7 ms·

Agree it's trivially easy to do, but as anyone you does a lot of qPCR knows, they're rife with false positives. Any environmental contamination will show up as

Agree it's trivially easy to do, but as anyone you does a lot of qPCR knows, they're rife with false positives. Any environmental contamination will show up as a positive, particularly using the non-quantatative end-point method mentioned above. There's simple controls for that, but still....

jey 7y ago
Aren’t the primers supposed to be pretty selective for the RNA sequences being targeted? Otherwise any other random RNA in the sample (like from some other viral infection) would result in a false positive, right?
- gravelc 7y ago
  Looking at the assay - it uses a dual labelled probe. That gives the specificity in addition to the PCR primers. Primers themselves presumably aren't selective enough.
- danarlow 7y ago
  Once you have a successful PCR, you have billions of copies of your target sequence that are easy to aerosolize and/or transfer by contact onto your pipettes, gloves, and other lab surfaces. When a few of these molecules find their way into a new PCR you just set up, you get a false positive. There are protocols clinical labs employ to avoid this (e.g. never open the cycled PCRs in same room where you set up new PCRs, etc.) but they require strict adherence. (Or you can just give up all your sensitivity and only detect the cases with a huge viral load.)
mullingitover 7y ago
> Agree it's trivially easy to do, but as anyone you does a lot of qPCR knows, they're rife with false positives. Honestly we'd be better off having a widely available test that gives 50% false positives. Worst case, a bunch of people quarantine unnecessarily, but we at least catch all the infected. The alternative is what we have now: widespread community transmission with no end in sight.
- glenstein 7y ago
  This is an interesting tradeoff to consider. Under many many circumstances I could see that rate of false positives being awful and intolerable. In the context of a bona fide pandemic with a massive shortage of desperately needed testing, however, this would be a palatable improvement upon the status quo.
  - jjeaff 7y ago
    In the case of a generally mild disease, it's much less of a problem. Usually, the problem with false positives is unnessary, risky treatments and overwhelming the medical system. But in this case, you just need to know whether to self quarantine. You only need treatment if symptoms become severe.
  - GarrisonPrime 7y ago
    Until the global economy unnecessarily collapses.
- awrence 7y ago
  This is a classic statistical fallacy. A test that is 50% accurate serves 0 purpose. You might as well consider coin flipping a valid test. If you tested America with this test you’d end up thinking half the country is infected. And within the ones that tested positive only half would actually be and within the negatives half would be and you would have missed them. A test needs to be materially more accurate than the odds of having the disease to be worth anything. Classic thought experiment: if 0.0001% of the population has a disease and a test is 99% effective and you test positive, what are the odds you have the disease? Answer: 1%. Complimentary thought experiment: if an expensive preventive drug was available in limited supply (for 0.1% of the population only) and the earlier you took it the more preventive it was should you give it blindly to as many positives as you can? Probably not because 99% of that would be going to waste. And you would run out of drugs to cover the actual sick. Only 10% of the sick would end up actually getting the drugs.
  - DangitBobby 7y ago
mkagenius 7y ago
> they're rife with false positives. Is it possible that some of the positive cases of Corona are actually positive cases of Influenza?
- acqq 7y ago
  No, it is not, see the numbers compared by the Italian National Biotechnology Association: https://en.wikipedia.org/wiki/File:Is_COVID-19_like_a_flu%3F_ENG.png https://en.wikipedia.org/wiki/File:Is_COVID-19_like_a_flu%3F... Each bar is one week. Flu has totally different speed of increase and the amount of people needing treatment and dying. We know what is the cause of the increase, the scenario repeats in many countries across the world, it's not one isolated setup.
  - mkagenius 7y ago
    I was curious about the possible mix up of flu and covid by the testing kit since they are similar, I am not denying that covid exists, just that if the tests are mixing the two up.
    - Tepix 7y ago
      No, the covid testing kit was tested with more than a thousand probes and there wasn't a single false positive. Source: Christian Drosten (he created the test) on the NDR Coronavirus Podcast
      - capableweb 7y ago
        There is another source (in German) claiming the same, HN comment here: https://news.ycombinator.com/item?id=22627958 https://news.ycombinator.com/item?id=22627958 and source here: https://www.ndr.de/nachrichten/info/16-Coronavirus-Update-Wir-brauchen-Abkuerzungen-bei-der-Impfstoffzulassung,podcastcoronavirus140.html https://www.ndr.de/nachrichten/info/16-Coronavirus-Update-Wi... > Regarding your question about if we might accidentally test for flu or other, already existing corona virii: > This was a topic of discussion in yesterday's talk [1] with Dr. Drosten, a virologist who played an important part in the development of the currently used PCR test. He said that there were extensive studies done with hundreds of samples from both flu patients and patients infected with other corona virii and none returned a positive result. The only other positive results were from corona virii that are special to certain animals (bats, some cows IIRC), but none of those are present in humans. So the accuracy of our current PCR test for SARS-CoV-2 seems to be extremely high. Edit: realize now that it's the same person (Dr. Drosten) so same source, but different format (podcast vs transcript)
mythz 7y ago
Given one of the best pieces of advice about managing COVID-19 is to "Act Like You Already Have it" [1], a less accurate test with more false positives isn't necessarily a bad thing. [1] https://www.huffingtonpost.com.au/entry/act-like-you-have-coronavirus_l_5e721aafc5b6eab7793fc120 https://www.huffingtonpost.com.au/entry/act-like-you-have-co...
cryptonector 7y ago
We really need a test for anti-bodies as well.
- diag 7y ago
  Antibody tests are also fairly unreliable in a number of circumstances as well.

