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Coronavirus: Justified Key Insights Thread

by Ben Pace 2 min read13th Apr 202032 comments

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This is a thread to list important insights and key open questions about the coronavirus and the coronavirus response. The inspiration for this thread is Eliezer's post below.

I'd like this thread to be a source of claims and ideas that are self-contained and well-explained. This is not a thread to drop one-liners that assume I've been following your particular news feed or know what's happening in your country or that I've read a bunch of studies on (say) viral load. There's a place for such high-context discussion, and it is not this thread.

Please include in your answers either a claim or an open question, along with an explanation or an explicit model under which it makes sense. I will be moving answers to the comments if they don't meet my subjective quality bar for justification – see the last justified answers thread for examples of what quality answers look like.

The purpose of giving models and data is to allow other people to build on your answer. Everyone can make arbitrary claims, but models and evidence allow for verification and dialogue.

The more concrete the explanation the better. Speculation is fine, uncertain models are fine; sources, explicit models and numbers for variables that other people can play with based on their own beliefs are excellent. 

This thread is inspired by a post by Eliezer Yudkowsky which I'll reproduce below, in which Eliezer lists eight answers that this sort of post would come up with. 

These are not justified to the standard of the thread, so you (you!) can get some easy karma by leaving an answer that justifies one of these with the sources/data/explanation needed to argue for it. It includes much of the discussion elsewhere on LW (e.g. by Wei Dai, Zvi, Robin, and others), so it shouldn't be hard to find the prior discussion.

Eliezer's post (link):

What do we early-warning cognoscenti now know about Covid-19 that others haven't currently figured out? What's the TOC of that blog post? @WilliamAEden @robinhanson

My stab at a TOC:

1: The Dose Hypothesis - the theory that C19 fatalities vary by how high the initial dose, and possibly how it's administered. 

1a: So: Human trials of variolation are hugely urgent. 

1b: So: Getting C19 from a roommate might be much worse than getting it on public transportation.

2: Challenge trials of vaccines save net lives.

3: Ventilators no longer look as important because they only save 15% of the patients on them. 

4: There's huge apparent variation in CFR by country, and explaining this, or explaining it away, seems kinda important. 

4a: CFRs may be underestimated by up to 3-fold, based on looking at excess death rates year-over-year. 

4b: CFRs may be overestimated because of too little testing. 

5: There was a huge EMH failure w/r/t C19, and it hasn't been explained away AFAIK.

6: Most of the economic damage from a real shock like this one is still due to the secondary demand shock, which can be prevented by decisive central bank action.

6a: We know the Fed isn't currently doing enough here because inflation expectations are dropping, showing the AD shock exceeds the AS shock. 

6b: Stock prices take into account the next 15+ years of earnings. The real C19 shock only damages the next 2 years of earnings. A financial recession would damage many more years. Stock prices mainly reflect central bank policy, not C19.

7: Face masks do work, though others seem to have mostly figured this out.

8: The mainstream media's words on C19 may be best interpreted as not intended to mean things; like the way that MSNBC's talk about Bloomberg being able to give each American over $1,000,000 can't have had a concrete model of reality behind it.

Any items I'm missing here?

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3 Answers

Claim: The true infection-to-fatality ratio is definitely about 0.5% to 1%, and most probably around 0.7%, with significant long term morbidity in at least several percent of survivors. Notions that this disease is already widespread or that it has flulike mortality and morbidity or most people are asymptomatic are definitively disproven.

This has been independently estimated in this range before, based on normalizing data from the Diamond Princess and areas where testing was thorough

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30243-7/fulltext

https://www.medrxiv.org/content/10.1101/2020.03.05.20031773v2

There are a few robust new pieces of data supporting this now.

1 - Blanket RNA testing in Austria.

https://www.theguardian.com/world/2020/apr/10/less-than-1-of-austria-infected-with-coronavirus-new-study-shows

Given a 0.3% current acute infection rate and some epidemiological modeling they estimate 1% of their total population has been infected at some point, with a death rate of 0.77%. Maybe a few false negative PCRs, which would lower that number.

