Fear and Loathing, a Rat Flu Odyssey

[Mazderati]

I notice the statement that a test with 14% false positives would be useless. But is such a test more likely to give repeat false positives on the same person? Because if not, two positives with the same test would be 98% reliable. Not that a better test isn't better, but shortage seems to be the current problem and doubling up on bad tests would be better than nothing...unless it's not.

If each test is an independent event the probability of false positive on any test is 14%. Prior results would not matter the same way ten blacks in a row at the roulette table doesn't mean red is more likely on the next spin.

[old goat]

I notice the statement that a test with 14% false positives would be useless. But is such a test more likely to give repeat false positives on the same person? Because if not, two positives with the same test would be 98% reliable. Not that a better test isn't better, but shortage seems to be the current problem and doubling up on bad tests would be better than nothing...unless it's not.

Presumably a false positive means that the test detects antibodies to other coronaviruses, not that there was an error in doing the test. So two false positives would not equal a true positive. Even if that were the case it would mean you would have to test every positive twice.

The problem is that it is unlikely that the companies that make the good tests can produce enough on their own. They could license their technology to other companies, but those companies' licensed tests would still have to be validated.

[mall walker]

If each test is an independent event the probability of false positive on any test is 14%. Prior results would not matter the same way ten blacks in a row at the roulette table doesn't mean red is more likely on the next spin.

....nonetheless the odds of ten blacks in a row at a roulette table is much less than 50%

[Mazderati]

Are you serious?
Free to choose how and where you spend your time?
Free to sleep, wake up, eat, drink, shit and piss when you want?
Free to speak freely, or avoid interaction entirely?

This is how I feel when I tell people I want to retire as early as possible and they ask what I would do with the extra time like it's a crazy concept. The answer is always whatever the fuck I want. Maybe that involves some cool part-time gig and maybe it's 24 hours of fanning my balls. Whatever the case, it's my choice.

[Mazderati]

....nonetheless the odds of ten blacks in a row at a roulette table is much less than 50%

That's true but does not negate the independence of each spin.


Edit: I see where you were going with this given Jono's clarification below. Series of tests potentially showing reduced false positivity.

[jono]

That's true but does not negate the independence of each spin.

I think you may have assumed I was asking a different question. See OG's response, which I take to mean that a "bad" test would be more likely to give a second false positive on the same person than it would be to give a false positive on a different (random) person because the cause would most likely persist. IOW: false positives are not truly random, which was really what I meant to ask.

Which brings another option for double testing: two different tests. There may be combinations of tests that each give a lot of false positives on their own but very seldom both give a false positive on the same sample. (Only relevant in the short run, one hopes.) If so, I would expect that could be pulled from the data they collected.

[XXX-er]

This is how I feel when I tell people I want to retire as early as possible and they ask what I would do with the extra time like it's a crazy concept. The answer is always whatever the fuck I want. Maybe that involves some cool part-time gig and maybe it's 24 hours of fanning my balls. Whatever the case, it's my choice.

it is actualy a crazy concept and not that easy so some retires can't handle it and just go back to work

[rideit]

Can any of you sciency types review this antibody test option we have here, and describe whether it is complete bullshit, or useful?
Thanks!

https://buckrail.com/new-nonprofit-o...ibody-testing/

[LegoSkier]

I feel it’s a good time for a discussion of ways to detect pathogens and our body’s response to them.

There are two basic ways to detect stuff floating around in your body.

1. Look for amino acids and their polymers. That means detecting proteins.
2. Look for nucleic acids and their polymers. That means detecting DNA or RNA.

Each of those has its advantages and disadvantages. For DNA/RNA the main advantage is that we have this technique of Polymerase Chain Reaction (PCR) which effectively can take one single strand of DNA/RNA and quickly make millions of exact copies of that strand. That way it is able to create a very powerful amplifier of that DNA/RNA “signal” that you can then detect much easier.

