12 ms·

> I have looked and I cannot even find how increasing CT values affect the false positive rate for the PCR testing. If my understanding is correct a single incr

by timr 5y ago

> I have looked and I cannot even find how increasing CT values affect the false positive rate for the PCR testing. If my understanding is correct a single increment of CT essentially doubles the sensitivity of the test, so difference between CT value of 35 and 40 is 32 fold. I have never used this particular set of primers, but have done a lot of PCR. In general, at 30+ cycles, PCR is prone to spurious amplification. It depends on the primers, temperature profile, and other details, but at these cycle counts you need to be skeptical of your results. It's easy to get noise. I've never been able to fathom how a PCR amplification at 30+ cycles with no downstream purification or gel visualization is considered definitive diagnosis of an illness. I strongly suspect that the goal was to cast a wide net (i.e. bias toward false positives) at the expense of accuracy, but then "cases" became some kind of top-line media metric...

mizzack 5y ago
> I strongly suspect that the goal was to cast a wide net (i.e. bias toward false positives) at the expense of accuracy, but then "cases" became some kind of top-line media metric... Then in January the WHO updated the diagnostic protocol [1] because of that false positive/low confidence problem. Unsurprisingly, case counts plummeted in the following weeks. [1] https://www.who.int/news/item/20-01-2021-who-information-notice-for-ivd-users-2020-05 https://www.who.int/news/item/20-01-2021-who-information-not...
- timr 5y ago
  Yep. It was stunning to me that this was rarely mentioned in the press.
- themark 5y ago
  When I bring this up in conversations with people they make me feel like a kook. I am not sure what to think anymore.
  - wut2doobiedo 5y ago
    Because what to do is highly variable doesn’t mean we need to take unnecessary risk to know literal truth. Urban area population density requires different mitigations than rural, except rural communities rely on urban ones as logistics pipelines. So normalize; mask up, stay home. Prefer all gas, no brakes, based on stats? There may not be enough real people to keep the internet on later. Nothing about the lockdown was for saving you or me specifically, but systems of behavior we rely on.
    - deleted 5y ago
      [deleted]
    - nradov 5y ago
      That isn't a valid reason. The infection fatality rate for most people who keep the Internet running is way less than 1%. https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scena...
  - simonh 5y ago
    For me this is interesting, but not really material to anything. Sure, the tests we have for this new virus have needed to be adjusted and calibrated as we learn more about it. It's unfortunate if the numbers are a bit messed up, it would be better if they were more accurate, but real life is messy. I don't think you're a kook, and I can only guess what those people were thinking. Maybe they just wondered... and therefore, what?
    - kook_throwaway 5y ago
      Abusing high cycle thresholds for false positives isn't a new strategy. PCR inventor Kary Mullis is on video calling Fauci out for doing exactly that. Unfortunately I can't even link the two videos because they keep getting memory holed. If you search around you might get lucky, otherwise I'll upload my saved copy when I get off work.
      - javagram 5y ago
        Note that the background for this is that Kary Mullis believed AIDS wasn’t caused by HIV and was therefore angry at Fauci and the entire medical/scientific establishment for linking HIV and AIDS. He died in 2019 so his criticisms of Fauci were related to HIV, not SARS-CoV-2. https://en.wikipedia.org/wiki/Kary_Mullis#Views_on_HIV/AIDS_and_climate_change https://en.wikipedia.org/wiki/Kary_Mullis#Views_on_HIV/AIDS_...
        themark 5y ago
        The video they are referring to has a very specific part about pcr testing (relevant to the discussion here). I think it is reasonable to trust his opinion on the matter regardless of what he thinks about AIDS.
        briefcomment 5y ago
        He is also a Nobel laureate.
        javagram 5y ago
  - mizzack 5y ago
    It didn't help that the WHO released the updated guidelines the day Biden was inaugurated. For that reason alone it became another thought-terminating political topic -- you're either dismissed as a conspiracy theorist for correlating these events, or you're dismissing the value of the vaccine rollout/lockdowns/other measures, or you're a sheep following the dominant media narrative.
    - beerandt 5y ago
      It's harder to dismiss when you also consider the first vaccine approvals kept getting delayed until they were released immediately after the election.
      - javagram 5y ago
        Note that it was hardly “delayed” since all initial predictions for the vaccine to be approved were around 12 months, in the end it only took about 10 months. Reports last year indicated Trump’s own FDA was responsible for setting out the needed time for data gathering and review that pushed it into mid-November. https://abcnews.go.com/Politics/white-house-okays-fda-months-monitoring-delaying-vaccine/story?id=73454563 https://abcnews.go.com/Politics/white-house-okays-fda-months... Meanwhile other countries including China and Russia didn’t approve their own vaccines faster, seeming to indicate the timeline had little to do with U.S. politics.
        jimmygrapes 5y ago
