This thread was created on 3/8/2020, or approximately one million years ago in virus time. It’s getting pretty bloated now, and a lot of things that were high value at the time have been eclipsed by events, making karma not a very useful sorting tool. So I’m declaring this thread finished, and asking everyone to move over to the April Coronavirus Open Thread.

Interested in what happened in this thread? Here’s the timeless or not-yet-eclipsed highlights:

  • Scott Alexander comes up with Hammer and Dance 6 days before Tomas Pueyo
  • Spiracular on why SARS-Cov-2 is unlikely to be lab-created.
  • Two documents collating estimates of basic epidemiological parameters, in response to this thread
  • Discussion on whether the tuberculosis vaccine provides protection against COVID-19.
  • Suggestive evidence that COVID-19 removes sense of taste and smell.
  • Could copper tape be net harmful?
March Coronavirus Open Thread
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China is following a strategy of shutting down everything and getting R0 as low as possible. This works well in the short term, but they either have to keep everything shut down forever, or risk the whole thing starting over again.

UK is following a strategy of shutting down only the highest-risk people, and letting the infection burn itself out. It's a permanent solution, but it's going to be really awful for a while as the hospitals overload and many people die from lack of hospital care.

What about a strategy in between these two? Shut everything down, then gradually unshut down a little bit at a time. Your goal is to "surf" the border of the number of cases your medical system can handle at any given time (maybe this would mean an R0 of 1?) Any more cases, and you tighten quarantine; any fewer cases, and you relax it. If you're really organized, you can say things like "This is the month for people with last names A - F to go out and get the coronavirus". That way you never get extra mortality from the medical system being overloaded, but you do eventually get herd immunity and the ability to return to normalcy.

This would be sacrificing a certai... (read more)

If you first do lockdowns to get new cases to ~0 and then relax, optimistically you will get localized epidemics that you can contain with widespread testing, contact tracing, and distancing if needed. Cost of testing & tracing and having to do occasional local/regional lockdowns could end up being manageable until treatment/vaccine arrives.

My main reason for optimism is Korea's and China's success containing a large outbreak. We will be expecting the secondary epidemics and reacting quickly, so they will be small when detected, so should be much easier to contain than the first surprise outbreak.

We'll get data on this in the coming months as China loosens restrictions. There is option value in containing asap and first trying things other than deliberate infections.

1Jackson L
Linking the The Imperial College paper here (which a lot of people have referenced lately) that addresses these two approaches: (a) mitigation, which focuses on slowing but not necessarily stopping epidemic spread –reducing peak healthcare demand while protecting those most at risk of severe disease from infection, and (b) suppression, which aims to reverse epidemic growth, reducing case numbers to low levels and maintaining that situation indefinitely. (https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf) The biggest issue with the suppression strategy is the time required for the lockdown - until R reaches low enough levels that eliminate human-to-human transmission, or until a vaccine is available. Estimated 12-18 months with a r0 of 2.4. In fact the more successful a strategy is at temporary suppression (China), the larger the later epidemic if the lockdown is lifted prematurely - due to lesser build-up of herd immunity (Figure 3, "post-September 2020"). Mitigation: "In the most effective mitigation strategy examined, which leads to a single, relatively short epidemic, the surge limits for both general ward and ICU beds would be exceeded by at least 8-fold under the more optimistic scenario for critical care requirements that we examined. In addition, even if all patients were able to be treated, we predict there would still be in the order of 250,000 deaths in GB, and 1.1-1.2 million in the US."
1AlexSchell
Their paper is not relevant as they do not analyze testing & contact tracing AT ALL, only mentioning it briefly in the Discussion section. I think everyone who thinks the strategy I describe might be feasible (which now seems to be most informed participants in the discussion on here & rationalist Twitter) more or less agrees with the Ferguson analysis if you assume you can't do testing & tracing & isolation or they won't work.
5Jackson L
Yes you are correct, succinctly addressed here " They ignore standard Contact Tracing [2] allowing isolation of infected prior to symptoms. They also ignore door-to-door monitoring to identify cases with symptoms [3]. Their conclusions that there will be resurgent outbreaks are wrong. After a few weeks of lockdown almost all infectious people are identified and their contacts are isolated prior to symptoms and cannot infect others [4]. " https://necsi.edu/review-of-ferguson-et-al-impact-of-non-pharmaceutical-interventions

I've spent some time thinking about endgames here. (Not that I feel like I've come to any conclusions. I wish I knew what e.g. the WHO thought the endgame was.) The biggest problem I see with this idea is the lag between input and output -- when you change your quarantine measures, you can't observe the result for at least the 5-7 days it takes the newly infected to get symptoms, and longer if you want to get a lot of confidence in your measurement, over the noise inherent in the system.

Control systems with high lag like this are incredibly difficult to work with. Especially in the presence of exponential growth like this system has -- if you accidentally let R get a bit too high, it will be a week or two before you notice, and in that time you will have seeded a ton of cases that you will have to track down and deal with.

I think the most hopeful endgame here, near-mid-term, is that we find a combination of antivirals with high effectiveness against COVID-19, which reduces the rate of severe pneumonia dramatically. At that point our hardest constraint, ventilators, will get relaxed. Beds are a lot easier to deal with a shortage of.

