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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.

信心恢复 房地产投资增速两年来首次出现回升

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.

房地产的“二线战场”:资本深入非核心城市

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

n. 部分,份,命运,分担的责任
在苹果(Apple)的蒂姆库克(Tim Cook)支持AR后,该技术可能是更大的机遇。苹果最新操作系统及新款手机iPhone X纳入了AR技术。

LED竞争格局加剧 海洋王等3家企业2015年净利走跌

Manal al-Sharif is best known for challenging laws and mores that keep women down in her native country.
Released in 2013, The Bling Ring is a satirical crime drama that chronicles the adventures of Hollywood Hills high schoolers who burgle the homes of local celebrities. The teens break into homes of icons like Megan Fox and Paris Hilton, stealing cash, clothes, handbags, and jewelry to help them emulate the excessive lifestyles they admire in magazines. The students are eventually caught and sent to jail after posting pictures of their hauls on social media.
Average age: 36 for English blended program
jewelry
2. Marc Faber's Doomsday warning on Bernanke's disastrous QE scheme
周一晚间,安卡拉方面证实,不欢迎荷兰驻土耳其大使返回土耳其。
是否有什么事情我一直放不下?我们不会总是能意识到我们在何时抓住有害但感觉安全熟悉的事情不放手,不论是一份不称心的工作,还是一段不健康的关系或者一种停滞不前的生活方式。看看你是否执着于对你没用的事情,想出小措施来改变和解脱吧。

We will promote coordinated urban development above and below the ground, and begin construction on at least another 2,000 kilometers of underground utility tunnels in cities. A three-year initiative will be launched to remove the risk of flooding in highly vulnerable urban areas; and further progress will be made in the development of sponge cities. All these efforts will make our cities more attractive and function better.
这一发现引起了历史学家的极大关注,因为这为了解理查三世提供了更加确凿的证据。理查三世于1485年死于博斯沃思战役,之后有关他的一生一直充满争议。
14. 另一方面。下面是一份今年大制片公司发行,由女导演执导的粗略名单:华纳兄弟五部!包括拉娜·沃卓斯基(Lana Wachowski)、安妮·弗莱彻(Anne Fletcher)、黛娜·纳彻曼(Dana Nachman)、南希·迈耶斯(Nancy Meyers)和派翠西亚·莱根(Patricia Riggen)。环球影业三部,包括萨姆·泰勒·约翰逊(Sam Taylor Johnson)、伊丽莎白·班克斯(Elizabeth Banks)和安吉丽娜·朱莉(Angelina Jolie);迪斯尼一部,尼基·卡罗(Niki Caro)。派拉蒙零部。福克斯零部。索尼零部。我没有把福克斯和索尼的独立部门包括进去。
这是第二枚被拍卖的诺贝尔和平奖奖牌,得主是第一个获得该奖项的拉美人——1936年诺贝尔和平奖奖牌被授予当年的阿根廷外长卡洛斯·萨维德·拉莫斯。
1月份,沃尔玛美国公司总裁兼首席执行官比尔西蒙承诺,这家全球最大零售企业将在今后五年内聘用10万名老兵。此外,作为美国最大的私营雇主,沃尔玛还表示它将邀请光荣退伍不到一年的老兵加盟公司。
"I'm not really worried about it, honestly," Bryant said. "My shooting will be better."
根据中国海关总署发布的数据,这些进出口贸易使11月中国的贸易顺差比10月的贸易顺差382亿美元提高20亿美元,至402亿美元,远超9月份的6个月低点286亿美元。11月的贸易差额也超过了经济学家预期的350亿美元。
She only learnt to walk five months ago, but 'Baby Beyoncé' is already strutting her stuff on stage at pageants.
根据报道,当地法院鉴于周某的年龄及其坦白承认自己的罪行,最终给予了周某一个宽大的判决。
“即便人们充分了解了(美联储政策的作用),市场动态也可能相对容易地变得不稳定或不利,”他说,“届时你将陷入一个卖盘压力自我强化的循环。”
周二在华盛顿DC倒下的大树把一条街拦住了。
10. "Arrow" (2.2 million)
从2016年6月1日至2017年6月1日,世界上收入最高的十位模特的税前总收入不算各项费用共计为1.095亿美元。
然而据北京出入境边防检查总站(Beijing General Station of Exit and Entry Frontier Inspection)称,只有14,000名旅客办理了过境免签手续,远低于官方此前预计的20,000人。

