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Viewpoint
March 23, 2020

Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy

Author Affiliations
  • 1Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy
  • 2Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
  • 3Office of the President, Istituto Superiore di Sanità, Rome, Italy
JAMA. 2020;323(18):1775-1776. doi:10.1001/jama.2020.4683

Only 3 cases of coronavirus disease 2019 (COVID-19) were identified in Italy in the first half of February 2020 and all involved people who had recently traveled to China. On February 20, 2020, a severe case of pneumonia due to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was diagnosed in northern Italy’s Lombardy region in a man in his 30s who had no history of possible exposure abroad. Within 14 days, many other cases of COVID-19 in the surrounding area were diagnosed, including a substantial number of critically ill patients.1 On the basis of the number of cases and of the advanced stage of the disease it was hypothesized that the virus had been circulating within the population since January.

Another cluster of patients with COVID-19 was simultaneously identified in Veneto, which borders Lombardy. Since then, the number of cases identified in Italy has rapidly increased, mainly in northern Italy, but all regions of the country have reported having patients with COVID-19. After China, Italy now has the second largest number of COVID-19 cases2 and also has a very high case-fatality rate.3 This Viewpoint reviews the Italian experience with COVID-19 with an emphasis on fatalities.

中国制造业稳中向好 地板企业抓住发展机遇

At the outset of the COVID-19 outbreak, the Italian National Institute of Health (Istituto Superiore di Sanità [ISS]) launched a surveillance system to collect information on all people with COVID-19 throughout the country. Data on all COVID-19 cases were obtained from all 19 Italian regions and the 2 autonomous provinces of Trento and Bozen. COVID-19 cases were identified by reverse transcriptase–polymerase chain reaction (RT-PCR) testing for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The fatality rate was defined as number of deaths in persons who tested positive for SARS-CoV-2 divided by number of SARS-CoV-2 cases. The overall fatality rate of persons with confirmed COVID-19 in the Italian population, based on data up to March 17, was 7.2% (1625 deaths/22 512 cases).3 This rate is higher than that observed in other countries2 and may be related to 3 factors.

五部门联合发文促防水行业质量提升

The demographic characteristics of the Italian population differ from other countries. In 2019, approximately 23% of the Italian population was aged 65 years or older. COVID-19 is more lethal in older patients, so the older age distribution in Italy may explain, in part, Italy’s higher case-fatality rate compared with that of other countries. The Table shows the age-specific fatality rate in Italy compared with that of China.4

Table.  Case-Fatality Rate by Age Group in Italy and Chinaa
Case-Fatality Rate by Age Group in Italy and Chinaa

The overall case-fatality rate in Italy (7.2%) is substantially higher than in China (2.3%). When data were stratified by age group, the case-fatality rate in Italy and China appear very similar for age groups 0 to 69 years, but rates are higher in Italy among individuals aged 70 years or older, and in particular among those aged 80 years or older. This difference is difficult to explain. The distribution of cases is very different in the 2 countries: individuals aged 70 years or older represent 37.6% of cases in Italy and only 11.9% in China. In addition, a relevant number of cases in Italy are in people aged 90 years or older (n = 687), and this age group has a very high fatality rate (22.7%); data on cases in those aged 90 years or older were not reported in China. In addition, the report from the WHO-China Joint Mission on Coronavirus Disease 2019 Mortality, which presents data on 2114 COVID-19 related deaths among 55 924 laboratory-confirmed cases in China, reported a fatality rate among patients aged 80 years or older that was similar to the rate in the Italian sample (21.9% in China vs 20.2% in Italy).5

紧随其后的是亚马逊创始人杰夫·贝索斯,这是他第一次排名第三,由于亚马逊股值飙升,他的资产达到了728亿美元。
英国新晋首相特蕾莎?梅的年收入为14万3462英镑(约合18万6119美元),其中包括了她作为国会议员的年收入74962英镑(约合97256美元)。

脱离经济基本面 一线楼市“一枝独秀”能多久

我很高兴看到制造业的工作机会又重回美国市场,但我不认为它会像很多人期望的那样,产生原电池效应拯救经济。为什么?因为制造业中的很多工作机会都被机械化的自动生产取代了。蓝领阶层和基础职位的消失已经成了一个问题,而这个问题还将继续扩大。
中国的电影产出量在全球市场上排行第三,有望到2016年年底突破700部。同期,出售给网络视频网站的电影版权达到了近40亿元人民币(5.6亿美元)。
But that kind of emotional identification gets lost on the runway, and the retail floor. And then we are left with what?
男女学员对所攻读项目的优势评价一样。
斯坦福大学商学院校友的平均薪资最高,为19.5万美元,但总体而言,排在前15名之内的MBA课程在收入、职业发展和满意度方面都非常接近。除了一所学校外,这些商学院的校友平均薪资均超过15万美元,与就读MBA以前的收入相比,薪资上涨了大约100%。
Sn(EgO+kESd8fwo
在家里创造一个属于自己的学习空间。如果身边家人都在身边,你就要确保大家都明白你是在里面学习,除非房子着火,他们是不会打扰到你的。