Mid-long-term, of course, we're all hoping for a va

... (read more)
2Roko
This is why you need to have borders on multiple scales and cancellation of large events. If one case slips through, in a week or two they will infect a handful of new people. If you have set up a system of regional and national borders, as well as cancelled large events, you will find out about this trace the contacts and temporarily increase the strength of the lockdown in only that region. This strategy nearly worked in South Korea, but then patient 31 was a superspreader: https://graphics.reuters.com/CHINA-HEALTH-SOUTHKOREA-CLUSTERS/0100B5G33SB/index.html
7Alexander Gietelink Oldenziel
Just like to chime in to say that this (=' flattening the curve/ herd immunity') fundamentally doesn't work, and you don't need to have a PhD in epidemiology from Imperial College to understand this [but you might need a PhD in epidemiology to misunderstand it], just basic arithmetic and common sense. Suppose 50% of the UK (33 million people) get the virus of which 5% (~ 1.8 million people) will need serious hospitalization [conservative estimate]. The current capacity of ICU beds in the UK is something on the order of 2000 beds , depending on occupancy rates, ability to scale up et cetera. Let's be extremely optimistic and somehow the UK is able to quintuple this capacity [as far as I can tell this is unlikely]. When somebody is sick they might need care for 2 weeks. The annual hospital capacity is: 25 weeks * 10.000 beds= 250k. At the moment the capacity is nowhere that (perhaps 50-100k). You can see that 1.8 million is far larger than 100k or even 250 k. Even wildly optimistic estimates will not yield anything realistic. This assumes that the government is somehow able to control the infection spreading over a year; instead of two months. There is no reason to think they can do this without extreme (partial) lockdown measures. Controlling the R0 is extremely hard. All the mild measures seem to help only a tiny little bit. If the R0 is only a bit over 1, we still have exponential growth; and you have merely pushed timelines back a few months. Can we perhaps expose young people but lock up older people for one-two years [when the vaccin might arrive]? I find this is extremely unlikely; you need only a couple people to flout the rules to wipe out an entire nursing home. Is it worth it to (partially) lock down the entire country for a year to save maybe a hundred thousand old people? There are only two real possible approaches: 1. Let the Boomers die. If we're lucky the death rate is ~0.7 percent. When (not if) hospitals overflow this will easily triple. Wi
3Roko
I agree with this analysis completely. There is a strategy bifurcation: Either you lock down hard and contain/eradicate, or you just accept the losses and tell people to go on as normal, with isolation of the vulnerable. The middle path is not favorable. You take both the human damage and the economic damage.
6Pablo
The South Korean approach seems to be roughly as effective as the Chinese approach but significantly less costly and disruptive. SK managed to halt exponential growth and currently cases are increasing linearly at a rate of 75 or so per day. This has been achieved without lockdowns or extensive border closings. Instead, the key ingredient appears to be rapid, extensive and largely free testing, and an educational campaign that stresses the importance of hand washing and staying at home.
5Raemon
I'm confused about why the second strategy works better than the first strategy at killing it permanently. If you shut down everything, shouldn't everything die out faster? (Unless you have open borders and let it in again, but wouldn't that also apply in the UK case?)

The first strategy leaves you with a huge population of people with no immunity to the virus, which means you have to keep holding the lid on it indefinitely or you're back to square one.

In the second strategy, everyone ends up either immune or dead, which doesn't mean the virus is gone -- it will remain endemic -- but there will be no giant flood of new cases when people resume their lives.

(Obviously it's not quite as simple as that if the virus doesn't generate durable immunity. Then you end up with something like the flu, where partial immunity keeps it vaguely tamped down with occasional flares.)

