LessWrong Coronavirus Agenda

post by Elizabeth (pktechgirl) · 2020-03-18T04:48:56.769Z · LW · GW · 21 comments

This is a question post.


  Who are we trying to help?
  How Are We Doing That?
  Spotlight Questions
    is the impact of varying initial viral load of COVID-19?
  The Full Agenda
    Ben Ab

I’ve gone through a lot of introductions to this post but maybe this is the most honest one:

I am scared. Quite scared, actually. My chances of catching COVID-19 are actually quite low, and my chances of surviving it if I do are quite high, and I’m still scared. What if I get into a car accident and have to go to the ER? Will they have a bed for me? Will I leave with coronavirus? What are my pregnant friends going to do? What is anyone over 70 going to do?

My goal, and the goal of everyone on the LW staff, and I assume most everyone who’s participated in all the coronavirus threads, has been to figure out what is happening and what we can do about it. We’ve already done a lot. Posts like Seeing the Smoke [LW · GW] got coronavirus on people’s radar faster than it otherwise would have been, aided by the numerous modeling threads [LW · GW] backing it up. The Quarantine Preparations [LW · GW] thread gave people a starting place to act from. The Justified Practical Advice [LW · GW] (summary [LW · GW]) thread let us share our expertise, in ways that led to concrete behavioral changes [LW · GW]. More recently we examined asymptomatic transmission [LW · GW]. I’ve had a legit, reasonably high ranking government official say they look at us to see where everyone else will be in weeks.

This is currently the LessWrong team’s top priority, and they’ve done a number of things over the recent weeks to facilitate research and action on coronavirus, including hiring me to be a point person on it. To facilitate as much progress as possible over the coming weeks, habryka and I have compiled a list of what we consider the most important questions in fighting COVID, and are asking anyone with the skill to help us answer them.

That list is at the end of this post [LW · GW]. But first, what is the overall plan here?

Who are we trying to help?

We have three broad categories of potential beneficiaries in mind:

  1. Individuals making choices for themselves and their loved ones, who need accurate information about the current threat level and how to lower it with existing tech.

  2. Individuals creating the tools for the people above, meaning anything from noticing that copper tape is anti-viral to creating plans for DIY non-invasive ventilators, who need accurate information about how COVID-19 operates and where the current gaps and bottlenecks are. We’d like to help people in this group get volunteers and money when appropriate.

  3. Organizations and institutions making decisions that affect many people, who need all the information the previous two groups do, plus more to know what the effect of their decisions will be.

How Are We Doing That?

I am managing a Coronavirus Agenda, composed of what myself and habryka think are the most important coronavirus-related questions to answer (think we missed some? Please comment). But the full agenda is kind of overwhelming, and there are benefits to coordinating multiple people around the same question, so every so often I’ll pull out Spotlight Questions to generate a critical mass of attention around the most critical questions. I want to say “every so often” will be once a week, but I feel like those kinds of commitments are for situations where I know within an order of magnitude how many people are going to die in that week. I will spotlight as often as seems merited by the situation at the time.

If your eye is caught by a question on the agenda that’s not currently spotlighted, of course pursue your interest. That’s the point of sharing the whole agenda. And if you think the agenda is missing something important, of course pursue that, and add a comment explaining it if you have time so I can add it.

Without further adieu, the spotlight questions...

Spotlight Questions

What is the impact of varying initial viral load of COVID-19? [LW · GW]

The hypothesis that lower initial viral load leads to better outcomes, and might be worth pursuing deliberately, is a central assumption is Zvi’s post Taking Initial Viral Load Seriously [LW · GW]. Is it true?

Economics Questions

The Full Agenda

These are the questions about coronavirus I and habryka (and in the future, commenters on this post) most want answered. We’ll be nudging LessWrong to pursue them over the coming weeks, but for clarity wanted to share the whole thing as a package.

Some of these someone has already answered, or attempted to answer, in which case I’ve linked to the (attempted) answers. I’ll continue to update as more answers come in:


answer by Davidmanheim · 2020-03-18T08:43:05.585Z · LW(p) · GW(p)

Build new vaccine production facilities.

It seems clear that focusing on the vaccine pipeline will become critical in the coming months, and we need to get ahead of it ASAP. Currently, the plan is to wait for safety approvals, then start manufacturing. That will obviously change - when we have moderate confidence that a vaccine is effective, we will want to start manufacturing, but there are several candidates, and too little productive capacity to make large quantities of several different vaccines. In fact, there is too little productive capacity to make any one vaccine in global quantities without stopping manufacture of other vaccines.

Vaccine manufacturing is very complex, and needs specialized facilities with clean rooms, sterilization facilities, very specific types of HVAC, etc. Building these is capital intensive, and there has been too little capacity for quite a while, leading to occasional vaccine shortages. I think we should be pushing large companies and governments to figure out how to create greater production capacity for vaccines. This is a global public good anyways. There are a few economic concerns for companies doing this, but right now is the perfect time to get government subsidies for such capital intensive projects.

comment by ChristianKl · 2020-03-18T22:05:37.464Z · LW(p) · GW(p)

How specific are vaccine production facilities to individual vaccines? To what extend can we build them before knowing which of our vaccines will succeed in the clinical trials?

