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A Third Solution (paulbuchheit.blogspot.com)
673 points by rafaelc on April 24, 2020 | hide | past | favorite | 516 comments

I was curious about the company that's being touted in this post so I did a little searching. The website doesn't seem to have much on it.

I guess it's a YC17 company. The founders are Caroline Landau, Tim Cornell, Walker McHugh. From 2016: Landau was an MBA candidate, the other two founders have biomedical research/medical backgrounds: Walker McHugh, Co-Founder, PreDxion Bio / Biomedical engineering candidate, University of Michigan Dr. Tim Cornell, Co-Founder, PreDxion Bio / Pediatric Critical Care Physician, University of Michigan (https://www.hbs.edu/openforum/openforum.hbs.org/goto/challen...)

At least until recently, the company focused on making diagnostics for immune disorders (microkine) for CAR-T patients which I can't find much detail on. I don't know if it's related to the SPR-based tests mentioned in the pb post.

They received a government business grant (SBIR) in 2018 and have some VC funding.

It looks like this post demonstrates their pivot to a specific infectious disease, and from a hospital provider setting to a public setting.

As an ex-advisor to a successful (in bio) VC fund, this is not something I would really spend a lot of time considering. There are too many non-technical hurdles that would need to be jumped before this was widespread, popular, effective, and profitable.

Hi, Walker here, one of the PreDxion co-founders. Up until recently we've been focused on developing our technogy as a point of care biosensor for us in patients experiencing dysfunctional immune responses (e.g., sepsis, ARDS, and the immune responses induced by certain cancer immumotherapies).

The technical implementation of a viral detection assay is much simiplier to implement than our quantitative, multiplexed small MW biomarker sensors... But there are certainly many other hurdles that remain as you point out as well as the additional biological uncertainty that remind around SARS-CoV-2 it's infectious course as well as our bodies subsequent immune responses.

There are certainly many hurdles left to be tackled but that's exactly what we're working towards.

It’s critical to not underestimate the non-technical steps here, in terms of how do you deploy at scale, convince venues to install, deal with throughput rates, tie results to individuals, etc. All solvable, but it’s important to think about those sooner rather than later. I have some experience on the security side here and how to deploy technologies like this at scale... happy to help (my email is in bio).

Yup, lets look at the actual and physical supply chain of “at scale” to be tackled to succeed.

And i am wishing them success, and my brother is the director of the VA for the entire state of Alaska, an Airforce Colonel (commander, tenth medical wing) and ive personally built/designed/commissioned 10+ hospitals (el camino, sf general, sequoia, nome, and more)

((All on the tech implementation and design side))

Anything i could contribute i would.

(My creds can be freely confirmed)

What TRL are you at for the original POC test, and what TRL are you at for viral detection? Any published papers for viral detection?

Are TRLs usually used outside of government R&D related things? If they got an SBIR I guess they'd be familiar with the technology, but I'm only familiar with it because of DoD funding applications and stuff, it's not terminology I've seen used in the private sector too much. Maybe it is, I'm curious to know if that's the case. I've usually only heard stages of tech development discussed in terms of preclinical, clinical stage, and other regulatory frameworks rather than tech readiness level necessarily.

I’ve seen TRLs used in tech transfer offices and engineering departments in academia; NIH and NSF (usually associated with SBIR programs) as well as the DoE; in medical device and pharma manufacturing; and in life science VC groups. In private companies and VCs I’ve heard it used most in management and BD contexts. I think TRLs can provide a useful second axis to the more common clinical or regulatory development staging.

Agreed. TRL (tech readiness level) isn't something commonly used outside government.

Right, I think we’ve probably missed boat on developing new diagnostic methods for Sars-CoV2.

In particular, this method appears to be antibody based? (Which has accuracy issues) and uses SPR, which may involve some technical risk.

However, I think there’s mileage in developing methods now for the next pandemic. My personal interest is in developing programmable qPCR-like systems [1]. So that kits can be deployed ahead of time, and then programmed to a specific target as required. If anyone is interested in discussing diagnostic approaches, please get in touch.

[1] http://41j.com/blog/2020/03/thoughts-on-a-new-approach-to-vi...

I'm not familiar with the acronym PSM. Can you expand?

Are you familiar with the work of Dr. Chui at UCSF? His group has done some really cool work using mNGS to detect/diagnose emerging/rare infections in critically-ill patients with refractory encephalopathy

Sorry, typo. I meant SPR (surface plasmon resonance).

I’ve worked at a number of NGS platform companies developing new sequencing approaches. The problem is that sequencing is still expensive at the per-run level. It’s possible to be cost competitive with qPCR if you multiplex samples. But this isn’t ideal.

It would be interesting to create a small/cheap sequencer which could be applied to point-of-care/at-home testing. However, most of the money has gone after attacking the market leader (Illumina) on a cost-per-base, rather than cost-per-run.

A 1USD per-run sequencer would be interesting. But I’ve not seen anything that will hit that target in development. If anyone reading this is developing such a system, let me know, I’d love to get involved.

The idea of a programmable qPCR system is to add some of the versatility of sequencing to qPCR.

We've developed something NGS-based we call SwabSeq. You can find out more here: https://www.notion.so/Octant-SwabSeq-Testing-9eb80e793d7e463...

You can get to $1/sample; but need >1000 samples/run at least to get to that cost level. Could run 10k/day without automation; likely a lot more (100k-1MM) with automation.

Oh, nvmd. I just saw you wanted a $1/run. Something ONT based perhaps.

Wouldn't many of the non-technical hurdles be reduced in the current situation? FDA approval steps for example have been relaxed for potential treatments. It's not my area, but I'm just curious what makes it so impossible or unlikely.


I would love to hear about your advisor role experiences with VC funds. Would you be up for a short chat/call? My email can be found in my profile.

Background: Chemistry/Startups, looking what to do next with my life.


Quotes from the article:

“It’s easy to fall into dystopian visions of the future — a world shut down by one virus after another”

“It doesn’t have to be that way. ..... Ubiquitous screening is the key.”

The approach is interesting and the possibility of eliminating large scale spread of covid, flu and others is attractive.

However the idea of requiring a saliva swab from every visitor to an office or event has the potential to create an equally terrifying dystopian future where those samples are used to collect and use other data (DNA for example).

How long before screening companies offers to provide free screening and access control systems in return for anonymised data?

This kind of solution needs to have very well thought out privacy rules supported by strong and enforceable legislation to protect the individuals rights.

Reminds me of that access control system in the movie Gattaca, where you had to give a blood sample ;-)


An easy fix would be to require that all saliva samples are disposed of into the same container, mixing all samples of all tested persons.

Or you do the test yourself, and just show the already-completed test to the guy at the office door, and keep the test hardware, just like you currently show but keep an ID badge.

Sure, some people could fake the test, but for this approach to work, all that matters is that most people don't fake it.

Perhaps, but if you think about how systems like this work today, for example scanning ID at the entrance to a nightclub or bar.

One way something like this is likely to be implemented is by validating a ticket or access card/token with a saliva swab. This is just too easy and attractive an opportunity for data collection to be passed up by some operators with business models that monetise the data as a revenue source.

The swab could be ok, but I’d get really annoyed if entering any place required me to wait around for 10 minutes.

My Millennium Prize challenge for those clamoring to reopen the economy is: How do you reopen Disneyland? (I think Disneyland was even referenced in the article.)

That's a giant social space people would be clamoring to go to. But given Disneyland's mystique and raison d'etre, the logistics right now are impossible.

I don't know how viable the solution proposed here actually is. The skeptics here raise some good points.

But if this solution turned out to be proven, I expect Disneyland would be one of the first places where it was deployed at scale. If we trusted the technology, I'm pretty sure both you and I would be happy to wait 10 minutes to get in. A free COVID screen as part of your price of admission. (It's interesting to consider how they would handle people who failed the screening. A balloon and hauled away in a cheerful corporate van? Maybe Disney starts running COVID resort sanitoriums?)

I also imagine Disney is one of the few organizations out there that could get the queuing sorted out. And I suspect that would be as important as anything. Once perfected, it could serve as a model for others.

Waiting in line for a venue can easily take 20-30 minutes. So why not deploy this to places like this. You get the test done while waiting in line at no extra time cost to you. So you wouldn't even be waiting 10 min to get in. That's already something you do.

At attractions and large events, maybe an app (or just a database linked to some sort of ID) to prove a person has passed the screening that day (or recently enough), so it doesn't all need to be done at the attraction/event itself?

For this purpose the screening would probably have to be carried out at locations that could confirm the sample came from the right person at the right time.

This isn't a unique idea. This is the mainstream view. Everyone knows we need more testing and that testing is the only way to effectively ease distancing rules. That was a pretty extensive writeup to say what we've been hearing from all rational information outlets for a month.

I have not found any mainstream sources that advocate screening everyone every day (which is very different from simply doing "more testing"). Would love some pointers if I'm wrong.

Paul Romer, an economist at NYU, has been advocating for testing millions of people a day for a few weeks. He is co-author of a piece in The Atlantic, "Without More Tests, America Can’t Reopen", https://www.theatlantic.com/ideas/archive/2020/04/were-testi...

Googling for "romer covid 19" should turn up a lot of news sources covering the notion of testing millions of people a day.

Yes, he is the best I've found. This proposal is still at least an order of magnitude more testing though :) (on the order of 100 million tests/day, not 1 million tests/day)

Romer has called for as much as 30 million tests a day, which I think was based on some simplistic modeling. I think he was targeting everyone in the US being tested every two weeks. I think the two approaches are similar: let's test lots of people all the time, however many X million tests a day that is, so that we can quickly isolate and treat them. People are spreading it before they know they have it, so let's just test everyone all the time and not wait until they have symptoms.

Basically like the porn industry.

This is a really good analogy actually. The porn industry has higher risk for STDs but lower incidence than the general population.

Paul Romer is also a recipient of the Nobel Prize in Economics.

> I have not found any mainstream sources that advocate screening everyone every day

That's because we currently aren't capable of testing everyone who is obviously sick just once. If we got there, we wouldn't even be close to being capable of testing key personnel (like health care workers). If we got there we wouldn't even be close to being able to test everyone once. If we got there we wouldn't even be close to being able to test everyone every day.

You haven't heard any advocating for OR against it because it is so far from achievable that it isn't worth considering.

If this concept would work in principle, covid could be reduced to scaling testing capacity. My impression is that estimates about achievable testing capacity don't assume a most-important-short-term-problem-of-mankind priority and resource allocation.

