加州大学旧金山 BioHub 小组关于 COVID-19 的讨论会小结，2020 年 3 月 10 日

与会者：

• 乔·德里西：UCSF的顶级传染病研究员。 陈扎克伯格生物中心（涉及UCSF/伯克利/斯坦福的合资企业）联席总裁。 在非典疫情中使用的芯片的共同发明者。
• 艾米莉·克劳福德：新肺特别工作组主任，诊断专家
• 克里斯蒂娜·塔托：快速反应总监， 免疫学家
• 帕特里克·艾斯库：领导疫情应对和监测，流行病学家
• 查兹·兰格利尔：UCSF传染病医生

下面基本上是小组成员发言原汁原味的记录。 少数不是原话会写在括号中。

• 主要观点：

在目前时点，美国已经错过了遏制期， 遏制基本上已是徒劳的了。 我们的遏制努力不会减少在美国感染的人数。
现在，我们只能努力减缓传播速度，帮助医生们应对需求高峰。 换句话说，遏制的目标是平缓曲线，以降低需求激增的峰值，减弱对医院的冲击程度。 并争取时间，希望药物可以尽快开发出来。
目前社区中有多少人已经感染了病毒？ 没人知道，我们正在从遏制阶段转到医护阶段。

美国目前处于意大利一周前的时点， 我们没有任何理由可以说我们将能避免发展到像意大利那样。

在未来12-18个月中，40%-70%的美国人口将感染COVID-19。 达到这个水平后，你可以开始获得一些抗体。 与流感不同，这病毒对人类是全新的，因此全球人口没有潜在的免疫力。[贝克实验室在3月1日晚餐上也告诉我感染率估计为30-70％]

[我们用这个的数字来估计死亡人数——表明大约150万美国人可能会死亡，小组成员并不反对我们的估计。相比之下，季节性流感平均每年有5万美国人死亡。 假设50%的美国人口，即1.6亿人感染新肺, 在未来12-18个月中，160万美国人将死亡，死亡率为1%。约10倍于流感死亡率。这个估计是基于未来没有开发出有效治疗药物的假设。
死亡率因年龄而异， 80岁以上死亡率可能为10-15%。
我们不知道COVID-19是否是季节性的，但即使夏天能消退，它可能会像1918年的流感那样在秋天又复发。

我只能明确地告诉你两件事，一，在情况好转之前情况肯定会变得更糟；二， 我们至少明年还会面对此病毒，明年我们的生活会和以前很不一样。

• 我们现在该怎么办？ 你能为你的家人做什么？我们知道在潜伏期也可能是有传染性的，但不知道在症状出现之前传染性有多强，但症状最强时病毒传染性也最强。 我们目前认为，在症状出现前2天到出现后14天（T-2至T+14），感染者具有传染性。

病毒能在体外存活多长时间？在物体表面上，根据不同表面类型，目前认为能存活 4-20 小时（也可是能几天），对此仍没有共识。
该病毒非常容易被常见的抗菌清洁剂消灭：漂白剂、过氧化氢、酒精。