Replies from: Davidmanheim
comment by Davidmanheim · 2020-03-19T10:52:16.838Z · LW(p) · GW(p)

From what I understand, we use eggs to incubate and clean-rooms to produce the final product for all of them, and I understood that vaccine producers can switch between which ones they make, with a couple month delay for incubation and switching over.

Replies from: brianwang712, Spiracular
comment by brianwang712 · 2020-03-25T12:27:20.064Z · LW(p) · GW(p)

FWIW, eggs are actually specific to influenza vaccine manufacturing. Page 3 of this book chapter ( https://reader.elsevier.com/reader/sd/pii/B9780128021743000059?token=F492A74B3C4545B108379536769CF93D7F1DB89321DADE859256496F5D85CB6259372D34376809219BBBE2FFFDEF25FB ) has a really nice table showing the production process of a number of different vaccines - they are all very different from one another. This is why we need new vaccine platform technologies - i.e., tech that can be used to produce multiple different vaccines. mRNA vaccines would fall into this category and is a reason why Moderna's mRNA vaccine candidate for COVID-19 would be so exciting if it works.

Replies from: Davidmanheim
comment by Davidmanheim · 2020-03-26T08:22:19.525Z · LW(p) · GW(p)

That's not quite right. I can't get to that book right now, but measles and mumps for MMR are also done in Chicken eggs, IIRC, as are Herpes and Poxviruses, while cell lines and other media can be used to grow other viruses - but the remainder of the facilities are still similar, and can be repurposed.

But I agree that we do need new platform technologies.

Replies from: brianwang712
comment by brianwang712 · 2020-03-26T12:34:58.708Z · LW(p) · GW(p)

Hmm, well that book chapter claims measles and mumps vaccines are produced in chick embryo cell culture, which is different from propagation on chicken eggs. My quick Googling revealed that we don't have a licensed herpes vaccine, and that while there might be one or two smallpox vaccines that are produced in chicken eggs, many are done in cell culture.

You might be right about the broader (and more important) point about ease of facilities repurposing, however - I don't know enough to say, although the table in the book chapter makes me doubtful, given that pretty much all steps in the manufacturing process (production, isolation, purification, formulation) seem unique to each vaccine.

Replies from: leggi
comment by leggi · 2020-03-26T12:54:15.423Z · LW(p) · GW(p)

yellow fever vaccine is one that springs to mind that also uses eggs in production

The yellow fever vaccine is made by growing yellow fever virus in mouse embryo cells and in chick embryo cells. The final preparation of the vaccine is made in eggs. Growing yellow fever virus in mouse and chick cells over and over again weakened it. Therefore, when this "live, weakened" virus is injected, a protective immune response develops without causing illness. SOURCE
Replies from: brianwang712
comment by brianwang712 · 2020-03-26T13:23:42.095Z · LW(p) · GW(p)

Good to know, thanks!

comment by Spiracular · 2020-03-19T20:19:38.613Z · LW(p) · GW(p)

I've heard that the eggs used are special, more sterile than usual (you don't want the chicken to have other diseases now, do you?), and usually require ordering at least a year in advance.

(Came up when I was researching flu-vaccine development.)

Some other vaccine production methods involve cell cultures, but the output of different cell cultures is pretty wildly variable and the preferred cell culture is different depending on the specific virus. This is probably a more expensive means of production. You may be able to scale it up faster and with less early prep-work, however.

Fair warning: While there have been coronavirus vaccines that have just worked, there have also been a lot of them that seemed to make the course of infection worse, probably due to antibody-dependent enhancement or a similar phenomenon. The set that were somewhat challenging to develop vaccines for seemed to include SARS-1. The lengthy process of animal testing would probably spot this, but it may make getting a reliable vaccine slower and harder than it would be with viruses that don't have this problem.

Replies from: ChristianKl
comment by ChristianKl · 2020-03-19T21:10:21.044Z · LW(p) · GW(p)

Why do you need the eggs in the first place? Couldn't you just feed animo acids that you get when you electrolyse proteins instead of having the proteins from the eggs?

Replies from: Spiracular, Davidmanheim
comment by Spiracular · 2020-03-20T09:18:46.646Z · LW(p) · GW(p)

...I'm confused about what method you're even trying to gesture at.

They're viruses*, they need a full set of environmentally-provided cell machinery to replicate or produce proteins: ribosomes, transcription machinery (ex: t-RNAs), ATP, the works. They need cells, so you'd need need at least a cell culture. All of biology has heavily optimized protein assembly lines, you're not going to beat it acellularly.

The cells near the outside of an egg are probably used because they're an elegant and self-contained little solution to sterilization (against everything but your virus) and the quality-control problems you'd have to contend with otherwise. It's not really about the protein content, mostly.

(Cell culture is probably more expensive than eggs because 1) bioreactors are kinda expensive, 2) bioreactors are a bit of a pain to maintain, and sterilization is hard, two problems that using an egg pretty neatly solves, and 3) which cell culture will work best is surprisingly hard to predict, you basically have to test it experimentally.)