        It is worth considering that maybe Sinovac (and whatever the Russian one(s) is/are called) may have been released far earlier than they would have been if the U.S. and others had not developed their own faster. Think of space wars - even if you lose the race to first, you still want to be in 2nd vs 500th. If they were developed at a more traditional pace, would they be more effective? Would any of them be? And what would be the consequences of waiting? Would it be millions more deaths, or would natural herd immunity emerge? Both? Would the more virulent variants have appeared without a marginally effective strain evolving as a result of marginally effective vaccines?
- beerandt 5y ago
  On inauguration day.
  - apercu 5y ago
    Sure, and it could be political. In fact, most things of this nature are at that level. So, maybe, the people in charge didn't like the previous US government admin so they didn't help improve its numbers. That is certainly more likely and believable than some vast left-wing conspiracy to implant Bill Gate's microchips in to your iPhone carrying ass to "track" you. :)
    - leereeves 5y ago
      Instead you're just talking about a left-wing conspiracy to lie to the public in order to take control of the government. Things like that make people suspicious, and make it easy for people who don't know the difference between a quantum dot[1] and a microchip to misunderstand when Bill Gates calls for a national tracking system[2]. 1: (a quantum dot to store medical information beneath the skin really was funded by Bill Gates) https://news.mit.edu/2019/storing-vaccine-history-skin-1218 https://news.mit.edu/2019/storing-vaccine-history-skin-1218 2: https://www.forbes.com/sites/mattperez/2020/03/18/bill-gates-calls-for-national-tracking-system-for-coronavirus-during-reddit-ama/ https://www.forbes.com/sites/mattperez/2020/03/18/bill-gates...
      - kook_throwaway 5y ago
        >Instead you're just talking about a left-wing conspiracy to lie to the public in order to take control of the government. To take control of the government or for good PR/propaganda? Governments have never had any issues conspiring and lying to the public, remember when Fauci said not to use masks because they didn't help? Or those WMDs that we will surely find any day now?
        deleted 5y ago
        [deleted]
        5y ago
- icegreentea2 5y ago
  Are you sure this is the right link? I looked at this notice, and compared to the previous version from December 2020 (https://www.terviseamet.ee/sites/default/files/MSO/2020_ohutusalane_teave/detsember/who_soovitused_sars-cov-2_testide_tulemuste_hindamise_kohta.pdf https://www.terviseamet.ee/sites/default/files/MSO/2020_ohut...) and they appear broadly similar... there's perhaps a bit more upfront on the need to deal with weakly positive results, but they both tell you to read your device IFU and adjust your thresholds accordingly.
  - xyzzy21 5y ago
    Probably changed post-publication. That's a super common thing now. And why you always need to both use an archiver site and possibly save a local copy.
    - javagram 5y ago
      Rather than speculate why didn’t you just do a google search? A quick google and check of archive.org finds the document released in December with an archive date of dec 16. https://web.archive.org/web/20201216033740/https://www.news-medical.net/news/20201214/World-Health-Organization-issues-notice-for-in-vitro-diagnostics-users.aspx https://web.archive.org/web/20201216033740/https://www.news-...
- blywi 5y ago
  This WHO statement has been widely misinterpreted, is is not the case that PCR tests were resulting in inflated numbers of false positives, see Reuters fact check [1] from February 4, 2021, and [2] from April 8, 2021. [1] https://www.reuters.com/article/uk-factcheck-who-instructions-pcr-guidan-idUSKBN2A429W https://www.reuters.com/article/uk-factcheck-who-instruction... [2] https://www.reuters.com/article/factcheck-who-pcr-idUSL1N2M10ID https://www.reuters.com/article/factcheck-who-pcr-idUSL1N2M1...
  - themark 5y ago
    “The WHO information notice is not a retraction; rather, it is a clarification for laboratory professionals on how to interpret PCR results.” Why would WHO feel the need to tell people to read the operating manuals closely? I’m sure its not because the accuracy was too high.
- robocat 5y ago
  WHO did give a good reason: “ WHO reminds IVD users that disease prevalence alters the predictive value of test results; as disease prevalence decreases, the risk of false positive increases (2). This means that the probability that a person who has a positive result (SARS-CoV-2 detected) is truly infected with SARS-CoV-2 decreases as prevalence decreases, irrespective of the claimed specificity.” Given that reason, cause and effect would be hard to pick.
a9h74j 5y ago
To a less-frequent degree than with 'cases' the meaning of 'gold-standard' seems to have changed as well, or be starting to. As I understand it, a proper gold-standard test is proven to have essentially 100% correlation to verified clinical symptoms or findings.
ssully 5y ago
Please correct me if I am wrong, but I feel like you are trying to say more with "but then 'cases' became some kind of top-line media metric". Should cases not be an important metric for people to know?
- analyte123 5y ago
  I think his point is that having a minute amount (possibly non-viable) of viral DNA in your respiratory tract does not necessarily make you a true "case" in terms of being actively infected with the virus.
- nickthemagicman 5y ago
  He's saying the definition of cases in 'actual science' vs 'the media' is different. Not a shocker that the media would sensationalize things. Science and PCR amplification... has a much looser definition with the possibility for much more false positives with such small number of cycles of amplification. It was done ostensibly for cautionary purposes but the media seized on it and painted red death map visualizations for people to see with inflated death counts.