9willbradshaw
Clarification: you don't need everyone to be immune or dead. Just enough people that the remaining population can't sustain a continuous epidemic.
4gwillen
Right, yes, agreed and good point -- my understanding is that a naive epidemiological model gives a fraction of 1 - (1/R_0) of the population needing to be infected, to drive the effective value of R (new transmissions per infected person) below 1, at which point the population can no longer sustain epidemic spread.
3Lukas Finnveden
Isn't this exactly what "flatten the curve" is about? Because a lot of people are talking about that as a solution, including some governments. The main problem is that the curve needs to get really flat for hospitals to have time with everyone. Depending on how overwhelmed you want your hospitals to be, you could be in lock-down for several years. Some calculations in this article.
1Mmv
Isn't "social distancing" the in-between strategy already? I was thinking of something similar today, when questioned whether to have a friend to my house. If I followed the strictest measures, I wouldn't. But then, if nobody did and we were essentially on self-quarantine mode, then the virus wouldn't spread at all or very, very, little and we would be hovering in small numbers for months, until next fall/winter, when it could get really risky again (presuming that weather has an influence, like with flu). So doesn't the social distancing strategy want some appreciable degree of transmission, high enough to get to herd immunity in a reasonable amount of time, but slow enough to avoid a hospital crisis? Are governments just relying on the idea that some people will ignore the suggestions, and we'll get a reasonable degree of transmission over time during social distancing?
1Liam Donovan
I'm pretty sure that's exactly what the UK is trying to do? I'm actually pretty confident that the UK government isn't planning to have " hospitals overload and many people die from lack of hospital care. ". Even if they were sure that was the best approach (and they just didn't think of your idea?) it would be completely unfeasible politically
1syllogism
But why can't we eradicate the virus? Let's say China shuts down international travel, keeps doing what they're doing, and then slowly eases back up in some area, letting the people in that city comingle and go back to work, but still restricting travel in and out. Let's say they get that city back running, with no coronavirus cases after a month. At the same time...Won't they also have basically eradicated other influenza there? Even if not entirely, there should be much less cold and flu, right? So as soon as coronavirus creeps back in, it should be much easier to contain. I guess my thinking here is, if coronavirus is much more virulent than the flu, and this type of containment works to almost eliminate the coronavirus, could China...actually eradicate the flu, at the same time? If not, why not? The problem comes in from other countries. If China goes to all this effort and the US, Europe, UK etc don't, do we would end up with this weird hazmat curtain? Asian countries would join China in eradicating the disease, and Australia and New Zealand would probably join them.
2gwillen
I've already heard that influenza cases are down in countries that enforced social distancing / lockdowns for coronavirus. However, it really only takes one country not doing this for influenza to return to typical incidence -- there's no real reason to believe it will be eradicated. (However, the same seems true for COVID-19, so I'm not sure what to expect there.)
1syllogism
I agree that actually eradicating influenza feels far-fetched. But on the other hand, it's quite a lot easier to work with than COVID-19. Influenza isn't nearly as infectious, most people have immunity, and it's barely transmissible at all when the carrier is asymptomatic. Imagine you actually did have the "hazmat curtain" situation. Everyone is asked to take their temperature on the way in, and significant fines (and potential visa cancellations) are imposed if you lie. At first nearly everyone is checked to verify, but this is relaxed to spot-checks as people get used to never breaking the rule. Few enough people are getting sick that when people do report influenza symptoms, they can be tested, and contact tracing can be employed to halt the outbreak and trace it back to how it was introduced. If there are no animal reservoirs for the disease, I think that could be viable? It's expensive, but influenza is a big cost in itself, in lost productivity and other problems. The big problem I see for eradicating coronavirus will be in poorer countries --- Africa, the middle east, etc. The outbreaks there are still pretty small, but there's no real resources to address them, so the problem could grow there until it's really hard to fix.

Update: the positions are now filled. See here for the official announcement.

Help wanted: pandemic.metaculus.com project lead

The high interest and proliferation of questions on the novel coronavirus calls for dedicated attention, which led to the formation of pandemic.metaculus.com. Managing it, though, is straining Metaculus's very limited staff and community moderator team. Contingent on acquisition of funding (which Metaculus is working to secure), Metaculus is looking to bring onboard someone to help manage this project. Components would include:

  • Managing the pandemic site and question series as a sort of "editor in chief" working with the community moderators (as Tamay does now for Metaculus in general.)
  • Helping build data products and analyses out of the questions and results.

The above indicates a range of skills including pretty strong understanding of Metaculus, and data analysis capability. Science background would be great, and huge bonus for actual medical knowledge. This is probably a part-time role but full-ish time is also imaginable depending upon the person, the duration, and funding.

If you're interested, please send a note and CV to jobs@metaculus.com.

If this news article is accurate, masks will not be scarce for much longer. That article claims that China is now producing masks at 116M/day, a 12x increase compared to the start of February (5 weeks ago), and that they will export them. This is in addition to mask production in other countries.

I  am not sure whether, when combined with production in other countries, this satisfies the entire world demand. But masks aren't complicated objects and aren't made of scarce materials, and this is pretty strong evidence that production can be scaled up even further, if necessary.

In a few weeks, a number of public figures may find themselves doing an awkward about-face from "masks don't work and no one should wear them" to "masks do work and they are mandatory".

(If you are able to buy masks for less than $1/each through ordinary channels, it means the shortage has abated, and you can buy them without worrying about depriving health care workers of those supplies, but you shouldn't stock up on more than you need in the short term until the price has been low for at least a few weeks.)

In a few weeks, a number of public figures may find themselves doing an awkward about-face from "masks don't work and no one should wear them" to "masks do work and they are mandatory".

I want to record and reward how this prediction seems to be correct: https://www.washingtonpost.com/health/2020/04/02/coronavirus-facemasks-policyreversal/

1agc
I wonder if China will direct the masks to politically friendly countries, or let the free marker decide.
3Emiya
They'd likely ship them out to everyone as fast as they can, this is their chance to regain political points after this disaster. They already helped out Italy by donating medical supplies and enough people on the social medias are starting to regard them with a better opinion than other European countries, so as a political move is hugely effective.
2jmh
I would think that would be the smart thing and the right thing. I suspect it also the thing they will do. That said, they have also already publicly stated (reported a few days back) they will offer that type of support "for those participating in their belt and road" initiative and I didn't notice (but did not read closely) if they mentioned nonparticipating countries and where they would stand. Might be more about prioritization in the line.

I heard a rumor of someone in the Bay area claiming to work in the intelligence community, to be terminally ill, and to have received an experimental COVID-19 vaccine. I think this rumor is false with respect to the specific person, but do note that "military officers with preexisting terminal illnesses who volunteer" is a group that may actually exist, and that at least one drug company claims to have shipped vaccines for a phase 1 trial on Feb 24.

This raises the question: if you're well resourced, desperate, competent, and in possession of expendable military volunteers, how long does development for a vaccine actually take?

Given a candidate vaccine, you need to do three things: find out if confers immunity (and how much immunity), find out if it causes side effects severe enough to not be worth it, and scale up production.