The linked article suggests a novel and much cheaper test, which would be great. But even if that didn't work out, what scale could possibly be feasible with existing tests? Pre-shortage, an RT-PCR seemed to be much cheaper than a missed day of work.

The concept for restarting the German football league involves daily testing of all players. So the idea is indeed widespread, but often enough just impractical for the numbers of tests required.

Testing a few hundred people daily would be doable, as Germany has relatively good testing capacity - probably one main reason for the overall better handling of the pandemic so far. But the concept still gets critisized, as this would mean a fast track to testing for the players while parts of the population don't have equal access to testing.

For the whole population, it would be a good first step to be test really everyone who has any assumptions of symptoms and some time later, everyone in contact. And perhaps a biweekly test for the general population.

I would expect where there's a large enough economic incentive, and wealthy-enough private group (say, the NFL, MLB, etc) who wouldn't need to wait for government policy or supply, we will see daily testing of their 'employees' so that they can get back to operating. May not be any fans in a live setting, but better than nothing.

> screening everyone every day (which is very different from simply doing "more testing").

That seems like the logical conclusion of "more testing" to me. If we could, why wouldn't we?

3blue1brown on YouTube did an analysis which similarly shows that fast quarantining is the best way to mitigate the virus: https://www.youtube.com/watch?v=gxAaO2rsdIs

I think governor Cuomo was saying he'd love to test every day if he could, but just doesn't have the capacity. Edit: as a side note he put out a call for companies that can help with testing saying that NY state might be willing to invest to bring things to scale. I believe he already wanted FDA approved tests but there's an opportunity there to work directly with a government to implement this sort of thing.

IIRC, mainstream objections tend to come from concerns of false positives, since that becomes a bigger problem with this frequent level of testing and could prove a huge disruption if you end up with too many quarantine still, or so many that testing positive becomes essentially meaningless in terms of telling you whether you have the disease or not if you test positive.

Gov Cuomo should call up Gov Pritzger. Illinois recognized the challenge of testing supplies and asked the state universities to solve the problem. They have. Illinois is reporting a lot more positive cases in the past week because they keep increasing the number of daily tests. I believe that today was well over 12000 tests in Illinois. Anyone who feels like getting tested is now allowed to get a test.

New York has done more tests and more tests per capita than any other state per latest numbers - the reason for more tests isn't just to test people who want it, it's to run large random tests, require tests before visiting nursing homes, get an accurate picture of the infection rate, etc. We're testing more per capita than most countries in the world and it's still not enough. We've tested approximately 4 times as many people with only about a 50% higher population than Illinois and it's still not enough.


Sorry, I wasn't clear. Illinois has built out their own manufacturing supply chain and testing facilities. They are self-sufficient. If New York wants to scale up testing and has money to invest in doing so, they should look at how Illinois managed to make that happen.

This is maddening reading this thread. What is the reason for a federal gov't but to coordinate such cooperation? It goes back to creation of the "United States"! (this is hypothetical question, not one i expect you to answer)

Honestly, at this point I wouldn't be surprised if New York has tested more people per capita than all the comparably-sized countries in the world. There's a few countries which have beaten them, but it's generally small ones like Iceland.

Christian Drosten (German virologist, one of the most prominent experts here) has been advocating daily testing of medical workers. This is a slightly easier situation, since you can trust them to swab themselves, and the logistics for collecting samples is already in place.

Can you trust them to swab themselves if their livelihoods depend on them attending work? The testing is only one component there I think.

In Germany, and generally in Europe, yes.

Being off work for such should not result in severe reduction in income unless your income was already high; at least that is the case here in Norway where laid off personnel get 80% of their normal salary up to a limit that is above average salary.

Edit: typos

Every single country that has had any success containing the virus, including the origin country of China, has had rigorous continuous testing to contain the spread. It's hard to find a country with success containing the outbreak that doesn't do constant ubiquitous testing.

> Every single country that has had any success containing the virus ... has had rigorous continuous testing to contain the spread

That's demonstrably false. There are numerous prominent examples in fact.

Taiwan is not doing a high rate of testing at all, they're most certainly not doing constant ubiquitous testing. Their per capita test rate is 1/7 that of the US.

Singapore and South Korea are not doing constant ubiquitous testing. The US has already tested at a higher rate than South Korea and will pass Singapore shortly given the continued ramp in US testing. Both are held up as marvels of virus containment.

Japan has barely done any testing. They're seeing a small spike in cases now, however they were not earlier (this is four plus months after the outbreak began and Japan is next to China). Their deaths from Covid are commonly 1/50 to 1/150 the per capita rate of the US and other higher outbreak nations, while doing 1/10 to 1/15 the testing. The only explanation is either that they're covering up ten thousand deaths, or the other non-testing approaches they've utilized work well. Compare Japan to Germany on Covid deaths - again, despite Japan being next to China - and then look at the testing rates. Now explain that.

Finland is testing below the US rate and has contained the outbreak to a stellar degree. That's because Helsinki is colder than Stockholm and Copenhagen. The same reason Moscow didn't get slammed until more recently as the weather began to warm up. There are other factors that impact the spread of the virus, including the rate of social activity and high temperatures (over ~60F / ~15.5C). We know this from several studies that have proven the role of temperature in the spread of SARS and SARS-CoV-2; as well as understanding how the spread benefits from greater social activity (which doesn't occur at the same rate in super cold climates).

Greece has a very low number of Covid deaths and no evidence of serious outbreak this entire time. Their testing rate is 1/3 that of the US. And they're wedged between Turkey and Italy. Much like southern Italy, they've been heavily shielded by their climate. Nobody wants to talk about this of course, it's the Mexico / Texas / San Diego / Baghdad / Lagos effect in action.

Iraq isn't seeing any consequential outbreak, thanks to its climate. Whereas Iran right next door got smashed, because Tehran has an entirely different climate from Baghdad.

Thailand and Vietnam are both testing at a very low rate, and there has been zero evidence of serious outbreaks in either country, despite the proximity to China. That's thanks to their hotter climates.

Nigeria is barely testing at all, with zero evidence of a consequential outbreak there. No crushing of their healthcare system with cases or deaths; no huge spike in deaths, hospitalizations or ICU cases. There are numerous countries across Africa seeing similar low outbreak results, with very little testing.

Colombia isn't seeing a consequential outbreak, their testing rate is super low. They're not seeing a healthcare crush either. They've contained it so far without a high rate of testing.

India and Pakistan were supposed to get buried by SARS-CoV-2 cases. It hasn't happened, week after week goes by and the predictions continue to fail to come true. They're barely doing any testing at all. There's zero evidence in either country of a massive outbreak or crushing number of ICU cases swamping their healthcare systems. It's because of how hot their cities are. I've yet to see a single other good explanation for why India isn't buried in Covid deaths by now. India isn't seeing the virus hit for the same reason Africa hasn't.

Egypt is barely doing any testing. Cairo should have millions of cases of the virus and a huge number of deaths by now. They should have 20,000 dead people from Covid at this point just in Cairo. Where is it? The Cairo metro has 20 million people. It's not far from Italy, Turkey, or Iran. Guess what? It's very hot in Cairo.

And if you want to see a belligerent demonstration of the climate impact in action: tell me that Florida has been dramatically more responsible in their behavior than Belgium has (or France, or Italy, or Spain, or the UK, or the Netherlands, or Switzerland), to warrant having a per capita Covid mortality rate 1/12th that of Belgium. If Florida had New York's climate, Florida would have 20k Covid deaths by now. Instead they have a mere 1,066 (and Florida has a lot of old people) despite doing almost everything wrong.

I suggested testing everyone every month about a month ago. This is a conservative testing frequency that would almost certainly put r0 under 1. Everyone every day is an overkill - why not everyone 4 times a day? What's the rationale for it other than it sounds good?

Because going out every day and knowing you are not infected feels pretty good?

Isn't this a minor upgrade on what the authorities did in Wuhan? They squashed the disease at the epicenter, faster than the tail-off in Italy, and a lot of it was massive screening and isolation of anyone showing symptoms, or with a high temperature (1), or testing positive, or anyone in contact with those.

If "it happened and it worked" isn't "mainstream" then I don't know what is.

1) https://www.bloomberg.com/news/features/2020-04-23/wuhan-s-r...

You won’t be able to scale your solution before a vaccine is out, rendering your entire solution useless unfortunately.

Johnson and Johnson have already started scaling their vaccine and plan to have 1 billion doses available by January 2021. If their vaccine is approved, it will be an instant solution and better than testing everyone every day.

Moderna has also started the process of scaling their solution as well but J&J have a head start and a known platform.

> You won’t be able to scale your solution before a vaccine is out

Why not? Scaling a test is a completely separate exercise to scaling a vaccine, and it has the advantage that multiple proven working tests exit now, they just need to be scaled. Both can be done, by different people.

You might also find that having a vaccine and a test is better than having just a vaccine.

> If their vaccine is approved

Multiple vaccines are in development. This is not a situation where we should stop doing X now because Y _might_ happen in 8 months or more time. None of the vaccines are guaranteed to be ready and working and scaled at any given date. None of them.

I have advocated it. Allegedly everyone who comes close to Trump gets swabbed and rapid tested on the Abbott machine.

How does your device detect viruses? Is it based on a protein or the RNA or what?

Everyone says "we need more testing", but there's actually very little discussion of how that testing would translate into lower transmission. I'm skeptical any program less aggressive than the one proposed here would get R0 < 1.

Testing by itself does nothing to reduce transmission. What it does do, though, is give you the opportunity to identify infected people and isolate them. And if you can identify and isolate them early enough in the course of their illness, you can prevent them from infecting many other people, and that’s what reduces transmission.

Given that it appears people with COVID-19 can shed the disease for many days before showing any symptoms, if your goal is to pinch off outbreaks before they become outbreaks, frequent, universal testing is the only way to get there.

Right, but I haven't seen anything to suggest our current testing plans will be universal or frequent enough to really solve this. So testing more is certainly better than not testing, but without constant testing of non-sick people it's not really going to help much.

"Quantity has a quality all it's own"

The article specifically is about a solution which would enable enormous amounts of people for cheap, so you can do universal tests.

Exactly. More testing is good, but actually stopping pandemic will require orders of magnitude more testing, which in turn requires a different approach to testing because the current way we do testing can't scale.

I mean in theory if you had a perfectly accurate test and everyone got tested before coming into contact with others, that gives you an R0 of 0. How close we can get to that standard is obviously very debatable, but simple logic tells us that it certainly could push the R0 below 1 given some (unknown) threshold of test accuracy and compliance.

R0 is less than 1 already in many regions...

Yes, at enormous cost.