  - ssully 5y ago
    I understand that. But I would hardly call it sensationalizing. It's a mixture of the best of what we had at the time (others have posted talking about how the tests have changed/improved), and the fact that reporting on things in a simple and straight forward manner is hard because people simply don't have the time, or don't give a shit about nuance.
    - mistermann 5y ago
      I suspect that a pattern of not disclosing that statistics that are implied to be factual are actually to some degree ~estimates contributed to the extreme level of polarization over "facts" and "the science", as well as the increasing distrust of the media. Sure, most people don't consider these things too logically, but then if those distributing the facts can't be bothered either, how shall we accurately assign blame for the final outcome?
cameldrv 5y ago
At the latest low point in the epidemic, some areas were seeing test positivity rates of under 0.5%. If false positives were a large portion of positives, this would seem to be impossible.
- dragonwriter 5y ago
  > At the latest low point in the epidemic, some areas were seeing test positivity rates of under 0.5%. If false positives were a large portion of positives, this would seem to be impossible. Its quite possible, especially if there is a testing bias toward people who are less likely to have the disease
  - deleted 5y ago
    [deleted]
  - cameldrv 5y ago
    Even if they were testing people that were all externally known not to have COVID, if only 0.5% of people are testing positive, that's the false positive rate. All the data we have indicates that false positives on PCR are extremely rare. The only place it gets fuzzy is the definition of positive. People who were previously infected can test positive, and people with very mild infections can also test positive. People who have never been infected though essentially do not test positive.
- aeternum 5y ago
  The problem is the false positive isn't truly independent of environmental factors. PCR determines how many exponential amplifications are necessary to get a detectable amount of the target RNA sequences. The amount of that target RNA floating around in the environment does slightly impact the base amount present in even covid-negative patients.
  - cameldrv 5y ago
    It's true that people who had COVID can still have viral RNA in their noses for a while and still test positive. The most sensitive tests have a limit of detection of a couple hundred copies/ml, and the collection kits usually use 1ml of VTM or equivalent. I find it hard to believe that a significant number of people will have enough viral RNA in their nose to put hundreds of copies onto a swab unless it's their own body that's producing those copies.
xyzzy21 5y ago
ANY molecular biologist will tell you that it's NOT. At 30+ cycles, you are generated false positives off of both everyday Common Cold coronavirus, influenza and probably even bacteria. Literally you are amplifying noise and then calling it a positive.
native_samples 5y ago
It is worth noting here, as you didn't say it explicitly, that COVID labs routinely report positives as late as 40 cycles.
- themark 5y ago
  This link was often cited by fact checkers last year. “Most tests, like the Broad Institute test used by MIT, use a 40-cycle protocol. If the virus isn’t detected within 40 amplification cycles, the test result is negative. If viral RNA is detected in 40 cycles or less, the PCR machine stops running, and the test is positive. Because you received a positive result, we know that the test detected the virus in your sample by the time it reached its 40-cycle limit.” https://medical.mit.edu/covid-19-updates/2020/11/pcr-test-result https://medical.mit.edu/covid-19-updates/2020/11/pcr-test-re...
simpleguitar 5y ago
A PCR test that is sensitive is a great tool. Remember the NBA bubble? A less sensitive test would have allowed outbreaks inside the bubble, making some player sick and unable to play, as well as eroding the public's confidence on PCR tests. Factories and meat packing plants used negative PCR tests to create their own bubbles and keep them running. There is large positive economic value to a highly sensitive test with a small false negative and a larger false positive. There is much less economic value in a test that allows escapes (rapid tests).
- timr 5y ago
  > A PCR test that is sensitive is a great tool. Remember the NBA bubble? A less sensitive test would have allowed outbreaks inside the bubble, making some player sick and unable to play, as well as eroding the public's confidence on PCR tests. A hammer is a great tool. It is not a great tool for repairing broken pottery. PCR is the ideal tool if you want to detect infinitesimal amounts of a specific nucleic acid sequence. It is not a great tool if you want to use it to define "illness" or "infectivity", for it cannot tell you anything about those questions. Can you use PCR to cast the widest possible net, and isolate literally everyone who has any shred of viral RNA? Yes. That's essentially what we've been doing. It is a strategy, and this strategy is appropriate in some situations. This strategy becomes a problem when you forget that you're allowing a lot of false positives to be caught up in the process, and start behaving as if "a positive" is a meaningful clinical diagnosis. Now that we have highly effective vaccines and are out of the acute phase of the crisis, it's time to adjust our definition of "infection" to more accurately reflect the true clinical meaning of the word.