All three of these can be done in parallel. If you have expendable volunteers, you don't need to start with an animal model; you can just give them the vaccine, and see whether they suffer side effects. Testing efficacy can be done in parallel, with the same volunteers, and takes about three weeks--you give the vaccine, wait a week, expose to virus, then wait i

... (read more)
5Ŀady Jade Beacham
For me, that fits my model of what the US intelligence agencies used to do during the cold war times, and we have unclassified documents about proactive, unethical experimentation they did - like Operation Sea Spray and MK Ultra. I don't know if the 2020 US intelligence community is up to the same task. I get the impression that capability and competence have fallen there, although it's hard to know since so much is classified. But judging by the fact that we have had several elections disrupted by pretty predictable cyberattacks without visible countermeasures, my estimation of their competence has fallen. On the other hand, here's an article about a UK laboratory infecting people with a non-covid coronavirus to help with vaccine research.
2Adam Zerner
But the space of possible vaccines is very large, I assume. So even with a ton of human testing that only takes three weeks, maybe this still doesn't help much?
4jimrandomh
In principle, with enough resources, multiple vaccines could be tested this way in parallel. Not that there are that many vaccine candidates to try, as far as I know; but if there were some software that bulk-generated candidate molecules, it could be done, in principle. The limiting input is mobilized resources, not time.
2ChristianKl
We have the genome of the virus. All the surface proteins of the virus are candidate molecules.
2Adam Zerner
Yeah, if you could reduce the space of possible vaccines to a smaller set of plausible ones, that certainly makes sense. This makes me wonder, why not just let people volunteer to test risky treatments in general? Because there'd be bad actors who try weird shit willy nilly and misrepresent it to people as more plausible than it really is, such that the harm done to people outweighs the advancements in knowledge? But what if you remove the profit motive and only give this power to government researchers? Would they have too many career-y incentives to be too aggressive?
2ChristianKl
Human trials are much more expensive then trials in mice. If you can already rule out a drug by giving it to mice you save a lot of money that you don't have to invest into your trial with humans.
2Adam Zerner
True. The downside would be that animal testing is slower, which is I think why jimrandomh was proposing human testing.
2ChristianKl
Speed is not an important variable for government researchers outside of a situation like this where you need a fast response to a pandemic. Speed matters a bit more for big pharma where it matters if you have one additional year of patent protection for your drug if you develop a year faster but even there the cost tradeoffs are in favor of doing animal testing.
2ChristianKl
It seems to me much more likely that the Chinese are doing human trials that skip animal testing then that the US intelligence community does that. Terminally ill patients don't make good subjects for clinical trials. If you run such a project outside of the reach of the FDA, it seems like a slight against the FDA. It's not a step in which companies that produce vaccines and that want to have good relationships with the FDA want to make. On the other hand the Chinese government has plenty of people in their prisons that they consider expandable and willing to sacrifice for the greater good. They should also have less institutional resistance to it
2jimrandomh
The "terminally ill" bit was part of the (probably false) rumor that I heard. Preexisting illness definitely screws with the safety-testing aspect, but there are also illnesses don't interfere with the efficacy testing. I agree that a competent agency uses healthy people for this if they could. If experimenting on healthy people wasn't possible or worth it, one possibility would be to do an efficacy trial on unhealthy people and a safety study on animals in parallel.
2ChristianKl
I have the impression that you ignore the institutional issues that are at play. The intelligence community can't simply deploy a vaccine on their own. They need buy in from the FDA.

Legally speak, yes they would. Practically speaking, however, the FDA has no enforcement power over secret programs in the intelligence community.

I think a lot of people are seriously overestimating the FDA's actual power, and that's causing pretty severe problems. Consider for example this tweet (and a long series like it) by the mayor of NYC, begging the FDA for approvals. While there is no legal precedent to refer to, it's extremely implausible that the FDA could ever get or enforce a judgment of the city of New York for actions taken during a state of emergency, when the FDA itself caused that emergency with culpable negligence.

0ChristianKl
The FDA has no power to stop the intelligence community running tests on patients but they do have the power to declare the results of the tests as not being enough to prove the resulting vaccines safe. Do you really think that you have a better idea of the institutional power of the various players then the mayor of NYC? The FDA has a lot of relationships that allow it to exert power that are distinct from direct legal tools.
1Original_Seeing
There are some articles today about people trying out a drug called remdesivir https://www.washingtonpost.com/business/economy/the-best-hope-for-coronavirus-treatment-is-an-experimental-drug-that-fizzled-against-ebola/2020/03/10/8a9e8cd4-5fe8-11ea-b29b-9db42f7803a7_story.html
-3eternaltraveler
In general vaccines are very easy to make. You grow the virus you want to vaccinate against, kill or weaken it, and inject it, often with an adjuvant. Viral illnesses that don't have vaccines today are the exception where it turns out that doesn't work and it's more challenging. These difficult ones are what all vaccine research today is focused on, so people think making vaccines is hard. It usually isn't. Small pox, measles, mumps, rubella, chicken pox, and polio are all gone. Flu is 4 new viruses we make brand new vaccines for every year.

Are the economic forecasts still too sunny?

(Warning: Long comment)

Two weeks ago Wei Dai released his financial statement on his bet that the coronavirus would negatively impact the stock market. Since then (at the time of writing) the S&P has dropped another 9%. This move has been considered by many to be definitive evidence against the efficient market hypothesis, given that the epistemic situation with respect to the coronavirus has apparently not changed much in weeks (at least to a first approximation).