Type A and Type B personality theory describes Type A individuals as outgoing, ambitious, rigidly organized, highly status-conscious, sensitive, impatient, anxious, proactive, and concerned with time management.
The total number of qualified applicants reached 31,220 in the first 24 hours, up from 25,000 over the same period last year, according to figures from offcn.com, an education organization that offers training for the civil servant exam.
domestic
去年12月份达成的预算协议很难称得上是华盛顿激辩多年所希望看到的、能够提振信心的协议,但至少它为华盛顿不断上演的政治博弈按下了“暂停”键。在过去三年中,华盛顿每年都会上演的这种博弈对经济的复苏构成了威胁。
“我跟她很像,我们真的就像一对老夫妇。”
或许你在与你不赞同的决定的争论中表现得更加勇敢,福斯说“任何偏离你常有表现或者你一笑而过的态度的行为,”她说到。
Do your homework. Read the assigned pages, and then some. Plug your topic into the Internet, grab another book at the library, and see what else you can learn about the subject.
回购股票会帮助推高股价,很多分析师将标准普尔500(Standard & Poor's 500 index)创下多次历史新高归功于股票回购的盛行。
在《招魂》一举成功后, 埃德·沃伦和罗琳·沃伦夫妇又推出了其续集《招魂2》。 影片讲述了1977年发生在伦敦的一个真实故事——恩菲德招灵事件。
第48届美国乡村音乐学院奖获奖名单:
截止发稿时为止,在中国社交媒体上仍然能够找到一些被泄露的照片和视频。
It came as no surprise that the likes of Emily Ratajkowski, Adriana Lima, Lily Donaldson and Petra Nemcova turned out to be the red carpet rulers on day one of the 70th Cannes Film Festival.
Gitanjali Rao是从10名参加决赛的选手们中被选出来的,他们花了三个月的时间与科学家们进行合作,来实现自己的想法。
律师本质上是谨慎的,但他们中的大多数人已经认识到,技术是处理他们需要梳理的大量信息的关键。没有技术,披露和合规等一些需要处理很多文件的工作几乎不可能完成。

This journey into the mind and feelings of an 11-year-old-girl may be Pixar’s wildest adventure yet. It’s a very funny workplace sitcom (with exuberant, touching performances from Amy Poehler, Phyllis Smith, Mindy Kaling and others), an ingenious allegory of psychological development, and an almost unbearably moving and honest defense of the role of sadness in our lives. (Read the review.)
这些排行榜是基于某个特定学科的研究能力而做出评价,与综合榜单评价方式不同。
Full marks to Prince George for giving the patronising high-five of the Canadian prime minister the eye.
1. The 2012 Ig nobel Psychology Prize
最后,今年只有两所学校首次登上开放课程排行榜。上海交通大学安泰经济与管理学院(Antai College of Economics and Management)直接排到第32名,而亚利桑那大学(University of Arizona)艾勒管理学院(Eller College of Management)在75所院校中排名第68位。
哈佛大学连续16年位居榜首,斯坦福大学和剑桥大学仍分别位列第二、第三名。

