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Comment by pmoriarty | Hacker News Reader

"Tests like this 15 min one are called "antigen" tests and are still accurate/helpful, but are known to produce more false negatives and false positives compared to molecular."

On a large scale, the wrong results from such tests don't matter if you test people often enough (say, every day). If you get a wrong result one day, it'll probably be corrected in the next day or two with more tests.

If there was a massive government initiative to manufacture such tests and subsidize them so that everyone got them every day this pandemic could be effectively halted in very short order, even without a vaccine.

Almost 6 months ago, the This Week in Virology podcast went in to great detail about this plan, starting at about 6'20" in to episode 640:

https://www.microbe.tv/twiv/twiv-640/

There was also at least one NYT article about it, and it was discussed on HN here:

https://news.ycombinator.com/item?id=23878954

Unsurprisingly the government did not do this, and we had six more months of deaths instead.

View on HN

On a large scale, the wrong results from such tests don't matter if you test people often enough

That assumes that for each test it is a sort of dice roll on whether or not there will be a false result. It might be that something about the individual person's biochemistry or health history (like prior exposure to a different corona strain) is the cause of the false result. If that's the case, then people who receive a false result on this type of test will tend to always receive false results, and testing more often won't help much.

If the goal is to lower Rt to below 1, however, it still may be acceptable. See:

https://advances.sciencemag.org/content/early/2020/11/20/sci... https://www.medrxiv.org/content/10.1101/2020.06.22.20136309v... (preprint of above)

Its the viral load, or the amount of virus, mainly. Most people have a large viral load when they are the most infectious, especially in the nose and throat. Testing daily would ensure that you know immediately when you're highly infectious.

A recent check of the rapid test used in the UK is that its largely unaware of the virus if the necessary PCR cycles are > 25, gets it right half of the time for CT between 20 and 25 and it gets very good if viral load is large enough to be detected by < 20 cycles. Other rapid tests are AFAIK somewhat better.

The main problem that most (western) countries failed to solve is to remove reasons to not take a test and not to self-isolate, and that's primarily inability to get proper support WRT work / monetary situation while self-isolating.

Make it easier for people to self-isolate than not to, and people will do it.

They can simply use a different test. It'd be much more resource efficient to use the rapid tests on those for whom it works as intended and use PCR (molecular) tests for those who get false positives every time.

I have friend who has a colleague who always produces a false pos. antibody test. They know it, they still test him. (At this point basically to make sure the test does something at all.)

After all, every kind of proactive/preventive measure helps a bit to keep a group/family/workplace safe.

Yep, if we can distinguish between who it does and does not work as intended. How do you verify a false positive? By performing a better test, but then you have to do it for everyone and we're back to square one. However I agree with other comments that even with false results, it's still very useful, just that frequent testing won't necessarily overcome all false results.

> but then you have to do it for everyone

Unless you are also worried about false negatives you only need to perfrom the better test on those that reported positive on the quicker test.

Sure I'd be worried about false negatives. Identifying the infected to allow them to isolate is the reason for it. I'm not worried about false positives because there is little harm done in having someone isolate uneccessarily. Much more harm is possible by keeping an infected person, who now thinks they're fine, out in public.

These assays are very skewed toward producing false positives.

Exactly for this reason.

It's not perfect. PCR can miss the early stages of the infection too.

These are just signals.

Luckily we know that viral load is the factor for transmission rate (infectiousness). So even if someone is (false) negative, but has symptoms, should self-quarantine.

You corrected some misconceptions I had about how straightforward things are

The governments of Slovakia and of the Bozen province in Italy both organized an antigen testing of their whole population over the course of a weekend (Slovakia did this two times, two weeks apart). From what I can see both attempts were largely unsuccessful in sensibly reducing the spread of Covid, even temporarily.

Testing the whole population of Bozen with antigen tests yielded way less positive results than expected, so the feeling was that the tests were just not as sensitive as advertised.

I don’t believe this is what GP is referring to. Rather continuously testing people, say 2 times per week, en masse.

Is it possible that less people were actually infected than was expected?