2 - Two serology surveys have now happened in Europe. One was in a hard-hit town in Germany, and one was in a hard-hit town in Italy at the epicenter of its outbreak. In both places, they got approximately a 15% seropositive rate. In Germany, we only have information on deaths with positive test results and it comes to 0.35%. In Italy, total excess deaths over this time last year are about 2.5x the confirmed positive deaths and account for 0.1% of the population, giving an infection fatality rate of 0.7%. It is easy to imagine that some deaths did not get positive tests in Germany which along with a less-old population could make up for the difference.

3 - New test data coming out of NYC.

https://www.nejm.org/doi/full/10.1056/NEJMc2009316

Hardly an unbiased sample, but of 200+ pregnant women coming into a hospital to give birth that were blanket-RNA-tested, 15.3% tested positive.

Of this set of positive tests, only 12% of them were symptomatic on admission, and a further 10% developed symptoms over the course of their 2-day-long stays bringing it to a total of 22% symptomatic upon discharge or transfer. Presumably already-symptomatic very-pregnant women were more likely to be in the hospital already.

Doing a little armchair epidemiology. Let's assume that half of the deaths of currently infected people have happened, due to the lockdown extending the doubling time from three days to more than a week. We get:

~8000 deaths * 2 / (15.3% of 8 million) = 1.3% infection to mortality rate.

If we assume that there were more symptomatic women who didn't show up to normal birthing due to going to the hospital for COVID symptoms, or that there is a good stock of people who have recovered in the city, we get a lower death rate. If 20% of the total population was ever infected, we get a 1% mortality rate. 30% ever infected, 0.67%.

EDIT: 4 - Apparently there is a similar maternity ward study in Stockholm, revealing 7% positive. There have been 550 deaths there, and a population of 2.3 million. If we again assume half of current cases that will die has died, we get a infection to fatality ratio of 0.68% without further corrections. I suspect they haven't crushed the doubling time as much as NYC, raising this number, which then can get lowered down again as I did above.

EDIT: 5, a meta analysis of a whole bunch of research comes to exactly my original conclusion, 0.5% to 1% with a central tendency of 0.8%.

https://t.co/51b3bJYg3e?amp=1

Claims:

Severe cases should be treated with anticoagulants

Inhaled interferon, antivirals, and other effective treatments are probably much more effective when taken early to prevent the first few replication rounds.

A case is probably followed by a period of immune suppression, and possibly some T-cell immunity amnesia.

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The virus may be causing abnormal inflammation and a whole-body, but especially concentrated in the lungs, hyper-coagulable state that is triggering microscopic blood clots in the lungs that are one of the main contributors to morbidity and mortality and ineffectiveness of ventilation. Effective treatment of severe cases should probably include anticoagulants unless there are contraindications, and another effective treatment has been an interleukin inhibiting antibody normally reserved for severe arthritis. See the entire recent twitter diggings of @_ice9.

There have been major reports from clinicians that the lungs of COVID patients are not responding the same way as typical ARDS. The ability to get oxygen in the blood is too low compared to the amount of air they can get into them. Autopsies are revealing lots of small clots, and blood tests are finding the most predictive measurement of outcome is an indicator of blood clot dissolution (D-dimer).

Children with non-severe cases are having anomalously high rates of sores and discoloration on fingers and toes, indicative of diffuse coagulation in small vessels causing mild tissue damage that seems to heal on its own afterwards.

This hyper-coagulable state *might* explain the reports of anomalously low oxygen measurements in people that would ordinarily indicate death or unconscoiusness. They might have small clots in the finger the sensor is on triggering temporary sporadic low blood flow. It also could explain more of the fact that ventilators are less useful than they thought - some people going on them probably didn't actually need them.

(Before anyone asks, that preprint that was making the rounds suggesting the virus was destroying hemoglobin was STUNNINGLY and EMBARRASSINGLY bad. Complete bullshit, not worth even hate-reading unless you find fantasy biochemistry from a universe in which chemical reactions have energies you normally associate with nuclear reactors and viruses do photosynthesis funny).

