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The case for C19 being widespread 2020-03-28T00:07:27.878Z
Preprint says R0=~5 (!) / infection fatality ratio=~0.1%. Thoughts? 2020-03-20T11:37:34.488Z

Comments

Comment by Hauke Hillebrandt (hauke-hillebrandt) on April Coronavirus Open Thread · 2020-04-17T10:12:34.838Z · LW · GW

[Years of life lost due to C19]

A recent meta-analysis looks at C-19-related mortality by age groups in Europe and finds the following age distribution:

< 40: 0.1%

40-69: 12.8%

≥ 70: 84.8%

In this spreadsheet model I combine this data with Metaculus predictions to get at the years of life lost (YLLs) due to C19.

I find C19 might cause 6m - 87m YYLs (highly dependending on # of deaths). For comparison, substance abuse causes 13m, diarrhea causes 85m YLLs.

Countries often spend 1-3x GDP per capita to avert a DALY, and so the world might want to spend $2-8trn to avert C19 YYLs (could also be a rough proxy for the cost of C19).

One of the many simplifying assumptions of this model is that excludes disability caused by C19 - which might be severe.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T18:28:20.113Z · LW · GW

Very good analysis.

I also thought your recent blog was excellent and think you should make it a top level post:

https://entersingularity.wordpress.com/2020/03/23/covid-19-vs-influenza/

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T16:15:37.612Z · LW · GW

Cheers - have taken this point out.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T16:09:54.494Z · LW · GW

Cruise Ship passenger are a non random sample with perhaps higher co-morbidities.

The cruise ships analysed are non-random sample: "at least 25 other cruise ships have confirmed COVID-19 cases"

Being on a cruise ship might increase your risk because of dose response https://twitter.com/robinhanson/status/1242655704663691264

Onboard IFR. as 1.2% (0.38-2.7%) https://www.medrxiv.org/content/10.1101/2020.03.05.20031773v2

Ioannidis: “A whole country is not a ship.”

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T15:46:43.107Z · LW · GW

Thanks Pablo for your comment and helping to clarify this point. I'm sorry if I was being unclear.

I understand what you're saying. However:

  • I realize that the Oxford study did not collect any new empirical data that in itself should cause us to update our views.
  • The authors make the assumption that the IFR is low and the virus is widespread and find that it fits the present data just as well as high IFR and low spread. But it does not mean that the model is merely theoretical: the authors do fit the data on the current epidemic.
  • This is not different from what the Imperial study does: the Imperial authors do not know the true IFR but just assuming a high one and see whether it fits the present data well.
  • But indeed, on a meta-level the Oxford study (not the modelling itself) is evidence in favor of low IFR. When experts believe something to be plausible then this too is evidence of a theory to be more likely to be true and we should update. An infinite number of models can explain any dataset and the authors only find these two plausible.
  • By coming out and suggesting that this is a plausible theory, especially by going to the media, the authors have gotten a lot of flag for this ("Irresponsible" - see twitter etc.). So they have indeed put their reputation on the line. This is despite the fact that the authors are prudent and saying that high IFR is also plausible and also fits the data.
Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T14:04:59.344Z · LW · GW

Cheers- corrected.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T10:45:28.298Z · LW · GW
It looks more like you listed all the evidence you could find for the theory and didn't do anything else.

That was precisely my ambition here - as highlighted in the title ("The case for c19 being widespread"). I did not claim that this was an even-handed take. I wanted to consider the evidence for a theory that only very few smart people believe. I think such an exercise can often be useful.

I don't think this is actually how selection effects work.

The professor acknowledges that there are problems with self-selection, but given that there are very specific symptoms (thousands of people with loss of smell), I don't think that selection effects can describe all the the data. Then he just argues for the Central Limit Theorem.

That the asymptomatic rate isn't all that high, and in at least one population where everybody could get a test, you don't see a big fraction of the population testing positive.

There's no random population wide testing antibody testing as of yet.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T10:30:28.158Z · LW · GW

I do not think that can be used as decisive evidence to falsify wide-spread.

This is a non-random village in Italy, so of course, some villages in Italy will show very high mortality just by chance.

