加州大學舊金山 BioHub 小組關於 COVID-19 的討論會小結，2020 年 3 月 10 日

與會者：

• 喬·德里西：UCSF的頂級傳染病研究員。 陳扎克伯格生物中心（涉及UCSF/伯克利/斯坦福的合資企業）聯席總裁。 在非典疫情中使用的芯片的共同發明者。
• 艾米莉·克勞福德：新肺特別工作組主任，診斷專家
• 克里斯蒂娜·塔托：快速反應總監， 免疫學家
• 帕特里克·艾斯庫：領導疫情應對和監測，流行病學家
• 查茲·蘭格利爾：UCSF傳染病醫生

下面基本上是小組成員發言原汁原味的記錄。 少數不是原話會寫在括號中。

• 主要觀點：

在目前時點，美國已經錯過了遏制期， 遏制基本上已是徒勞的了。 我們的遏制努力不會減少在美國感染的人數。
現在，我們只能努力減緩傳播速度，幫助醫生們應對需求高峰。 換句話說，遏制的目標是平緩曲線，以降低需求激增的峰值，減弱對醫院的衝擊程度。 並爭取時間，希望藥物可以儘快開發出來。
目前社區中有多少人已經感染了病毒？ 沒人知道，我們正在從遏制階段轉到醫護階段。

美國目前處於意大利一周前的時點， 我們沒有任何理由可以說我們將能避免發展到像意大利那樣。

在未來12-18個月中，40%-70%的美國人口將感染COVID-19。 達到這個水平後，你可以開始獲得一些抗體。 與流感不同，這病毒對人類是全新的，因此全球人口沒有潛在的免疫力。[貝克實驗室在3月1日晚餐上也告訴我感染率估計為30-70％]

[我們用這個的數字來估計死亡人數——表明大約150萬美國人可能會死亡，小組成員並不反對我們的估計。相比之下，季節性流感平均每年有5萬美國人死亡。 假設50%的美國人口，即1.6億人感染新肺, 在未來12-18個月中，160萬美國人將死亡，死亡率為1%。約10倍於流感死亡率。這個估計是基於未來沒有開發出有效治療藥物的假設。
死亡率因年齡而異， 80歲以上死亡率可能為10-15%。
我們不知道COVID-19是否是季節性的，但即使夏天能消退，它可能會像1918年的流感那樣在秋天又復發。

我只能明確地告訴你兩件事，一，在情況好轉之前情況肯定會變得更糟；二， 我們至少明年還會面對此病毒，明年我們的生活會和以前很不一樣。

• 我們現在該怎麼辦？ 你能為你的家人做什麼？我們知道在潛伏期也可能是有傳染性的，但不知道在症狀出現之前傳染性有多強，但症狀最強時病毒傳染性也最強。 我們目前認為，在症狀出現前2天到出現後14天（T-2至T+14），感染者具有傳染性。

病毒能在體外存活多長時間？在物體表面上，根據不同表面類型，目前認為能存活 4-20 小時（也可是能幾天），對此仍沒有共識。
該病毒非常容易被常見的抗菌清潔劑消滅：漂白劑、過氧化氫、酒精。