Is it because the discussion isn't needed? Anyone who is of moderate intelligence and thinks for a few seconds can see the next logical step. I don't know pb and he might be wonderful and original etc, but I have to agree with the original comment - this is just miles from an original idea. The constraint is tests, not ideas of what to do when we have simple/fast/abundant testing available.... "A third solution" makes it seem like it's... an original idea.

I think calling it a third solution is totally fair. Whether it's a novel solution is separate.

The two solutions that are being debated now are (1) staying in lockdown until a vaccine or treatment is available, and (2) reopening and attempting to manage the spread using existing protocols/ideas (relatively low amounts of testing, quarantining after a period of infectiousness, some form of contact tracing, lots of finger crossing). At least, that's generally what I hear being debated: reopen or not, or when to reopen.

The post suggests that if we had quantitatively much more testing, we could pick a qualitatively different third solution -- namely, reopen pretty freely and realistically control the spread.

Sure, you can view that as a variant of the "reopen" option, but in my mind reopening feels very different with a realistic way to isolate people before they've had a chance to spread it very far. It's proactive vs reactive. If we fully reopen with even 2 orders of magnitude more testing than we're currently doing, it's just going to be a matter of closing back up wherever it gets out of hand. In practice, the openness will fluctuate, things will be spread out over time, politicians will continue to do the exact wrong things, and lots of people will continue to die.

In short: (1) stay in lockdown until vaccine/treatment, (2) reopen without a strategy, (3) reopen with a strategy.

Imo, those are the currently discussed solutions because of the lack of available testing. Ie, with the current constraints. It's akin to two people discussing how to use the budget of $1 million and a third saying "I have a third solution: Make the budget $100 million and do everything". Sure, it's not wrong, and it's different to the first two, but... who cares? Everyone kind of already knows if you have the $100 million you have a much better option.

I think the main point is that he's pointing toward a specific test being developed that is intended to facilitate greatly increased degrees of testing. It is of course generally understood that if we could test everyone daily (or even a large section of people regularly), it could allow the virus to be contained without such widespread distancing and shutdown measures.

> This test gives results in ten minutes using a small amount of saliva which is taken into a disposable tube and then run through a scanner.

> We’re planning to start operating the first scanner within a month. If all goes well, there will be millions of scanners deployed by this fall, ensuring that every school and essential business can reopen while remaining safe and virus-free.

Agree to that point. The German, French and other media repeat that idea in the past weeks.

One of the oldest and largest biomedical institutes, the Robert Koch Institute in Germany, recently had a few press releases, urging for tests for at least ALL respiratory tract infections.

What one of the leading experts, Prof. Drosten, also mentioned is that current (PCR) tests have considerable false positives. The effect of such FP at large scale can hardly be estimated.

I really hope that you are able to find a solution and can bring up a scalable and reliable solution, after the promises. If not, there will only remain the impression that this could be a Silicon Valley type of talk the walk, as people heard it from other companies in the past.

Testing isn't the only way.

Some people just advocate for isolating the elderly and having everyone else mingle.

The life expectancy loss from just letting it run its course would be less than a tenth of the life expectancy difference between the second and third wealth quartiles in the USA. And if we aren't worried about that difference, then why are we imposing a quality of life reduction that's much larger than the quality of life difference between those two quartiles for a much smaller gain in life expectancy? (similarly the economic costs of bringing the lowest quartile up a year or two would be much lower than the cost of this lockdown)

(I'm no epidemiologist etc.)

Because that's a terrible idea that doesn't make any sense. I understand the logic and why it's tempting, and I've even read some of the evidence supposedly backing it up. I find it thoroughly unconvincing.

I won't address the moral side, just the practical.

The virus disproportionately effects the elderly, yes, but far from exclusively. We have seen the non-elderly death rates with distancing in effect. If we could confidently say that >70% of the non-elderly population already had the virus, then this might make some sense. But since at the moment we cannot say that, then this is a method for quickly getting to >90% of the population, and killing off an unknown but far from trivial percentage of us.

Also, I have seen some evidence that the magnitude of symptoms is partly dependent on the degree of exposure. If that is the case, I really really do not want to be sitting between two infectious people in a movie theater or sports arena. But this would be commonplace with the whole "let's just sacrifice the elderly" approach.

The idea would be to isolate the vulnerable and let everyone else get it.

As a society we have shown time and time again that we only care about "disasters", not the continuous but far greater and less expensively solved losses. Nuclear power vs coal, air plane accidents vs car accidents, the life expectancy reduction of poverty vs COVID-19...

I really hope this works. Without some new testing technology, I just don't see how we can stop the spread of this disease. A month ago, the US did about 100,000 tests per day. Yesterday, the US did about 200,000 tests. Growth in testing started off as exponential but now it looks linear.[1] Even if testing capability doubled every month, it would take 8 months before we could test every American once a week. (200,000 * 2^8 == 51,200,000, which is 15% of the population.)

It only took a couple of months for 20% of New Yorkers to get infected.[2] If we assume that half the population will get this disease over the next two years, and we assume an infection fatality rate of 0.3%, that's around 500,000 deaths. (328,000,000 * 0.5 * 0.003 == 492,000). Those are optimistic projections. The IFR is likely higher and the R0 is somewhere between 3 and 9[3], so that means at somewhere between 60% and 90% of the population needs to be infected before we get herd immunity.[4]

Unless there are radical improvements in testing and/or treatment, I think we'll end up with at least 500,000 deaths in the US. That would mean we're about 10% of the way through this catastrophe. So strap in, it's gonna be a long ride.

1. https://twitter.com/COVID19Tracking/status/12538071759457443...

2. https://twitter.com/NYGovCuomo/status/1253353516803993600

3. https://wwwnc.cdc.gov/eid/article/26/7/20-0282_article

4. For the relationship between R0 and herd immunity, see figure 2 of this paper: https://academic.oup.com/cid/article-pdf/52/7/911/847338/cir...

Making this worse, the final size of an epidemic can be estimated as not p=1-1/R0, but rather p=1-e^-R0 [1]. With this, those R0 estimates give a final infected population of 95%-~100%... we can't let herd immunity be the solution.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506030/

> Even if testing capability doubled every month, it would take 8 months before we could test every American once a week.

At this point, I'd consider that a success.

The post refers to an alternative method of testing for COVID-19 based on surface plasmon resonance that would have significant advantages, but unfortunately it provides absolutely no real substantiation that the test exists or works. The link about surface plasmon resonance goes to a generic Wikipedia page, the link about saliva is a small scale study that was conducted on RT-PCR not surface plasmon resonance, and the actual link to the team goes to a nothing more than splash screen with the company logo on it.

If there is substance to this then it would be massively in Paul's (and the company's) interest to better link to that in both the post and the company web site. At the moment, it looks like at worst vaporware or at best, something so early stage it's years out from viability.

Hi, Walker here, one of the PreDxion Bio co-founders. Heres a some more information on the technology underlying the test we are developing: https://pubmed.ncbi.nlm.nih.gov/25790830/.

Unfortunately, up until about a month ago us like many folks, were blissfully minding our business developing a rapid point of care cytokine detection platform for use in monitoring patients experiencing certain immune responses following cancer immunothereapies, you can read more here: https://pubmed.ncbi.nlm.nih.gov/31597044/.

Currently, we are very much focused on techical/clinical validation. We will have many more details to share on our approach, the technology, as we continue to move things forward.

I worked at Integrated Plasmonics in 2012–14, the major problem you will face is fluidics and sample handling not so much the sensor design. You should consider stochastic plasmonic features grown using dna self-assembly on the surface of a cmos sensor (lots more recent work on DNA-based plasmonic nanostructures). I worked on varieties of ways to characterize a chemical signal even from stochastically distributed plasmonic features by running calibration during manufacturing. We were able to use support vector regression to characterize known chemical reaction signals on a per sensor basis.

If you have to do that for every sensor the cost goes up a lot. Also, "stochastic plasmonic features" without knowing much more sounds like something that varies by time of day, wind currents in the lab, whether you hit it ten minutes ago with a socket wrench or didn't.

Thanks for engaging with the HN community. I'm a bit disappointed that the original article doesn't say if the author is associated with your company. At one point he says "We", but it's never clear. Did I miss something? Your comment doesn't address this issue at all. Investor? Employee?

Ethics are an important thing.

What do you think of the article's claim that eliminating the cold virus would be a good thing? I think I read somewhere that early exposure to cold viruses reduces the chance of acute lymphoblastic leukemia, which makes me wary of trying to eliminate them completely...

There’s a lot of really interesting work left to be done in this area. In our company’s other life we’re involved in CAR-T research, which involves exploiting natural pathways in our immune systems to target them at cancer cells. It’s a super exciting area of research and is bleeding edge in terms of breakthrough therapies coming into the clinic. These therapies[0][1] cure upwards of 90% of what would otherwise be incurable cancers, but they also induce severe inflammatory responses (cytokine storm) which results in respiratory failure and neurological adverse events (that’s a nice clean clinical way of saying putting them in a coma).

The holy grail would be real-time targeted therapeutics to modulate our immune systems up and down in response to various cues. We’re a long way off from that but it’s an idea that’s beginning to get wider acceptance in the medical community. [0] - https://www.novartis.us/sites/www.novartis.us/files/kymriah.... [1] - https://www.gilead.com/-/media/files/pdfs/medicines/oncology...

Don't worry. We're not going to run out of cold viruses any time soon, and the pitch was hyperbolic in virtually every way.

OK, but what are you detecting? Antibodies? Viral proteins? RNA? The messages from Paul and your team have been contradictory. The message is confusing, and this makes people skeptical. It would be great if you could clarify the detection strategy.

He should also disclose any personal interest in it more clearly at the top of the article.

At this point all our personal interests are to stay virus free as long as possible, given what we don't know might kill us. I really don't care why he's speculating about the things he is. Many of the things we postulate may be proven wrong simply by waiting long enough to get more data - i.e. it's not always necessary to formulate a test for disproving an idea, sometimes they evaporate on their own. (Software features for example frequently meet their ends this way).

I just found out about Covid Toes. What will come tomorrow?

And now, a shameless plug for a next-day delivered PPE from Amazon built from a full faced snorkel, a vacuum filter and a 3D printed adapter I designed: https://3dprint.nih.gov/discover/3dpx-013899. There's a video too, which shows a bit cheaper version's assembly: https://www.youtube.com/watch?v=wydRpFpQD4I

I haven't been into an indoor shared space without it on for almost 3 weeks. You probably shouldn't use Gorilla Tape on it, because it might off gas something. Try surgical tape.