* Well, technically it's weakened viruses, or single-gene plasmids, or something similar. The need for cells still holds either way.

Replies from: ChristianKl
comment by ChristianKl · 2020-03-20T13:10:21.866Z · LW(p) · GW(p)
...I'm confused about what method you're even trying to gesture at.

Eggs do have a lot of ovalbumin where it's not really desireable for that to end up in your final vaccine but I don't think this is a discussion to have at a point where our key issue is scaling up vaccine production.

If you have to order the steralized eggs a year in advance, and we want our COVID-19 vaccine before a year is over, that suggests to me that we also have other problems.

If I understand the work Moderna is doing for their COVID-19 vaccine and read the paper where they describe their framework, it seems to me that they use human cell lines:

The modified mRNA was synthesized enzymatically and packaged into lipid nanoparticles (LNPs). Incubation of LNPs containing IgE signal-prM-E mRNA (IgEsig-prM-E) with 293T or HeLa cells resulted in efficient expression and secretion of ∼30 nm SVPs

Just like Moderna, CureVac which is another of the companies that want to produce a COVID-19 vaccine also focuses on delievering mRNA and not viruses. I didn't immediately find information about how CureVac gets their mRNA but it wouldn't surprise me if they also don't use eggs.

Replies from: Spiracular
comment by Spiracular · 2020-03-20T22:47:36.460Z · LW(p) · GW(p)

Whoah, lipid-coated mRNA vaccines, not as an intermediate step but as the actual delivery method? That's actually new to me! Sounds like it's mRNAs coding for some subset of the viral proteins, which probably get assembled into proteins in your cells and then get used as something for antibodies to respond against. mRNAs should then just degrade themselves with time.

I have no idea what the most efficient method for producing those is; I am very used to vaccines being protein-based. This probably is in the realm where it's simple enough that modifying PCR-protocols to produce RNA instead might actually work reasonably well, although RNA is generally more fragile and error-prone and that could be a problem.

You'd be using nucleotides, not amino acids, but mRNA from DNA is a short-enough assembly line that you might not need cells to do it.

(Protein production has a lot of dependencies. mRNA transcription should basically just require your DNA of interest, nucleotides (x4), and a transcriptase protein. Maybe add a transcription factor or two.)

HeLa definitely is a human cell line (although that was for Ebola, they may end up using a different cell line). That's good, that probably scales up easily.

Replies from: ChristianKl
comment by ChristianKl · 2020-03-21T14:05:44.980Z · LW(p) · GW(p)

From last year: From CEPI awards US$ 34M contract to CureVac to advance The RNA Printer™

“Disease X could emerge suddenly and have deadly consquences—we’ve seen this happen with Ebola, MERS coronavirus, Zika, and countless other diseases. That’s why we’re striving to develop rapid-response vaccine platforms—like CureVac’s mRNA technology—to defend against these unknown pathogens. CEPI has now established partnership agreements totaling more than $50 million in three such platforms”.

It seems that the third mRNA vaccine company is BioNTech.

It seems that Johnson & Johnson is still developing a vaccine the traditional way:

Johnson & Johnson appears to be using a more traditional approach in which the virus is inactivated so it can't replicate but can still express viral proteins. The approach takes a little longer for both the development and manufacturing scale-up steps. On the plus side, Johnson & Johnson's slow-but-steady approach could create a vaccine with a better immune response.

There's a forth company with Inovio Pharm that also develops a COVID-19 vaccine. It's technology is based on delievering DNA based.

I have the impression that the mRNA/DNA ways of vaccine delievery allow for faster development of a vaccine then the old fashioned protein based way.

comment by Davidmanheim · 2020-03-20T07:38:37.393Z · LW(p) · GW(p)

At scale? Not easily - eggs are cheaper, more effective, and easier to deal with.

comment by Matthew Lewis (matthew-lewis) · 2020-03-30T04:37:40.659Z · LW(p) · GW(p)

The peer-reviewed literature has several papers talking about GI symptoms of COVID19, and there are several GI cells that are ACE2+ that are plausible targets. What I am wondering is the following a potential vaccine strategy?

innoculate with live strain in GI tract to avoid respiratory infection

Replies from: Davidmanheim, jmh
comment by Davidmanheim · 2020-03-31T07:14:22.518Z · LW(p) · GW(p)

Interesting - I'd ask Robin Hanson if that fits with his variolation suggestion.

comment by jmh · 2020-04-01T17:57:22.849Z · LW(p) · GW(p)

Related to that observation I have wondered, but never posted/asked, if how one gets infected might influence severity as well. If I touch a contaminated surface and then rub my eye or then eat a sandwich without washing my hand is that more likely to end up somewhere other than my upper and lower respiratory systems?

comment by ryan_b · 2020-03-19T17:28:07.021Z · LW(p) · GW(p)

If the same type of facility works for almost every kind of vaccine, do we think there would be interest in constructing the facilities as a speculative venture? Consider:

1. The economy is in chaos and may remain so, which I expect to produce unusually affordable access to design firms, construction crews, raw materials, and land.