Possible, but seems unlikely.

In Bozen they mass-tested 65% of the population over the course of 3 days.

They were getting 540 positive PCR tests every 100k people a week in the week before the mass screening; the latter yielded 900 positive antigen results every 100k people; they got 435 positive PCR tests every 100k people in the week after the screening.

This 20% reduction in positive PCR tests seems mostly due to the lockdown, given that the week before the mass screening the reduction had been even greater, 32%.

The antigen test also seems to be ineffective at detecting igg antibodies months after infection due to their half life and very few non clinically researched focused tests for t or b cells seem to have been carried out anywhere

These are antigen tests, not antibody tests.

The US has 330 million people. A weeks worth of testing is 2 billion tests/week. Lets assume they can manufacture 330 million tests a day.

Test Costs - $60 billion/week. Shipping Costs - $4-5 billion/week. USPS delivers about 180 million letters a day. Their volume would triple![1]

This assumes all of the other problems like 100% participation and zero tech support issues are non-existent.

[1] - https://facts.usps.com/one-day

Nah, bundle up tests in 30 day increments. 300 million tests a day becomes 10 million boxes a day. Large, but not impossible.

lots of ways to optimize, but the scale is still immense.

We already manufacture and distribute paper products on an immense scale even without it being a national (or global) emergency.

Again, according to that TWiV episode, making the tests is not much more complicated than just printing some antibodies on pieces of paper.

It could definitely be done, we just need the will to do it.

A Manhattan Project for testing could have saved hundreds of thousands of lives and probably trillions of dollars.

I missed the link to the TWiV episode. do you have it?

6'20" in to episode 640:

https://www.microbe.tv/twiv/twiv-640/

You wouldn't be delivering 1 test per person per day. You'd deliver a month's worth for a whole household. There's about 52 million households divided by 30 days = 1.7 million packages per day. A 1% increase. I wonder how much of an increase in shipping Christmas is.

There's certainly lots of ways to optimize this (30 day supply in 1 box). The scale is still immense.

The scale is enormous but so is the scale of actions we did take. Billions of dollars in aid to individuals and aid/loans to businesses. Government funding for operation warpspeed to develop vaccines. High unemployment and a reduced economy for months as the pandemic continued.

Exactly. This is literally chump change compared to how much did the pandemic cost the economy.

This is a no brainer.

Okay, now do the math on loaves of bread that manage to make it into homes. Or rolls of toilet paper. If the price really could be down to $1 per test, and manufacturing capacity exists (or could be made to exist), the market would figure out a way to get these tests in enough places to be massively effective. And the government could even fill in some gaps.

The market would also find a way to jack the price up.

As with everything else, the market would simultaneously have offerings with higher prices and offerings with lower prices. There's not just one price.

I bet some companies are working on a repeatable device that runs / re-runs tests. Think of it like a thermometer - you can reuse it as often as you like and get results in seconds.

Of course that doesn't exist yet, but it would solve all the problems you mention.

I'm sure. However the previous comment was lamenting that the government didn't do this for us at the beginning. Even If the test existed (it didn't), and had the money to do so (which is also huge), scaling manufacturing is a real challenge, mailing to 128m households is a huge challenge.

There's no need to mail tests to each individual end user.

The tests could be manufactured locally and picked up in bulk by the end users from centralized locations.

But even if they did have to be mailed to the end users in the hundreds of millions, that's not exactly an insurmountable challenge.

Just a little while ago hundreds of millions of people got mailed ballots and plenty of other information so they could vote in the Presidential Election. That's not to mention all the junk mail each of us gets every single day.

Look at the massive effort put in to the Manhattan Project and the Space Race. There's no reason the government couldn't have done something like that for mass testing, and saved hundreds of thousands of lives and trillions of dollars.

The head of government knew exactly how dangerous the virus was in early February, but chose not to do anything about it.

https://science.sciencemag.org/content/369/6510/1409

One cannot be certain why, but perhaps it is due to the fact that the prior qualifications of this individual were:

1. Operating some mixed-use buildings in New York, and casinos in Atlantic City purchased through extensive family loans 2. Owning and operating a few golf courses 3. Licensing their name to some adult learning courses that were later revealed to be scams 4. Being the star of a reality TV show

Without passing any sort of judgement on this person, they were completely unqualified to orchestrate anything anywhere near the complexity of the Manhattan Project or Space Race.