I gathered the same thing. Basically the gist is, if we can develop a cheap, fast, and effective test for COVID-19 then we can test everywhere and re-open everything.

Hasn't that always been everyone's argument? That's the crux of Pueyo's "dance" [1], that as long as you've contained the initial outbreak, you can pretty much go back to normal if you track movement and have the capacity to test everyone who comes in contact with an infected person.

[1]: https://medium.com/@tomaspueyo/coronavirus-learning-how-to-d...

This has been one major argument. The others have been: "flatten the curve - just extend the time until everyone gets it" (obvious problem, exponential growth can't work that way), "shelter in place 'till a vaccine appears" (not very practical) and "it's really not that bad, there are so many asymptomatic carriers that in the end it's not actually worse than the flu after all or at least there's nothing we can do." (not that plausible, not appealing, non-fatal cases still much worse than the flu).

I think this is the best position, however but it still needs to be argued for since it's not the only position.

Edit: Also, it looks like the US has plateaued at this point but in a situation with a fairly dysfunctional testing arrangement. It is going to be hard to argue for people to sit tight until tests are in place so I'm not terribly optimistic.

> "flatten the curve - just extend the time until everyone gets it" (obvious problem, exponential growth can't work that way)

Just to nitpick a little here, it's more like "flatten the curve - stretch the time while everyone gets it, so we don't overwhelm hospitals". Even with exponential growth, you would rather deal with it over a longer period than have a massive spike where all services are overwhelmed.

The characteristic of exponential is that things tend to come all once. In the final double period, you get as many cases as all the other doubling periods combined.

Which is to say, you can stretch out exponential growth a lot and still not have enough. If you exponential growth from 1,000 to 1,000,000 cases over a year, the last month will overwhelm your services entirely and constitute the bulk of both cases and death.

There's a reason all those early graphs showed parabolas, not actual exponential curves, you can't even give plausible visual representation of this process, because it isn't plausible.

""flatten the curve - just extend the time until everyone gets it" (obvious problem, exponential growth can't work that way)"

Huh? One goal is to flatten the curve so that we don't have exponential growth. Another is to flatten the curve so much that, even if might still be exponential growth, the growth is slow enough for our health care systems to absorb the peak.

One goal is to flatten the curve so that we don't have exponential growth

The aim of mitigating measures is reducing the growth rate of the disease. But the mechanism of the disease is that you generally have a basic situation where X people infect at time t results R*X people at time t+1. That's fundamentally exponential process (even though you can extra factors, the process doesn't change 'till you get close to having infected everyone). If we can make R small enough, this become exponential decay, a good thing but still an exponential process. But when you do exponential growth. you have a doubling and on the last double, you get more cases than all the cases combines. So the peak is just MUCH higher than the rest of the curve and you can "flatten" a lot and still wind-up overwhelmed in the end if the growth process continues.

Sure. Yes. Of course you can flatten a lot and still wind up overwhelmed. Or, you can flatten enough that you don't.

"Flatten the curve" and "shelter in place" aren't mutually exclusive with a necessity to ramp up testing or develop a vaccine, they are just things that laypeople can be doing in the mean time to mitigate the negative effects of the virus while those other solutions are prepared.

That post, which was very popular, immediately came to my mind too.

It also feels like the logical next step to the very widespread testing found in countries like South Korea.

Is this what you're looking for? Scientists at NTNU St. Olav's Hospital has made a test that can check 150,000 patients per week for Corona infection [1]. (Yes, it's the same uni that used the USA as an example in warning students abroad against poorly developed health systems lol.) Already testing is a lot more frequent in Norway because of it, and they're cautiously re-opening some businesses and services, the first of which are kindergartens and hair dressers.

The Norwegian health authorities also published an app that can be voluntarily downloaded, that tracks and warns about infected, while also collecting research data for future use. [2] The app has garnered some criticism for leaking user data, and for discharging the battery too quickly. The retort is that it's of course voluntary and anonymous, and that it's actually tracking less data than Facebook or Google.

[1]: https://norwegianscitechnews.com/2020/04/from-thousands-of-t...

[2]: Norwegian language source: https://www.fhi.no/nyheter/2020/ny-app-fra-folkehelseinstitu...

The relevant quote actually concerned the collective infrastructure in the US, including health insurance. The actual quality of care in the US is great, particarly for specialty cases... for the few that can comfortably pay for it.

Relevant part of their tweet:

"This applies if you are staying in a country with poorly developed health services and infrastructure and/or collective infrastructure, for example the USA. The same applies if you do not have health insurance."

As well as a message, now apparently removed but archived by others, on their website:

"This also applies for countries with poorly developed collective infrastructure, for example the USA, where it can be difficult to get transport to the airport if you don’t have a car. The same applies if you don’t have health insurance."

Yeah but maybe we shouldn't. We have the technology to compartmentalise our society WAY more than it currently is, at relatively little cost. COVID-19 is a fantastic dress rehearsal for the next disease, which will be far scarier and will come relatively soon. Humanity is a monoculture and like all such, is very vulnerable to pathogens. We need to start building social distancing into our culture the same way we built protection for sex into our culture.

Ever since 2000, we've have a pandemic once every decade. The next one will occur soon, but it's not certain whether it'll be as scary as COVID-19.

> We need to start building social distancing into our culture the same way we built protection for sex into our culture.

While I agree with the general gist of your comment, I should emphasize that what we need is physical-distancing, not social. Humans are social beings at core, and depriving them of social interactions is as deadly as the virus itself. What we should be practicing more than ever before is washing our hands, minding our coughs, and in general, being responsible to the society. The individualistic lifestyle - which is pretty much dominant in the West - shouldn't stop us from caring about our community as a whole and our duties towards other people. Technology can only help us get so far; the rest depends on how much we - as responsible social beings - take care of ourselves and each other.

> I should emphasize that what we need is physical-distancing, not social.

Good distinction. We should be focusing more on hygiene while finding ways to connect remotely with the people who are important to us.

> while finding ways to connect remotely with the people who are important to us

Good stop-gap, but not remotely viable long-term. Humans aren't made for isolation, even if video calls help take the edge off soon. FaceTime and Zoom have a significant cognitive load, too. As long as we're talking about how society should adapt to this sort of risk, we can't just go to living in individual hermetic pods with internet connections. The mental health cost will be monstrous.

> FaceTime and Zoom have a significant cognitive load, too

Why the cogntive load would be lesser in a face to face conversation than digital assuming the internet connectivity is good ?

I don't know why or how, but I can confirm that remote connections have a significantly higher cognitive load than in-person interactions. Perhaps it's the same reason as why talking on the phone while driving is much more dangerous than talking to the passenger in the seat next to you.

"We are for the most part more lonely when we go abroad among men than when we stay in our chambers."

- Henry David Thoreau

According to my biochem-undergrad kid, surface plasmon resonance is a thing; it had come up in classes. "It's like doing an ELISA with no secondary antibody". Someone here will know what that means. I don't!

A regular ELISA/immunoassay is: surface->Ab->protein<-Ab+signal. In school these are taught as "sandwich-assays". Basically you have one antibody to bind your molecule of interest to your substrate, and then another second which binds the bound molecule... which has been bound to the surface. This second antibody is decorated with an enzyme which will do something fancy (color-change) or a fluorescent protein to light-up if we shoot it with a laser. SPR is a label-free approach which results in an optical response in real-time as molecules associate with the SPR sensor. Detection is then a function of how long you need to let things bind to the sensor before your ability to detect the signal optically.

Sounds like your undergrad kid has been paying attention in class...

It's a very sensitive detection technique that uses some cool properties of light. We used it 20+ years ago in grad school (they were very expensive machines that were extremely hard to master; everything from calibration to routine operation was significantly more challenging than most devices I worked with) and I think it has quite a history before that. Never heard of it being used for rapid detection in a public environment; my experience is that things that work in a lab setting often don't externally unless somebody comes up with a good technology improvement (think vacuum tubes -> transistors -> small radios).

Can confirm that. Source: Worked with SPR/OW spectrocopy many a time during my time in research.

It’s a thing, but doing a saliva test with limited sample prep (which you need to be beat PCR, otherwise you might as well just make more known to work qPCR machines) is not something anyone has accomplished with it for any virus. It’s a promising technology; but not for having a widely deployable test before we have boring old ELISA antigen tests. Which we have developed for plenty of viruses, and which some individual companies alone can manufacture at a rate of several per second with existing production capacity.

I’m glad more money is being put towards research in this tech (I used to study plasmonics from the physics side), I don’t think it’ll make a difference for COVID specifically before it’s too late to matter.

Test complexity (sample prep, test workflow) is a real challenge to achieving testing scales at orders of magnitude above what is presently available.

We should hopefully have boring old ELISA antigen tests shortly, thanks to Abbott and many of the other folks we've all heard from. The real challenge is scaling testing beyond what can be reasonably implemented from central lab facilities.

ELISA tests don’t need to be done at central lab facilities; there are plenty of machines on the market with varying levels of automation (and many already in hospitals, even in ones that aren’t particularly outstanding). I’m curious what barrier to scaling those with COVID (either by making more of these machines, or repurposing other test capacity) you’ve identified that makes bringing a totally new machine to market more attractive, from a scaling perspective.

> The real challenge is scaling testing beyond what can be reasonably implemented from central lab facilities

The SPR machines I’m familiar with are not inexpensive. Are there machines appropriate for these tests that are less expensive such that it could be rolled out widely? Sample cost is low, but a warehouse shift change of several thousand people isn’t going to need only one machine for screening as the load on the machines will be very bursty.

If one is clever, one can use SPR to interrogate a surface: monitor the surface and you can “see” the surface changing when stuff is sticking to it. If you have something with specific binding properties on that surface, like an antibody (as is used in an ELISA), with some additional effort you can maybe have an assay that detects something binding to that antibody.

And it's a public kiosk that you spit in?

I'm not so sure about this!

You can rank people by the likely benefit of testing them. Interestingly, it goes up as the square of the number of people they interact with daily. (Because their risk of having it increases, and also the number they are likely to spread it to.)

So you can allocate tests by sorting by (# of daily contacts in a closed space) ^ 2.

But as PB says, it should be practical to test everyone every day.

Curious to know how you are getting power of 2 exactly. Are you just saying it's some sort of power law growth and approximately 2, or is there an actual way of deriving it?