2. There will be a strong incentive for regulators/inspectors to move with best speed, and the current administration at least in the US has a track record of being friendly to shortcuts.

3. If the facilities are already built, this allows a limit to the risk the companies producing the vaccines need to absorb in order to increase supply.

4. We could squeeze out unscrupulous opportunists.

answer by landfish · 2020-03-18T20:37:29.656Z · LW(p) · GW(p)

Contact Tracing at Scale!

One thing we need, that the Less Wrong community could likely help with, is contact tracing capability at scale. I know of one such project in the US - https://www.covid-watch.org/ The Covid Watch project, based out of Stanford.

I think the major tech companies need to set up and throw a ton of engineering and design resources at contact tracing efforts. They currently control the software supply chain to most mobile devices on earth, and thus are ideally placed to help track the spread of infections.

The more testing we have, the more effective contact tracing will be, so this needs to be paired with an increase in testing world-wide, as previously mentioned in the thread.

comment by landfish (jeff-ladish) · 2020-03-19T00:21:23.091Z · LW(p) · GW(p)

https://www.lesswrong.com/posts/fxfsc4SWKfpnDHY97/landfish-lab?commentId=4ftZGNxtNRiwgXTbf [LW(p) · GW(p)]

My collection of links to the projects I know about in this space and some news coverage of them.

comment by ChristianKl · 2020-03-23T17:00:37.523Z · LW(p) · GW(p)

There might be benefits to having an privacy sensitive open-source solution like the one proposed in Covid-Watch over a Google/Facebook solution.

answer by romeostevensit · 2020-03-18T06:55:01.080Z · LW(p) · GW(p)

I would strongly encourage people to try brainstorming some questions. Even if you don't come up with anything directly useful you might jog someone else's creativity. Remember to go for quantity over quality on your first pass.

Epidemiology questions that, while we probably can't do much about, would be useful to try to ad hoc model given how bad official info has been so far:

Are estimates of doubling time off from bad modeling of rapid test ramping making it seem faster than it is?

What is actual hospital elasticity? Is there an existing gathering of data on this from previous disasters?

How long do human trials need to be before they are rolled out to the majority of the population? Just to the extremely vulnerable? What is the gears level model here?

What granularity of travel restriction makes the most sense? In general, how can cities and counties act knowing that federal response may (will continue to be) be too slow?

Which physical objects have longer supply chains and thus can be expected to be less robust to disruption?

What mental health problems can we expect to spike hard in the next 1-6 months given people feeling shut in and helpless?

What are the most predictable second order disasters?

Does moral hazard show up anywhere here?

What's most likely to be ignored during this? Civil liberties? Already seen discussion of that. What's even more ignored?

I've seen people from a Stanford lab asking on facebook about being put in touch with someone from an MIT lab. How can lab cross talk increase?

If UV 210nm turns out to be effective, how can you build your own flashlight/lightsaber (from the virus' perspective) out of off the shelf parts?

Which continuing failures of the FDA are highly predictable? What can be done to mitigate that expectation at the hospital and lab level?

How can models take into account reference classes. e.g. Many models are averaging naively which means essentially all the data points are from the least controlled regions with the widest error bars.

comment by Eli Tyre (elityre) · 2020-03-18T22:31:52.926Z · LW(p) · GW(p)
I would strongly encourage people to try brainstorming some questions. Even if you don't come up with anything directly useful you might jog someone else's creativity. Remember to go for quantity over quality on your first pass.

Thanks Romeo.

Setting a 5 minute timer:

  • How will this effect markets / supply chains etc, assuming it lasts for different lengths of time.
  • How likely are various containment interventions by governments?
  • How does de-escalating quarantine / lock-down in countries that have instituted those work? Is there a chance the the virus will bounce back after de-escalation?
  • How long do I have to wait before interacting with an object / location in order to make sure it is safe? (eg could I rent an airbnb, or a rental car, several days in advance, and then use it without risk of catching the virus?)
  • How bad is this really for people in my age group? I would love to have information from people I know, who catch it.

Pushing to get to a total of 10 items:

  • How much health risk is there to social isolation?
  • Do I still need to have extreme hand-washing / disinfectant procedures if I'm not leaving the house?
  • What could be done to help emergency workers and other parts of the medical system not get sick?
  • Are there resources on maintaining a balanced diet of non-perishable foods?
  • What skills should I be rapidly acquiring to be most useful to this whole situation?

And one more.

  • Am I better off if I drive to some cabin out in the boonies?
comment by romeostevensit · 2020-03-19T03:59:45.038Z · LW(p) · GW(p)

The requirements on multiplying ventilator use through sharing is

1. Equal tube lengths.
2. Equal lung capacity.
3. Equal lung resistance.
4. Same patient weight (approx)
the question is can any of these requirements be broken though clever use of 3d printed valves or other JIT solutions?

comment by jmh · 2020-03-18T20:29:32.094Z · LW(p) · GW(p)
What is actual hospital elasticity? Is there an existing gathering of data on this from previous disasters?