One hypothesis for why the stock market reacted as it did seems to be that people are failing to take exponential growth of the virus into account, and thus make overly optimistic predictions. This parallels Ray Kurzweil's observations of how people view technological progress,

When people think of a future period, they intuitively assume that the current rate of progress will continue for future periods. However, careful consideration of the pace of technology shows that the rate of progress is not constant, but it is human nature to adapt to the changing pace, so the intuitive view is that the pace will continue at the current rate. [...] From the mathematician’s
... (read more)

The idea that smart investors don't understand exponential curves is absurd on its face

I don't think this is necessarily absurd or false. Like, this is what Black Swan Farming was about.

I think people in finance are used to exponential curves with doubling times of 20 years, and this doesn't give them much of an edge when it comes to doubling times of 2 days. Like, even in semiconductor manufacturing, the progress of Moore's Law over someone's 40-year career corresponds to about a month of viral growth at that rate. 

Startup finance people do work with stuff at roughly the same scale, and correspondingly freaked out much more.

The sheer insanity of such a prediction should give you an idea of how uncertain this whole thing still is.

I don't think this is crazy, once you consider healthcare system failure. What does the world look like if no one receives medical care for any condition besides a COVID infection for the next three months?

3romeostevensit
I don't have a strong stance either way but I think there are some interesting points for the other side. Let's say this is on the order of a ww2 number of deaths. Look at the impact of ww2 on the economy. Except with the present situation there's no need to halt international trading, and none of the productive assets get bombed. This still leaves a lot of room on the side of it being worse than many of these sunny projections, but what I want to point at is that it is also really common to drastically underestimate how bad things can look locally and still have trends mostly do alright due to the enormous differences of scale between what it takes for things to look bad and what it takes for things to be bad everywhere.

This blog post argues that the now popular idea of "flattening the curve", in the sense that most people get exposed but slowly enough to not overwhelm the health care system, is not feasible. The result is that we'll either achieve containment or at least widespread regional health care system collapse (and maybe Wei Dai's global health care collapse outcome). I haven't spent much time modeling this yet, but tentatively it looks like flattening the curve requires very precise fine-tuning of R0 to stay on a path very close to 1 for at least several months, which seems impossible to pull off.

It feels to me now that flattening the curve is just a nice graphic without anyone checking the math, but I am confused that many informed-seeming experts are promoting the idea. Anything I'm missing?

ETA: I made an epidemic + hospitalization model (Google Sheets), it sure looks like the usual flatten-the-curve chart is a comforting fiction. Peak hospital bed demand in the uncontrolled epidemic scenario is usually drawn at 2-3x hospital capacity. I'm getting 25x and the chart looks a lot less reassuring. My shakiest assumptions are hospitalization / intensive ca... (read more)

Disclaimer: I don't know if this is right, I'm reasoning entirely from first principles.

If there is dispersion in R0, then there would likely be some places where the virus survives even if you take draconian measures. If you later relax those draconian measures, it will begin spreading in the larger population again at the same rate as before.

In particular, if the number of cases is currently decreasing overall most places, then soon most of the cases will be in regions or communities where containment was less successful and so the number of cases will stop decreasing.

If it's infeasible to literally stamp it out everywhere (which I've heard), then you basically want to either delay long enough to have a vaccine or have people get sick at the largest rate that the health care system can handle.

5Sammy Martin
South Korea, Singapore, Italy The UK. We're running an interesting experiment to see which approach works. One potential benefit is that the world will be able to observe which of the two strategies is viable and switch between them, at least theoretically. Practically, switching from 'suppress/contain' to 'flatten curve' seems a lot more feasible than the alternative of trying to suppress after not taking tough measures, as the UK will have to do if its strategy means cases grow out of control. South Korea could still try to use curve-flattening as a backup plan. However, for the reason given in the blog post, suppression will be a viable backup even if switching from curve-flattening to suppression is intrinsically harder than the other way round.
5AlexSchell
Still seems to me like you should be able to isolate those problem areas from the rest of the country. Then even if you can't contain the epidemic inside, you spare most of the country (for the moment). But I think we mostly agree. A scenario that seems increasingly likely to me is that governments will intervene in increasingly strict ways until we get very close to true containment (before ~15% of the world is infected), and then will loosen movement restrictions in more-contained areas while playing whack-a-mole with a sequence of localized outbreaks for 1-2 years until a vaccine is ready.
2Roko
Borders, travel restrictions, cancellation of large events, contact tracing and testing will solve this. Borders are necessary precisely because of this dispersion issue.

That's an interesting question that seems like it ought to be able to be checked numerically.

I made an attempt using this simulator of the fairly-naive "SIR" model of disease transmission:

http://www.public.asu.edu/~hnesse/classes/sir.html?Alpha=0.3&Beta=0.07&initialS=1000&initialI=100&initialR=0&iters=50

Note that this simulator appears to be someone's class project. However, its behavior seems to track more or less with what I'd expect. But I'd love for someone with more experience to reproduce this relatively simple model and check it.

You can read about the model at https://en.wikipedia.org/wiki/Compartmental_models_in_epidemiology#The_SIR_model .