That region of Italy has high smoking rates, very bad air pollution, and the highest age structure outside of Japan.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T09:44:05.659Z · LW · GW
By the end of its odyssey, a total of 712 of them tested positive, about a fifth.

Perhaps other on the ship had already cleared the virus and were asymptomatic. PCR only works for a week. Also there might have been false negatives. I disagree that the age and comorbidity structure can only lead to skewed results by a factor of two or three, because this assumes that there are few asymptomatic infections (I'm arguing here that the age tables are wrong).

In my post, I've argued why the data out of China might be wrong.

Iceland's data might be wrong because it is based on PCR not serology, which means that many people might have already cleared the infection, and it is also not random.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T02:39:31.136Z · LW · GW

That's true and that's what they were criticized for.

They argued that the current data we observe can be also be explained by low IFR and widespread infection. They called for widespread serological testing to see which hypothesis is correct.

If in the next few weeks we see high percentage of people with antibodies then it's true.

In the meantime, I thought it might be interesting to see what other evidence there is for infection being widespread, which would suggest that IFR is low.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T02:35:36.080Z · LW · GW

No. My ambition here was a bit simpler. I have presented a rough qualitative argument here that infection is already widespread and only a toy model. There are some issues with this and I haven't done formal modelling. For instance, this would be what would be called the "crude IFR" I think , but the time lag adjusted IFR (~30 days from infection to death) might increase the death toll.

Currently, also every death in Italy where coronavirus is detected is recorded as a C19 death.

FWIW, if UK death toll will surpass 10,000, then this wouldn't fit very well with this hypothesis here.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T02:32:43.350Z · LW · GW
The point remains: given that some people have such a different theory, it's unclear how many supporting pieces of evidence your should expect to see, and it's important to compare the evidence against the theory to the evidence for it.

Yes, that's what I'm trying to do here. I feel this is a neglected take and on the margin more people should think about whether this theory is true, given the stakes.

Presumably some of these people are hypochondriacs or have the flu? Also, I bet people with symptoms are more likely to use the app.
With all due respect it's not that hard to get data that you yourself find convincing, even if you're a professor.

""Our first analysis showed we're picking up roughly that one in 10 have the classical symptoms," he said. "So of the 650,000, we would expect to see 65,000 cases.

"Although you can have problems of self-selection and bias, when you’ve got big data like this you tend to trust it more. What we're seeing is a lot of mild symptoms, so I think having this data should help people relax a bit more and stop seeing it as an all or nothing Black Death situation.

"Other symptoms are cropping up. Thousands of people are coming forward to say they have loss of taste, and we may start to see clusters of symptoms.""

https://www.telegraph.co.uk/news/2020/03/25/monitoring-app-suggests-65-million-people-uk-may-already-have/

They do meet more different populations of people though. So if a small number of cities have relatively widespread infection, people who visit many cities are unusually likely to get infected.

You'd expect to see people to many severe cases amongst people who travelled for business a lot in January and February.

Not likely. About 1% of Icelanders without symptoms test positive, and all the stats on which tested people are asymptomatic that I've seen (Iceland, Diamond Princess) give about 1/2 asymptomatic at time of testing (presumably many later get sick).

I don't quite understand what you're saying here.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T01:48:52.622Z · LW · GW

I'm not impressed by the comment about this paper here on LW or the twitter link in it.

This paper was written by an international team of highly cited disease modellers who know about the Diamond Princess and have put their reputation on the line to make the case that this the hypothesis of high infections rate and low infection fatality might be true.

I think it is a realistic range that this many people are already infected and are asymptomatic. Above I've tried to summarize and review the relevant evidence that fits with this hypothesis.

But I'm not ruling out the more common theory (that we have maybe only 10x the 500k confirmed cases). I just find it less likely.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T01:38:34.045Z · LW · GW
There were a few dengue in Australia and Florida where it is unusual

Dengue "popping up in unusual places", makes me think that it's more likely that massive Dengue outbreaks in Latin America might have a high proportion of C19.

One person had persistent negative swab, but tested positive through fecal samples...
“Chinese journalists have uncovered other cases of people testing negative six times before a seventh test confirmed they had the disease.”