Testing Strategies

这表明,一般而言,大学教育从长期看来收益良多。
Length of program: 21 months
GMAT平均分:700分
United States emissions had been declining because of increased burning of natural gas in power generation, which emits less carbon dioxide for each unit of energy than does coal. But the nation reported an increase in 2013 as coal regained some market share. If that trend continues, it could prove to be a challenge for the Obama administration as it seeks to institute tighter policies on greenhouse gases.
Over the past three years, drawing conclusions about China's box office growth has been complicated by Beijing's decision to include new service fees in official revenue totals.
Song “Unforgettable” (Li Guyi, Zhang Yingxi and students from Confucius Institute)
calendar
但是我们波士士顿波士顿咨询集团不认为中国本次改革会导致中国经济不稳定。我们相信中国经济在习主席的领导下会持续高速增长。我们相信上个星期的改革(三中全会)会确保中国经济从现在一直增长到(至少)2020年。根据我们已掌握的资料,我们预测中国经济在未来10年会增加4万亿美金(而书中说是6.4万亿。2012中国GDP为8.3万亿美金)。如果加上印度,亚洲两大国未来的增长总量会达到10万亿美金。在此期间,中产阶级会迅速膨胀,进而增强对经济增长的乐观态度。当然,没有人能完美地预测未来,在我们的近期的一本关于中国和印度经济发展的书中(《Trillion Prize:Captivating the Newly Affluent in China and India》),我们也描述了一些经济增长缓慢的例子。不过总体上我们还是对中国的未来保持乐观态度。
1. “Timbuktu”(Abderrahmane Sissako)
没有比5个月前林赛·罗韩贴子中的麻木不仁和无动于衷更过分的了。
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。
7.思想控制仿生腿
源于:virtues(n 美德天使:九级天使中的第五级)
在接受《第一财经》采访时,中国建设银行(CCB)董事长提到,中国各银行面对的最大挑战在于不良贷款不断上升。
The potential for conflict will force China and the US to redefine their roles in a shifting environment that neither is comfortable with. Tensions will be aggravated by anti-China sentiment during the American elections. Asian countries are in a position to delineate the boundaries of influence for these two powers but, given their varied interests, alliances will shift depending on individual concerns.
时间管理类
“It’s na瘀攀 not to recognize we’re at a pretty serious moment,” said Anthony Crichton-Stuart, director of the London dealer Agnew’s. “There has been a massive taste shift. But when a good old master does come up at auction and it is priced correctly, you do get some excitement.”
The economy has registered a slower but stable performance with good momentum for growth.

Other countries have different testing strategies. For example, the Republic of Korea has adopted a strategy of widely testing for SARS-CoV-2. This may have led to the identification of a large number of individuals who had mild or limited symptoms, but a much lower case-fatality rate compared with Italy (1.0% vs 7.2%) because many patients with mild disease who would not be tested in Italy were included in the denominator in Korea.2

Conclusions

碧昂斯与妮琪·米娜(Nicki Minaj),《完美》(Flawless, Remix),Parkwood/Columbia
vi. 流通,循环,传播
“悲观、消极”的小说家阿斯利·埃尔多安正在努力加工处理自己的可怕经历:数月的牢狱生活。
James Bond Themes Honorable Mention: "Surrender" by K.D. Lang
Wages will finally accelerate after years of stagnation
它还体现在萝塞拉·亚尔迪尼(Rossella Jardini)为莫斯奇诺(Moschino)设计的2009年春夏系列的蝴蝶结和宽松裙子上以及以玛丽·匡特(Mary Quant)为灵感的2013年春季系列中。
The number of country rankings published this year rose to 42, up from 38 last year. The newly featured countries are Argentina, Mexico, Pakistan and Romania.
他说,到1997-98年亚洲金融危机爆发时,美联储的回应已变得更加迅速,它退出了紧缩周期,担心东南亚的动荡会影响美国经济。
《 佛罗里达乐园》

格里芬高中时代的样子与现今相差无几,原因是他离开高中才四年。我们能想象得出,暴力美学的格里芬在NBA里再锻炼上一两年年,他会变得更“怪兽”。
9. Never trust the polls
10. Drawing Words Helps Your Brain Recall Them
The only family comedy/drama you need to see this year.
单词avoid 联想记忆:
rob
单词complex 联想记忆:
adj. 不稳定的,易变的
而至于他自己的教育问题:他在考虑是留在英国,还是为了离硅谷更近而去读美国的大学。再或者,他也许会放弃学业,全然专注于他的事业。他说,我非常想再创办一家公司,连续创业家们都是对创新上瘾的人。我希望能保有热情。如果我不能尝试新的事物,我会感觉很糟。
在不同产业和不同城市之间,年终奖的数额也有很大不同。金融机构的平均年终奖为1.72万元人民币,而教育部门年终奖则平均不到这一数额的一半,只有不足7500元人民币。

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Article Information

Corresponding Author: Graziano Onder, MD, PhD, Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Via Giano della Bella, 34-0161 Roma, Italy (graziano.onder@iss.it).

Published Online: March 23, 2020. doi:10.1001/jama.2020.4683

Correction: This article was corrected on April 16, 2020, to correct a data error reported in the eighth paragraph (number of women in the subsample was 106).