They were unable to even prioritize and orchestrate the allocation of adequate PPE to healthcare facilities, as well as adequate testing capacity for 50% of Americans to be tested on a monthly basis let-alone daily.

Again, no judgement on this individual, but they were totally unprepared and unwilling to manage the crisis and their failure to act likely hamstrung any meaningful attempt to coordinate the type of effort you are describing, which would have required federal buy-in.

According to that TWiV episode, such tests could cost just $1.

So, according to your estimates of 2 billion tests per week, that would make for $2 billion per week, not $60 billion per week.

As for shipping, the tests need not be shipped via USPS nor need they be shipped individually to every person.

They might be locally manufactured, there could be centralized distribution locations, and people could stock up for a month's or a year's worth of tests at one time, greatly reducing shipping costs (assuming enough tests could be made, of course).

The tests could also be at the very least targeted at locations where there are a lot of infections, further reducing how many tests would need to be manufactured and used.

> it'll probably be corrected in the next day or two with more tests.

Can take 3 tests at the same time to eliminate error, or does the waiting time between repeat tests matter?

The test is very good at detecting the virus if you have a high viral load. Waiting a day and doing another test means that the low-level infection you missed yesterday has had another day to replicate, making it easier to detect.

You're also probably much more infectious when the virus is at levels that are detectible by the antigen tests, so even if you miss it when it's at a low level, as long as you detect it when you get really infectious it can help lower your chances of transmitting it.

> If there was a massive government initiative to manufacture such tests and subsidize them so that everyone got them every day this pandemic could be effectively halted in very short order, even without a vaccine.

Absolutely, except that people need to be willing to take the tests. Here in Austria they did a round of free mass testing. The plan was to test the whole population, however only 17% of eligible people showed up. They just don't care.

In fact, acquaintances asked me "why did you get tested if you didn't have any symptoms?? don't you have anything better to do with your time?".

For the next round of mass testing they are considering paying people €50 just to show up!

"In fact, acquaintances asked me "why did you get tested if you didn't have any symptoms? don't you have anything better to do?"."

This is a simple matter of educating the public.

The government has done this effectively in, say, wartime, when the importance of acting a certain way (ex. "Loose Lips Sink Ships") is emphasized.

You can get nearly everyone on board if the government is competent, on the same side of the issue, and determined.

Sadly, in the US we have bickering, incompetent, and ignorant government officials which are often making things worse by ignoring the science or acting directly contrary to it.

You need both good leadership and good support. The sense of unity should extend to an actual implementation of unity as well: monetary support for people while they self-isolate would go a long way, for example.

Unfortunately I'm afraid that at this point its way too late. The window has moved and the new accepted normal seems to be lots of people dying from the virus. Due to privacy protection those people are also largely invisible to the majority of the population, except for their loved ones - an abstract number. There is also a general sense that "testing doesn't work" - even more so accentuated by the repeated insistence of various medical professionals that rapid tests are "not reliable" (which misses the point - they are not for diagnosis but they're a good infection control tool) and a focus on the vaccines.

Success for rapid tests is therefore highly unlikely at this point. Could have worked 3 or 4 months ago. Maybe if there are huge incentives to get tested and a large campaign to inform the public, it could work - but otherwise I doubt it.

_The government has done this effectively in, say, wartime, when the importance of acting a certain way (ex. "Loose Lips Sink Ships") is emphasized._

That was a long time ago when the vast majority of media available to people was willing to go along with what the government told them was ok or not ok to print. Even if you got 90% of the media on board today, think of the number of Facebook clicks and thus fat stacks of ad revenue one media outlet could generate by just posting a couple of stories a week that "present another viewpoint" or "ask questions" about "the debate".

In funding our news via ad revenue we have turned all issues into a decision of Coke versus Pepsi and tossed any idea of a mutually-agreed upon reality out the door.