If we assume (key) that the probability of becoming infected is directly proportional to the number of people you interact with, and consider that the probability of spreading infection given that you are infected is obviously directly proportional to the number of people you interact with, the product gives a quadratic function:

[probability of becoming infected and spreading] = [probability of becoming infected] * [probability of spreading] ~ [people you meet]^2

Okay so something like:

probability of spreading = a * n probability of infected = b * n

where: a,b = some blackbox function for spreading/infection ratio? n = number of people you meet

Assuming both are independent events we get:

p = a * b * n^2

I can see how we get n^2 with that. The way I'm using a, and b seems clumsy though, is there a better way?

In math and (especially) physics it is common to express "proportionality" laws usually with a symbol that looks like LaTeX \propto. So for instance the activity A of a radioactive sample is written A \propto e^(-t/T) where t is time and T is the mean lifetime of a single particle. For convenience \propto is often transliterated as ~ when typing. So that becomes

p_catch ~ n

p_spread ~ n

p_relay = p_spread * p_catch ~ n^2.

Thanks, that's a much clearer way to think of it.

This isn't quite right. For one, the probability of being infected is not linear (it's capped at 1). If you do the math, the expected number of people you infect (given you are not infected) is roughly linear-ish.

> the probability of being infected is not linear

Correct, it's not. But it is roughly linear in the limit of small numbers of people with a small constant probability of becoming infected per interaction. (This assumption becomes problematic when you see "clustering" of highly social people with other highly social people.)

To be specific, if P is the probability of becoming infected when interacting with a single person, then the probability of becoming infected after interacting with N people is 1-(1-P)^N = NP - O(N^2 P^2). It's easy to see that the limiting infection probability is 1 in this simplified model, and that if N*P < 1 you're looking at close-to-linear growth.

Wouldn't it also vary by percent of population without immunity, perhaps demographics in the underlying population, and other environmental things (weather?). Seems like a (useful) aproximation.

If you have N nodes and completely connect the nodes, there are O(N^2) edges. This comes from the formula for the sum(1...N).

Edit: I’m not sure I interpreted the original statement correctly.

That's what I was about to answer. That's where squaring comes from, in this case. However, as others have noted, you could just sort by # of people contacted, since squaring just gives you larger numbers for no benefit in analysis here.

Since squaring is a monotone transform over nonnegative numbers, why not just sort by (# of daily contacts in a closed space)?

> If we were able to identify and quarantine everyone who is contagious, including those who are asymptomatic, then we could let everyone else out of lockdown and resume ordinary social and economic activity.

> Even with imperfect screening, if we are able to prevent 90% of disease transmission, then the virus’s reproductive number, or R0, will drop below one and the pandemic will quickly fade. There is no risk of reintroduction from the outside because any new outbreaks will quickly be caught and contained. If used consistently, there will be no second wave, ever.

I'm not sure this "test and release" strategy works unless absolutely everybody gets tested simultaneously.

Even if testing of the total population can be completed in a week (a highly ambitious timeframe), there's still time for people released on Day 1 to be reinfected by people who don't get tested until Day 6.

Then you have to go through who knows how many follow-up rounds of testing absolutely everybody not in quarantine to identify those people. When responding to new outbreaks involves re-testing large populations of people, you're going to run into many problems. Notification, compliance, testing fatigue, etc.

Sounds like a logistical nightmare.

It's daily screening for exactly that reason. Is there something I should change to make that more clear?

But how realistic is daily screening on a wide scale? You're going to face major issues with compliance.

That's why I think testing at the door is the more straightforward way to start. We can reopen factories, office buildings, even shopping malls, but no one gets in without passing the screen.

This test takes 10 minutes. That is probably still too long to implement at the doors for most places. It will end up creating a bottleneck of people waiting to enter the building and another avenue to spread the virus. Making the inside of the mall safe from the virus isn't going to matter if everyone is exposed to the virus while waiting in the 30 minute line to get into the mall.

The article is suggesting daily testing and used "testing at the door" as an example.

Wouldn't it stand to reason that you could be tested once per day, in the parking lot to a mall or some other shopping establishment, and thereafter _verify_ that you had been tested that day for the remainder of your commercial transactions?

Thinking in those terms, 10 minutes per day is not so great of an imposition. We could formalize it and create drive-through test centers where you drive up, spit into the tube, have a bar code on your phone scanned, and drive off. On your way to the mall you get a text message with your results. Everywhere else you visit that day scans your phone upon entry and confirms that you've been tested.

You can't just ignore people who don't travel by car. The hardest hit place in the country in New York City. Most New Yorkers don't own cars and many go months at a time without entering one. And even outside of cities, it is still classist to only allow people with cars to reenter society.

The system also becomes much more complex and requires a bigger infrastructure if you aren't literally testing people at the door. How do you verify someone has had a test today? In your bar code idea, can the bar code be faked? Is there some centralized database behind the system that tracks who tests positive? Is that database politically feasible? Some comments here are already objecting to that idea.

A solution that works outside of the vicinity of New York, would still allow at least 47 other states to open up.

As for checking who has a test, simply give colored stickers. If someone wants to “beat” the system, so be it. Social disapproval and common sense will keep most people honest.

New York City isn't the only place in which car ownership is low. What about Chicago, Philadelphia, San Francisco, Los Angeles, Boston, DC, etc? If your plan for reopening the nation doesn't include reopening our cities, it isn't a real plan for reopening the nation.

You need a plan for people who want to beat the system because they present a huge danger. The whole idea behind this system is to allow the people inside the secured bubble to return to normal behavior. They aren't going to be wearing masks, social distancing, or taking other precautionary measures. Therefore one person acting inappropriately could present a huge problem for the people on the inside. Keep in mind there are still people who think this entire thing is a conspiracy and that COVID-19 is no worse than the flu. You have to consider what happens with people like that who might not participate in this system in good faith.

I wouldn’t plan on reopening the nation, since it was never closed from the top down to begin with. Individual states, and in many cases cities and counties, made the decision and continue even now to enforce rules different from one another.

Hawaii is an island, thousands of miles away from the rest of the USA, so why shouldn’t it open on a different schedule?

Even China, ground zero for the crisis, close and reopened different providences, districts, and even neighborhoods independently.

that also doesn't mean that if you come up with a plan that only partially works you stop working on it. Perfect is the enemy of good.

Could you protect a food processing plant with this method? Yes. Does it cover testing in LA? No. Does LA need food and other shipments? Yeah they do.

You could probably use an app or just get their mobile phone number. It seems likely to me based on reading a lot of case studies that this virus is largely spread through talking, yelling, and singing. If we tell people not to talk for 10 minutes while they wait for their result, it could work if you could get people to comply.

But that just moves the compliance and logistics problem back one step. Who's doing this massive amount of testing? If it's the government, you'd need armies of workers spread out everywhere. If it's the owners of these buildings, who checks to ensure compliance?

Imagine trying to enforce this on every non-residential building in, say, NYC. It would be practically impossible.

> If it's the owners of these buildings, who checks to ensure compliance?

Who checks to make sure every restaurant follows the standards of cleanliness? They have inspectors who (theoretically) show up randomly, so it ensures most places comply voluntarily, because the cost of getting caught is very high.

A combination of random inspections and steep fines would solve the compliance problem.

Edit: I just had another idea. Offer cash rewards to people who can prove they they weren't tested when entering a public place (which the business pays for via fines). You'd have people running around trying to find missed testing for the cash reward.

To your point, many businesses and facilities implement safety measures because they fear civil liability for preventable damages. I don’t think that’s likely in this case but if you can get most businesses and facilities to be mostly compliant most of the time, that might be enough.

There are many unlawful activities that could be solved with cash rewards for people reporting said activities.

There are many that are. Don't people get rewards for reporting malfeasance to the SEC, or ADA violations? I'm sure I've read about that, as well as about how some people think it's a questionable system. But privatization of enforcement of some regulations is a thing.

For this to work I think you would need a much stricter compliance than what is enforced in restaurant cleanliness.

It doesn't have to be good enough to catch all cases immediately, just good enough that isolated outbreaks can't sustain themselves.

It doesn’t need perfect compliance to push down the R0 significantly. Lockdowns in the US are mostly not being strictly enforced, but enough people are complying to have a major impact.

I think economic incentives are also fairly well aligned here. If tests are widespread, a significant segment of the market is likely to prefer locations that are testing to those that don’t, just like the market tends to prefer clean restaurants to unsanitary ones.

Now imagine going out shopping, you’re stopped at the door, and you test positive. What happens then? The government puts you in a car and sends you... back to your apartment? Sounds like a dystopian nightmare, to be honest.

we're in the middle of a pandemic. at some point you've got to accept that dystopia is here, and the dystopian things that are happening are realistic ways of dealing with the situtuation.

you can't reject solutions because they sound dystopian unless you've got better, non-dystopian solutions. and everybody has to stay in their homes at all times and all non-essential services are shut down is not a less dystopian solution.

Fair enough. But I hope that line of reasoning has limits. After all, it would be safer to send everyone by truck to a quarantine camp instead of back to their apartment where they might infect their neighbors in the lobby, wouldn’t it?

That's actually how China handled it. If you test positive, you don't go home - you go to a facility to be quarantined and treated if necessary.

That's been proposed in the northeast US (MA, NY, NJ, CT, RI). Hotels would be used for mandatory quarantine. Tests and contact tracing (manually, then smartphone) would determine who gets isolated.

The flu comes every year, and it’s not even a order of magnitude less fatal. Maybe COVID will come back every year too.

What “solution” are you looking for to solve this relatively small share of “death from natural causes” that we call COVID? How much damage should we inflict upon ourselves in this moral quandary?

How many people should die because we’re willing to spend trillions of dollars due to our innate fear of a virus rather than our innate fear of much much bigger problems, like poverty or starvation?

Why can we muster so much energy in this case, and so little on much bigger problems? My theory is that you can’t catch hunger on the subway, you can’t catch underprivilege from a doorknob, and you can’t catch climate change from shaking hands with constituents.

There’s a lot wrong with our planet, it’s too bad we’ll all go bankrupt and unemployed chasing such a trifling disease as COVID when there were actual real problems we could have solved with mountains of cash that large, rather that burning the cash in effigy for modest to no effect once COVID has run its course.

Can you please stop posting in the flamewar style to HN? This sort of rhetoric and polemic destroys curious conversation, which is what the site exists for.


It seemed in-kind with the “dystopia is here” rhetoric, but I understand answering in the same vein doesn’t make things better.

If I could still edit the comment, I would replace the first “you” with “we”, as none of the comment is meant to be directed personally at OP.

The dystopia we have is purely one of our own creation. One which TFA seems to not only welcome with open arms, but seeks to capitalize upon. It’s really quite sad.

There are two things that don't make sense to me about your original post.

One is that cash is not a resource. It's even less of a resource when it's not only not metal, but mostly not paper either.