I have limited confidence that I've understood it correctly, so take this for what it's worth. It looks to me the time step used in this simulator is one day. So the gamma parameter (rate of recovery per unit time) should be (Wikpedia says) 1/D where D is the duration of the disease. (For transmission modeling purposes, this should be the infectious duration, not the duration of symptoms.) I chose gamma=0.7, meaning D ~= 14 days, semi-arbitrarily, based on https://www.medrxiv.org/content/10.1101/2020.03.05.20030502v1 (

... (read more)

Thanks for pointing me in this direction. I think the key worry highlighted in the post is that the health care system gets overwhelmed with even just a few percent of the population being infected. So even if we can bring peak infections down by a factor of 2-4 by slowing transmission, the health care system is still going to be creamed at the peak.

I've now built a discrete-time, Bay Area version of the SIR model (+ hospitalization) in this Google sheet. I assume 20% of infections need hospitalization, of which 20% need intensive care, and use raw bed-to-population ratios (non-COVID utilization vs stretching capacity should roughly cancel out). Hospital bed availability at peak infections is 4% (25x over capacity) in the uncontrolled beta=0.25 scenario and only improves to 10% (10x over capacity) in the "controlled" beta=0.14 scenario. Even if my hospitalization/ICU numbers are too high by a factor of 5 the "controlled" scenario still looks pretty terrible. Any feedback on the model assumptions would be super useful.

5gwillen
I haven't checked your models quantitatively, but qualitatively I absolutely believe you that the options here are "bad" and "really really bad", and that neither one of them gets us down to where we need to be. The difference between 4% and 10% could still save a lot of lives; at that level it may be close to 1:1 (every bed freed up is a life saved), since only the most critical cases will be getting beds at that point. But you're right that this is clearly not adequate, and the graphic showing the flatter curve as peaking under the capacity line is pretty misleading. (There are versions of the graphic which don't, but they appear to have been memetically outcompeted by those that do.) I think it's still true that "flattening the curve" will save lives, potentially a lot of lives, so even if the graphic might be a bit misleading as to the possibility of flattening it below the critical threshold, I think it's still a reasonable meme to promote. But really the ultimate goal has to be reducing R below 1, which will arguably flatten the curve, just not quite in the way the meme seems to be trying to get at. I don't want to steer too close to dark side epistemology here, but if the meme gets people to stay inside, cancel their parties, and wash their fucking hands... it's hard for me to be too against it, and I think it's probably true enough?
4AlexSchell
I don't know how other people react. I took the epidemic fairly seriously but my initial reaction to the meme was one of reassurance/complacency - OK so I can't avoid eventual exposure anymore, but at least things will proceed in a somewhat orderly fashion if we cancel big events, wash hands, stop touching our face, etc. I feel like this is the sort of attitude that contributes to, and allows the public to accept, decisions like the capitulation in Sacramento. The mental image of mitigation is "basically trying to mitigate the risk to those who are most at risk: the elderly and those with chronic underlying conditions". The reality is that we'll be forced to let all the old and sick die in hospital parking lots. It seems to me fairly likely that the public will ultimately accept the Hubei-style lockdowns that will result in containment, but this meme probably is responsible for delaying that moment by at least a few days :(

I saw the meme as mostly targeting people who were currently even more complacent "eh, there's nothing we can do, so fuck it", and getting them to instead go "okay, there's stuff that's actually worth doing."

4AlexSchell
You're probably right.
3WilliamKiely
Alex, I'm looking at your spreadsheet and I don't understand where you got these bold numbers from. It looks like you tweaked your sheet a bit since writing this comment, but still I can't figure out what you are looking at when you say 25x and 10x over capacity. Could you explain?
4AlexSchell
Yeah I got better hospitalization/ICU rates from Bucky and upped beta to 0.3 in uncontrolled scenario to make a point on Twitter. Hospital/ICU bed availability % is graphed in each scenario tab, by overcapacity I mean the inverse of availability. Alternatively take ratio of peak to line in the Charts tab. Looks like ~15x and 5x now for hospital beds.

That's a really interesting blog post, and it made me update (towards the idea that containment efforts in most countries will keep ramping up until containment actually succeeds). How did you come across it? I've been following Twitter, a couple of FB groups, and Reddit, and it didn't get linked by any of the posts I saw.

It feels to me now that flattening the curve is just a nice graphic without anyone checking the math, but I am confused that many informed-seeming experts are promoting the idea. Anything I’m missing?

I'm wondering this too.