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the following members of the COVID-19 Surveillance Group who were involved in the collection of data used in this report: Xanthi Andrianou, Antonino Bella, Stefania Bellino, Stefano Boros, Marco Canevelli, Maria Rita Castrucci, Alessandra Ciervo, Fortunato D'Ancona, Martina Del Manso, Chiara Donfrancesco, Massimo Fabiani, Antonietta Filia, Cinzia Lo Noce, Alberto Mateo Urdiales, Luigi Palmieri, Patrizio Pezzotti, Ornella Punzo, Valeria Raparelli, Flavia Riccardo, Maria Cristina Rota, Andrea Siddu, Paola Stefanelli, Brigid Unim, Nicola Vanacore.

References
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Grasselli  G, Pesenti  A, Cecconi  M.  Critical care utilization for the COVID-19 outbreak in Lombardy, Italy: early experience and forecast during an emergency response.   JAMA. Published online March 13, 2020. doi:10.1001/jama.2020.4031PubMedGoogle Scholar
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Livingston  E, Bucher  K.  Coronavirus disease 2019 (COVID-19) in Italy.   JAMA. Published online March 17, 2020. doi:10.1001/jama.2020.4344PubMedGoogle Scholar
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Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. Vital surveillances: the epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19)—China, 2020. China CDC Weekly. 2020;2(8):113-122. Accessed March 18, 2020. ‘Our hope is that the Worst Passwords of the Year list will cause people to take steps to protect themselves online.’
5.
Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). Published February 16, 2020. Accessed March 18, 2020. 合作公寓和共管公寓
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Conflicts of Interest Disclosure

1. Discipline them: Of course disciplining our children is a given in any home. But we need to ask ourselves if we are disciplining our children properly? Who

毋庸置疑,改造比创造容易。任何曾经对着白纸一筹莫展的人都知道这一点。但是,在过去七年里,时尚界对60年代的普遍模仿至少暴露出,这个行业缺乏想象力——不只是对于服装和消费者缺乏想象力,而且对于文化与服装的关系也缺乏想象力。
特斯拉表示,在该公司的展厅里,每平方英尺的面积带来的销售额是苹果公司(Apple)的两倍,而苹果目前被公认为是行业领军者。
As for Dirk, nobody should ever go out the way they do, but it happens all the time. In some ways, maybe it's easier if the reckoning is this painful.
2.告诉你的朋友在世界杯期间无论如何也不要忙着生孩子、结婚或办丧事,因为我们是不会去的。
survey
这些弊端是很现实的,但是也有很多方法来回避它们。比如说,你可以利用你的谋生工作向雇主展示你努力工作的诚意。并且你也可以在工作之余继续找其他的好工作。

欧盟新规迫使重庆家具放弃国外市场转攻内销

这些利好消息为特斯拉带来了极为惊人的估值。一位名叫佐尔坦o班的特斯拉观察人士在金融网站“寻找阿尔法“(Seeking Alpha)上指出,特斯拉现在的估值,相当于它每年已经能够卖出几十万辆汽车,但实际上今年它只能卖出35,000多辆车。从另一个角度来说,特斯拉公司今年卖出的每一台车,估值相当于高达100万美元。
18. Most Interesting Apology (tie) On Nov. 18, The Hollywood Reporter disgorged a 1,200-plus word apology for not including any nonwhite performer in its Oscar actress round table. Soon after, the director Alex Proyas and Lionsgate apologized for the lack of diversity in the cast in their new movie “Gods of Egypt.”

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    18 Comments for this article
    EXPAND ALL
    Why are Healthy Patients Dying of COVID-19?
    David Carter, MD | Broome Pediatrics, SUNY Upstate Medical University
    If the primary cause of death in COVID-19 is ARDS with significant pulmonary inflammation resulting in massive cytokine release causing V/Q mismatch manifesting as patchy infiltrates and ground-glass opacities, why then aren't patients being given high dose inhaled steroids? This has been studied in pediatric asthma, and is considered safe and effective. Why are we looking for novel or investigational antivirals when corticosteroids are cheap, safe and known effective reducers of cytokine release?
    CONFLICT OF INTEREST: None Reported
    Immune Status
    Mona Sheikh |
    Nicely written article, very informative, and I agree with the writer that countries need to be transparent in reporting cases. For example, the number of cases in Japan and India is low, given that they are very close to China and compared to Western countries which have more cases and higher mortality.