The other is that the flu comparison doesn't make sense to me on multiple levels. Given deaths from COVID at the moment are nearly ten times flu on an annualized basis, given the partial shutdown, obviously they would be more than ten times without the shutdown...but what is even significant about exactly one order of magnitude?

Thanks for the feedback!

I’m not quite sure what to say to “cash is not a resource”. Even if just a proxy for attention cash is obviously a resource. But really, cash in itself is a resource. $10 trillion dollars can do a lot of things if spent wisely. $10 trillion dollars can also be destroyed for practically no benefit at all.

I agree it’s not strictly $1 spent on A means $1 less to spend on B. But it’s at least true to some extent, and again, as a proxy for attention and willingness to enact change, it’s a valid measure.

So the flu comparison is because they are both respiratory illnesses which kill a lot of people. In the 2017-2018 season the flu killed 61,000 in the US. Hospitals in NYC were stretched very thin. Nobody really noticed. It wasn’t even declared a pandemic.

Obviously it’s impossible to say with certainty if we have seen 1/4th, 1/3rd, or 1/2 of the total deaths that we are going to see from this SARS-CoV-2. But I think nobody is currently out there claiming that we’ve only seen 1/10th of the total deaths from SARS-CoV-2 that we’ll get by the time it’s over. (SARS-CoV-3 is another story?)

“Ten times flu on an annualized basis...” So 50k times 4 is 200k. That’s not nearly 600k. Just trying to follow your math. If we’re halfway through now (IHME thinks we’re about 3/4 through) then we‘ll have seen in COVID the equivalent of two bad years of flu.

Orders of magnitude generally provide rough measures of classification and are a nice rule of thumb for telling if one thing is “radically different” than another thing. So, flu kills up to 650k globally per year. Maybe COVID will do roughly the same, maybe 2-3x, but I think at least we’ve long past the days of claims that COVID will kill 5 million worldwide are being tossed around. And it’s not because no one’s caught it and we just need to keep hunkered down. It’s because a massive number of people caught it and overall its just not that deadly.

If governments around the world had done their jobs and shared data and been truly prepared and with a little luck and a lot of hard work this whole thing perhaps could have been avoided by early and arduous contact tracing. That day is long behind us.

I worry that by now so much energy and ink has been spilled getting the country into lockdown, and people are so politically invested in it, and all the social pressure campaigns have ramped up to max,... that now as data finally emerges which demonstrate it was all a gross overreaction, we will be too slow to correct.

In the meantime 10s of millions have lost their jobs, perhaps millions have lost their businesses. A $1T deficit seems like a quaint memory (sorry grandkids!).

And it was all for, what, exactly? When herd immunity is the endpoint and the IHME hospitalization predictions were wrong by 10x... overbending the curve only causes suffering and does not save lives. Bending the curve too far into next winter could actually cost lives, which the CDC acknowledged earlier this week in a very roundabout way. And bending the curve at all only helps if additional medical treatment availability would have actually saved more lives, something which I have not seen a strong case for.

"$10 trillion dollars can also be destroyed for practically no benefit at all."

$10 trillion is probably over twice the (financial) cost of WWII adjusted for inflation. Having numbers of that size written down, deleted, moved around, doesn't mean we are suffering that level of loss.

As far as comparing covid to flu, I was talking about annualized daily deaths from covid, compared to a normal year of flu. That was deliberate. I'm saying, if it neither increases nor decreases from this point on, it's nearly ten times the rate in the long run.

You are comparing the total deaths from covid, assuming it declines and goes away in due time. That would be fine in a vacuum, but you're using the consequences of trying to stop it to argue the efforts to stop it are unnecessary. What is the point of this sophistry?

The store does not permit you to enter and you are asked to go home and self-quarantine.

What if you infect someone on your way back?

You’re still in a much better position than we are today, where you’d infect several people in the store, and again the next day, and the next.

I'm weirded out by this binary thinking arguing against masks or testing. It's like the people who say that helmets don't prevent all injuries, which they conclude means one shouldn't be wearing one. Except that where helmets are only individual protection, measures against infection are affective at a population level, where you profit from others' actions.

You are handed a free mask that serves as warning people to give you space, and you are simultaneously logged as being infected with the CDC.

Not only you, but everyone who was recently within six feet of you as determined by contact tracing (manual now, bluetooth later). If you don't live alone, you go to a mandatory isolation center, possibly a designated hotel. Kids can be separated from parents.


Now is the time to express opinions on these "proposals"..

How about the doors being to planes?

The cheap flight was what made this epidemic a pandemic.

We can continue lockdown until everyone who has got it has recovered and is no longer infected. This is a matter of weeks and we are mostly there.

Once we get to no new cases per week for a couple of weeks then we can end the lockdown and get on with our lives.

To prevent reinfection then anyone that flies in gets quarantined unless they come from a plague free country. The same applies to other border crossings, e.g. ferries and roads.

This approach works with rabies in the UK and with other historical plagues. No widespread daily testing is needed this way just the health service testing we have now.

This approach is the only realistic option using what we can do now. However there is little talk of quarantine being used for those that fly. Quarantine means forty days.

Paul, I posted this is part of another comment also, but for places like shopping malls, testers could also test people while they're in the parking lot.

No lines to spread the disease, and better throughput if you're testing many cars simultaneously rather than whoever is at the front of the line. (Although I suppose many people could be tested near the front of the line too.)

Frankly this is the idea that a software guy comes up with. It’s like you translated the idea of checking every API request for malicious payload to a real-world situation and left out the 99.997% of the parts that make the problem hard. It’s like assuming the existence of a teleporter.

What door? You mean my front door? I'm not letting anyone in, and I'm not leaving either. What are you going to do, call the cops to kick in the doors to test me?

No, I mean the door to the office building, shopping mall, or other place where groups of people gather and potentially transmit the virus.

it is pretty clear, but the conclusion of the parent is still pretty strong:

> Sounds like a logistical nightmare.

Making most people a coffee every day also seems like a logistical nightmare. But we built that infrastructure.

Using coffee as an example, there's enormous diversity in how people make it and what (mostly unnecessary) resources they put in.

> I'm not sure this "test and release" strategy works unless absolutely everybody gets tested simultaneously.

This is misunderstanding exactly the text you are quoting. The goal with epidemic management is NOT to seek out and destroy every last case of the disease.

All we need to do is reduce the spread rate so the exponent in the equation goes from above one to below one. At that point, the outbreak will shrink over time on its own. Critically, new/undetected outbreaks with an R0<1 won't get purchase and grow, because they can't.

At that point, the population is "safe". Individuals aren't, people might still get sick randomly. But this isn't a policy for individual safety per se.

Compliance is tough. And my main concern would be false positives- if we are screening more people more frequently, we would have a lower expected percent of true positives, and even a small false positive rate could lead to significant overdiagnosis and disruption. The more often the test the more stringent that requirement. I dont know much about the testing method described in the article, but I wonder if it has unique characteristics beyond ease of administration to support that broad use case

A reasonable policy is to go home when the machine at the door to your office gives a positive result. Then get a more specific PCR test, and maybe come back to work. So the cost of a false positive can be one lost day.

The false positive rate of lockdowns is 100%.

Exactly. While this plan would certainly result in some disruption, it would be a lot less than the current status quo. And you can't really compare it to simply "opening back up" without a plan like this, because the simple fact is that even without government-enforced lockdowns, many (perhaps most) people won't return to a normal level of activity if they don't feel safe doing so.

> “...because the simple fact is that even without government-enforced lockdowns, many (perhaps most) people won't return to a normal level of activity if they don't feel safe doing so.“

you’re underestimating the pain that many americans are feeling after just a few weeks of (soft) lockdown. it’s not that people want to be unsafe, it’s that their livelihoods are in grave danger if the lockdowns last for months. many people are willing to take some risk now that the pandemic hasn’t turned out to be plague-levels of badness that some initially feared. few people are economically secure enough to say ‘no’ to opening back up sooner rather than later.

"many people are willing to take some risk now that the pandemic hasn’t turned out to be plague-levels of badness that some initially feared"

Without expressing an opinion of my own, how can you write as though from a twilight zone without causal relationships?

I mean, you, or anyone, can doubt that the lockdown is necessary. You might be right!

But you must acknowledge and challenge the causal connection between the lockdown and "not plague levels of badness". Comments that just ignore the possibility creep me out, because I can't imagine what the writer is thinking, except maybe "wishing will make it so".

All the more reason why extensive testing, allowing them to go back to work safely, would be great!


> The false positive rate of lockdowns is 100%.

If that were true lockdowns would make absolutely no difference in R0. Clearly, they do make a difference.

I don't follow your reasoning. Maybe we use a term differently? Here's how I understand them:

- A false positive means that a test shows someone is infected when they are not. For most tests that's somewhere between 0.1% and 2%.

- Lockdown means everyone stays at home. Different from PB's plan, where only people with a recent positive test stay home.

- R0 (technically Re) is the expected number of people each newly infected person spreads it to.

When I say a lockdown has a false positive rate of 100%, it means a lockdown is the same as if you tested everyone but the test always (100%) reported positive, so everyone had to stay home every day.

Re is a different number based on what proportion of the population is immune. Here we are talking about R0.

The point I am making is that some of the people who are on lockdown are truly positive for the virus. That’s why it works. They don’t have the opportunity to spread it outside their habitation unit.

> I'm not sure this "test and release" strategy works unless absolutely everybody gets tested simultaneously.

They don't all have to get tested literally simultaneously; but the "release" part of the strategy can't start until the "test" part has covered everybody, or at least close enough to "everybody" that the difference doesn't matter. Note that that's how the strategy is stated in what you quote: if we can identify everyone who is contagious, then we can release everyone else. The "if" has to be complete before the "then" starts; that's what "if"-"then" means.

But contagious status is not fixed. If you test someone, they're negative, but despite sheltering in place they pick up the virus while at a necessary doctor's appointment, then their status changes. Granted, frequent follow-up tests might identify that change, but daily tests of a sufficiently large portion of the population have a number of challenges beyond just access to the tests.

The difference here is that you test everyone entering a certain location, not everyone in general. This is much easier, and allows testing to be focused on most needed areas. In effect, if you only go to the groceries once a week, you will be tested once a week. If you go back to office, you will be tested every day. The more you interact with people the more you get tested to keep the interactions safe

Straw-man. Many scenarios exist to get most of the benefits without resorting to 'everybody simultaneously'.

E.g. 'test and release' where only folks who've been tested are 'released' into the public. Track outbreaks and retest those cohorts thoroughly. And so on.