No answer here but a subquestion might be what are the essentials for an effective "hospital bed" for a COVID-19 patient? What are the binding/constraining elements? We know ventilators for critical cases are one. Others? What about those for serious versus critical -- if we can treat serious cases well but in some makeshift hospital room (say an empty hotel) does that help us limit the demand for ICU space?

Second thought here. You have investors like Ackman suggesting a slow bleed process may well kill hotel owners. Is there an opportunity to address two things as once? If government (and insurance companies) can support quarantining and treating less serious cases in hotels then the industry gets some relief and society perhaps gets both better allocation of medical resources and improved quarantines.

answer by moridinamael · 2020-03-18T12:26:48.380Z · LW(p) · GW(p)

Scaling up testing seems to be critical. With easy, fast and ubiquitous testing, huge numbers of individuals could be tested as a matter of routine, and infected people could begin self-isolating before showing symptoms. With truly adequate testing policies, the goal of true "containment" could potentially be achieved, without the need to resort to complete economic lockdown, which causes its own devastating consequences in the long term.

Cheap, fast, free testing, possibly with an incentive to get tested regularly even if you don't feel sick, could move us beyond flattening the curve and into actual containment.

Even a test with relatively poor accuracy helps, in terms of flattening the curve, provided it is widely distributed.

So I might phrase this as a set of questions:

  • Should I get tested, if testing is available?
  • How do we best institute wide-scale testing?
  • How do we most quickly enact wide-scale testing?
comment by John_Maxwell (John_Maxwell_IV) · 2020-03-24T05:22:46.982Z · LW(p) · GW(p)

Relevant thread: https://www.lesswrong.com/posts/pjLgE2efAozz82JmR/sars-cov-2-pool-testing-algorithm-puzzle [LW · GW]

I'd love to work on this if someone can put me in contact with a medical professional who understands how these tests work.

Replies from: ChristianKl
comment by ChristianKl · 2020-03-24T07:52:46.463Z · LW(p) · GW(p)

Whenever you ask people to create a contact it would make sense to be explicit about why the contact would be valuable, and what good will come out of it.

Replies from: John_Maxwell_IV
comment by John_Maxwell (John_Maxwell_IV) · 2020-03-24T23:20:23.318Z · LW(p) · GW(p)

I want to develop a web app that will make group testing fast and easy. This problem happens to relate closely to my machine learning research interests, and I have an algorithm in mind that I'm excited about. However, the first step to developing software is always to talk to potential users and understand their needs in order to make sure your software will actually solve them. You can share my linkedin profile if you think that will help.

answer by ioannes (ioannes_shade) · 2020-03-19T18:11:26.485Z · LW(p) · GW(p)

Why doesn't Japan have a huge outbreak already? (924 reported cases today, according to the Johns Hopkins tracker): https://www.bloomberg.com/news/articles/2020-03-19/a-coronavirus-explosion-was-expected-in-japan-where-is-it

Why does India have so few cases? (160 reported cases today): https://www.weforum.org/agenda/2020/03/quarantine-india-covid-19-coronavirus/

answer by ioannes (ioannes_shade) · 2020-03-20T00:39:51.174Z · LW(p) · GW(p)

For each country – what proportion of newly reported cases comes from ramping up testing, and what proportion comes from newly infected people?

answer by ioannes (ioannes_shade) · 2020-03-21T19:12:22.186Z · LW(p) · GW(p)

Will the economic impact of coronavirus be inflationary or deflationary on net? (for USD)

answer by ChristianKl · 2020-03-19T16:23:59.993Z · LW(p) · GW(p)

It would be great to have a list with the current teams that are working on a COVID-19 vaccine. Is such a list out there or otherwise, does someone want to create one?

answer by ioannes (ioannes_shade) · 2020-03-20T00:42:43.903Z · LW(p) · GW(p)

Why haven't we ever created a vaccine for a coronavirus before?

Is coronavirus vaccine development more limited by need for technological innovation or economic incentive?

comment by Elizabeth (pktechgirl) · 2020-03-20T01:04:19.098Z · LW(p) · GW(p)

There was a twitter thread I didn't save that said:

1. we have vaccines for cat and dog CVs

2. Human CVs are unrewarding to vaccinate against because they only cause 30% of colds, so you can only advertise a reduction, not total prevention, of colds.

Replies from: leggi
comment by leggi · 2020-03-20T07:27:10.330Z · LW(p) · GW(p)

Same virus family. Different pathogenesis and shouldn't be directly compared but more for information:

There are vaccines for coronavirus for dogs and cats. They are not commonly used for multiple reasons.

The main species that get vaccinated are cattle.

Bovine coronavirus (BCoV) is an important livestock pathogen with a high prevalence worldwide. The virus causes respiratory disease and diarrhea in calves and winter dysentery in adult cattle.

Bovine coronavirus disease info.

Vaccine methods:

  • pregnant cows (to create antibodies to pass immunity to calves via colostrum) info on a product available. (multi-virus vaccine)
  • intranasal (IN) vaccination of calves with a modified live BCoV

(It's been years since I've worked with cattle but don't think the situation has changed)

answer by ioannes (ioannes_shade) · 2020-03-31T19:34:00.584Z · LW(p) · GW(p)

Does hydroxychloroquine + azithromycin effectively treat COVID-19?