    I wished you would have analyzed the immune system status of patients who died from the virus.
    CONFLICT OF INTEREST: None Reported
    The Italian Anomaly
    Edoardo Cervoni, M.D. | LD4U Ltd.
    There are significant challenges in interpreting the overall case fatality rate (CFR) in Italy as it is substantially higher than in China and many other countries. It is also clear that the CFR has increased further since this document was presented, perhaps reflecting a health system overwhelmed by the pandemic. In fact, the picture is irregular throughout the Italian territory as is the presence of positive subjects. However, it emerges that age cannot absolutely justify the differences. For example, the CFR in Japan is substantially lower than in Italy, although the population is even older. A thorough analysis seems extremely necessary and useful for the months that follow.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    COVID 19:IS COMPARISON WITH CHINA SO IMPORTANT?
    Giuliano Ramadori, Professor of Medicine | University clinic ,Internal Medicine,Göttingen,Germany
    The Italian patient number one (38 year old) has just been released from the hospital San Matteo. His pregnant wife, who was also infected, was already at home.The patient`s father, however, unfortunately died of COVID-19. We are informed by very transparent Italian journalism. This makes comparison of numbers coming from other countries around the world very difficult.

    On the other hand it is important to focus on Italian numbers which mostly come from Lombardy. In some of the areas of Lombardy, the number of deaths are five times higher compared with those of the same period
    of last year. This in a region with the best health care system in Italy. What went wrong? This is the question politicians will have to answer as soon as the pandemic will be over.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Percent with active cancer
    T Christopher Bond, PhD | Bristol Myers Squibb
    What should we make of the percentage with active cancer? How much of this is prostate cancer in elderly men?
    CONFLICT OF INTEREST: I am an employee of Bristol Myers Squibb
    High Mortality Due to Not Testing Enough Patients with Mild Symptoms
    Hunasikatti Mahadevappa, MD FCCP | INOVA Fairfax Hosptial, Fairfax, VA and INOVA Alexandria Hospital, VA
    HIGH MORTALITY: The authors state that "The overall case-fatality rate in Italy (7.2%) is substantially higher than in China (2.3%). When data were stratified by age group, the case-fatality rate in Italy and China appear very similar for age groups 0 to 69 years, but rates are higher in Italy among individuals aged 70 years or older, and in particular among those aged 80 years or older". However, this may be due to not testing many asymptomatic or patients with mild symptoms. Testing should be widely available to get an accurate assessment of Case Fatality Ratio. It is irrational to assume high CFR in Italy with better health care system.

    EARLY USE OF INVASIVE MECHANICAL VENTILATION: Mortality could have been reduced if they did not use non-invasive ventilation and go to on mechanical ventilation with endotracheal Intubation. BIPAP/CPAP may spread the disease with aerosolization of droplets.

    STEROIDS: They also could have used steroids in patients with acute Respiratory distress syndrome. But these could have helped us to treat future patients.

    SUDDEN INFLUX OF PATIENTS: Sudden influx of COVID-19 patients might have resulted in inability of the system to handle them. It is time for every nation to 'stress test' their system to see if they can handle the pandemic. They should have stockpiles of ventilators in every major city of the country. That could have also decreased the mortality.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Over 70s Reverse Triage
    Fraser Magee, MBChB | Royal Melbourne Hospital
    Is the difference in mortality rates between Italy and China in the over 70 year old age group not at least partially explained by ICU admission restrictions in the elderly Italian population?

    There have been widespread reports of "not for mechanical ventilation" decisions being made in the over 80 and over 70 age groups when bed pressures became intense in Lombardy and Emilio-Romano.
    CONFLICT OF INTEREST: None Reported
    Calculating Case Fatality Rate at the Beginning of Pandemics
    ANDRE R FREITAS, PhD, MD | Faculdade São Leopoldo Mandic, Department of Epidemiology , Campinas, Sao Paulo, Brazil
    This paper uses the number of deaths divided by the total number of cases to calculate the case fatality rate. This method of calculation, when used at the beginning of a pandemic, which is still exponentially increasing underestimates the case fatality rate. This is because a large part of the patients are still evolving and we do not know the final outcome of healing or death. At the present time, a simple and adequate way to calculate the case fatality rate would be to divide the number of deaths by the sum of the deaths plus those recovered, as proposed by Ghani et al (Am J Epidem, 2005).
    CONFLICT OF INTEREST: None Reported
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    Underestimation of the Role of the Italian Regional Healthcare System on Critical Patients' Care
    Federico Gheza, MD | University of Brescia, Brescia, Italy
    The mortality rate among ICU patients is relatively low in northern Italy compared to other European Countries. In our large community hospital in Brescia we admitted about 2000 positive patients in the last 30 days and 850 are currently under treatment here. Our ICU mortality rate is extremely low and comparable with WHO data for Germany or South Korea. The vast majority of deaths occur outside the ICU, in-hospital or at home. Intensive care units in Bergamo, Milan, and Brescia are renowned centers of excellence. An obvious selection bias is lowering the ICU death rate due to admissions of younger people with better chances to survive.