Not trying to show bravado or anything, just pointing out that I and probably others feel this way; I would fight tooth and nail against pervasive, mandatory "test and release" policies on humans (and the necessary concomitant growth of the surveillance state). The second-order social and political effects of such a policy would be disastrous - orders of magnitude worse, in the long run, than the population-level health effects of this virus. People anticipating these effects would probably be prone to civil disobedience, making the logistical nightmare even worse than what you would get with a fully passive and compliant population.

This position truly baffles me. I can understand people who have reservations about tracking everyone with phone apps to do more effective contact tracing. But objecting to widespread, low-cost testing for virus infection as an extension of the surveillance state? I don't even know how to argue against that because it simply doesn't make any sense to me. Right now the population is clamoring for more widespread and effective testing. Why would people rebel against it? You think people would prefer to remain locked down, or to sacrifice 0.5-1%^ of the population, than be regularly tested for infection? Why?

^or whatever the true number ends up being

I think it's the mandatory part that's rankling centimeter, and I see their point. Once you give powers to the state in an emergency situation it's really hard to roll them back. See the PATRIOT act for example. Is there a way to effectively get universal compliance without implicitly granting permanent new powers to violate civil liberties?

I suspect relying on people to test themselves daily without mandating it would do a reasonable job, but I have no idea if it would be enough.

Edit: typo.

I'm not sure new state powers would be required. The state already can (and does and should) compel people who are known to be infected to be quarantined, or at least self-isolated. As far as testing, companies can already require employees to be tested as a requirement to work. A lot of companies already do drug testing of employees, something I actually don't agree with in most cases, but it's already a norm. In normal times they likely won't have sufficient incentive to do virus testing though, and so probably wouldn't given the cost.

But during an outbreak, the ability to roll that kind of thing out, especially in workplaces with vulnerable populations (like senior care homes and hospitals) or necessarily close working conditions (like restaurant kitchens or some factories) could certainly be a game-changer. And that just seems entirely reasonable to me. There's a outbreak happening, so in order to enter [place where transmission would likely occur] you have to be tested first. If found to be infected, you must isolate. Otherwise, you'd be knowingly exposing others, which already isn't something considered acceptable.

So to me this simply looks like an effective use of existing powers in this situation. I'm not sure how it would slide down a slippery slope. The government decides to keep doing virus screening? I mean, I doubt they would incur the cost, but if they do, good! Maybe as Paul mentioned, we could significantly knock down cold and flu as well. If people are worried about infringing on the rights of people with viruses to live normally, I would ask what about the rights of others not to be infected by them? That besides the fact that if these measures are effective very few people will be getting sick in the first place.

Ok, simple basic counterargument.

When is the pandemic over? When does the pervasive testing stop? The argument can - and will - be made that "unless we keep testing until the end of the human race, you will all die tomorrow of a horrible virus-ridden death."

I don't particulary mind doing pervasive testing for awhile. I would desperately not want to live in a world where I could not feed my family unless I give into it.

> When is the pandemic over? When does the pervasive testing stop?

When we stop seeing non-trivial numbers of test results. The idea that governments want to spend billions on mandatory virus testing outside every building until the end of the human race out of some Orwellian enjoyment of inconveniencing people is not supported by evidence. Even China isn't doing this. Back in the real world, even the SARS vaccination research programmes, which cost relatively little and inconvenienced nobody, were shut down when SARS stopped circulating and the even keeping a few scientists employed as part of a pandemic task force looking out for the future was a step too far for the US govt.

Fair enough, I accept that premise. Let's revisit in like... 8 months.

You work at a hospital, you're required to get a flu shot. I don't know how long this has been the case, but I can say firsthand over a decade.

This is a decentralized proposal similar to going through a metal detector to enter a building.

"Test and release" only works in science fiction. In the real world there is no absolute test that would enable practical test/catch-and-release processing of infected persons. From an epidemiological perspective, when applied to an entire population even tiny false negative rates will let countless infections slip through. False positive rates will see some people doomed to perpetual lockdown as, for whatever reason, they repeatedly test positive.

Setting aside the science of disease, the concept of government agents performing a test to determine one's ability to conduct basic civil liberties (movement, work, basic speech etc) is antithetical to liberal democracy. Such things were not contemplated at the height of the AIDS panic, or SARs, or ebola. It would take something far worse than COVID-19 to implement such a regime in the western world. COVID is a threat to our way of life, to our economies. It isn't an existential threat to the state let alone the species.

Can you be sure it's not an existential threat?

Can you guarantee that a healthy person who gets this 3 times doesn't have a 100% fatality rate (i.e. it gets worse each time?)

Can you guarantee asymptomatic people don't become sterile? (Not saying they do, but if they did this would be an existential crisis and lead to our extinction after a generation).

Can you guarantee asymptomatic people still won't have lung damage permanently? (some asymptomatics athletic types have shown severe decline in lung abilities following covid19).

SARs was bad, but was wiped out so it's moot, AIDS is easier to avoid -don't have sex. ebola I think isn't as viral, and has been mostly contained, iirc they may have a vaccine launched or soon will and better treatments -- it's never gone full global like this.

Covid-19's problem is it's severe viralness and r0. It spreads and keeps on spreading, and there's a ton we don't know about how bad having had it will be to even those with minor cases. until we know for sure on all these factors, the more we can quell it the better.

>> (some asymptomatics athletic types have shown severe decline in lung abilities following covid19)

Which is 100% normal for any pneumonia. I myself once had a bad lung infection (on my back for over a week). It took months before I could swim laps as fast as I did before. That's not anything special. Infections always have secondary medium-to-long term impacts.

Did you have trouble breathing when you had the pneumonia? These are cases of people with 0 or low # of symptoms, and only knew they tested positive of the virus. I'd imagine they just didn't realize they were sick, and then they eventually start feeling fatigue and run down when doing 'normal' things even after the virus passing their system.

ACE2 is in high concentration in the testes too, could this cause fertility issues? Sure it'd be good for the environment but a lot of couples really do want and enjoy their children or to have some someday.

It'd be nice to know as much as possible before we open the flood gates.

These are part of worst case scenarios that are not published openly. We need more data, and until then the responsible actions are taken by almost all govs.

This is essentially what South Korea did. Granted it was done in a different way but everyone was “tested.” I was there just as covid-19 was on the rise and every shop, every station, and every high traffic area had people set up with thermal guns. Shop staff were having their temps checked before their shifts started. Everyone was gloved and masked. And once they had a proper test in place it was made easily accessible — even set up drive through testing.

And now they are pretty much back to normal while much of the world is still at a standstill.

They learnt from the previous SARS bout, reportedly thanks to a number of political factors aligning properly.

The sad thing is that basically nobody else did, among major players. Even other countries in the area (i.e. Japan and China) just went “phew!” after SARS and didn’t substantially review their response strategies. Which is how China was caught napping, Japan is still fundamentally in denial, and everyone else got their asses handed to them by covid19.

China had dispatched detachments of specialists to evaluate the unknown disease in mid December. They knew they were facing a new coronavirus ala SARS end of December and started closing Wuhan then other provinces in January. Not the chill lockdown like Europe, real lockdown where they close all transports, scan all citizens at checkpoints and have the police beatup people going out without masks.

Napping is not the word for that.

But of course you need to package it as an unique, never seen before, game changing solution and write a blog post about it. He’s shilling his startup

Really interesting read and sounds like it could be a game changer for testing - I know in NY we've been clamoring for increased testing for a while to help us reopen. I've got two questions I'm curious about:

0) Sensitivity/specificity: Any data yet on what the sensitivity and specificity of this form of test for SARS-COV-2 will be? And, is work in characterizing all of that far enough along that we can expect to see emergency authorization by the FDA and scale up happening sooner rather than later?

1) Reagent supply: The biggest problem with PCR tests and all seems to have been reagent shortages and supply chains dependent on manufacturers not able to scale. Assuming the test is approved, are there any operational advantages to this approach in terms of securing reagents to overcome that problem?

Thanks for the fascinating read!

0) From a clinical perspective this is data we are generating on an on going basis. Analytically this is a largely a function of the characteristics of the affinity, specificity of the capture molecule used to capture the target (viral particle). As you point out EUA gives opportunities to launch sooner... But it's still critical to validate technogies both internally and externally probably to a greater extent than the de minimus EUA reqs

1) great question. Our approach is novel which allows us to tap into new supply chains that are inherently more scalable (think semi-conductor Fab) but the trade off is execution risk.

Thanks for your reply! Makes sense with regards to the specificity and sensitivity. Are those more scalable supply chains ones that expose you to risk with international suppliers? My understanding, at least from what we've been hearing from our governor's press conferences (so take it with a big political grain of salt obviously), is that while we have high throughput machines capable of large numbers of tests, the reagent supply chains all go back to china leaving domestic companires reliant on international trade negotiations to be able to get the inputs they need to scale. Is that a valid type of concern and are there concerns that even if it's technologically easily scalable, the political and operational logistics of relying on third parties with different incentives could negate that advantage? I don't knwo how valid a concern that is, but that's the narrative we keep hearing here.

I think we're up against many of the same challenges everyone else (Roche, Abbott, et al.) is up against. At the end of the day if we could all wave a magic wand and fix supply chains we would. Technically, we (the collective diagnostics hive-mind) know how to detect viruses. We haven't yet figured out how to deploy these technologies on scales orders of magnitude above our baseline implementations.

How is chip fabrication is more scalable than plastic 384-well plates and cotton swabs? Nothing shy of a home pregnancy test is more scalable than qPCR.

Great question.

This is one of the implementations we're actually developing. One of the challenges with the implementation of testing on this scale is not necessarily on the technology/assay but on implementation. How do you reasonably test millions of folks each and every day, or said another way actually get millions of nasal swabs, saliva, etc on 384 well plate?

I think our ultimate approach is much more akin, albeit with a bit more sensor voodoo magic, to a at home pregnancy test than 384-well plate qPCR tests at central labs.

OK well, having used a Biacore perhaps two decades ago, I'll just have to imagine your "magic" must be pretty good to compete with plastic multiwell plates and cotton on a stick.

50 or 100 sites, each with say a few dozen liquid handling robots. Let’s say each site runs 200 plates per day.. doesn’t seem unreasonable. The only hard parts are the funding and regulatory requirements.

You're getting downvoted but I think it's a fair question actually. I'd assumed they were referring to tapping into non-stressed supply chains. What you mention is valid though and something I'm curious about as well. Are the consumables reliant on chip fabrication? I don't think PCR machines themselves are scalable, maybe chips are more scalable than the optics systems for qPCR, but a valid point about whether the consumables are more scalable as well.