It isn't just a matter of education. It's a matter of setting incentives as well. If the downside of getting tested when asymptomatic, and getting a positive result, is having to quarantine and losing two weeks of work then no level of education will get enough people to do that. If you also guarantee their wages, then that's different.

> "why did you get tested if you didn't have any symptoms? don't you have anything better to do?"

I mean, I've been known to use the blood pressure machines that drug stores make available mostly because I like the feeling of pressure on my arm. Maybe you didn't have anything better to do. People do lots of things.

Fortunately, this doesn't appear to be a problem where I live. They're telling us not to get tested because too many people are getting tested without symptoms.

With the current tests, that is the right answer. Unless the test results are quick, there really is no reason to test everyone. If there is a significant length of time between the test and the results then the people who have it will spread it while waiting for the results.

Results come in less than 15 minutes...

>If there was a massive government initiative to manufacture such tests and subsidize them so that everyone got them every day this pandemic could be effectively halted in very short order, even without a vaccine.

Provably false, since over the past 10 months we've seen people all along the way going to parties, restaurants, rallies, airline flights...all after having tested positive. Mooks and celebrities, it hasn't mattered.

Your false assumption is that strangers care whether anybody around them dies a painful and lonely death. That's before you even get to the practicality of isolating people who test positive, or to isolate themselves, especially among science disbelievers, Christian congregations, and 2nd Amendment activists.

At $30 per test, I doubt we will get much regular testing with this. Family of four would by $120 per day of testing.

Yeah, it should be subsidized so its at least 10 times cheaper. $30 should be a pack of 10 rapid tests.

In addition there should be mechanisms to support people who are self-isolating that are sufficient so that its equally easy to self-isolate as it is not to self-isolate

Again, according to that TWiV episode this could be done for $1 per test.

And it could be subsidized by the government for those who couldn't afford it.

That wouldn't have had the fancy electronics and cell phone app that force the user to show up in government statistics, though. It would just let the user know if they were infectious or not and act accordingly.

…which would be plenty of info for the primary endpoint of "saving lives".

The government's desire for a legible set of stats should take a backseat to the urgent need to inform people how to protect themselves. Let's help people save themselves by not making useful tools illegal. Pretty charts for bureaucracies can wait.

Yes, ideally that's what would happen. But it's hard for the FDA to approve any new medical device that's worse along a metric the FDA cares about than existing methods. Honestly, the FDA has basically never cared about price and availability before so I'm really surprised they're even letting this one through given that it's less sensitive than a standard PCR. Given how disastrous the FDA's (and CDC's) actions around testing were in February and March I'm relieved things are currently going as well as they are.

> On a large scale, the wrong results from such tests don't matter if you test people often enough (say, every day).

But is anyone going to be getting the test every day? Particularly when it apparently costs $30. At that price, once is fine but nobody is going to be doing it over and over; they'll just treat whatever result they get (positive or negative) as binding.

"But is anyone going to be getting the test every day? Particularly when it apparently costs $30."

This is why it needs to be subsidized by the government.

Also, according to that TWiV episode it could be done for something like $1 per test.

$330 million per day or nearly 10 billion per month, not counting distribution costs.

And could we manufacture 10 billion of them a month?

"could we manufacture 10 billion of them a month?"

Yes, it could be done.

According to that TWiV episode (which, again, I encourage everyone to listen to) the tests are very simple: just a piece of paper with some antibodies on it.

As for the $10 billion per month cost, from the TWiV episode (about 31 minutes in):

It just boggles my mind, the enormity of this problem. This is killing enormous numbers of people every day. It's costing the country trillions -- literally trillions of dollars. This should just be part of the national emergency.

It's one thing to make vaccines, it's one thing to make therapeutics, but these are things that necessarily take time. We have to wait to see what the efficacy is, we have to... it's really hard to make therapeutics. A diagnostic test should be a no-brainer. Make a $1 test. Get it to everyone. Change the way we view these things, and that should be completely being plowed through by the federal government.