jey 7y ago

Aren’t the primers supposed to be pretty selective for the RNA sequences being targeted? Otherwise any other random RNA in the sample (like from some other viral infection) would result in a false positive, right?

gravelc 7y ago
Looking at the assay - it uses a dual labelled probe. That gives the specificity in addition to the PCR primers. Primers themselves presumably aren't selective enough.
danarlow 7y ago
Once you have a successful PCR, you have billions of copies of your target sequence that are easy to aerosolize and/or transfer by contact onto your pipettes, gloves, and other lab surfaces. When a few of these molecules find their way into a new PCR you just set up, you get a false positive. There are protocols clinical labs employ to avoid this (e.g. never open the cycled PCRs in same room where you set up new PCRs, etc.) but they require strict adherence. (Or you can just give up all your sensitivity and only detect the cases with a huge viral load.)

mullingitover 7y ago

> Agree it's trivially easy to do, but as anyone you does a lot of qPCR knows, they're rife with false positives. Honestly we'd be better off having a widely available test that gives 50% false positives. Worst case, a bunch of people quarantine unnecessarily, but we at least catch all the infected. The alternative is what we have now: widespread community transmission with no end in sight.

glenstein 7y ago
This is an interesting tradeoff to consider. Under many many circumstances I could see that rate of false positives being awful and intolerable. In the context of a bona fide pandemic with a massive shortage of desperately needed testing, however, this would be a palatable improvement upon the status quo.
- jjeaff 7y ago
  In the case of a generally mild disease, it's much less of a problem. Usually, the problem with false positives is unnessary, risky treatments and overwhelming the medical system. But in this case, you just need to know whether to self quarantine. You only need treatment if symptoms become severe.
- GarrisonPrime 7y ago
  Until the global economy unnecessarily collapses.
awrence 7y ago
This is a classic statistical fallacy. A test that is 50% accurate serves 0 purpose. You might as well consider coin flipping a valid test. If you tested America with this test you’d end up thinking half the country is infected. And within the ones that tested positive only half would actually be and within the negatives half would be and you would have missed them. A test needs to be materially more accurate than the odds of having the disease to be worth anything. Classic thought experiment: if 0.0001% of the population has a disease and a test is 99% effective and you test positive, what are the odds you have the disease? Answer: 1%. Complimentary thought experiment: if an expensive preventive drug was available in limited supply (for 0.1% of the population only) and the earlier you took it the more preventive it was should you give it blindly to as many positives as you can? Probably not because 99% of that would be going to waste. And you would run out of drugs to cover the actual sick. Only 10% of the sick would end up actually getting the drugs.
- DangitBobby 7y ago

mkagenius 7y ago

> they're rife with false positives. Is it possible that some of the positive cases of Corona are actually positive cases of Influenza?

acqq 7y ago
No, it is not, see the numbers compared by the Italian National Biotechnology Association: https://en.wikipedia.org/wiki/File:Is_COVID-19_like_a_flu%3F_ENG.png https://en.wikipedia.org/wiki/File:Is_COVID-19_like_a_flu%3F... Each bar is one week. Flu has totally different speed of increase and the amount of people needing treatment and dying. We know what is the cause of the increase, the scenario repeats in many countries across the world, it's not one isolated setup.
- mkagenius 7y ago
  I was curious about the possible mix up of flu and covid by the testing kit since they are similar, I am not denying that covid exists, just that if the tests are mixing the two up.
  - Tepix 7y ago
    No, the covid testing kit was tested with more than a thousand probes and there wasn't a single false positive. Source: Christian Drosten (he created the test) on the NDR Coronavirus Podcast
    - capableweb 7y ago
      There is another source (in German) claiming the same, HN comment here: https://news.ycombinator.com/item?id=22627958 https://news.ycombinator.com/item?id=22627958 and source here: https://www.ndr.de/nachrichten/info/16-Coronavirus-Update-Wir-brauchen-Abkuerzungen-bei-der-Impfstoffzulassung,podcastcoronavirus140.html https://www.ndr.de/nachrichten/info/16-Coronavirus-Update-Wi... > Regarding your question about if we might accidentally test for flu or other, already existing corona virii: > This was a topic of discussion in yesterday's talk [1] with Dr. Drosten, a virologist who played an important part in the development of the currently used PCR test. He said that there were extensive studies done with hundreds of samples from both flu patients and patients infected with other corona virii and none returned a positive result. The only other positive results were from corona virii that are special to certain animals (bats, some cows IIRC), but none of those are present in humans. So the accuracy of our current PCR test for SARS-CoV-2 seems to be extremely high. Edit: realize now that it's the same person (Dr. Drosten) so same source, but different format (podcast vs transcript)

mythz 7y ago

Given one of the best pieces of advice about managing COVID-19 is to "Act Like You Already Have it" [1], a less accurate test with more false positives isn't necessarily a bad thing. [1] https://www.huffingtonpost.com.au/entry/act-like-you-have-coronavirus_l_5e721aafc5b6eab7793fc120 https://www.huffingtonpost.com.au/entry/act-like-you-have-co...

cryptonector 7y ago

We really need a test for anti-bodies as well.

diag 7y ago
Antibody tests are also fairly unreliable in a number of circumstances as well.