    Even if for many reasons nobody wants to stress here selection criteria to admit or not a patient to intensive care given the very small number of available spots, I want to focus on another Italian-only issue: our health organization can be defined as mainly public, with an increasing amount of private hospitals in a sort of integrated system. This was not a limit and the public/private coordination worked pretty well locally. However, it is less known outside Italy that our health care organization is regional with central coordination. Unfortunately our direct, first-line experience and preliminary data seem to suggest that the inter-regional support was not so virtuous. So, when counting the death rate in relationship with the total number of ICU beds, we must consider the regional beds only, with dismal inter-regional availability. This was our primary regret, if we consider that all of northern Italy can be encircled in a 200 mile range around the "red area" of Bergamo/Brescia. Hopefully, epidemiological studies will explain our anomaly of such a high mortality rate, but if confirmed, our observation must lead to a more integrated, national fronting of pandemic diseases.
    CONFLICT OF INTEREST: None Reported
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    Even Worse Case-fatality Rates in Italy?
    Caterina Zanetti, Dr. | University Hospital of Padua, Italy
    As a possible explanation for Italy's high case-fatality rates the authors mention the more stringent testing policies in place since February, 25, so that more mild cases, with low fatality rate, were thus no longer counted in the denominator.

    I'm concerned that the worst cases, too, are no longer counted in the numerator, as they die before getting tested, seeing as the health care system is overwhelmed (1).

    REFERENCE 

    Mirco Nacoti, MD, et al. At the Epicenter of the Covid-19 Pandemic and Humanitarian Crises in Italy: Changing Perspectives on Preparation and Mitigation. NEJM Catalyst. Vol. No. |
    March 21, 2020. DOI: 10.1056/CAT.20.0080
    CONFLICT OF INTEREST: None Reported
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    Complete Anamnesis?
    Hedley Quintana, PhD | Gorgas Memorial Institute for Health Studies, Panama
    When I was an intern, I was obliged to write down a complete anamnesis (history) of every patient.

    I don't understand why descriptive papers after been peer-reviewed lack information regarding medical background and physical examination. Smoking and medications are almost universally lacking!

    Regarding treatments, I strongly discourage pharmacological interventions without being tested with an RCT.

    Regarding support treatment, I am surprised how little is mentioned regard invasive cardiovascular monitoring. Deceased patients in this paper clearly point out how relevant it is to closely assess the fluid balance, and to address the causes of septic shock,
    particularly in patients with multiple comorbidities.
    CONFLICT OF INTEREST: None Reported
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    Spreading of Disease in Early Stages
    RIchard Levicki, BSc MSc | Gaiadoc
    In the UK at present there are political issues such as the Government mixing the construction profession and health professionals on the London Underground, an area where we have a high concentration of current deaths. The health workers do not have adequate protection and even face masks being needed and therefore it seems that we may be spreading the disease ourselves in the early onset period. At the same time the political decisions are it seems taken on economic grounds whilst the Government has used contradictory arguments to take martial law powers. These factors mean that the UK Government cannot be trusted to give the world accurate data as they have a conflict of interest in terms of their own actions. To what extent has this affected current data and how can we progress in these troubling times with these issues in play?
    CONFLICT OF INTEREST: None Reported
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    CFR Italy vs Germany
    Rajat Dhameja, MD, MHA | Hospital Administration Executive
    The information and research in the publication bridges gaps and helps in understanding the data made available from Italy. Several media sources point to Germany's low fatality rate despite high rates of infection. Parallels can be drawn between the high testing rate of Germany and South Korea. Germany and Italy also seem to contrast in how each are reporting fatalities where it concerns comorbidities. Together with demographic variances, this paper further clarifies how data is collected and interpreted for the general public.
    CONFLICT OF INTEREST: None Reported
    Managing COVID-19 at Home (and by Phone)
    Paolo Mazzarello, MD | and Giovanni Pietro Corsini, MD, Genoa, Italy
    Dr Carter wonders whether COVID-19 patients could give high dose inhaled steroids. In two mild to moderate COVID-19 suspected cases, patients reported bronchostenosis together with upper airway allergy symptoms. We prescribed by phone a standard dose of inhaled steroids together with montelukast 10 mg once a day (1). In COVID-19, inflammatory cytokines and chemokines levels are high. Montelukast is a leukotriene receptor antagonist; leukotrienes induce both the production of inflammatory cytokines and that of chemokines. In practice, in lungs, montelukast decreases inflammation and relaxes smooth muscle. In our cases, one should use it only for a short time and without relevant side effects. More, there is evidence of its inhibition of Zika virus infection and we wonder whether montelukast is active against other viruses (2).