See Gautret et al. 2020, a small trial of this (not randomized) that found a big effect.

comment by ioannes (ioannes_shade) · 2020-03-31T21:15:40.805Z · LW(p) · GW(p)

I looked into this a bit with a friend who's an MD, and it turns out that this paper isn't very good.

Study not randomized, groups not balanced by disease severity, several treatment-group patients excluded from the data after trial started because they got worse (some went to ICU; one died).

From p. 10 of the paper:

We enrolled 36 out of 42 patients meeting the inclusion criteria in this study that had at least six days of follow-up at the time of the present analysis. A total of 26 patients received hydroxychloroquine and 16 were control patients.
Six hydroxychloroquine-treated patients were lost in follow-up during the survey because of early cessation of treatment. Reasons are as follows: three patients were transferred to intensive care unit, including one transferred on day2 post-inclusion who was PCR-positive on day1, one transferred on day3 post-inclusion who was PCR-positive on days1-2 and one transferred on day4 post-inclusion who was PCR-positive on day1 and day3; one patient died on day3 post inclusion and was PCR-negative on day2; one patient decided to leave the hospital on day3 post-inclusion and was PCR-negative on days1-2; finally, one patient stopped the treatment on day3 post-inclusion because of nausea and was PCR-positive on days1-2-3.
The results presented here are therefore those of 36 patients (20 hydroxychloroquine-treated patients and 16 control patients). None of the control patients was lost in follow-up.
Replies from: CellBioGuy
comment by CellBioGuy · 2020-04-02T18:21:04.411Z · LW(p) · GW(p)

That paper is indeed a piece of crap.

This being said, there is other preliminary data from Asia that chloroquine and hydroxychloroquine could hasten recovery, and there were multiple biochemical reasons to suspect it could help which are the reasons it was being used in the first place. I would call the French studies nearly useless to determine actual efficacy, but I am still fairly optimistic they will have at least some positive effect.

answer by Ben Ab · 2020-03-25T21:10:51.079Z · LW(p) · GW(p)

To Address the Problem: “How do I convince others to act?”

By now it seems clear that social distancing and shelter-in-place protocols are the most effective for reducing the spread of infection. I don’t know about other regions, but compliance in the US is unfortunately low. If increasing compliance is desirable, even when balanced against economic concerns, how do we encourage it?

Part of the problem is that people have to seek out information to become informed. Time and energy have to be invested for a person to figure out how important it is to stay home, and what sources of information are reliable.

Proposed Solution: Hospitals and medical groups should write letters to their entire mailing list pleading with people to stay home if possible. A message from your doctor’s office is far more persuasive than a general government announcement or news report. It’s local, personal, and credible. Everyone opens an email from their doctor.

Medical providers can explain the staff and resource shortages they face. They can explain that if everyone stays off the road as much as possible, this reduces accidents and frees up first-responders and scarce emergency room capacity (how significant would this be?). They can encourage a moratorium on other risky activities like extreme sports, even though those don’t violate social distancing rules (how significant would this be?).

This proposal is virtually costless, near effortless, can be implemented immediately, and would hopefully be effective.

Is it worthwhile to focus on getting medical providers to do this? If so, how do we reach out to them and maximize the number who do it ASAP?

answer by brook · 2020-03-22T20:38:29.208Z · LW(p) · GW(p)

What sources are governments using for decision-making?

The biggest impacts seem to me to be via influencing government. The UK government, for instance, is still very reticent to enforce widespread testing or mandatory quarantine. Their 'quarantine guidance' for households with symptoms looks like this, which seems patently foolish for a number of reasons.

Influencing governments' decision making is high-impact and potentially tractable via getting modelling and trial data to them. The UK Government publish their 'scientific basis for decision making' but it appears to be weeks out of date and unreferenced.

With that in mind, how do we get better decision-making information into government? What theory of change can we find for influencing policy makers? I believe this should be primarily targeted towards larger organisations and researchers who can have more direct influence, but may be useful for individuals as well.

comment by ChristianKl · 2020-03-23T12:37:07.766Z · LW(p) · GW(p)

Sir Patrick Vallance seems to be the key figure behind the UK policy. The guy was a professor of medicine in the past and who heads the Government Office for Science. Their policy is likely much more driven by modeling then the policy of other countries where the policies are decided by politicians instead of people with that kind of credentials.

To the extend that they have data on that page that's weeks out of date it's likely because the page has little to do with their actual decision making processes.

Vallance might still be wrong, but I think it's wrong to model him as being simply misinformed.


Comments sorted by top scores.

comment by Elizabeth (pktechgirl) · 2020-04-21T01:25:00.285Z · LW(p) · GW(p)

Hey everyone who is following this closely- I've been sprinting madly for the last six weeks and hit my limit. You can expect a retrospective post and perhaps a phase 2 agenda in the next few weeks, but for now I am resting.