This is just to lend credence to the paper that shows there had been 2 million infections in China in January.

I find it very unlikely on the face of it that China, or any country for that matter, managed to suppress completely a disease so contagious that it's now on almost every country on earth.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T01:31:44.105Z · LW · GW
This seems pretty hard to evaluate because with a large number of published pre-prints on the outbreak, it's not very surprising that there would be many suggesting higher-than-expected spread.

No, this is different. I'm not just cherry picking the tail-end of a normal distribution of IFRs etc. The Gupta study in particular and some of the other studies suggest a fundamentally different theory of the pandemic.

Presumably some of these people are hypochondriacs or have the flu? Also, I bet people with symptoms are more likely to use the app.

Yes, but similarly there are many asymptomatic people who do not use the app. The King's Professor seems to find this number convincing.

Couldn't this be explained by those populations travelling more, shaking more hands, meeting more people, etc.?

Tom Hanks, Prince Charles and Boris Johnson don't talk meet more people everyday then your typical Uber driver cashier etc. There millions of people working in retail. We don't see them all having it. My theory is that they're tested often and not that "there's a lot of C19 in Westminster"

Iceland has 2 deaths and 97 recoveries. I would say that isn't good evidence for an IFR of under 0.3%.

Crucially depends on the asymptomatic rate, which might very well be very high.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on The case for C19 being widespread · 2020-03-28T01:00:52.970Z · LW · GW

If the Gupta study is true, then a rough approximation (ignoring lag) would be that it's:

IFR = Number of UK deaths (~750) / 36-68% of the UK population (66 million).

So 0.002% to 0.003%.

In Italy, with almost 10k deaths it would be 0.02%-0.04%

Comment by Hauke Hillebrandt (hauke-hillebrandt) on Preprint says R0=~5 (!) / infection fatality ratio=~0.1%. Thoughts? · 2020-03-24T20:21:18.485Z · LW · GW

Another preprint suggesting that half or more of the UK population is already infected:

FT coverage:

https://www.ft.com/content/5ff6469a-6dd8-11ea-89df-41bea055720b

study:

https://www.dropbox.com/s/oxmu2rwsnhi9j9c/Draft-COVID-19-Model%20%2813%29.pdf?dl=0

Comment by Hauke Hillebrandt (hauke-hillebrandt) on Preprint says R0=~5 (!) / infection fatality ratio=~0.1%. Thoughts? · 2020-03-21T16:55:04.805Z · LW · GW

from supplementary materials:

"DISCLAIMER: The following estimates were computed using 2010 US Census data with 2016 population projections and the percentages of clinical cases and mortality events reported in Mainland China by the Chinese Center for Disease Control as of February 11th, 2020. CCDC Weekly / Vol. 2 / No. 8, page 115, Table 1. The following estimates represent a worst-case scenario, which is unlikely to materialize. • Maximum number of symptomatic cases = 34,653,921 • Maximum number of mild cases = 28,035,022 • Maximum number of severe cases = 4,782,241 • Maximum number of critical cases = 1,628,734 • Maximum number of deaths = 3,439,516"

https://drive.google.com/drive/folders/18qaRKnQG1GoXamnzJwkHu2GG9xCe4w8_

Comment by Hauke Hillebrandt (hauke-hillebrandt) on Preprint says R0=~5 (!) / infection fatality ratio=~0.1%. Thoughts? · 2020-03-21T16:45:49.804Z · LW · GW

And yet another preprint estimating the R0 to be 26.5:

Quotes from paper:

"The size of the COVID-19 reproduction number documented in the literature is relatively small. Our estimates indicate that R0= 26.5, in the case that the asymptomatic sub-population is accounted for. In this scenario, the peek of symptomatic infections is reached in 36 days with approximately 9.5% of the entire population showing symptoms, as shown in Figure 3."

I think they estimate about 1 million severe cases in the US alone if left unchecked at the peak.

"It is unlikely that a pathogen that blankets the planet in three months can have a basic reproduction number in the vicinity of 3, as it has been reported in the literature (19–24). SARS-CoV-2 is probably among the most contagious pathogens known. Unlike the SARS-CoV epidemic in 2003 (25), where only symptomatic individuals were capable of transmitting the disease. Asymptomatic carriers of the COVID-19 virus are most likely capable of transmission to the same degree as symptomatic."