by timr 5y ago

mizzack 5y ago

> I strongly suspect that the goal was to cast a wide net (i.e. bias toward false positives) at the expense of accuracy, but then "cases" became some kind of top-line media metric... Then in January the WHO updated the diagnostic protocol [1] because of that false positive/low confidence problem. Unsurprisingly, case counts plummeted in the following weeks. [1] https://www.who.int/news/item/20-01-2021-who-information-notice-for-ivd-users-2020-05 https://www.who.int/news/item/20-01-2021-who-information-not...

timr 5y ago
Yep. It was stunning to me that this was rarely mentioned in the press.
themark 5y ago
When I bring this up in conversations with people they make me feel like a kook. I am not sure what to think anymore.
- wut2doobiedo 5y ago
  Because what to do is highly variable doesn’t mean we need to take unnecessary risk to know literal truth. Urban area population density requires different mitigations than rural, except rural communities rely on urban ones as logistics pipelines. So normalize; mask up, stay home. Prefer all gas, no brakes, based on stats? There may not be enough real people to keep the internet on later. Nothing about the lockdown was for saving you or me specifically, but systems of behavior we rely on.
  - deleted 5y ago
    [deleted]
  - nradov 5y ago
    That isn't a valid reason. The infection fatality rate for most people who keep the Internet running is way less than 1%. https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scena...
- simonh 5y ago
  For me this is interesting, but not really material to anything. Sure, the tests we have for this new virus have needed to be adjusted and calibrated as we learn more about it. It's unfortunate if the numbers are a bit messed up, it would be better if they were more accurate, but real life is messy. I don't think you're a kook, and I can only guess what those people were thinking. Maybe they just wondered... and therefore, what?
  - kook_throwaway 5y ago
    Abusing high cycle thresholds for false positives isn't a new strategy. PCR inventor Kary Mullis is on video calling Fauci out for doing exactly that. Unfortunately I can't even link the two videos because they keep getting memory holed. If you search around you might get lucky, otherwise I'll upload my saved copy when I get off work.
    - javagram 5y ago
      Note that the background for this is that Kary Mullis believed AIDS wasn’t caused by HIV and was therefore angry at Fauci and the entire medical/scientific establishment for linking HIV and AIDS. He died in 2019 so his criticisms of Fauci were related to HIV, not SARS-CoV-2. https://en.wikipedia.org/wiki/Kary_Mullis#Views_on_HIV/AIDS_and_climate_change https://en.wikipedia.org/wiki/Kary_Mullis#Views_on_HIV/AIDS_...
      - themark 5y ago
        The video they are referring to has a very specific part about pcr testing (relevant to the discussion here). I think it is reasonable to trust his opinion on the matter regardless of what he thinks about AIDS.
        briefcomment 5y ago
        He is also a Nobel laureate.
        javagram 5y ago
- mizzack 5y ago
  It didn't help that the WHO released the updated guidelines the day Biden was inaugurated. For that reason alone it became another thought-terminating political topic -- you're either dismissed as a conspiracy theorist for correlating these events, or you're dismissing the value of the vaccine rollout/lockdowns/other measures, or you're a sheep following the dominant media narrative.
  - beerandt 5y ago
    It's harder to dismiss when you also consider the first vaccine approvals kept getting delayed until they were released immediately after the election.
    - javagram 5y ago
      Note that it was hardly “delayed” since all initial predictions for the vaccine to be approved were around 12 months, in the end it only took about 10 months. Reports last year indicated Trump’s own FDA was responsible for setting out the needed time for data gathering and review that pushed it into mid-November. https://abcnews.go.com/Politics/white-house-okays-fda-months-monitoring-delaying-vaccine/story?id=73454563 https://abcnews.go.com/Politics/white-house-okays-fda-months... Meanwhile other countries including China and Russia didn’t approve their own vaccines faster, seeming to indicate the timeline had little to do with U.S. politics.
      - jimmygrapes 5y ago