    Giuseppe Paolo Mazzarello, MD, General Practioner, ASL 3 Genovese, Genoa, Italy
    Giovanni Pietro Corsini, MD, Psychiatrist, Ospedale San Martino, Genova, Italy

    References

    1. Dong L, Hu S, Gao I
    Discovering drugs to treat coronavirus disease 2019 (COVID-19).
    Drug Discov Ther, vol. 14, n°1, 2020 pp 58-60.
    DOI:10.5582/ddt.2020/01012

     2. Chen J, Li Y, Wang X, Zou P
    Montelukast, an Anti-asthmatic Drug, Inhibits Zica Virus Infection by Disrupting Viral Integrity.
    Front Microbiol 2019; 10: 3079
    doi: 10.3389/fmicb.2019.03079
    CONFLICT OF INTEREST: None Reported
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    Air Pollution and Tobacco use
    Jose Ramiro Cruz, DSc Virology/Immunology | Independent Consultant
    The EEA Air Quality in Europe - 2019 Report indicates that Italy has one of the highest indicators of air pollution by particulate matter, ozone, and nitrogen dioxide and other substances (Map 9.1, page 64). Within the country, Lombardi shows the most contaminated air. Additionally, the World Population Review summarizes tobacco smoking by country and shows that, in 2015, 24% of Italians (28.30% of males, 19.70% of females) were smokers. The accumulated exposure to both air pollutants and tobacco smoke produces important morbidity and mortality by itself. These factors should be taken into consideration when examining case fatality rates associated with SARS-CO2 in different parts of the word.
    CONFLICT OF INTEREST: None Reported
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    CFR in Italy Explained By Age Structure of Positive Cases
    Simona Bignami, PhD | Université de Montréal
    The crude CFR is an inaccurate measure of the disease severity since the pandemic is still unfolding. With the goal to improve its comparability over time and across countries at this stage, we have developed a demographic adjustment of the CFR that addresses the bias arising from differential case ascertainment by age (1). When applied to publicly released data for Italy, we show that until March 16 our adjusted CFR was similar to that of Wuhan. This indicates that our adjusted CFR improves its comparability over time, making an important tool to chart the course of the COVID-19 pandemic across countries. Since March 16, the Italian COVID-19 outbreak has entered a new phase, with the northern and southern regions following different trajectories. As a result, our adjusted CFR has been increasing between March 16 and March 20. Data at the subnational level are needed to correctly assess the disease severity in the country at this stage.

    REFERENCE

    1. https://medrxiv.org/cgi/content/short/2020.03.23.20040998v1
    CONFLICT OF INTEREST: None Reported
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    Sporting Event in Lombardy and COVID-19 Viral Transmission
    Giuliano Ramadori, Professor of Medicine | University Clinic,Internal Medicine,Göttingen,Germany
    The soccer fight Atalanta Bergamo against Valencia which took place in Milan on February 19 may become a milestone in the history of epidemiological studies. About one third of the population of Bergamo attended the match. One can only imagine what happened in Bergamo when the fans went back to Bergamo from Milan after their team had won the match.

    On march 16 th the news paper La Repubblica published an article :Spagna,Valencia:“ il 35% di noi positivi dopo aver giocato a Milano“ ("35% of us are positive after playing in Milan).

    Two days after the match the
    first (official) COVID 19-positive patient appeared at the Codogno-Hospital because of influenza-like symptoms. He was patient number 1 in Italy while a Chinese couple was treated in Rome since the 28 th of January. At the same time however, a 78 year-old man in Vó Euganeo fell ill on February 20th and died the next day of COVID-19 infection. He was the first person in Italy who died of the COVID-19. The area around Codogno (about 50.000 inhabitants) and the area around Vó were locked down, but not the area around Bergamo (ca 1.3 million people).

    The number of new infections became such that the doctors at the university hospital in Bergamo, Papa Giovanni Paolo II, did not have time to decide who  should be treated by mechanical ventilation.This was mainly because the Italian health care system does not have intermediate structures between home doctors and the hospitals.