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Additionally, there are two bits of immunology that explain parts of this virus's behavior and suggest ways of hurting it. First, the virus evolved in bats in which the interferon response is on an absolute hair trigger, and accordingly in human cells it almost completely escapes the interferon response. This allows it to replicate to absurd viral loads before the immune system notices it, explaining the extreme infectiousness shortly before symptoms develop. Then when the immune system notices it, it goes all out on a huge viral infection, triggering an inflammatory response that is all out of whack and can do a lot of damage. This means that it is vulnerable to inhaled interferon pretreatment (https://www.biorxiv.org/content/10.1101/2020.03.07.982264v1). On top of this, it may be that anything that reduces the replication of the virus in this period before the adaptive immune system mounts a robust response could reduce the probability of progression to severe disease. If antivirals work out or if chloroquine is effective (given the biochemistry I am very hopeful!), they will probably be most effective early via reducing the fraction of patients that progress to severe disease.

Second, there is evidence that the virus is able to enter and destroy (but not replicate within) T-cells using the same receptor it uses everywhere else, triggering immune suppression and altering the inflammatory profile (https://www.nature.com/articles/s41423-020-0424-9). It lacks HIV's obscene dirty tricks and isn't actually replicating within them, so this would be a temporary thing until recovery.

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That last bit may sound bad, but it is far from unique. When looking for other examples, one should look to the Measles virus. It too basically escapes the interferon response and grows to absurd highly-communicable levels (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC112268/), and it actually infects and replicates within T-cells and B-cells which it then rides throughout the body. This causes people who get the measles to basically forget 70% of their adaptive immune responses from before they were infected, and go through a period of immune suppression afterwards. I expect the loss of immune memory to be smaller in this case because the new bug doesn't seem to infect B cells or all types of T-cells from what I have seen.

Hi everyone. I've been reading Less Wrong and related material off and on for a few years, and I finally made an account and this is my first comment.

5: There was a huge EMH failure w/r/t C19, and it hasn't been explained away AFAIK.

I also wondered why it took so long for the market to react in February to the likelihood of a pandemic, especially after cases were increasing in Italy and Iran suggesting it could easily spread worldwide. I'm not a big trader, basically just buying and holding index funds for the long term, and the only thing I did differently was to hold off buying more at the peak - instead waiting for what seemed like an inevitable fall before buying (although I didn't wait long enough). After reading Wei Dai's posts about his strategy during this time, it seemed clear that the EMH hadn't performed well here and I wished I had been more confident in my own analysis beforehand.

Later, it occurred to me that there are relatively few individuals who trade at high enough volumes to actually influence market prices, most of whom work for financial institutions. I've never worked in that industry, but I imagine employees are subject to the same social pressures as any company, including a reluctance to act differently than what is culturally acceptable within the organization (especially to take a culturally unacceptable risk which may look foolish initially). Since financial firms generally believe in the EMH, it would be very difficult for an individual employee to act otherwise. A low or mid-level trader is probably authorized to make trades based on any financial news, but they probably can't just go their manager and say "I think I know better than the entire world that this pandemic will be worse than expected and lower stock prices, and the EMH hasn't priced it in yet." Even if a few investors do trade on that assumption, they will initially be overwhelmed by algorithmic trading which would tend to revert prices back to the previous EMH-based equilibrium. The markets wouldn't actually move until either 1. effects from the pandemic start to change actual financial data, and the trading algorithms begin to account for that, or 2. most of the top leaders of financial institutions become convinced prices should go down, and make it socially acceptable for their employees to sell large volumes of stock or change their trading algorithms accordingly.

Until then, there could be a temporary inadequate equilibrium where nobody who has the power to move market prices has a socially acceptable reason to do so. In this situation, rational individual investors who don't face these organizational social constraints may be able to outperform the EMH.

Maybe a version of the EMH that takes this into account would be "stock prices accurately reflect all public information that is socially acceptable for high-volume traders to base trades on" or something similar.

Others have written here about similar thoughts on the EMH failure, including Matthew Barnett and Alex Shleizer, but I haven't seen it proposed explicitly as a result of social pressures or incentives within organizations before, so I thought this could add to the discussion. As I mentioned, I don't work in the financial industry, so I welcome the comments of those who have more relevant experience in the field.