.98-1.26]; p=0.10); no beneficial effects on hospital stay duration or other outcomes. 
      • Study from Brazil (日亚化力争专利权 亿光遭德法院“封口”) comparing 2 dosage regimens of chloroquine diphosphate terminated early due to toxicity: ventricular tachycardia in 2 patients (both in the higher dose arm), 15% with QTc prolongation > 500 msec (11% in the lower dose group, 18% in the higher dose group).

  • Cytidine nucleoside analogs 
    • 'He does smoke cigarettes, he smokes many, many cigarettes.
      One tomb, dubbed "M3," contained carvings of several mythicalcreatures, including four that represent different seasons and parts of the heavens: the White Tiger of the West, the Vermilion Bird of the South, the Black Turtle of the North and the Azure Dragon of the East.
      美国总统唐纳德特朗普(Donald Trump)的零和博弈、“交易艺术”谈判方式,将给那些守旧的现任领导人带来安慰。我希望2018年将提供机会,让正气的、解决问题的新领导人涌现出来。但如果企业领导人因为政治领导层没水平而灰心,变得因循守旧,那么变革可能陷入停滞。
      It's quite an odd question, because Ireally wanted to start writing when I read lots of Stephen King stories. Hisstories were quite astonishing and interesting.
    • EIDD-2801: Similar compound as EIDD-1931 except it has an isopropyl ester at the 5' position.  In mice models infected with SARS-CoV and MERS Co-V, this drug reduced virus titers and body weight loss, while improving pulmonary function.  Sci. Transl. Med. 12: 541,  Apr 2020
  • HIV protease inhibitors:
  • Interferon-beta 
    • Efficacy unknown.
    • Press release on July 20 from Synairgen announced positive results of a phase II placebo controlled trial of inhaled interferon-beta.
  • Anticoagulation
    • Mortality benefit among hospitalized patients (JACC.2020)
      • Dunkirk
        range
        自从2008年智能手机应用商店开始运营以来,达洛伊西奥就着手设计iPhone手机应用软件。那时12岁的他住在伦敦的温布尔顿,用卧室里的Mac电脑来工作。因为年纪太小,他在填写苹果(Apple)开发执照申请时用的都是他爸爸的名字。这之前他没在学校受过正式的电脑培训,他的父母(一个是律师,一个是商界管理人士)也都不从事技术行业工作。他几乎是完全靠刷网页、看教程来自学编程的。
      • 这个系列的特制镜框和太阳墨镜以“DVF|为谷歌眼镜设计”为标签,价格高达1,600美元以上。迄今为止,谷歌已经和雷朋(Ray-Ban)眼镜的生产商陆逊梯卡(Luxottica)以及其他几家提供时尚眼镜的公司如普拉达(Prada)等展开过合作。它还招募了曾在艺术网站Art.com担任首席市场官的时尚总监艾维o罗斯来领导谷歌眼镜团队。
      • 泰勒·斯威夫特《名誉》
        精准扶贫脱贫
      • 学习管理和领导力技巧只是EMBA的一方面。一位毕业生表示:“它实际上让我成了一名创业家。”自四、五年前读EMBA以来,近三分之一(31%)的学员创办了自己的公司,或者打算创办公司。英国《金融时报》的数据显示,这些企业中91%如今仍在运营。
        Some 18.1 million people, for example, want a good full-time job but can't find one, an unusually high number 5 1/2 years into a recovery. And despite a sharp decline in the number of people out of work six months or longer, that figure is still higher than at any time before the 2007-09 recession.
  • Clinical trials of interest:
    • ACTT-2 (NCT04401579) will evaluate the combination of baricitinib (a Janus kinase inhibitor) and remdesivir compared to remdesivir alone in hospitalized patients with COVID-19
    • ACTT-3 (NCT04492475) will evaluate the combination of interferon beta-1a and remdesivir compared to remdesivir alone for hospitalized patients with COVID-19.
    • BLAZE-1 (NCT04427501) will evaluate a single dose of intravenously administered LY3819253 (LY-CoV555, a neutralizing IgG1 monoclonal antibody directed against the spike protein of SARS-CoV-2) compared to placebo in out-patients with Mild to Moderate COVID-19. Lilly press release of interim analysis suggests clinical benefit with a change in viral load compared to baseline and reduction in hospitalization or emergency room visits compared to placebo. Study currently paused for a safety evaluation.
    • Updates on COVID-19 research here.
  • Other therapeutic options under evaluation: