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向李文亮醫生致敬

2020/2/7 — 15:06

1月31日Nature雜誌 (註一) 發表了一篇討論新型冠狀病毒疫情的發展方向。該文主要提出了兩個問題。

病毒的擴散

第一個問題是病毒的擴散規模。現時基本上有三個電腦模型(Modelling)預測病毒的擴散和存在於武漢巿的總受感染人數。它們分別是香港大學公共衛生學院Professor Joseph Wu在1月31日發表的數學模型;其二 (註2) 是Jonathan M. Read, Jessica R.E. Bridgen, Derek A.T. Cummings, Antonia Ho, Chris P.,Jewell 等人在1月24日發表的模型;其三(註3)是Matteo Chinazzi, Jessica T. Davis, Corrado Gioannini, Maria Litvinova, Ana Pastore y Piontti1, Luca Rossi, Xinyue Xiong, M. Elizabeth Hallora, Ira M. Longini Jr., Alessandro Vespignani1 等人在1月27日發表的模型。

Professor Joseph Wu 是哈佛大學公共衛生學院的 Center for Communicable Diseases Dynamics (CCDD) 的成員,他的專長是對疫制制作數學和統計模型,報告掛名的有梁卓偉;Dr Jonathan Read是英國蘭卡斯特大學生物統計學的高級講師 (Senior Lecturer in Biostatistics);Matteo Chinazzi是美國著名私立研究型大大學的科學家,專長研究數學模型 (Associate Research Scientist at the Laboratory for the Modeling of Biological and Socio-Technical Systems)。

廣告

梁卓偉在1月21日記者會上估計,按相關模型推算,武漢市最大可能有多達1343宗新型冠狀病毒個案。其時國家衛生健康委公布,累計確診病例為291例(湖北省270例)。

Jonathan M. Read估算武漢市只能發現約5.1%的患者,它的估計武漢實際受感染者約為19萬人,約為武漢巿人口的0.6% (以一千一百萬居民計),在這期間中國的官方告佈的累計確診個案約為一萬。Jonathan M. Read估計疫情會在包括香港在內的各大城巿在2月4日出現社區爆發,它也指出在武漢封關已經太遲,將有四分之三的病毒向外傳播。

廣告

Matteo Chinazzi估計武漢及鄰近區 (以三千萬居民計) 約有三萬九千人受感染,即約為0.13%。他也估計受感染的旅客約在10日被確診。

We assume that exposed individuals are potential travelers for an average time of τd = 10 (21; 22) days before developing symptoms and being detected (an exponential distribution is assumed).

Matteo Chinazzi把倫敦、南韓等地的受感染風險定為0.002至0.006,中國各城巿的風險約大10倍,但當中香港為最高,風險值為0.066;上海第二,風險值為0.57;廣東置中,為0.034。即香港的風險比廣東省大一倍。

所有的模型都承認這些是初步估算,因為數據來源不足‧筆者的流行病學專家朋友表示疫情過後才有機會估算可信的數值,尤其是數據不是隨機,無法知道社區疫情‧目前的官方數字都是來自醫院,如比香港政府想知道港人的對政府的滿意程度,但他們只到馬會俱樂部進行問卷調查‧而且,數學模型不是流行病學家的主要工具。

中國官方數字

筆者從中國官方公佈的數字中注意到幾點:

(一) 新增重病病從2月1日開始有落有上,隨後一直反覆;

(二) 新增疑似病例開始收窄,在2月5日又急升;

(三) 死亡個案一直局限在湖北省。

筆者的流行病學教授朋友表示這些數據不科學,因為不清楚中國如何定義重症病例,也懷疑中國作假。

會否發展為地區性季節性流行病?

文章的另一個重點是擔心武漢病毒的高傳播率、低發病特癥,與沙士不同,不會在夏季後完全散去,而是長期困擾社區。若屆時治療手法和疫苗不能及時研制出來,就成問題。

沙士的死亡率約為10%,武漢病毒估計為2至3%,但已遠比季節性流感的0.1%高20至30倍。季節性流感致死的每年人數約為29萬至65萬。假若武漢病毒在未來演變成為地區流行病之後,它在中國每年導致的死亡人數可以很高‧但專家估計武漢病毒變為地區流行病的機會較低。

治療藥物

有報導指2種藥物在試片上有效地抑制武漢病毒,它們是曾用在美國35歲受感染青年的 「瑞德西韋」 ( Remdesivir)和Chloroquine (註4)。Remdesivir是一種未做人體測試的藥,因而目前不能在商業上巿。Chloroquine則是人們熟識的金雞納霜,它在第二次世界大戰時已廣泛地用作治療瘧疾。(但有熟識藥物研發的朋友指出,新藥從試片測試到動物測試到人體測試到臨床應用的可以是十多年的時間,並對金雞納霜是否有效持懷疑態度。)