要避免去音乐会、电影院、任何拥挤的场所。我们已经取消了商务旅行。

要做好基本的卫生，如洗手和避免触摸脸。

提前储存好你的常用处方药，许多连锁药店的供应链在中国，制药公司通常储备有2-3个月的原材料，因此，若中国制造业中断，可能储备会耗尽。

注射常规肺炎疫苗可能会有所帮助， 不预防COVID-19，但降低你身体变弱的机率，降低得COVID-19后恶化的可能性。

明年秋天请一定要接种流感疫苗，虽然不能预防COVID-19，但同样能减少你身体变弱的机率，降低得COVID-19后恶化的可能性。

我们会建议任何60岁以上的人都呆在家里，除非万不得已请不要出门。 美国CDC内部也一直在在讨论是否应规定60岁以上的人不得乘坐商业航空飞机出行。

UCSF同仁们正在将自己的高龄父母从养老院等迁回到自己的家里，不让他们走出家门，家里的其他成员一进家门必须先洗手。

新肺病毒感染的三条途径：手到嘴/脸；唾沫/气溶胶传播；粪便到嘴的传播。

• 如果有人生病怎么办？如果有人生病，让他们呆在家里并避免与任何人接触。 任何在医院里能做到事， 你在家里也都能做到。 大多数人病状是温和的，但是，如果他们病情变重，或者是70岁以上的老年人，或本来就有肺或心血管问题，必须带他们去看急诊。
迄今为止，COVID-19没有办法治疗。 医院能提供的只是支持性护理（如静脉输液、吸氧气），帮助你维持生命，靠自己的免疫力战胜病毒，预防败血症。
如果病人到了危重症期，你可以尝试让他们申请服用Remdesivir作为“同情用药”，该药物目前同时在旧金山总医院、UCSF、和中国做临床试验。 你需要联系在那两个医院里的医生，申请加入临床试验。 Remdesivir 是一种来自 Gilead 的抗病毒药物，在灵长类动物中表现出对中东呼吸综合征的有效性，目前正在做针对 COVID-19 的人体试验。 如果试验成功，明年冬天可能上市，因为扩大药物的生产规模比开发疫苗要快得多。

为什么老年人的死亡率要高得多？你的免疫系统在50岁以后会下降，
死亡率与病人之前是否有基础疾病密切相关，尤其是呼吸道或心肺疾病。 这些基础疾病在老年人中概率较高，老年人患肺炎的风险也较高。

• 能否对所有人都做 COVID-19 检测？不现实，因为没有足够的测试能力。 原因如下，目前除了 PCR 测试之外，没有其他测试可以区分COVID-19与流感或其他十几个正在传播的呼吸道病菌。聚合酶链反应 （PCR） 测试可以检测 COVID-19 的 RNA。 然而，我们仍然对测试的准确性没有信心，即我们不知道假阴性的发生率。

PCR 测试需要带试剂的套件，并且需要临床实验室来处理试剂盒。
虽然可以迅速扩大试剂套件生产规模，但实验室处理能力不能很快增加。领先的临床实验室公司Quest和Labcore每天能为全美国处理1000个试剂盒，扩大实验室处理能力需要时间、建筑空间和设备、还要通过认证，很难在短期内建好。UCSF 和加州大学伯克利分校已将其研究实验室捐赠出来处理试剂盒，但每个实验室每天只能处理 20-40 个试剂盒，并且尚未获得临床认证。其他新的测试方法也在尝试中，但目前还没成熟，测试能力也都很小。

• 美国社会对这个疾病的冲击做好准备了吗？
医院正在增加收治能力， UCSF的帕纳苏斯校区在停车场搭起了帐篷，他们把病房改造成负压的，这是控制病毒所必需的。 他们正在考虑重新开放关闭的锡安山的设施。
关闭学校是最大的社会冲击之一，在关闭学校（特别是小学）之前，我们需要认真权衡得失，因为会有连锁反应。 如果小学生不上学，那么一些医院工作人员要照看子女而不能来上班，这降低了病人激增时医院的救治能力。

美国的公共卫生系统具有应对持续数周的短期疫情的能力，如脑膜炎的爆发。 但没有能力应对持续数月的疫情，必须找到其他解决办法。
【陆德注】：
此文中所说的Remdesivir“同情用药”，是指我们所称的“瑞德西韦”药物。现中美两国正在“中日友谊医院”等机构的科研人员在做临床实验。希望能及早研制成功！）

下面是英文版(https://www.dailykos.com/stories/2020/3/13/1927193/-UCSF-COVID-19-Panel-Notes)

I am attaching a more detailed set of notes from the UCSF panel referenced in Mark Sumner’s column from one of the audience members.  I urge everyone to spend some time on them.  Long, but worth it.

BioHub Panel on COVID-19

March 10, 2020

Panelists
Joe DeRisi:  UCSF’s top infectious disease researcher.  Co-president of ChanZuckerberg BioHub (a JV involving UCSF / Berkeley / Stanford).  Co-inventor of the chip used in SARS epidemic.
Emily Crawford:  COVID task force director.  Focused on diagnostics
Cristina Tato:   Rapid Response Director.  Immunologist.  
Patrick Ayescue:   Leading outbreak response and surveillance.  Epidemiologist.  
Chaz Langelier:   UCSF Infectious Disease doc
What’s below are essentially direct quotes from the panelists.  I bracketed the few things that are not quotes.