        It is worth considering that maybe Sinovac (and whatever the Russian one(s) is/are called) may have been released far earlier than they would have been if the U.S. and others had not developed their own faster. Think of space wars - even if you lose the race to first, you still want to be in 2nd vs 500th. If they were developed at a more traditional pace, would they be more effective? Would any of them be? And what would be the consequences of waiting? Would it be millions more deaths, or would natural herd immunity emerge? Both? Would the more virulent variants have appeared without a marginally effective strain evolving as a result of marginally effective vaccines?
beerandt 5y ago
On inauguration day.
- apercu 5y ago
  Sure, and it could be political. In fact, most things of this nature are at that level. So, maybe, the people in charge didn't like the previous US government admin so they didn't help improve its numbers. That is certainly more likely and believable than some vast left-wing conspiracy to implant Bill Gate's microchips in to your iPhone carrying ass to "track" you. :)
  - leereeves 5y ago
    Instead you're just talking about a left-wing conspiracy to lie to the public in order to take control of the government. Things like that make people suspicious, and make it easy for people who don't know the difference between a quantum dot[1] and a microchip to misunderstand when Bill Gates calls for a national tracking system[2]. 1: (a quantum dot to store medical information beneath the skin really was funded by Bill Gates) https://news.mit.edu/2019/storing-vaccine-history-skin-1218 https://news.mit.edu/2019/storing-vaccine-history-skin-1218 2: https://www.forbes.com/sites/mattperez/2020/03/18/bill-gates-calls-for-national-tracking-system-for-coronavirus-during-reddit-ama/ https://www.forbes.com/sites/mattperez/2020/03/18/bill-gates...
    - kook_throwaway 5y ago
      >Instead you're just talking about a left-wing conspiracy to lie to the public in order to take control of the government. To take control of the government or for good PR/propaganda? Governments have never had any issues conspiring and lying to the public, remember when Fauci said not to use masks because they didn't help? Or those WMDs that we will surely find any day now?
      - deleted 5y ago
        [deleted]
      - 5y ago
icegreentea2 5y ago
Are you sure this is the right link? I looked at this notice, and compared to the previous version from December 2020 (https://www.terviseamet.ee/sites/default/files/MSO/2020_ohutusalane_teave/detsember/who_soovitused_sars-cov-2_testide_tulemuste_hindamise_kohta.pdf https://www.terviseamet.ee/sites/default/files/MSO/2020_ohut...) and they appear broadly similar... there's perhaps a bit more upfront on the need to deal with weakly positive results, but they both tell you to read your device IFU and adjust your thresholds accordingly.
- xyzzy21 5y ago
  Probably changed post-publication. That's a super common thing now. And why you always need to both use an archiver site and possibly save a local copy.
  - javagram 5y ago
    Rather than speculate why didn’t you just do a google search? A quick google and check of archive.org finds the document released in December with an archive date of dec 16. https://web.archive.org/web/20201216033740/https://www.news-medical.net/news/20201214/World-Health-Organization-issues-notice-for-in-vitro-diagnostics-users.aspx https://web.archive.org/web/20201216033740/https://www.news-...
blywi 5y ago
This WHO statement has been widely misinterpreted, is is not the case that PCR tests were resulting in inflated numbers of false positives, see Reuters fact check [1] from February 4, 2021, and [2] from April 8, 2021. [1] https://www.reuters.com/article/uk-factcheck-who-instructions-pcr-guidan-idUSKBN2A429W https://www.reuters.com/article/uk-factcheck-who-instruction... [2] https://www.reuters.com/article/factcheck-who-pcr-idUSL1N2M10ID https://www.reuters.com/article/factcheck-who-pcr-idUSL1N2M1...
- themark 5y ago
  “The WHO information notice is not a retraction; rather, it is a clarification for laboratory professionals on how to interpret PCR results.” Why would WHO feel the need to tell people to read the operating manuals closely? I’m sure its not because the accuracy was too high.
robocat 5y ago
WHO did give a good reason: “ WHO reminds IVD users that disease prevalence alters the predictive value of test results; as disease prevalence decreases, the risk of false positive increases (2). This means that the probability that a person who has a positive result (SARS-CoV-2 detected) is truly infected with SARS-CoV-2 decreases as prevalence decreases, irrespective of the claimed specificity.” Given that reason, cause and effect would be hard to pick.