We don't have to make 300 million of them overnight. We just have to focus them at the moment in places where the cases are worst... it's just astounding that we don't see a flurry of activity from the US Army...

I don't know who makes it, but take every manufacturing company that knows how to print paper, adapt their tools to print monocolonal antibodies on to those sheets and just start slicing it up and shipping it out. It's as easy as that.. well, you know, I'm simplifying it a bit but...

$10 billion per month is far, far less than either 1) the economic losses of the pandemic to society, or 2) the amount of money the pandemic is costing the government. I have no knowledge on whether it's feasible, but if it significantly reduced the impact of the pandemic, the economic decision is easy.

Maybe a year ago this would have been worth it. But the resources should be used for mass vaccination instead.

Unfortunately, it seems a lot of people are afraid of getting vaccinated.

Those people, at the very least, should be getting tested.

Also, it's going to take a long time for even those who want to get vaccinated.

Finally, we don't know how long the immunity given by the vaccination will last. If it only lasts a couple of months people might need to get revaccinated again and again throughout the year, which will probably lead to even less people willing to be vaccinated.

So vaccines are very unlikely to be a complete solution by themselves.

We still need mass testing.

I'm going to make an educated guess and say that there isn't a ton of overlap between people who will refuse a vaccine and people who will voluntarily submit to continuous testing.

Maybe I'm underestimating how fast they can ramp up production on these tests, but you'd need billions a month to just test everyone every week.

>Maybe a year ago this would have been worth it. But the resources should be used for mass vaccination instead.

Given that it will be at least 6-9 months before an appreciable fraction of the population can be vaccinated, frequent testing still makes a whole lot of sense.

As to the effort/expense, you'd think we'd be able to walk and chew gum at the same time, no?

>Given that it will be at least 6-9 months before an appreciable fraction of the population can be vaccinated, frequent testing still makes a whole lot of sense.

What makes you think we can ramp up production on these faster than that? You'd need a billion of them to test each America once every three months.

>As to the effort/expense, you'd think we'd be able to walk and chew gum at the same time, no?

Only if the resources used were entirely unrelated, which I doubt. Every public health offical's man-hour should be dedicated to setting up vaccination sites. Every medical manufacturing facility should be making vaccine components and accessories.

I very much doubt you could set up mass testing of asymptomatic people without making trade offs regarding resources for mass vaccinations.

> This is why it needs to be subsidized by the government.

If it were subsidized by the Government, they'd be charging 10x that per test.

Not if the government is the only real buyer

How much can the unit price reduce with further scale.

The usual for chemical batches is that scale is the major determinant to price, but there are always exceptions.

The functional part of the test, the piece of paper that lines appear on, is less than $0.10 a piece. It is mass manufactured, you could mail people a hundred test strips. You could reuse the $1 plastic housing. What do you think people are doing in other countries? This is a failure of leadership.

As a citizen of another country, I'm not aware of any country that is shipping tests to citizens at their homes. Maybe your numbers you quote are correct - there are other problems, like relying on people to report their positive test results and isolate. A lot of people would, but many also wouldn't, because they can't afford the loss of wages. You'd have to cover wages lost, or some percentage anyway, and that would mean requiring another test at a trusted facility, which increases the complexity again...

Maybe the concept would be workable, but it's also not a simple slam dunk, and again, I don't know that any country is doing anything like it.

> What do you think people are doing in other countries?

They're not shipping dozens of tests (that didn't exist until now) to their citizens at no cost, which I what you seem to be implying...

The tests that they used in Austria cost 7€ a piece, and apparently there are even tests available for 4€ (bulk price obviously)

A friend of mine recently ordered a pack of 25 tests for less than 200€ (he only had to check a box confirming that he was a medical professional). They test the kids with a throat swab every time before they visit their grandparents.

Frequent testing is absolutely feasible if you really want to.

I wouldn't have a problem with the testing at my school if they didn't basically forcefully evict you (and by forcefully, they just threaten you being a student there anymore if you don't leave) or tell you to go into quarantine housing. Which requires you cannot leave your apartment for 14 days. Period no exceptions. And they only give you 4 hours to do it. Even several people moving one person's stuff in 4 hours is absurd.