Top takeaways
At this point, we are past containment.  Containment is basically futile.  Our containment efforts won’t reduce the number who get infected in the US.  
Now we’re just trying to slow the spread, to help healthcare providers deal with the demand peak.  In other words, the goal of containment is to "flatten the curve", to lower the peak of the surge of demand that will hit healthcare providers.  And to buy time, in hopes a drug can be developed.
How many in the community already have the virus?  No one knows.
We are moving from containment to care.  
We in the US are currently where at where Italy was a week ago.  We see nothing to say we will be substantially different.
40-70% of the US population will be infected over the next 12-18 months.  After that level you can start to get herd immunity.  Unlike flu this is entirely novel to humans, so there is no latent immunity in the global population.
[We used their numbers to work out a guesstimate of deaths— indicating about 1.5 million Americans may die.  The panelists did not disagree with our estimate.  This compares to seasonal flu’s average of 50K Americans per year.  Assume 50% of US population, that’s 160M people infected.  With 1% mortality rate that's 1.6M Americans die over the next 12-18 months.]  
The fatality rate is in the range of 10X flu.
This assumes no drug is found effective and made available.
The death rate varies hugely by age.  Over age 80 the mortality rate could be 10-15%.  [See chart by age Signe found online, attached at bottom.]
Don’t know whether COVID-19 is seasonal but if is and subsides over the summer, it is likely to roar back in fall as the 1918 flu did
I can only tell you two things definitively.  Definitively it’s going to get worse before it gets better.  And we'll be dealing with this for the next year at least.  Our lives are going to look different for the next year.
What should we do now?  What are you doing for your family?
Appears one can be infectious before being symptomatic.  We don’t know how infectious before symptomatic, but know that highest level of virus prevalence coincides with symptoms.  We currently think folks are infectious 2 days before through 14 days after onset of symptoms (T-2 to T+14 onset).
How long does the virus last?
On surfaces, best guess is 4-20 hours depending on surface type (maybe a few days) but still no consensus on this
The virus is very susceptible to common anti-bacterial cleaning agents:  bleach, hydrogen peroxide, alcohol-based.
Avoid concerts, movies, crowded places.
We have cancelled business travel.  
Do the basic hygiene, eg hand washing and avoiding touching face.
Stockpile your critical prescription medications.  Many pharma supply chains run through China.  Pharma companies usually hold 2-3 months of raw materials, so may run out given the disruption in China’s manufacturing.
Pneumonia shot might be helpful.  Not preventative of COVID-19, but reduces your chance of being weakened, which makes COVID-19 more dangerous.
Get a flu shot next fall.  Not preventative of COVID-19, but reduces your chance of being weakened, which makes COVID-19 more dangerous.
We would say “Anyone over 60 stay at home unless it’s critical”.  CDC toyed with idea of saying anyone over 60 not travel on commercial airlines.
We at UCSF are moving our “at-risk” parents back from nursing homes, etc. to their own homes.  Then are not letting them out of the house.  The other members of the family are washing hands the moment they come in.
Three routes of infection
Hand to mouth / face
Aerosol transmission
Fecal oral route
What if someone is sick?
If someone gets sick, have them stay home and socially isolate.  There is very little you can do at a hospital that you couldn’t do at home.  Most cases are mild.  But if they are old or have lung or cardio-vascular problems, read on.
If someone gets quite sick who is old (70+) or with lung or cardio-vascular problems, take them to the ER.
There is no accepted treatment for COVID-19.  The hospital will give supportive care (eg IV fluids, oxygen) to help you stay alive while your body fights the disease.  ie to prevent sepsis.
If someone gets sick who is high risk (eg is both old and has lung/cardio-vascular problems), you can try to get them enrolled for “compassionate use" of Remdesivir, a drug that is in clinical trial at San Francisco General and UCSF, and in China.  Need to find a doc there in order to ask to enroll.  Remdesivir is an anti-viral from Gilead that showed effectiveness against MERS in primates and is being tried against COVID-19.  If the trials succeed it might be available for next winter as production scales up far faster for drugs than for vaccines.  [More I found online.]