For Proteins, we have no equivalent way to amplify the signal. The best we can do is attach things to the protein molecules that make them easier to see like dyes or phosphorescent molecules that light up. But still there is only a one-to-one ratio of proteins to detect in the original sample to lighted things to detect in the test, whereas with PCR DNA/RNA test, there is a one-to-millions ratio.
Next, comes where we get the “sample” from. The thing we are trying to detect can either be from:

A. The pathogen itself.
B. Our body’s response to the pathogen (our immune response).

So far with COVID we have the following:

- The RT-PCR test which is a DNA/RNA test detecting the pathogen itself. Combining the two lists above that is option 2A.
- Antibody tests which detect protein antibodies produced by our immune system in response to the virus. That is option 1B.

Now the PCR test is great in that it is super sensitive at detecting the presence of RNA from the viral genome. Sometimes perhaps too sensitive in that it can detect RNA that is not at all from a “viable” virus. i.e. it is just detecting the desiccated remains of a virus that was once there but cannot actually infect you anymore. In addition to being very sensitive, they also tend to be very specific in that cross contamination and the reasons for it are very well understood and managed through proper primer design. The downside to this is of course it is only directly looking for the pathogen so it only tells you “you are actively infected and shedding the virus”. It tells you noting about how your body is responding to the virus or if you already had it.

The antibody test is the opposite of that. It is detecting that your body has seen this virus and has started to respond to it. These protein-based tests are easy to create, easy to manufacture at a large scale, can be very cheap, and can even be packaged to be administered at home (pregnancy test). The main problems with them are that if you have the virus but your immune system hasn’t started to respond yet, it won’t tell you that. It also is of course a protein test so there is no magic way to amplify the signal like DNA/RNA has with PCR, so they are less sensitive. They also tend to be less specific in that it is easier for other similar antibodies to cross-react or interfere with the results. Finally, with them being cheaper, easier to make, and available outside of controlled lab environments, the prevalence of user error is much higher than with PCR based tests.

So the whole thing is definitely a balancing act. Which one to use changes by what question you are are asking. Option 2A? 1B? Both? Then add in time, environment, and a whole host of other factors. It is all about gathering the proper information to give you the best available data to make the decisions you need to make.

You will also notice that 2A and 1B aren’t the only options from the list above. You could also have option 1A, where you are detecting proteins present in the pathogen. Or you could have option 2B, where you are detecting the DNA of our body’s immune response, effectively looking at a genetic picture of how our body is responding to the virus during the course of the disease.

[iceman]

Can any of you sciency types review this antibody test option we have here, and describe whether it is complete bullshit, or useful?
Thanks!

https://buckrail.com/new-nonprofit-o...ibody-testing/

Well I'm not a scientist but it doesn't say which tests they as using. But as a general thing, it seems legit and if you have been exposed or think you have it or have had it, sure why not?

I also have a strange desire to buy a house from McPeak Realty for some reason.

[iceman]

I feel it’s a good time for a discussion of ways to detect pathogens and our body’s response to them.

There are two basic ways to detect stuff floating around in your body.

1. Look for amino acids and their polymers. That means detecting proteins.
2. Look for nucleic acids and their polymers. That means detecting DNA or RNA.

Each of those has its advantages and disadvantages. For DNA/RNA the main advantage is that we have this technique of Polymerase Chain Reaction (PCR) which effectively can take one single strand of DNA/RNA and quickly make millions of exact copies of that strand. That way it is able to create a very powerful amplifier of that DNA/RNA “signal” that you can then detect much easier.

For Proteins, we have no equivalent way to amplify the signal. The best we can do is attach things to the protein molecules that make them easier to see like dyes or phosphorescent molecules that light up. But still there is only a one-to-one ratio of proteins to detect in the original sample to lighted things to detect in the test, whereas with PCR DNA/RNA test, there is a one-to-millions ratio.
Next, comes where we get the “sample” from. The thing we are trying to detect can either be from:

A. The pathogen itself.
B. Our body’s response to the pathogen (our immune response).

So far with COVID we have the following:

- The RT-PCR test which is a DNA/RNA test detecting the pathogen itself. Combining the two lists above that is option 2A.
- Antibody tests which detect protein antibodies produced by our immune system in response to the virus. That is option 1B.