Tests are R&D in Norway that could test entire population in 2-3 weeks. It's developed to scale, so may improve. It's coming and soon, though there will be a ramp-up.

A very recent Yale study suggests promises for saliva-based detection:

“While saliva has shown promise for SARS-CoV-2 detection, very few studies have directly compared it to the current gold standard, nasopharyngeal (NP) swab. So, we compared NP and saliva samples from COVID-19 patients and self-collected samples from asymptomatic healthcare workers”

“COVID-19 patients: SARS-CoV-2 detection from saliva is comparable to (or better than!) NP swabs and more consistent over time ...”

“Plus, the detection of SARS-CoV-2 from the saliva of two asymptomatic healthcare workers (...and counting!) who tested negative from their NP swabs suggests that saliva could be a viable alternative for identifying mild or subclinical infections.”


They're in a "startup incubator" for bio firms in South San Francisco.[1][2] The incubator is run by a unit of Johnson and Johnson. Multiple companies (51 are listed, but some may no longer be there) share 30,000 square feet of workspace there. "We welcome new resident companies with the infrastructure and tools they need to get up and running on day one. This capital efficient model takes time and investment out of the equation—eliminating the normal setup typically required of a startup."

[1] https://businesssearch.sos.ca.gov/Document/RetrievePDF?Id=04...

[2] https://jlabs.jnjinnovation.com/locations/jlabs-ssf

[3] https://jlabs.jnjinnovation.com/JLABSNavigator#/location/Bay...

PB, can you elaborate on which other possible answers you've found for fast, easy, and abundant tests?

I'm working with a team that has a test that detects proteins associated with covid. It works like a pregnancy test and does not need a special scanner. Would love to discuss further.

I'd love to hear more! Part of the reason I put this out is to encourage other people with technology for fast, easy, cheap testing come forward.

Is your protein test able to detect as soon as people become contagious? That's where a lot of ideas fail, but I think getting R0 < 1 likely requires it.

Solutions like this give me hope that we can actually return to something resembling normal life in the future. I hope Paul's got everything he needs in funding and resources to pursue all three of his goals.

I hope everyone has noticed that if this approach could wipe out COVID-19 it could wipe out influenza and even the common cold.

Imagine how naive our immune systems would become. It could have unpredictable effects, like increasing the rate of novel zoonotic disease transmissions.

Maybe something like this is what set the stage for the common cold wiping out the aliens in War of the Worlds.

We would still be exposed to a wide variety of diseases even if there were no more common cold viruses floating around. The common cold viruses haven’t helped us deal with COVID-19 :(

> The common cold viruses haven’t helped us deal with COVID-19

We don’t actually know that yet.

A fourth way: We throw as many resources as we can at sampling undiagnosed populations, like the recent NYC study that suggests 20% of the city (10% of the state) has antibodies already.

We could get real confidence that it's safe enough to return to normal, acceping that COVID is a new disease that's just going to be around, the 5th coronavirus that we deal with seasonally.

The arithmetic on that is ~1 million early deaths in the US.

The screening in the article would cost billions of dollars.

If it worked, we could then reuse the infrastructure to kill the flu. And then start on the colds.

> The arithmetic on that is ~1 million early deaths in the US.

Sorry that's baseless histeria. We can easily think through how healthy people go back to normal (exponentially lower fatality rate than elderly/sick), while vulnerable take more precaution, how then getting to 60% of population gives us herd immunity which grinds R0 to a halt. Then a vaccine arrives in 18 months. Not to mention heat/humidity/summer is being shown to slow the disease from recent studies.

New York (state) deaths per infection assuming ~10% overall spread:

10000/(0.1 * (20 million)) = 0.005

Arithmetic to scale that to ~60% of the US:

0.005 * 0.6 * 330 million = 990000

Of course that is hugely sensitive to the assumptions about the overall infection rate in New York and the immunity factor, but like I said, the arithmetic on what you said leads to ~1 million early deaths.

No, if elderly/vulnerable continue precaution, more like range(.001 - .0001) x .6 x 330 million = 20k - 200k deaths

Add in supposed summer slow down and before we get a vaccine the numbers could be 10x less

There are 12k cases in Singapore and 12 deaths because they almost exclusively tested foreign worker dormitories, healthy working people (and the 12 are all elderly).

I like how you're ignoring the organ damage in even younger survivors like it's rosacea or something.

Cite something -- anything -- legitimate that points long-term organ damage in young, otherwise healthy people. Newspaper anecdotes don't count.

All evidence so far is that a small fraction of people sick enough to be in the ICU end up with some sort of non-lung organ involvement. The vast majority (>99.98%) of young (<50 years), healthy people don't end up in the hospital at all, let alone the ICU.


Right. So a day after you make your comment implying lots of young people are experiencing long-term organ damage, the WaPo discusses an as-yet-unpublished paper discussing a small number of stroke victims who may or may not have been influenced by this virus.

If this is the best you can do, you're grasping at straws.

I like how you're pulling the fear card instead of contributing to a real discussion

There is an episode of Sliders (Fever, Season 1, Episode 3), where they slide into a world affected by an infection with no cure, and scanners have been placed at the entrance to every store to detect if you have it.

In the show the disease is used as a classist thing or something. Anyways, its bacterial not viral, and they discover than antibiotics were never discovered so the Professor scrapes some fungus off some trash and takes it and is cured.

I remember that episode!

Love the Sliders reference. I might stream that all weekend.

Cheap & working saliva test would be such a tracking game changer that I am really hoping it works, so good luck!

A) Does he have any financial interest in PreDxion Bio? This sounds like another smaller startup claiming bullshit.

B) Testing for O2 levels using already cheap + widely available pulse oximeters is probably an insufficient but necessary measure.

Thank you Paul. Two questions :

Does this approach bypass the reagent shortages ?

What are the specificity / sensitivity metrics ?

Couple of things at play here. First is we are developing a non-PCR based viral detection test. Many of the molecular tests approved rely on many of the same ancillary components (RNA extraction kits, flocked nasal swabs, viral transport media) as well as instrument systems. What we are developing is a non-molecular based test to directly detect SARS-CoV-2 particles in fluids, specifically saliva.

We've just begun our clinical testing so don't have specificity/sensitivity metrics yet, but will be sharing them when they're available.

Paul, is there anything HN readers can do to help with this?

Ah, of course. We create a new type of [patentable] ubiquitous technology and sell our way out of this. Leave it to the entrepreneurial mind...

Sorry for being cynical -- I just feel suspicious of this particular tired mindset to addressing complex public health and social issues, ones that intersect with (and aggravate) many other pre-existing social dilemmas. There are a thousand other ways to look at this that don't involve a small cornered market, I just doubt the entrepreneurial mind knows how to parse for it on its own. When you have a hammer...

Wake me up when someone's talking about this sort of thing amongst members of a consortium building open patents, not from some guy with plain-as-day zero-to-one ambitions. I'll root for someone who sees the interlocking opportunities, not someone who speaks about personal aspirations to "wipe out COVID-19" in 2020

I’m having difficulty understanding why SPR would be more scalable than LFAs for this type of frequent screening? And what does the ROC look like for this startup’s SPR assay?

Frankly, I don’t understand how this test is supposed to work, and I’ve used a Biacore! It might be helpful to have a technical explanation available, for domain experts to evaluate.

There didn't seem to be any details at all. Is there some sort of functionalized surface that specifically binds the virus, if so what molecule/chemistry, how?

edit: this is all I found about the company:



Good sleuthing! As you suspect we functionalize the our sensor surface to specifically bind the virus. We've partnered with a therapeutics company developing highly specific monoclonal mAbs against SARS-CoV-2 which we leverage in our diagnostic platform.

> Even with imperfect screening, if we are able to prevent 90% of disease transmission, then the virus’s reproductive number, or R0, will drop below one and the pandemic will quickly fade. There is no risk of reintroduction from the outside because any new outbreaks will quickly be caught and contained. If used consistently, there will be no second wave, ever.

This is dangerously wrong.

If you reduce R0 below 1, you may stop community spread. You will not eradicate it however, unless this is done globally for a prolonged period of time with no error. This cannot be done with the proposed solution.

We can (probably) stop this from hurting the vulnerable population while we find a long term solution like an inoculation, but we cannot just skip that and call everything good after some period of low / no new cases in a region.

Also remember this is literally a virus that emerged from animals in the first place (zoonotic transmission).

There will always be animal reservoirs of this.

For that reason, and those you outlined, we could achieve the flawless techno-totalitarian state that so many well-intentioned citizens are practically begging for, and we would still be screwed.

The only stable long-term solution is widespread exposure; ie how humanity has dealt with pretty much every other global pandemic we’ve been encountered with.

Thus why those who are trying to demonize the concept of “herd immunity” and make it a dirty word are playing a very dangerous game.

I really feel like we're spitting into the wind. There are very few who agree with this position.

The latest on the COVID-19 R0 is a median of 5.7, up from the previously thought range of 2.2 - 2.7.


This means herd immunity kicks in at 82% of the population.

Antibody testing appears to be showing infection rates are a lot higher than previously thought as well.

Both of those things together mean that 1) "there's no way to stop it" 2) "it might not be as dangerous as we thought".

But who knows, right? There's a ton of science that needs to be done to find out what's really going on. Large-scale, accurate, randomized testing will hopefully fill out the data picture.

Because the US has an awful medical system where access to care comes through your job, it seems to me that more people will die (from non-virus causes) than from the economic damage than from the virus itself.

I guess we'll know more in a few years.

> The latest on the COVID-19 R0 is a median of 5.7

Pet peeve of mine: R0 is not a property of a virus; it's a property of a virus in a certain environment. 5.7 is the estimate for covid-19 in Wuhan, a dense environment. It is nowhere close to that in the vast majority of the United States -- estimates are <3 in say Seattle or Norcal.

> Antibody testing appears to be showing infection rates are a lot higher than previously thought as well. > 2) "it might not be as dangerous as we thought".

The more reliable ones are about what we did think on both points, at least for those who rely on Imperial College's models (https://www.thelancet.com/journals/laninf/article/PIIS1473-3...)

> "there's no way to stop it"

Contact tracing is enough to keep r < 1. If we keep this thing at under 20 cases/million/day for the next few years until there's a vaccine, I think we can go about our lives.

> infection rates are a lot higher

in certain urban cores. herd immunity requires well mixed populations

Not sure if I'm missing something, isn't Saliva based testing almost/basically here?

1. https://finance.yahoo.com/news/orasure-technologies-receives...

2. https://www.politico.com/states/new-jersey/story/2020/04/23/...

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