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Meanwhile, villages within the city's boundaries will be overhauled and low-end manufacturers and logistics companies removed.
8.Suicide Squad
最糟糕地利用社交媒体奖
a朝向,void空-空城计-避开
Social scientists, after crunching data from both sides of the Atlantic, have discovered something surprising: it’s not the amount of racial or ethnic diversity in a community that predicts white resentment and support of anti-immigrant policies, but the pace of change.

Testing Strategies

Having reached the current stage of development, China can now advance only through reform and innovation. We have the largest quality workforce as well as the largest pool of scientists, engineers and professionals in the world, and their potential for innovation is truly tremendous.
The Fate of the Furious was the top-grossing foreign film, ranking second on the list.
民粹主义的兴起(即使在美国和英国这样的就业人数众多的国家也是如此)使得政客们认识到,就业的质量和数量同等重要。
交通运输部科学研究院近日发布的报告显示,北京位居全国十大最拥堵城市排行榜第三,排在济南、哈尔滨之后。
单词commercial 联想记忆:
adj. 流行的,大众的,通俗的,受欢迎的
More advanced components are in short supply, however, which could leave many customers waiting long after September to get hold of the new iPhone. That presents an opportunity for rivals such as Samsung’s new Note 8 or Essential, the smartphone maker led by Android co-founder Andy Rubin, which is targeting premium customers such as Apple’s with its slick $699 device. Google is also said to be preparing a new version of its Pixel smartphone, which has proved popular with early adopters.
另一种看法是,油价在过去三年中的变动,是长期结构性变化的开始,预示着下一个50年里,能源价格按实际值计算将显著低于上一个50年。简单地说,持这种看法的人认为,供给的增长潜力超过需求增长。
汤森路透2015年全球创新百强名单是基于对专利相关的标准进行深入研究,寻找真正的创新企业。
Roles With Bite
2013年排名:14
China has 731 million Internet users as of December 2016, roughly the size of Europe's population, according to a report released by the China Internet Network Information Center (CNNIC).
上证综指下跌6.85%,以科技版块为重点的深证综指下跌8.22%。
This year, the average sales price for an apartment in New York City topped $1 million, a milestone with far-reaching implications. As the city’s population soars, prices and buildings are rising in neighborhoods that missed the last housing boom.
4. OPEC’s Next Move.OPEC deserves a lot of credit (or blame) for the remarkable downturn in oil prices last year.While many pundits have declared OPEC irrelevant after their decision to leave output unchanged, the mere fact that oil prices crashed after the cartel’s November meeting demonstrates just how influential they are over price swings. For now OPEC – or, more accurately, Saudi Arabia – has stood firm in its insistence not to cut production quotas. Whether that remains true through 2015 is up in the air.
译者:清远
2.你突然变成Twitter上面思想领军人物。
So with such a strong South American contingent, where will the main challenge come from ? Well, the big guns from Europe is the obvious answer. And where else could you look for a team of Champions than Spain. Having won the last World Cup, sandwiched between two European Championship triumphs, this is a team that not only knows how to play fantastic football, but that knows how to win. So whilst Messi and Ronaldo get all the annual plaudits and player of the year titles, the likes of Xavi and Iniesta go about winning all the major trophies. So will they be as string this year ? Well, worryingly for the rest of the world, yes. Not only are most of the old guard still there but talented youngsters such as Koke and Thiago Alcantara have joined the ranks. Not only that, but they've managed to grab a prolific striker, Diego Costa, from under the noses of the host nation, with the Atletico Madrid forward opting to play for Spain, rather than the nation of his birth.