Now the PCR test is great in that it is super sensitive at detecting the presence of RNA from the viral genome. Sometimes perhaps too sensitive in that it can detect RNA that is not at all from a “viable” virus. i.e. it is just detecting the desiccated remains of a virus that was once there but cannot actually infect you anymore. In addition to being very sensitive, they also tend to be very specific in that cross contamination and the reasons for it are very well understood and managed through proper primer design. The downside to this is of course it is only directly looking for the pathogen so it only tells you “you are actively infected and shedding the virus”. It tells you noting about how your body is responding to the virus or if you already had it.

The antibody test is the opposite of that. It is detecting that your body has seen this virus and has started to respond to it. These protein-based tests are easy to create, easy to manufacture at a large scale, can be very cheap, and can even be packaged to be administered at home (pregnancy test). The main problems with them are that if you have the virus but your immune system hasn’t started to respond yet, it won’t tell you that. It also is of course a protein test so there is no magic way to amplify the signal like DNA/RNA has with PCR, so they are less sensitive. They also tend to be less specific in that it is easier for other similar antibodies to cross-react or interfere with the results. Finally, with them being cheaper, easier to make, and available outside of controlled lab environments, the prevalence of user error is much higher than with PCR based tests.

So the whole thing is definitely a balancing act. Which one to use changes by what question you are are asking. Option 2A? 1B? Both? Then add in time, environment, and a whole host of other factors. It is all about gathering the proper information to give you the best available data to make the decisions you need to make.

You will also notice that 2A and 1B aren’t the only options from the list above. You could also have option 1A, where you are detecting proteins present in the pathogen. Or you could have option 2B, where you are detecting the DNA of our body’s immune response, effectively looking at a genetic picture of how our body is responding to the virus during the course of the disease.

Thanks for the information. It seems like you'd want to bundle two tests together if possible, either the protein tests or the RNA/DNA tests. That way you'd be able to determine which of the 4 categories the person is in: Negative, Active, Active with Antibodies and Post-Active (antibodies but no virus). So get on that and report back.

[snowaddict91]

Well I'm not a scientist but it doesn't say which tests they as using. But as a general thing, it seems legit and if you have been exposed or think you have it or have had it, sure why not?

I also have a strange desire to buy a house from McPeak Realty for some reason.

Yup. Without knowing whose assay they are running we don't know if its a "good" one or not. There are currently only 4 serological/antibody tests that have been approved through the FDA EUA. There are many more tests out there that are not fully approved. That does not necessarily mean they aren't "good" tests, but they have not Yet been validated and approved by the FDA.

Any CAP/CLIA accredited lab will validate their own test (or manufactured kit that they are using) in-house, possibly more thoroughly than the FDA validations themselves.

Also, good summary lego skier!

[snowaddict91]

Thanks for the information. It seems like you'd want to bundle two tests together if possible, either the protein tests or the RNA/DNA tests. That way you'd be able to determine which of the 4 categories the person is in: Negative, Active, Active with Antibodies and Post-Active (antibodies but no virus). So get on that and report back.

This would be the most informative way to test everyone, if we had the testing capacity. 2A/1B would use the gold standard for both methodologies. Down the road with increased testing capacity we will probably see patients tested for both concurrently, but it is also somewhat wasteful since if a patient is symptomatic, they likely have virus but possibly no antibodies, and if they are post-symptomatic they likely have antibodies but no (or low) viral load.

[LegoSkier]

FYI, the company I work for basically invented the “other” option 2B, where we can detect and decode the immune response to a disease at the genetic level. You can read about our covid projects at https://www.adaptivebiotech.com/adap...inst-covid-19/

[Rideski]

Sounds like the SEC isn’t the only one that will be breaking down your door.
https://www.cnn.com/2020/04/25/polit...rch/index.html

[iceman]

This would be the most informative way to test everyone, if we had the testing capacity. 2A/1B would use the gold standard for both methodologies....