a9h74j 5y ago

To a less-frequent degree than with 'cases' the meaning of 'gold-standard' seems to have changed as well, or be starting to. As I understand it, a proper gold-standard test is proven to have essentially 100% correlation to verified clinical symptoms or findings.

ssully 5y ago

Please correct me if I am wrong, but I feel like you are trying to say more with "but then 'cases' became some kind of top-line media metric". Should cases not be an important metric for people to know?

analyte123 5y ago
I think his point is that having a minute amount (possibly non-viable) of viral DNA in your respiratory tract does not necessarily make you a true "case" in terms of being actively infected with the virus.
nickthemagicman 5y ago
He's saying the definition of cases in 'actual science' vs 'the media' is different. Not a shocker that the media would sensationalize things. Science and PCR amplification... has a much looser definition with the possibility for much more false positives with such small number of cycles of amplification. It was done ostensibly for cautionary purposes but the media seized on it and painted red death map visualizations for people to see with inflated death counts.
- ssully 5y ago
  I understand that. But I would hardly call it sensationalizing. It's a mixture of the best of what we had at the time (others have posted talking about how the tests have changed/improved), and the fact that reporting on things in a simple and straight forward manner is hard because people simply don't have the time, or don't give a shit about nuance.
  - mistermann 5y ago
    I suspect that a pattern of not disclosing that statistics that are implied to be factual are actually to some degree ~estimates contributed to the extreme level of polarization over "facts" and "the science", as well as the increasing distrust of the media. Sure, most people don't consider these things too logically, but then if those distributing the facts can't be bothered either, how shall we accurately assign blame for the final outcome?