3AlexSchell
Don't recall how I ended up seeing it, but it was through this tweet by the author: https://twitter.com/DanielFalush/status/1236918870780198912 (ETA: Razib Khan RT'd him)
2Sammy Martin
Perhaps the numbers work out better when you include cocooning of populations that disproportionately make use of hospital resources
5Unnamed
I think each little bit of curve flattening makes things a little less bad (since a smaller number of cases are beyond capacity, and a little more time is created to prepare), but the graphs tend to draw the "capacity" line unrealistically high. This graph is more realistic than many since the flattened curve still peaks above the capacity line, but it still paints too rosy a picture.
4Bucky
Nice model. For hospitalisation / intensive care, the original data from China had 14% "severe" and 5%"critical" cases. These are percentages of diagnosed cases so you would need to modify these with the diagnosis rate. For the Diamond Princess about 50% of cases were asymptomatic so that is likely an upper limit on diagnosis rate. Ascertainment rates from these papers are highly variable so an actual number here is hard to estimate. That suggests hospitalisation is probably no more than 10% and intensive care no more than 2.5%. These numbers are a bit lower than your model but not enough to get us out of the woods.
4Sammy Martin
From the blog post: I have heard '5-15%' and '20%' and '12%' for hospitalization/'no-treatment fatality' rates, with a trend that the newer estimates tend to be lower. The initial figure from China was a blood-curdling 20%, as you said, while a current projection based on evidence from real overwhelmed healthcare systems is a merely very bad 3-5%. This is lower by a larger factor than most of the reductions to the CFR that account for undocumented cases - perhaps indicating there are more undocumented cases than those corrections imply? Also, of relevance to the UK's strategy (cocooning older people from infection), how does this breakdown by age? This poster has estimated that young, male, no pre-existing condition have 1/4th the risk of hospitalization (assuming a 50/50 chance that the intersection of age-30/no-pre-existing condition has a much lower risk than either alone) - which means if older and vulnerable people can be 'cocooned', the actual rate of hospitalization can be slashed again by a factor of 4 to something bearable, around 1%, if you take 4% as the baseline. (note that the corrections in this paper for delay to death and underreporting skew the death rates even more strongly towards older patients, with the fatality rate among 20-29 barely changing after adjustment but the fatality rates among 60+ doubling). That means you could surf a wave of a few hundred thousand people having the virus at a time and still provide adequate ICU space. With some expansion in capacity, that could be even higher.
4AlexSchell
Thanks for digging these up! I updated the model. Still terrible.
3jmh
I'm wondering why you are also coming up with a LOT more hospitalization than even cases reported in China. In early April, if I'm readying this right, you are expecting the Bay area to need over 80,000 hospital beds for COVID-19 for the uncontrolled case (I assume that is merely a comparison scenario) and then after 3 months, say starting July, in the controlled scenario about 81,000 hospital beds will be needed. Then things keep going up. That seems like something is missing there. Why would the Bay area really expect to see such drastically higher impact than China as a whole? Using your 20%, 20% assumption and saying China is at 85,000 now, the total demand for hospital beds would have been 20,400 over the entire December - March time period.
4AlexSchell
China locked down Wuhan at ~500 confirmed cases and many other Hubei cities the next day, which immediately lowered transmission (see Chart 7 here) to R0 below 1. This is very far from the uncontrolled scenario and still overloaded the health care system. This is much of the point of the post I linked -- the degree of hospital overload in an uncontrolled scenario is so high that even huge reductions in transmission don't realistically avoid overload if R0 stays above 1.
1jmh
I do get that point, and do think it is one that is well made. At the same time, I find the numbers produced a bit on the high side. Clearly the 20,400 number being within existing capacity for the Bay area completely ignores current patients unrelated to COVID-19. But perhaps under a regime of social distancing, containment and isolation of both known cases and by the more concerned both the speed of growth and the total number your model is producing would be much closer to manageable.
3jmh
I think it might also be worth considering hospital beds -- to some extent -- is not a fixed quantity to can expand as demand increases. Consider using hotels or other (these days rather vacant) building/structures. That's basically what China has done here (and in other cases with their "legos" 10 day to build hospitals -- rejected the concept of what a hospital is and how fixed the supply is. Just as an assumption check, was your hospital bed/ICU bed value an average for, say the USA, or some other country level metric or an average of the local hospital to service area metric?
2AlexSchell
I used overall US numbers. I didn't consider capacity expansion but also didn't take out already-occupied beds, as I think both are roughly on the order of 2-5x in opposite directions. The only Bay Area-specific numbers are population and day 0 infected (I assumed ~10x confirmed cases).
1zby
It worked in 1918: https://qz.com/1816060/a-chart-of-the-1918-spanish-flu-shows-why-social-distancing-works/
2AlexSchell
I should have made it clearer I don't deny we can literally flatten the curve, but rather the idea that Unclear to me how well St Louis did on the health care system front. Also, the pairing of Philadelphia and St Louis is a bit convenient if you consider the raw scatterplot (panel C bottom left - ETA Philadelphia is the dot closest to Pittsburgh per this table).

I think it would be valuable to compile a list of estimates of basic epidemiological parameters of the coronavirus, such as incubation rate, doubling times, probability of symptomatic infections, delay from disease onset to death, probability of death among symptomatics, and so on. I find that my inability to model various scenarios accurately is often due to uncertainty about one or more of these parameters (uncertainty relative to what I suspect current expert knowledge to be, which is of course also uncertain to a considerable degree).

For current expert knowledge, this list of values from lots of different papers might be helpful.

2Pablo
Wonderful, thank you so much.

Did you end up finding one besides the MIDAS network, or develop your own? I'm assembling a parameter doc for inputs to a rough model that accounts for ventilator & hospital bed capacity, since it seems like we're lacking that.