Yeah the reason I said put the protein tests together or the RNA/DNA tests togther was to make manufacturing and analyzing them easier, they might not be as accurate as technically possible but it should be easier to produce and analyze the results from large quantities of them faster. I'd imagine.

But whatever works.

[old goat]

Can any of you sciency types review this antibody test option we have here, and describe whether it is complete bullshit, or useful?
Thanks!

https://buckrail.com/new-nonprofit-o...ibody-testing/

The company they are working with doesn't produce tests--it organizes research and does other administrative type stuff. Sounds like the company will be working with actual test makers, but without knowing which tests it will be using no one can comment on whether it's worth taking the test or not. Getting a false positive and acting like you're immune would be dangerous. For that matter, without knowing the extent of immunity antibodies give you it would be dangerous to act like you're immune with a true positive. One thing that matters with antibodies is titer--how much. I don't know if any of the tests are quantitative or just yes/no.

[ate'em]

I feel it’s a good time for a discussion of ways to detect pathogens and our body’s response to them.

Thank you Lego.

[old goat]

Sounds like the SEC isn’t the only one that will be breaking down your door.
https://www.cnn.com/2020/04/25/polit...rch/index.html

All the research and data on Covid 19 should be open source. No one should need to hack it. The govt should be reimbursing companies and hospitals for the research they do and controlling the patents, licensing them to anyone for a nominal fee. It is in our interest for China, Russia, Iran, N Korea etc to have access to the best technology. We are not safe if they are not safe. This should not be a profit making opportunity.

[Tri-Ungulate]

FYI, the company I work for basically invented the “other” option 2B, where we can detect and decode the immune response to a disease at the genetic level. You can read about our covid projects at https://www.adaptivebiotech.com/adap...inst-covid-19/

I like Adaptive's approach, since it not only has the possibility of determining infectious exposure, but also give insight into maladaptive immune responses that lead to inferior outcomes. I suppose it depends on how robust the machine learning algorithms are. A question I'm sure they're addressing is how sensitive the approach is in convalescent patients, when the monoclonal T-cell and B-cell titres drop.

[rideit]

Brett McPeak is a straight shooter, best agent in town, by far. And a good friend.

[iceman]

I was just goofing because his ad showed up in the link.

[Benny Profane]

California is offering 3 free meals per day delivered to seniors and other high risk people. Idea is not only to feed vulnerable people but to increase restaurant employment. Most of the money is coming from FEMA.

I would knock that down to two. It's not as though the recipients are burning calories.

[rideit]

I was just goofing because his ad showed up in the link.

Yeah, I figured, I just wanted to give him props.

[old goat]

I would knock that down to two. It's not as though the recipients are burning calories.

I'm sure the meals won't be overabundant. However, among the older cohort of the elderly malnutrition and weight loss are very common, as opposed to the obesity problem in younger people. Also, there's a reason poor people are fatter than rich people--low cost filling food is high calorie and fat. Fruits and vegetables are expensive. For someone who is obese I have no doubt that 3 nutritionally planned meals a day will help them lose weight.

Another aspect of opening the economy-- https://www.washingtonpost.com/busin...s-coronavirus/
People fulfilling orders for nonessential goods are reluctant to trade their health for a paycheck. This economy will not recover to preCovid levels until people feel as safe as they did pre Covid.

Which also raises the question--will California's meals program be able to recruit enough restaurant and delivery workers to make it work?

A question for Mitch McConnell--why is it OK to bail out big corporations that risk failing because of enormous debt incurred to acquire competitors and buy back stock, but not ok to bail out governments that have big pension obligations? I'm sure Mitch is counting on his pension; why should he be allowed to stiff a sanitation worker? I'd also point out that those mergers and acquisitions and buybacks do nothing to drive the economy but are purely financial manipulation while the vast majority of pension dollars are spent immediately on goods and services. I wish I believed in god, because I could rest easy knowing the man will be going to hell.