    While in Codogno only symptomatic persons were tested for COVID 19-infection ( all 78 chinese citizens were negative), all the inhabitants  of Vó Euganeo,a town near Padova, 3.500 persons, were tested and asked to stay home. Seventy persons were tested positive at the beginning of the 14-day quarantine and seven of them were still COVID-19 positive when the quarantine was officially terminated. Eight Chinese citizens were negative (1)

    As far as I know none of the positive persons became ill (with the exception of the 78 year old man who died first) during the quarantine. The experience of VÒ demonstrates that there are asymptomatic persons who can transmit the virus.It also demonstrates that quarantine may help to avoid the the appearence or worsening of symptoms in infected persons bevfre the virus is eliminated.

    Two regions, Lombardy and Veneto, close to each other, each have two different approaches with different epidemiology. As of 01.04.2020 (April 1), the Veneto has tested 112,000 persons and found 9625 COVID-19-positive persons; 1,718 have been hospitalized and 350 are being treated at an ICU. Lombardy has tested 121,000 persons and 44.773 were positive,11927 are hospitalized and 1342 are being treated at the ICU.

    The lesson is to test as many persons as possible.If one needs to choose whom to test then it should begin with workers in the different health care structures.

    REFERENCE
    1.These zu Corona Herkunft. Brachten Chinesen das Virus nach Italien? Tageschau.de.26.03.2020.
    www.tagesschau.de › faktenfinder › italien-coronavirus-china-101
    CONFLICT OF INTEREST: None Reported
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    Really surprising outcomes?
    Alessandro Capone, MD | Statistics for Health Economic Evaluation Group (external collaborator), Department of Statistical Science, University College London, London, UK
    When Onder et al. published their paper, Italian epidemiological data on COVID-19 were just preliminary and often not fully integrated. Epidemiology is a dynamic science and parameters such as case-fatality rate (CFR) or R0 may vary as function of time, and hence be subject to biases early in an epidemic by definition. Nonetheless, explanations provided by authors concerning the supposed higher CFR value compared to China (especially in elderly and/or in patients affected by several comorbidities) are solid and rational. Indeed, Italy was not as ready to manage a so-rapid and dramatic pandemic, as many other countries were, actually. The last Italian National Plan for Preparedness and Response to an Influenza Pandemic was published in 2007 and slightly updated in 2016 [1, 2]. The gathering of data and assessment of consequences associated with current infections in Italy took some time and appropriate responses (i.e. quarantine and social distancing measures) could be delayed a bit. This event may also have contributed to smoothing the viral transmission and worsening some patients’ clinical conditions. China responded swiftly, on a mind-boggling large scale: "They rolled out probably the most ambitious, and I would say, agile and aggressive disease containment effort in history. From old-fashioned measures, they very quickly moved to a science-and-risk-based approach, which was really tailored to allow it to use different containment approaches and measures, depending on the context, the capacity and the nature of the virus circulation". This is the assessment of epidemiologist Bruce Aylward (leader of the joint mission between WHO and China on COVID-19) during the press conference at the WHO’s headquarters in Geneva, on February 24, 2020 [3]. China’s massive efforts have been generally successful and indicate that the virus can be contained [4]. Unfortunately, what is being observed now in Italy (infections, deaths, containment measures and massive pressure on the national health service) will be seen in several other countries sooner or later. What is the most important lesson we should learn from this dramatic experience? Italy as well as other European nations (acting as a single country), China, USA and all other countries should pay much more attention to the elaboration of constantly updated pandemic plans which must be integrated with proper contingency solutions.

    REFERENCES

    1. Ministero della Salute. Piano Pandemia Infuenzale. http://www.salute.gov.it/portale/influenza/dettaglioContenutiInfluenza.jsp?lingua=italiano&id=722&area=influenza&menu=vuoto
    2. Ministero della Salute. National Plan for Preparedness and Response to an Influenza Pandemic. Full text available for download from the web site: http://www.salute.gov.it/imgs/C_17_pubblicazioni_511_allegato.pdf
    3. World Health Organization (WHO). Subject: Press Conference of WHO-China Joint Mission on COVID-19. February 24th, 2020. Full text available for download from the web site: https://www.who.int/docs/default-source/coronaviruse/transcripts/joint-mission-press-conference-script-english-final.pdf?sfvrsn=51c90b9e_2
    4. World Health Organization (WHO). Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). Geneva, February 16-24, 2020. Full text available for download from the web site: https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf
    CONFLICT OF INTEREST: None Reported
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