"This study shows that the population of individuals with asymptomatic COVID-19 infections are driving the growth of the pandemic. The value of R0 we calculated is nearly one order of magnitude larger than the estimates that have been communicated in the literature up to this point in the development of the pandemic"

Comment by Hauke Hillebrandt (hauke-hillebrandt) on Preprint says R0=~5 (!) / infection fatality ratio=~0.1%. Thoughts? · 2020-03-20T23:48:13.992Z · LW · GW

And another preprint saying there were +700k cases in China on 13th of March:

"Since severe cases, which more likely lead to fatal outcomes, are detected at a higher percentage than mild cases, the reported death rates are likely inflated in most countries. Such under-estimation can be attributed to under-sampling of infection cases and results in systematic death rate estimation biases. The method proposed here utilizes a benchmark country (South Korea) and its reported death rates in combination with population demographics to correct the reported COVID-19 case numbers. By applying a correction, we predict that the number of cases is highly under-reported in most countries. In the case of China, it is estimated that more than 700.000 cases of COVID-19 actually occurred instead of the confirmed 80,932 cases as of 3/13/2020."

also implying a lower CFR than previously thought (perhaps less than 0.5%). 3k deaths in China / 700k actual cases)

Comment by Hauke Hillebrandt (hauke-hillebrandt) on Preprint says R0=~5 (!) / infection fatality ratio=~0.1%. Thoughts? · 2020-03-20T23:23:33.548Z · LW · GW

New editorial about the asymptomatic rate in Nature - the author of the preprint above are featured in this as well. They say asymptomatic and mild case rate might be up to 50% of all infections and that these people are infectious.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on Preprint says R0=~5 (!) / infection fatality ratio=~0.1%. Thoughts? · 2020-03-20T15:29:58.879Z · LW · GW

As mentioned in a comment above, one of the (pretty highly credentialed) authors of this preprint has written two papers on the Diamond Princess, and so, excuse the appeal to authority, but any argument against this paper based on Diamond Princess doesn't seem likely to invalidate conclusions of this preprint .

Also this squares seemingly squares more with John Ioannidis take on Corona:

"no countries have reliable data on the prevalence of the virus in a representative random sample of the general population."

And that airborn-ish transmission is highly likely.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on Preprint says R0=~5 (!) / infection fatality ratio=~0.1%. Thoughts? · 2020-03-20T15:19:02.104Z · LW · GW

Not sure: the Diamond Princess is mentioned in this preprint and in fact one of the authors of this preprint wrote two papers on the Diamond Princess:

https://scholar.google.com/citations?hl=en&user=OW5PDVgAAAAJ&view_op=list_works&sortby=pubdate

So I think they thought about this,

Comment by Hauke Hillebrandt (hauke-hillebrandt) on Should we build thermometer substitutes? · 2020-03-20T12:00:35.820Z · LW · GW

The first paper that I cite has a very illustrative video and is a seminal paper in this field.

Table 8 in the review paper that you refer to shows a trend of estimation techniques getting better over time. In the latest study from 5 years ago the mean error was down to 6.47.

My broader point is:

  • the error rate might be brought down even further by better methods, video quality, and priors
  • this might so that it a valid proxy for fever
  • This might be very cost-effective on a population level, given the zero marginal cost of software

However, I do agree that this is not trivial.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on Should we build thermometer substitutes? · 2020-03-19T21:25:43.795Z · LW · GW
That's false. The accuracy isn't high. I learned from the last conversation I had with EA who had a startup that did this, that the accuracy isn't high enough to be useful medically.

Interesting data point - there are several papers on this that say it's a reliable way to measure heart rate (less than 10bpm; see "Heart rate estimation using facial video"). Perhaps this could be brought down much further by throwing more engineering brains, computation and priors at it.

Where do those ≥38°C come from? From what I read the Chinese are using 37.3°C as a cut of for medical decision making with COVID-19.