cameldrv 5y ago

At the latest low point in the epidemic, some areas were seeing test positivity rates of under 0.5%. If false positives were a large portion of positives, this would seem to be impossible.

dragonwriter 5y ago
> At the latest low point in the epidemic, some areas were seeing test positivity rates of under 0.5%. If false positives were a large portion of positives, this would seem to be impossible. Its quite possible, especially if there is a testing bias toward people who are less likely to have the disease
- deleted 5y ago
  [deleted]
- cameldrv 5y ago
  Even if they were testing people that were all externally known not to have COVID, if only 0.5% of people are testing positive, that's the false positive rate. All the data we have indicates that false positives on PCR are extremely rare. The only place it gets fuzzy is the definition of positive. People who were previously infected can test positive, and people with very mild infections can also test positive. People who have never been infected though essentially do not test positive.
aeternum 5y ago
The problem is the false positive isn't truly independent of environmental factors. PCR determines how many exponential amplifications are necessary to get a detectable amount of the target RNA sequences. The amount of that target RNA floating around in the environment does slightly impact the base amount present in even covid-negative patients.
- cameldrv 5y ago
  It's true that people who had COVID can still have viral RNA in their noses for a while and still test positive. The most sensitive tests have a limit of detection of a couple hundred copies/ml, and the collection kits usually use 1ml of VTM or equivalent. I find it hard to believe that a significant number of people will have enough viral RNA in their nose to put hundreds of copies onto a swab unless it's their own body that's producing those copies.

xyzzy21 5y ago

ANY molecular biologist will tell you that it's NOT. At 30+ cycles, you are generated false positives off of both everyday Common Cold coronavirus, influenza and probably even bacteria. Literally you are amplifying noise and then calling it a positive.

native_samples 5y ago

It is worth noting here, as you didn't say it explicitly, that COVID labs routinely report positives as late as 40 cycles.

themark 5y ago
This link was often cited by fact checkers last year. “Most tests, like the Broad Institute test used by MIT, use a 40-cycle protocol. If the virus isn’t detected within 40 amplification cycles, the test result is negative. If viral RNA is detected in 40 cycles or less, the PCR machine stops running, and the test is positive. Because you received a positive result, we know that the test detected the virus in your sample by the time it reached its 40-cycle limit.” https://medical.mit.edu/covid-19-updates/2020/11/pcr-test-result https://medical.mit.edu/covid-19-updates/2020/11/pcr-test-re...

simpleguitar 5y ago

A PCR test that is sensitive is a great tool. Remember the NBA bubble? A less sensitive test would have allowed outbreaks inside the bubble, making some player sick and unable to play, as well as eroding the public's confidence on PCR tests. Factories and meat packing plants used negative PCR tests to create their own bubbles and keep them running. There is large positive economic value to a highly sensitive test with a small false negative and a larger false positive. There is much less economic value in a test that allows escapes (rapid tests).

timr 5y ago
> A PCR test that is sensitive is a great tool. Remember the NBA bubble? A less sensitive test would have allowed outbreaks inside the bubble, making some player sick and unable to play, as well as eroding the public's confidence on PCR tests. A hammer is a great tool. It is not a great tool for repairing broken pottery. PCR is the ideal tool if you want to detect infinitesimal amounts of a specific nucleic acid sequence. It is not a great tool if you want to use it to define "illness" or "infectivity", for it cannot tell you anything about those questions. Can you use PCR to cast the widest possible net, and isolate literally everyone who has any shred of viral RNA? Yes. That's essentially what we've been doing. It is a strategy, and this strategy is appropriate in some situations. This strategy becomes a problem when you forget that you're allowing a lot of false positives to be caught up in the process, and start behaving as if "a positive" is a meaningful clinical diagnosis. Now that we have highly effective vaccines and are out of the acute phase of the crisis, it's time to adjust our definition of "infection" to more accurately reflect the true clinical meaning of the word.