Replies from: pktechgirl
comment by Elizabeth (pktechgirl) · 2020-06-17T20:17:55.266Z · LW(p) · GW(p)

Welp, I did not make that deadline. Unfortunately the conditions that led me and the LW team to miss that deadline- high opportunity costs- are not likely to change soon, so instead of holding out for perfection I'm just going to share a couple of thoughts.

I was brought on to lead covid research efforts at LW as an experiment. The hope was that there was significant untapped research capacity, which could be unlocked by providing some structure (hence the research agenda [LW · GW]). The structure was not only supposed to give people a sense of what would be useful to research, but reassurance that their research would actually be used, and social reinforcement. This mostly did not pan out- I think I did useful research during the time in question, I think other people produced useful research during that time, but questions I asked tended to be answered by only me.

The experiment was well worth running, and the team got a lot of information on infrastructure useful to support coordinated research (most notably it led to some reworks of Questions). But after 6 weeks it was not achieving its stated goal and had not found something clearly high value to pivot to, so I called it.

comment by Adam Scholl (adam_scholl) · 2020-03-19T01:02:55.640Z · LW(p) · GW(p)

I'm currently working with Kyle Scott and Anna Salamon on an estimate of deaths due to hospital overflow (lack of access to oxygen, mechanical ventilation, ICU beds), which we'll hopefully post in the next few days. The post will review evidence about basic epidemiological parameters.

Replies from: habryka4
comment by habryka (habryka4) · 2020-03-19T01:08:33.044Z · LW(p) · GW(p)

Great, looking forward to the post!

Replies from: adam_scholl
comment by Adam Scholl (adam_scholl) · 2020-03-22T20:24:53.745Z · LW(p) · GW(p)

Update: We decided not to finish this post, since the points we wished to convey have now mostly been covered well elsewhere. But Kyle may still write up his notes about the epidemiological parameters at some point.

Replies from: habryka4
comment by habryka (habryka4) · 2020-03-22T20:40:02.510Z · LW(p) · GW(p)

Alas. Could you briefly link to the other places that have conveyed the ideas sufficiently well for your tastes? 

Replies from: adam_scholl
comment by Adam Scholl (adam_scholl) · 2020-03-25T00:16:32.841Z · LW(p) · GW(p)

I wouldn't describe any posts I've seen as conveying the idea sufficiently well for my taste, but would describe some—like this NY Times piece—as adequately conveying the most decision-relevant points.

When I started writing, there was almost no discussion online (aside from Wei Dai's comment here [LW(p) · GW(p)], and the posts it links to) about what factors might prove limiting for the provision of hospital care, or about the degree to which those limits might be exceeded. By the time I called off the project, the US President and ~every major newspaper were talking about it. I think this is great—I much prefer a world where this knowledge is widespread. But given how fast COVID-related discourse was evolving, I think I erred in trying to make loads of points in a single huge post, rather than publishing it in pieces as they became ready.

There is one potentially decision-relevant point that I hoped to make, that I still haven't seen discussed elsewhere: there may be two relevant hospital overflow thresholds. The ICU bed threshold and the ventilator threshold are fairly low; given our current expected supply in a crisis, we'll exceed them if more than about 70k people require them at once. But I think (not confident in this yet) that our capacity for distributing oxygen is something like 10x higher. And if that threshold gets exceeded, the infection fatality rate may rise by something like 10%. So on this model, while it would obviously be ideal to push the curve below both thresholds, it's imperative to at least flatten the curve beneath the oxygen threshold. Which is easier, since it's higher.

I'm not sure this model is accurate, and I haven't yet decided whether to try figuring it out/writing it up. I feel a bit hesitant, after having wasted 10 days or so underestimating the efficiency of the coronavirus modeling market, but it does seem useful to propagate if true. If someone else is interested in looking into it, I would happily talk them through what I've learned.

comment by Elizabeth (pktechgirl) · 2020-03-22T17:07:13.929Z · LW(p) · GW(p)

I'm looking for opinions on this video, by a virology professor. which so far is my favorite explanation of basic coronavirus science. It covers basic things others didn't (that there are literally no enzymes in a coronavirus capsule, it's just mRNA), and some more specific things that I really wanted to know (like where in the lifecycle chloroquine and azithromycin appear to be disruptive). Before I crown it king, I'd like to get feedback on how easy-to-understand and useful this is for other people.

Caveats: spends a fair amount of time on things I found interesting but not on a straight path to usefulness, like swine flu.

Other contenders are

comment by Elizabeth (pktechgirl) · 2020-03-24T01:04:22.097Z · LW(p) · GW(p)

This post was edited on 3/22 to add answers

This post was edited on 3/23 to add new questions to the agenda and swap out the spotlight questions. (Thanks to elityre and romeostevensit for suggestions)

This post was edited on 3/30 to add two answers to "What are the basic epidemiological parameters of C19?"

This post was edited on 4/6 to:

comment by willbradshaw · 2020-03-19T15:41:00.261Z · LW(p) · GW(p)

What is the basic science of coronavirus? E.g. this guide is trying, but requires more background knowledge than ideal and leaves a lot out.