  • I encourage folks to add parameters w/ citations to the doc, I'll be active on it for the next few days.
  • If anyone knows of models that incorporate actual healthcare capacity, please share!
6Pablo
Thanks for putting this list together. I stopped looking after Bucky supplied the link to the MIDAS network list, since it seemed so comprehensive. For models that incorporate actual healthcare capacity, see this thread. One limitation of the models I've seen is that they fail to account for growth in such capacity. China responded to the realization that they didn't have enough hospitals by quickly building more hospitals. Maybe Western countries are less competent than China and it will take them longer to build the needed capacity. But it seems implausible that they will be so incompetent that capacity-building efforts will not make a significant difference.
5Eli Tyre
Having a list of of values of interest, with estimates and citations for each, would be great. But in addition, I gotta say, this seems like just about a perfect use-case for prediction markets: we have a bunch of individual, well operationalized scalars, for which accurate estimates that incorporate all of the existing information are of high value. Is anyone in a position to set up, or to subsidize, a market on these values?
4habryka
I second this.
2romeostevensit
And to start compiling a list of common problems with the parameter estimates being used. Eg I am seeing some models extrapolate naively from the fact that most cases are coming from the least controlled places with the widest uncertainty bars.
1rocurley
I'm also very interested in this. Here are some numbers I've been using: * Ratio of confirmed to unconfirmed cases (USA): 34 (50%), or 5 (5%) to 94 (95%) This is based on https://twitter.com/trvrb/status/1234589598652784642 , which estimated the true number of coronavirus cases in Seattle (as of 2020-03-01). I divided that by the number of confirmed cases in Seattle at that time. * Doubling time (USA): 4 ish (which I'm treating as 2 (5%) to 7 (95%). https://en.wikipedia.org/wiki/Template:2019–20_coronavirus_outbreak_data/WHO_situation_reports is how I'm getting 4ish. There are papers that estimate higher: https://www.nejm.org/doi/full/10.1056/NEJMoa2001316 gives 7, for example, but that appears to be in Wuhan post-containment.
3jmh
South China Morning Post had a story line a day or so back where Chinese experts were suggesting a 10 fold increase every 19 days. Interestingly the rate seems to be about double that if you look at the last 19 days. I did not look past the totals but suspect that is highly dominated by South Korea (seems to be slowing), Italy and Iran (these two do not seem to be slowing). Might also be interesting to put a latitude metric in as well -- while I have a "sense" that more equatorial areas have a lower incident (and may be spread rate) I've not seen that data plotted anywhere.

Paper on some of nCOV's mutations

Incidentally, also strong evidence against it being a lab-strain. It's a wild strain.

Closest related viruses: bats and Malayan pangolins

Mutation Descriptions

Polybasic Cleavage Sites (PCS): They seem to have something to do with increased rates of cell-cell fusion (increased rate of virus-induced XL multi-nucleated cells). Mutations generating PCS have been seen in Influenza strains to increase their pathogenicity, and they had similar effects in a few other viruses. So it's not exactly increasing virus-cell fusion, it's actually... increasing the rate at which infected cells glom into nearby cells. Fused cells are called syncytia.

O-linked glycans : Are theorized (with uncertainty) to help the virions masquerade as mucin, so hiding from the immune system. (Mutation unlikely to evolve in a lab on a petri dish)

Arguments strongly in favor of it being a wild strain

  • It's not that similar to one of the known lab-strains, so it probably was wild
  • The "polybasic cleavage site" and "O-linked glycans" mutations would have required a very human-like ACE-protein binding site, so basically only human or ferret cells
  • O-linked glycans are usually evolved as an immune defense, which isn't something cell cultures do.

(Just following the recommendation to move this out of shortform so it can be tagged later.)

8Spiracular
Chinese virology researcher released something claiming it SARS-2 might even be genetically-manipulated after all? ZC45 and/or ZXC21 backbone. Claims that the RaTG13 genome was a concocted cover-up. After assessing, I'm not really convinced of the GMO claims, but the RaTG13 story seems to have something weird going on. https://zenodo.org/record/4028830#.X2EJo5NKj0v See here for my further thoughts on this. EDIT: After assessing, I'm not finding the GMO claims convincing. The RaTG13 story does seem to have something weird going on, and there's several people and papers that note weird inconsistencies (See the further thoughts, I don't have a simple explanation.).
4Spiracular
Additional little bit that reminded me of that cell-cell fusion trait... another paper described the SARS-CoV-2 autopsy results, and included this: Translation: The paper-thin, high-surface-area (for gas exchange) cells wrapping your lung balloons (the pneumocytes in your alveoli) fuse together with each other into an ineffectual, clumpy mess with a way lower surface-area-to-volume ratio. These are fragile cells to begin with; they don't even replicate themselves (other cells have to replace them when they break). They don't seem to be producing virus themselves, but they do seem to be getting badly screwed up by things the virus is doing.
3ChristianKl
What exactly does "lab-strain" mean here? Does it means a strain with a already published sequence?

More specifically:

  • It was not genetically modified for use as a bioweapon
    • The mutations don't resemble other well-known and well-characterized pathogenicity mutations too closely, in sequence or location
  • It probably wasn't cultured as cell-culture in a lab-setting for an extended period
  • The virus was not notable to science prior to this event

Or in other words, it doesn't look planned. Its most recent mutations look much more like a "natural variation let it jump species" sort of situation.

This doesn't address situations like, for example, "dead bats with a wild-type virus being left near a bunch of ferrets or pangolins," or something to that effect.

(ETA: Or... accidental release like this is still possible.)

1Spiracular
Despite the virus being characterized in pangolins, after looking into this, I now think it is basically incorrect to think of this as primarily a "pangolin virus." The pangolins were a dying canary in a coal mine, and probably caught it from something else that serves as the real reservoir species for this nCOV precursor*. See: further explanation here