要避免去音樂會、電影院、任何擁擠的場所。我們已經取消了商務旅行。

要做好基本的衛生，如洗手和避免觸摸臉。

提前儲存好你的常用處方藥，許多連鎖藥店的供應鏈在中國，製藥公司通常儲備有2-3個月的原材料，因此，若中國製造業中斷，可能儲備會耗盡。

注射常規肺炎疫苗可能會有所幫助， 不預防COVID-19，但降低你身體變弱的機率，降低得COVID-19後惡化的可能性。

明年秋天請一定要接種流感疫苗，雖然不能預防COVID-19，但同樣能減少你身體變弱的機率，降低得COVID-19後惡化的可能性。

我們會建議任何60歲以上的人都呆在家裡，除非萬不得已請不要出門。 美國CDC內部也一直在在討論是否應規定60歲以上的人不得乘坐商業航空飛機出行。

UCSF同仁們正在將自己的高齡父母從養老院等遷回到自己的家裡，不讓他們走出家門，家裡的其他成員一進家門必須先洗手。

新肺病毒感染的三條途徑：手到嘴/臉；唾沫/氣溶膠傳播；糞便到嘴的傳播。

• 如果有人生病怎麼辦？如果有人生病，讓他們呆在家裡並避免與任何人接觸。 任何在醫院裡能做到事， 你在家裡也都能做到。 大多數人病狀是溫和的，但是，如果他們病情變重，或者是70歲以上的老年人，或本來就有肺或心血管問題，必須帶他們去看急診。
迄今為止，COVID-19沒有辦法治療。 醫院能提供的只是支持性護理（如靜脈輸液、吸氧氣），幫助你維持生命，靠自己的免疫力戰勝病毒，預防敗血症。
如果病人到了危重症期，你可以嘗試讓他們申請服用Remdesivir作為“同情用藥”，該藥物目前同時在舊金山總醫院、UCSF、和中國做臨床試驗。 你需要聯繫在那兩個醫院裡的醫生，申請加入臨床試驗。 Remdesivir 是一種來自 Gilead 的抗病毒藥物，在靈長類動物中表現出對中東呼吸綜合徵的有效性，目前正在做針對 COVID-19 的人體試驗。 如果試驗成功，明年冬天可能上市，因為擴大藥物的生產規模比開發疫苗要快得多。

為什麼老年人的死亡率要高得多？你的免疫系統在50歲以後會下降，
死亡率與病人之前是否有基礎疾病密切相關，尤其是呼吸道或心肺疾病。 這些基礎疾病在老年人中概率較高，老年人患肺炎的風險也較高。

• 能否對所有人都做 COVID-19 檢測？不現實，因為沒有足夠的測試能力。 原因如下，目前除了 PCR 測試之外，沒有其他測試可以區分COVID-19與流感或其他十幾個正在傳播的呼吸道病菌。聚合酶鏈反應 （PCR） 測試可以檢測 COVID-19 的 RNA。 然而，我們仍然對測試的準確性沒有信心，即我們不知道假陰性的發生率。

PCR 測試需要帶試劑的套件，並且需要臨床實驗室來處理試劑盒。
雖然可以迅速擴大試劑套件生產規模，但實驗室處理能力不能很快增加。領先的臨床實驗室公司Quest和Labcore每天能為全美國處理1000個試劑盒，擴大實驗室處理能力需要時間、建築空間和設備、還要通過認證，很難在短期內建好。UCSF 和加州大學伯克利分校已將其研究實驗室捐贈出來處理試劑盒，但每個實驗室每天只能處理 20-40 個試劑盒，並且尚未獲得臨床認證。其他新的測試方法也在嘗試中，但目前還沒成熟，測試能力也都很小。

• 美國社會對這個疾病的衝擊做好準備了嗎？
醫院正在增加收治能力， UCSF的帕納蘇斯校區在停車場搭起了帳篷，他們把病房改造成負壓的，這是控制病毒所必需的。 他們正在考慮重新開放關閉的錫安山的設施。
關閉學校是最大的社會衝擊之一，在關閉學校（特別是小學）之前，我們需要認真權衡得失，因為會有連鎖反應。 如果小學生不上學，那麼一些醫院工作人員要照看子女而不能來上班，這降低了病人激增時醫院的救治能力。

美國的公共衛生系統具有應對持續數周的短期疫情的能力，如腦膜炎的爆發。 但沒有能力應對持續數月的疫情，必須找到其他解決辦法。
【陸德注】：
此文中所說的Remdesivir“同情用藥”，是指我們所稱的“瑞德西韋”藥物。現中美兩國正在“中日友誼醫院”等機構的科研人員在做臨床實驗。希望能及早研製成功！）

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.