Remdesivir現在成了大紅大紫的藥物,可是有報導指大陸巧立名目申請它為自己的某些用途的專利權。我的流行病學教授朋友認為:「這班人真是無恥到極,把根本不屬於自己,亦無能力生產的別國藥物搶先在中國作應用專利註冊。應用專利是使用這藥來治療某一種病的專利,比如我也可以申請用remdesivir 來治不舉的專利,如果批淮,雖然我不能生產這藥,但任何人用remdesivir 來治陽痿就要俾專利費俾我,真的是無本生利。這種申請外國多不批准,但強國就大有可能,尤其而家Gilead 免費俾中國人生產,這樣恩將仇報,真是無恥之尤!」

「瑞德西韋」幫了其研究公司吉列德一大把。吉列德一直苦於如何將實驗式藥物Remdesivir用人做測試。吉列德現在主要與大陸合作,同好一家便宜,兩家著數,找中國人當白老鼠。

醫學權威雜誌刺針在2月4日有文章指治療類風濕關節炎新藥——巴瑞替尼 (baricitinib) 可以是研究方向 (註5)。刺針在2月6日有文章指出在沙士期間被廣泛使用的皮質類固醇(corticosteroid) 已被證明不適合用於新型冠狀病毒。

道歉

筆者在「武漢新型冠狀病毒疫情之一」中談及沙士時期的用藥Ribavirin的討論在資料上出錯。

Ribavirin的確在試片和臨床都被證明不能有助於沙士治療,也可以帶來嚴重副作用,但當年藥石亂投的最大問題不在Ribavirin而是香港使用了重劑的皮質醇methyl-prednisolone,它的過量使用導致骨枯症和將該不死的打死。

這裏也有段古,建議使用重劑皮質類固醇是大陸的鍾南山、香港的沈祖堯有份為在港引用拍扳,歷史就是諷刺,在沙士後,他們成了沙士英雄。

 

〈備註〉

註一

Coronavirus outbreak: what’s next? 31 JANUARY 2020

This has led to one prediction that the virus could infect about 39,000 of the 30 million people living in the region of Wuhan

One big question is whether the coronavirus is also here to stay. If efforts to contain it fail, there’s a high chance that it will become endemic. As with influenza, this could mean that deaths occur every year as the virus circulates, until a vaccine is developed. If the virus can be spread by people who are infected but don’t have symptoms, it will be more difficult to control its spread, making it more likely that the virus will become endemic.

Currently, the virus has caused severe illness, and death, mainly in older people, particularly those with pre-existing conditions such as diabetes and heart disease. A 36-year-old Wuhan man with no known pre-existing health conditions is the youngest victim reported so far.

With 213 deaths so far out of nearly 10,000 infections, the new coronavirus has a death rate of 2–3%. This is significantly lower than SARS, which killed around 10% of the people it infected.

If the virus spreads throughout the world, the number of deaths could be substantial. The current death rate of 2–3% — while not as high as for SARS — is still quite high for an infectious disease, says Adam Kamradt-Scott, a global health-security specialist at the University of Sydney, Australia. The 1918 influenza outbreak, known as the Spanish flu, infected around half a billion people, one-third of the world’s population at the time, and killed more than 2.5% of those infected; some have estimated that as many as 50 million people died.

The China coronavirus probably won’t trigger such an apocalyptic scenario, because it isn’t typically infecting or killing young, healthy people, says Kamradt-Scott.

註2

Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions Jan. 24, 2020

We estimate that only 5.1% (95%CI, 4.8–5.5) of infections in Wuhan are identified,

We also predict that by 4 Feb 2020, the countries or special administrative regions at greatest risk of importing infections through air travel are Thailand, Japan, Taiwan, Hong Kong, and South Korea

Our model suggests that travel restrictions from and to Wuhan city are unlikely to be effective in halting transmission across China; with a 99% effective reduction in travel, the size of the epidemic outside of Wuhan may only be reduced by 24.9% on 4 February

註3

Preliminary assessment of the International Spreading Risk Associated with the 2019 novel Coronavirus (2019-nCoV) outbreak in Wuhan City  January 27, 2020

In a worst-case scenario, some 190,000 people could be infected in Wuhan, according to another prediction model.

註4

2019-nCoV Treatments Coronavirus Today February 6th, 2020

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro

註5

Baricitinib as potential treatment for 2019-nCoV acute respiratory disease

Lancet February 04, 2020

註6

Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury

Lancet February 06, 2020

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