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

迁移工程也是京津冀一体化计划的一部分,其目的在于缓解首都交通拥挤,为地区提供更加均衡的发展。
伊丽莎白?泰勒和理查德?伯顿的爱情之
大银行已经或多或少地放弃了用高薪留住人才的尝试。自金融危机以来,有一件事很清楚:如果你想暴富,就得去硅谷。露丝波拉特(Ruth Porat)在2015年树立了一个标杆,她放弃了摩根士丹利(Morgan Stanley)首席财务官约1300万美元的年薪,跳槽谷歌(如今的Alphabet)获得五倍于此的薪酬。
吕特在周一晚间的辩论中重申,他不会与维尔德斯所属的政党组建联合政府,他甚至还表示不可能组建一个依赖这个反移民政党支持的政府。吕特表示:“我不会再次与这样的政党合作。”在2010年选举之后,吕特组建的首个少数派政府受到自由党的支持。
Wages will finally accelerate after years of stagnation
可以这样说美国银行首席执行官布莱恩?莫尼汉这个人:他很会说话。在给股东的信中,莫尼汉特地感谢美国纳税人,正是由于他们,美国银行才获得了450亿美元的不良资产援助资金。他还说自己如今正在金融改革方面同“政策领导人”紧密合作。不过他是否能做好,比如转变美国银行的境遇,就是另外一回事了。虽然美国银行的确在去年12月偿还了援助资金,但是它仍然有数十亿美元的高风险住房与商用房房贷,这也是为什么它要在年度报告中花8000字来讨论风险了。
Artificial pancreas, however, knock insulin into your body automatically. The device looks much like a regular insulin pump, which slips you insulin continuously through your skin, but this one monitors your blood sugar at all times and adjusts itself accordingly. So even when the wearer sleeps, there's no danger of falling into shock if their sugar drops too low.
Amy Kazmin
“The individual sent an email blast to the entire staff.”

We will ensure that foreign trade continues to pick up and register steady growth.
There are two concerns about taking a so-called survival job. It could distract you from your job search, and potential employers may have trouble envisioning you in your previous professional role.
但大部分海外岛屿则会出售永久产权。
The number of initial public offerings (IPO) and the amount of funds raised in the Chinese mainland's A-share market fell sharply year-on-year during the first half of 2016, according to statistics released by PwC last Monday.
与官方PMI指数相比,财新赞助的系列调查的样本是数目少得多的民营企业,其结果的波动性往往更大。而官方PMI指数则主要关注规模更大的国有企业。
7. 举重训练可以帮助提高长期记忆力
获奖者:侯任总统唐纳德?特朗普和希拉里·克林顿(共同获奖)
单词amnesty 联想记忆:
今年1月份CPI同比上涨1.8%,去年12月同比上涨为1.6%。不过该指数仍落后于北京方面“3%左右”的目标。
法国兴业银行(Societe Generale)国际策略师基特?朱克斯(Kit Juckes)说,过去30年破灭的三个世界级金融大泡沫背后,都是“美联储(Fed)太久时间将政策利率维持在名义经济增长率之下”。

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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. 8.Your Boss Sucks
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Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). Published February 16, 2020. Accessed March 18, 2020. 英语中,男女用语的7个大不同
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Every point we think we've reached where James cannot be better than he has been, he then blows past it like a poor center switched onto him. What will be discussed most is his all-encompassing skill, but this is also a testament to the work that James puts in. You can mock all those Instagram videos he puts up, but those are the real reason he's still able to do this; James has never cheated the game, not a day in his life, and the result is incomparable performance night in and night out.

“The US economy is likely to grow by 3 per cent plus this year as well as next year.
但并非所有记者──比如笔者本人──都认同这个最终评估结果。
Call Me By Your Name
达福目前可能是最佳男配角的领跑者。
The report by iResearch Consulting Group and Sina Weibo, China's most popular microblogging platform, was released at a forum in Shanghai, co-organized by Weibo and telecom giant Huawei .
2. “Inside Out” (Pete Docter)

家居五金建材抱团办展

[i'nili]
con共同,duct引导-引导大家的行为举止

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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
    READ MORE
    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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