It's like these bureaucrats don't know human psychology. Youre essentially shaming people to a leper colony for a short time just to save face. It wouldn't be so bad if they just told you stay put. But the administration doesn't want to risk seeming incompetent so they heard the sheep in the way that's easiest for them.

>On a large scale, the wrong results from such tests don't matter if you test people often enough (say, every day). If you get a wrong result one day, it'll probably be corrected in the next day or two with more tests.

Huh?

Continuing to accumulate bad data just leads to a higher accumulation of error.

If you have a high percentage of false results and you continue to test over and over the data are still not reliable. How would you know which the correct results are?

Say you test 14 days in a row, over those 14 days you've experienced no symptoms, yet 6 tests showed positive and 8 showed negative.

Do you have any better idea after those 14 days of testing as to whether you've got covid or not?

Large scale testing is likely aimed at public health, where the goal is to lower Rt < 1. Missing some positives is tolerable. Also, the antigen tests are more sensitive when the person is most likely to be contagious.

It depends on the error rate of the test. If it's close to 50/50 then obviously the test is worthless. But these tests are much more reliable than that, so a population scale the wrong results will be corrected with more testing.

I don't have the analysis in front of me, but I encourage you to listen to that TWiV episode yourself and listen to the panel of virologists discussing this. They were initially skeptical also, but after questioning the plan's author they were eventually convinced and became excited because the plan could actually work.

With n multiple tests you are much more likely to approach the mean of positive results, which for an actually positive patient is (1-p1)n and for an actually negative patient is p2n, where p1 and p2 are false result probabilities. If p1, p2 << 1 then the means are sufficiently apart that you can compute the probability of getting your result (whatever that is) under the actual positive/negative scenario and one probability will be significantly higher than the other.

Assuming the tests are independent, which is unrealistic. If the antigen test is positive because it's cross-reacting to the common cold or because of something unique to you, then testing more tells you nothing.

So, thinking about surveillance in e.g. schools.

If your choice is to test all the students monthly -- e.g. 3% of them per day -- with a molecular test that has a couple day turnaround... This works pretty much only well enough to detect rampant, uncontrolled spread, and will not break a transmission chain very often.

Or to test all the students weekly -- 14% per day -- with an antigen test that returns results in 30 minutes... Even if there's some false negatives, you'll still interrupt many transmission chains and effectively lower Rt.

This is wrong. Too false positive and people will start ignoring the results. Thats what happened in the current climate. You need consistently good days otherwise over the long haul people will distrust and ultimately not follow.

You mean false positives? This assay doesn't false positive that much-- specificity is estimated to be 96-97%.

That's a false positive every day in a normal-sized school.

Yes. And then it’s not just one kid. It’s the entire class plus teacher. It would be a fire drill per day. And then they would need to take the tests every day until they are cleared. It’s not feasible.

It isn't quite that bad, because the tests aren't independent. You end up with a few people who are disproportionately likely to test positive and can adjust appropriately your testing strategy for them.

And even if that wasn't the case-- you keep a few people home (them + close contacts) until followup molecular testing returns a negative. Yes, it's a big hassle-- you're "falsely" forcing 10% of the student body into remote learning, but probably better than remaining closed.

Yes thank you I corrected.

As I understand it, these tests rarely produce a false positive, but often produce a false negative. So a positive test result on 6 occurrences is a much stronger signal than a negative result on 8 days. If you get a positive result from a rapid test, you should either self isolate or take a PCR test to confirm.

Think about what you would do if you wake up with cold or flu symptoms these days - there's a chance you don't have covid, but you still need to be extremely careful. These rapid tests should be thought of as a more effective version of the "do I have symptoms" test everybody does subconsciously every day.

Sensitivity of these tests is 95%, but specificity is 97%. So it can definitely be wrong in both directions.

Some rapid tests go as high as 99.97% specificity.

Its not randomly unreliable but its significantly more unreliable when you have low viral load. (As it happens thats also when you're much less likely to be infectious)

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