It's very unclear to me how you can simultaneously overcome both "requires more background knowledge than ideal" and "leaves a lot out", at least without just giving someone a stack of textbooks to read.

I'm like ~2/3 of the way through writing a post on coronavirus structure, which might turn into a series of posts on coronavirus biology if I have time, and this is actually pretty hard. The amount of background knowledge required to really understand what's going on is huge; I have a biology PhD and I'm only skimming it.

So any post that attempts to attack this has a high chance of being at least two of incomprehensible, useless, very long, and dull. I'm doing my best to overcome this, but it's tricky.

Replies from: pktechgirl
comment by Elizabeth (pktechgirl) · 2020-03-19T18:13:04.033Z · LW(p) · GW(p)

I ended up being pretty happy with both of the following, although neither was complete.

Replies from: willbradshaw
comment by willbradshaw · 2020-03-20T18:28:14.139Z · LW(p) · GW(p)

Okay, but those are textbook chapters. If you're looking for those I recommend Chapter 28 of Fields Virology, 6th edition (similar information to Fehr & Perlman, better presentation, somewhat more comprehensive).

But do you really think LessWrong should be going for something more comprehensive than that? I don't really see the value in that, as opposed to getting a smart-person's-summary that links to more comprehensive resources.

Replies from: pktechgirl
comment by Elizabeth (pktechgirl) · 2020-03-20T19:06:16.422Z · LW(p) · GW(p)
But do you really think LessWrong should be going for something more comprehensive than that

...no, for the reasons you state. And I'm not sure why you think I do. Having found those I wasn't planning on actively searching for a better answer (although I'm looking forward to checking out both the chapter you recommend and the posts you are writing).

Replies from: willbradshaw
comment by willbradshaw · 2020-03-20T20:50:09.927Z · LW(p) · GW(p)

Sorry, I think these comments came across as more aggressive than I was intending. I think there's mutual confusion/talking at cross-purposes here. I'm not sure it's worth digging into too much since I'm not sure there's actually any decision-relevant disagreement, so feel free to disregard the following (uh, even more than usual) if you don't fancy digging into this further. :-)

I'm not sure why you think I do.

From my perspective, my confusion arises from the following:

  1. You included basic coronavirus biology on something called a LessWrong coronavirus agenda, as an example of something you wanted to "nudg[e] LessWrong to pursue";
  2. You then gave a counterexample of something that both assumed too much background knowledge and left too much out, suggesting that you'd like whatever LessWrong pursued in that area to not have those deficiencies;
  3. This suggested to me that you'd like LessWrong coverage of basic coronavirus biology that simultaneously assumed less background knowledge and left less out than that counterexample;
  4. But I don't see how that would be possible without someone on LessWrong writing a complete from-first-principles molecular biology course.

Based on this conversation I think I'm probably misinterpreting what inclusion on the agenda implies you'd like to see LessWrongers do.

comment by gwillen · 2020-03-18T18:14:41.842Z · LW(p) · GW(p)

Please apply the Coronavirus tag to this post.

Replies from: Vaniver
comment by Vaniver · 2020-03-18T18:21:27.290Z · LW(p) · GW(p)


comment by Sachi · 2020-03-26T21:00:46.635Z · LW(p) · GW(p)

From what I understand, the lack of proper protection in healthcare workers is a huge issue. I've heard that some hospitals don't even have enough masks for doctors and nurses, this could potentially (or is already) cause a massive increase in healthcare professionals infected. Is there a possible solution to this?

comment by adamzerner · 2020-03-18T07:26:57.941Z · LW(p) · GW(p)

To answer these questions it seems like it would be quite helpful to have domain specific expertise. So then, along the lines of comparative advantage, wouldn't it be more effective to earn to give? And following that thought, while the coronavirus is certainly scary, is it actually worth putting resources towards over things like existential risk reduction?

Perhaps the response to these points is that in practice, the coronavirus is particularly salient, and people are more likely to help out by doing research into these questions than they are with eg. existential risk reduction or earning to give.

Replies from: pktechgirl
comment by Elizabeth (pktechgirl) · 2020-03-18T16:31:46.318Z · LW(p) · GW(p)

Do you know of places that would make good use of donations? If so, I strongly encourage you to write them up, ideally as an answer here [LW · GW].

I also think a top-level post making the case for or against focusing on COVID vs. (other?) X-risk is a great idea.

Replies from: adamzerner
comment by adamzerner · 2020-03-18T22:49:41.621Z · LW(p) · GW(p)
Do you know of places that would make good use of donations? If so, I strongly encourage you to write them up, ideally as answer here [LW · GW].

No, I don't know of places that would be particularly good to donate to. The WHO seems like a safe bet. Also, GiveWell is looking in to it (which I also noted in the other post).

Personally I suspect that even without knowing the best place to donate to, earning to give would be a more efficient use of time. However, I don't feel too confident in that. I don't know enough about how effective professionals actually are in practice, and LessWrongers in general seem to be extremely capable, even when venturing outside of their areas of expertise.

I also think a top-level post making the case for or against focusing on COVID vs. (other?) X-risk is a great idea.

I agree. I just posted this question [LW · GW].