I saw this number in some places - for instance:

https://www.who.int/csr/disease/coronavirus_infections/InterimRevisedSurveillanceRecommendations_nCoVinfection_03Dec12.pdf

https://www.nejm.org/doi/full/10.1056/NEJMc2003100

But perhaps your number is better (source: https://www.who.int/csr/disease/coronavirus_infections/InterimRevisedSurveillanceRecommendations_nCoVinfection_03Dec12.pdf ).

I think there might be non-trivial differences due to time of the day and ethnicity as well.

Comment by Hauke Hillebrandt (hauke-hillebrandt) on Should we build thermometer substitutes? · 2020-03-19T15:29:03.827Z · LW · GW

I had this idea below and pitched it to OpenAI - they said ""we looked into this and dont think we can do a great job with it :(" - but perhaps people here might be interested to explore it further.

Idea for zero marginal cost, digital thermometer to help contain coronavirus:

  1. Heart rate can be estimated via (webcam or smartphone) video of someone’s face with high accuracy (even with poor video quality).[1],[2]
  2. This heart rate might then be used to detect fever[3] (perhaps even to estimate core temperature).[4]  priors such as demographic data could be used to aid detection. For instance, mean heart rate over an hour of +80 in young healthy men seems to be a robust predictor of fever.3
  3. Fever (body temperature ≥38°C) is the most typical symptom of C19 - in 88% of confirmed cases.[5] (Though some C19 transmission might be asymptomatic[6] and presymptomatic.[7],[8])
  4. A smartphone or web app (ala donottouchyourface.com) could be a digital fever thermometer. A webcam could continuously monitor people’s temperature and alert them to it if they have a fever (might detect anomalous increases in heart rate).
  5. ‘Thermometer Guns’ have drawbacks: they’re more expensive, you need to get close to someone’s head to take temperature, they are not very accurate, they don’t provide continuous measurement- yet it is still used for coronavirus containment.[9]

This might be a very cost-effective intervention to diagnose coronavirus.

Audio could be recorded to detect dry cough.[10], [11]

Can Smart Thermometers Track the Spread of the Coronavirus?

Non-EEG Dataset for Assessment of Neurological Status v1.0.0

[1] "Detecting Pulse from Head Motions in Video - People.csail.mit ...." http://people.csail.mit.edu/balakg/pulsefromheadmotion.html. Accessed 18 Mar. 2020.

[2] "Heart rate estimation using facial video: A review - ScienceDirect." https://www.sciencedirect.com/science/article/abs/pii/S1746809417301362. Accessed 18 Mar. 2020.

[3] "Fever and Cardiac Rhythm | JAMA Internal Medicine | JAMA ...." https://sci-hub.tw/https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/606966. Accessed 18 Mar. 2020.

[4] "Real-time core body temperature estimation from heart ... - NCBI." 13 May. 2015, https://www.ncbi.nlm.nih.gov/pubmed/25967760. Accessed 18 Mar. 2020.

[5] "Report of the WHO-China Joint Mission on Coronavirus ...." https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf. Accessed 18 Mar. 2020.

[6] "Presumed Asymptomatic Carrier Transmission of COVID-19 ...." 21 Feb. 2020, https://jamanetwork.com/journals/jama/fullarticle/2762028. Accessed 18 Mar. 2020.

[7] "Potential Presymptomatic Transmission of SARS-CoV ... - NCBI." https://www.ncbi.nlm.nih.gov/pubmed/32091386. Accessed 18 Mar. 2020.

[8] "Transmission interval estimates suggest pre-symptomatic ...." 6 Mar. 2020, https://www.medrxiv.org/content/10.1101/2020.03.03.20029983v1. Accessed 18 Mar. 2020.

[9] "'Thermometer Guns' on Coronavirus Front Lines Are ...." 14 Feb. 2020, https://www.nytimes.com/2020/02/14/business/coronavirus-temperature-sensor-guns.html. Accessed 18 Mar. 2020.

[10] "A Cough-Based Algorithm for Automatic Diagnosis of ... - NCBI." 1 Sep. 2016, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008773/. Accessed 18 Mar. 2020.

[11] "Cough Sounds | SpringerLink." https://link.springer.com/chapter/10.1007/978-3-319-71824-8_15. Accessed 18 Mar. 2020.