Why is the fatality rate much higher for older adults?
Your immune system declines past age 50
Fatality rate tracks closely with “co-morbidity”, ie the presence of other conditions that compromise the patient’s hearth, especially respiratory or cardio-vascular illness.  These conditions are higher in older adults.  
Risk of pneumonia is higher in older adults.  
What about testing to know if someone has COVID-19?
Bottom line, there is not enough testing capacity to be broadly useful.  Here’s why.
Currently, there is no way to determine what a person has other than a PCR test.  No other test can yet distinguish "COVID-19 from flu or from the other dozen respiratory bugs that are circulating”.
A Polymerase Chain Reaction (PCR) test can detect COVID-19’s RNA.  However they still don’t have confidence in the test’s specificity, ie they don’t know the rate of false negatives.
The PCR test requires kits with reagents and requires clinical labs to process the kits.
While the kits are becoming available, the lab capacity is not growing.  
The leading clinical lab firms, Quest and Labcore have capacity to process 1000 kits per day.  For the nation.
Expanding processing capacity takes “time, space, and equipment.”  And certification.   ie it won’t happen soon.
UCSF and UCBerkeley have donated their research labs to process kits.  But each has capacity to process only 20-40 kits per day.  And are not clinically certified.
Novel test methods are on the horizon, but not here now and won’t be at any scale to be useful for the present danger.
How well is society preparing for the impact?
Local hospitals are adding capacity as we speak.  UCSF’s Parnassus campus has erected “triage tents” in a parking lot.  They have converted a ward to “negative pressure” which is needed to contain the virus.  They are considering re-opening the shuttered Mt Zion facility.
If COVID-19 affected children then we would be seeing mass departures of families from cities.  But thankfully now we know that kids are not affected.
School closures are one the biggest societal impacts.  We need to be thoughtful before we close schools, especially elementary schools because of the knock-on effects.  If elementary kids are not in school then some hospital staff can’t come to work, which decreases hospital capacity at a time of surging demand for hospital services.  
Public Health systems are prepared to deal with short-term outbreaks that last for weeks, like an outbreak of meningitis.  They do not have the capacity to sustain for outbreaks that last for months.  Other solutions will have to be found.
What will we do to handle behavior changes that can last for months?
Many employees will need to make accommodations for elderly parents and those with underlying conditions and immune-suppressed.
Kids home due to school closures
[Dr. DeRisi had to leave the meeting for a call with the governor’s office.  When he returned we asked what the call covered.]  The epidemiological models the state is using to track and trigger action.  The state is planning at what point they will take certain actions.  ie what will trigger an order to cease any gatherings of over 1000 people.  
Where do you find reliable news?
The John Hopkins Center for Health Security site.   Which posts daily updates.  The site says you can sign up to receive a daily newsletter on COVID-19 by email.  [I tried and the page times out due to high demand.  After three more tries I was successful in registering for the newsletter.]  
The New York Times is good on scientific accuracy.
Observations on China
Unlike during SARS, China’s scientists are publishing openly and accurately on COVID-19.  
While China’s early reports on incidence were clearly low, that seems to trace to their data management systems being overwhelmed, not to any bad intent.
Wuhan has 4.3 beds per thousand while US has 2.8 beds per thousand.  Wuhan built 2 additional hospitals in 2 weeks.  Even so, most patients were sent to gymnasiums to sleep on cots.
Early on no one had info on COVID-19.  So China reacted in a way unique modern history, except in wartime.  
Every few years there seems another:  SARS, Ebola, MERS, H1N1, COVID-19.  Growing strains of antibiotic resistant bacteria.  Are we in the twilight of a century of medicine’s great triumph over infectious disease?
"We’ve been in a back and forth battle against viruses for a million years."  
But it would sure help if every country would shut down their wet markets.  
As with many things, the worst impact of COVID-19 will likely be in the countries with the least resources, eg Africa.  See article on Wired magazine on sequencing of virus from Cambodia.